Difference between revisions of "Medical kidney diseases"

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This article describes '''medical renal disease''' or the '''medical kidney'''.  Much in medical kidney depends on the clinical information.  Most of the disease seen by pathologists is... glomerular disease.  If in doubt... the answer to most questions is ''diabetes mellitus'' or ''systemic lupus erythematosus''.  Medical kidney is niche area in pathology.  It is one of the few areas that routinely requires electron microscopy.
[[Image:Acute thrombotic microangiopathy - pas - very high mag.jpg|250px|thumb|[[Micrograph]] showing a glomerulus with an [[thrombotic microangiopathy|acute thrombotic microangiopathy]]. [[PAS stain]].]]
This article describes '''medical renal disease''' or the '''medical kidney'''.  Much in medical kidney depends on the clinical information.  Most of the disease seen by pathologists is... glomerular disease. It is one of the few areas that routinely requires [[electron microscopy]].
   
Medical kidney is niche area in pathology. In the context of exams for general pathologists, if in doubt... the answer to most questions is ''[[diabetes mellitus]]'' or ''[[systemic lupus erythematosus]]''.   


Kidney tumours are dealt with in the ''[[kidney tumours]]'' article.
Kidney tumours are dealt with in the ''[[kidney tumours]]'' article, and ''[[pediatric kidney tumours]]'' article.  
 
==Clinical==
===Glomerular filtration rate===
*Abbreviated ''GFR''.
*Ultimate measure of renal function.
*Declines with age.
*Normal range (dependent on age): 116-75 mL/min/1.73m<sup>2</sup>.<ref>URL: [http://www.kidney.org/professionals/KLS/gfr.cfm http://www.kidney.org/professionals/KLS/gfr.cfm]. Accessed on: 8 November 2010.</ref>


=Clinical=
===Creatinine===
===Creatinine===
*The standard screening test for renal function.
*The standard screening test for renal function.
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Notes:
Notes:
*Dinosaurs use the units mg/dL; normal with these units is: 0.8 to 1.4 mg/dL.<ref>URL: [http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm]. Accessed on: 8 November 2010.</ref>
*In some parts of the world they use the units mg/dL; normal with these units is: 0.8 to 1.4 mg/dL.<ref>URL: [http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm http://www.nlm.nih.gov/medlineplus/ency/article/003475.htm]. Accessed on: 8 November 2010.</ref>
*Conversion: 1.0 mg/dL = 88.4 umol/L.<ref>URL: [http://www.sydpath.stvincents.com.au/other/Conversions/ConversionMasterF3.htm http://www.sydpath.stvincents.com.au/other/Conversions/ConversionMasterF3.htm]. Accessed on: 8 November 2010.</ref><ref>URL: [http://www.unc.edu/~rowlett/units/scales/clinical_data.html http://www.unc.edu/~rowlett/units/scales/clinical_data.html]. Accessed on: 8 November 2010.
*Conversion: 1.0 mg/dL = 88.4 umol/L.<ref>URL: [http://www.sydpath.stvincents.com.au/other/Conversions/ConversionMasterF3.htm http://www.sydpath.stvincents.com.au/other/Conversions/ConversionMasterF3.htm]. Accessed on: 8 November 2010.</ref><ref>URL: [http://www.unc.edu/~rowlett/units/scales/clinical_data.html http://www.unc.edu/~rowlett/units/scales/clinical_data.html]. Accessed on: 8 November 2010.
</ref>
</ref>
====Glomerular filtration rate====
*Abbreviated ''GFR''.
*Ultimate measure of renal function - usually estimated from the serum creatinine using a formula.
*Declines with age.
*Normal range (dependent on age): 116-75 mL/min/1.73m<sup>2</sup>.<ref>URL: [http://www.kidney.org/professionals/KLS/gfr.cfm http://www.kidney.org/professionals/KLS/gfr.cfm]. Accessed on: 8 November 2010.</ref>
===Urine protein to creatinine ratio===
===Urine protein to creatinine ratio===
*Indicator of proteinuria.
*Indicator of proteinuria.
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Cut points:<ref>URL: [http://www.fpnotebook.com/urology/lab/urnprtntcrtnrt.htm http://www.fpnotebook.com/urology/lab/urnprtntcrtnrt.htm]. Accessed on: 8 November 2010.</ref>
Cut points:<ref>URL: [http://www.fpnotebook.com/urology/lab/urnprtntcrtnrt.htm http://www.fpnotebook.com/urology/lab/urnprtntcrtnrt.htm]. Accessed on: 8 November 2010.</ref>
*Normal (2 years and older): <0.2 g protein / g Creatinine
*Normal (2 years and older): <0.2 g protein / g Creatinine
*Nephrotic range: >3.5 g protein / g Creatinine.  
*[[Nephrotic syndrome|Nephrotic]] range: >3.5 g protein / g Creatinine.  
 
===Complement===
C3, C4 levels:<ref name=pmid4549215>{{cite journal |author=Levo Y, Pick AI |title=The significance of C3 and C4 complement levels in lupus nephritis |journal=Int Urol Nephrol |volume=6 |issue=3-4 |pages=233–8 |year=1974 |pmid=4549215 |doi= |url=http://www.springerlink.com/content/l1657797661468g1/fulltext.pdf}}</reF>
*Changed:
**[[Systemic lupus erythematosus]] (SLE); levels decreased = increased disease activity.
**[[Post-infectious GN]] - decreased.
**[[MPGN]] - decreased. (???)
**Infection.<ref name=pmid3892188>{{cite journal |author=Nusinow SR, Zuraw BL, Curd JG |title=The hereditary and acquired deficiencies of complement |journal=Med. Clin. North Am. |volume=69 |issue=3 |pages=487–504 |year=1985 |month=May |pmid=3892188 |doi= |url=}}</ref><ref>URL: [http://www.google.com/url?sa=t&source=web&cd=3&sqi=2&ved=0CB0QFjAC&url=http%3A%2F%2Fwww.beckmancoulter.com%2Fliterature%2FClinDiag%2FBulletin%25209282C3_C4.pdf&rct=j&q=C3%2C%20C4%20decreased%2C%20l&ei=0evYTPLHHcX9ngfetNDzCQ&usg=AFQjCNFR26FHyAmy4lZ3tm-tLgW-oD73Zg&cad=rja beckmancoulter.com]. Accessed on: 9 November 2010.</ref>
**Hemolytic [[anemia]].<ref name=pmid3892188>{{cite journal |author=Nusinow SR, Zuraw BL, Curd JG |title=The hereditary and acquired deficiencies of complement |journal=Med. Clin. North Am. |volume=69 |issue=3 |pages=487–504 |year=1985 |month=May |pmid=3892188 |doi= |url=}}</ref><ref>URL: [http://www.google.com/url?sa=t&source=web&cd=3&sqi=2&ved=0CB0QFjAC&url=http%3A%2F%2Fwww.beckmancoulter.com%2Fliterature%2FClinDiag%2FBulletin%25209282C3_C4.pdf&rct=j&q=C3%2C%20C4%20decreased%2C%20l&ei=0evYTPLHHcX9ngfetNDzCQ&usg=AFQjCNFR26FHyAmy4lZ3tm-tLgW-oD73Zg&cad=rja beckmancoulter.com]. Accessed on: 9 November 2010.</ref>
*Normal:
**[[Minimal change disease]].
**Chronic pyelonephritis.
**Renal vein [[thrombosis]].
**[[Amyloidosis]].
 
===ANCA===
Types:<ref name=pmid21339221>{{Cite journal  | last1 = Kallenberg | first1 = CG. | title = Pathogenesis of ANCA-associated vasculitides. | journal = Ann Rheum Dis | volume = 70 Suppl 1 | issue =  | pages = i59-63 | month = Mar | year = 2011 | doi = 10.1136/ard.2010.138024 | PMID = 21339221 }}</ref>
*MPO-ANCA (myeloperoxidase antineutrophil cytoplasmic autoantibody).
**Previously p-ANCA.
**Seen in ANCA-[[vasculitides]], esp. [[microscopic polyangiitis]].
*PR3-ANCA (proteinase 3 antineutrophil cytoplasmic autoantibody).
**Previously c-ANCA.
**Seen in ANCA-[[vasculitides]], esp. [[granulomatosis with polyangiitis]] (Wegener granulomatosis).
 
===C4d===
*Suggests humoral immunity (antibody-mediated immunity) at play.
*Important in monitoring of renal transplant recipients.
*[[Immunostain]] also available - see below.
 
===Other blood work===
*ANA, dsDNA -- to screen for [[systemic lupus erythematosus]].
*[[Hepatitis B]].
*[[Hepatitis C]].
*[[HIV]].
*Serum protein electrophoresis (SPEP) -- to screen for [[plasma cell neoplasm]]s.
**Often done together with ''urine protein electrophoresis'' (UPEP).
 
===Renal ultrasound===
*Normal adult kidney size ~10.8+/-0.8 cm.<ref name=pmid8125561>{{Cite journal  | last1 = Guzman | first1 = RP. | last2 = Zierler | first2 = RE. | last3 = Isaacson | first3 = JA. | last4 = Bergelin | first4 = RO. | last5 = Strandness | first5 = DE. | title = Renal atrophy and arterial stenosis. A prospective study with duplex ultrasound. | journal = Hypertension | volume = 23 | issue = 3 | pages = 346-50 | month = Mar | year = 1994 | doi =  | PMID = 8125561 }}</ref>
*Good for assessing the major vessels, drainage system and parenchymal lesions.
**Renal artery stenosis?
**Hydronephrosis?
**Pelviectasis?
**Renal cyst?
**Renal mass?


===Urine dip===
===Urine dip===
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*Hemegranular casts = acute tubular necrosis, transplant rejection.
*Hemegranular casts = acute tubular necrosis, transplant rejection.


===Complement===
Notes:
C3, C4 abnormal:<ref name=pmid3892188>{{cite journal |author=Nusinow SR, Zuraw BL, Curd JG |title=The hereditary and acquired deficiencies of complement |journal=Med. Clin. North Am. |volume=69 |issue=3 |pages=487–504 |year=1985 |month=May |pmid=3892188 |doi= |url=}}</ref><ref>URL: [http://www.google.com/url?sa=t&source=web&cd=3&sqi=2&ved=0CB0QFjAC&url=http%3A%2F%2Fwww.beckmancoulter.com%2Fliterature%2FClinDiag%2FBulletin%25209282C3_C4.pdf&rct=j&q=C3%2C%20C4%20decreased%2C%20l&ei=0evYTPLHHcX9ngfetNDzCQ&usg=AFQjCNFR26FHyAmy4lZ3tm-tLgW-oD73Zg&cad=rja beckmancoulter.com]. Accessed on: 9 November 2010.</ref>
*"Active sediment" = RBCs, RBC casts;<ref>URL: [http://emedicine.medscape.com/article/238158-overview http://emedicine.medscape.com/article/238158-overview]. Accessed on: 9 November 2010.</ref> implies glomerulonephritis.
*Rheumatoid arthritis.
**Some include the above (RBCs, RBC casts) + WBCs & protein.<ref>URL: [http://www.nephrologychannel.com/agn/index.shtml http://www.nephrologychannel.com/agn/index.shtml]. Accessed on: 9 November 2010.</ref>
*Systemic lupus erythematosus.
*Glomerulonephritis.
*Hemolytic anemia.
*Infection.


====Urine crystals====
====Urine crystals====
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====Mixed====
====Mixed====
*Features of nephritic syndrome and nephrotic syndrome.
*Features of nephritic syndrome and [[nephrotic syndrome]].
 
=Clinical DDx=
==Renal failure 101==
*Prerenal.
**Shock - cardiogenic, hypovolemic, neurogenic, septic, anaphylatic.
*Renal.
**What this article deals with.
*Postrenal.
**Outflow obstruction, e.g. [[prostatic nodular hyperplasia]] ([[AKA]] BPH).
 
==Renal causes==
*Isolated hematuria.
*Isolated proteinuria.
*Nephrotic syndrome.
*Nephritis syndrome.
*Rapidly progressive glomerulonephritis.
*Chronic renal failure.
*A combination of any of the above.
 
The clinical presentations suggest a pathologic DDx.<ref>URL: [http://www.emedicine.com/med/topic886.htm http://www.emedicine.com/med/topic886.htm] and [http://www.emedicine.com/ped/topic1564.htm http://www.emedicine.com/ped/topic1564.htm]. Accessed on: 8 November 2010.</ref>
 
===Isolated hematuria===
*[[IgA nephropathy]].<ref name=pmid19949735>{{Cite journal  | last1 = Kim | first1 = BS. | last2 = Kim | first2 = YK. | last3 = Shin | first3 = YS. | last4 = Kim | first4 = YO. | last5 = Song | first5 = HC. | last6 = Kim | first6 = YS. | last7 = Choi | first7 = EJ. | title = Natural history and renal pathology in patients with isolated microscopic hematuria. | journal = Korean J Intern Med | volume = 24 | issue = 4 | pages = 356-61 | month = Dec | year = 2009 | doi = 10.3904/kjim.2009.24.4.356 | PMID = 19949735 }}</ref>
*[[Alport syndrome]].
*[[Thin glomerular basement membrane disease]].
 
===Proteinuria===
*[[Diabetic nephropathy]].
*Classic causes of nephrotic syndrome:
**[[FSGS]].
**[[MCD]].
**[[MN]].
*Paraprotein-related:
**[[Renal amyloidosis]].
**Monoclonal immunoglobulin deposition disease (MIDD).
*Weird stuff:
**[[Fibrillary glomerulopathy]].
**[[Immunotactoid glomerulopathy]].
 
===Nephritic syndrome===
Classic:
*[[Post-infectious glomerulonephritis]].
**Classically streptococcal.
*Crescentic glomerulonephritis ([[AKA]] rapidly progressive glomerulonephritis (RPGN)).
 
Others:
*[[IgA nephropathy]].
*[[Lupus nephritis]].
 
====Rapidly progressive glomerulonephritis====
Classification:<ref>URL: [http://bestpractice.bmj.com/best-practice/monograph/207/basics/classification.html http://bestpractice.bmj.com/best-practice/monograph/207/basics/classification.html]. Accessed on: 17 November 2011.</ref>
#Linear immune deposits.
#*[[Antiglomerular basement membrane disease]] & Goodpasture's syndrome.
#Granular immune deposits.
#*Immune complex diseases.
#**[[Systemic lupus erythematosus]].
#**[[IgA nephropathy]].
#**Others.
#Pauci-immune.
#*ANCA vasculitides.
#**[[Wegener's granulomatosis]].
#**[[Microscopic polyangiitis]].
 
===Nephrotic syndrome===
*Minimal segmental disease (MSD) - [[AKA]] ''minimal change disease'' (MCD).
*[[Focal segmental glomerulosclerosis]] (FSGS).
*[[Membranous nephropathy]].
 
===Mixed presentation===
*[[IgA nephropathy]].
*[[Focal proliferative glomerulosclerosis]] (FPGS).
*[[Membranoproliferative glomerulonephritis]] (MPGN).


==Normal==
=Normal kidney=
===Epithelium<ref name=Ref_PBoD956>{{Ref PBoD|956}}</ref>===
===Cells of the glomerulus===
*Podocytes.
*Mesangial cells.
*Endothelium.
 
===Epithelium===
Features:<ref name=Ref_PBoD956>{{Ref PBoD|956}}</ref>
*The glomeruli visceral epithelium is part of the capillary wall (part of the glomerular tuft).   
*The glomeruli visceral epithelium is part of the capillary wall (part of the glomerular tuft).   
*The parietal epithelium is part of Bowman's capsule.
*The parietal epithelium is part of Bowman's capsule.
Remember: '''v'''isceral has '''v'''essels.
Remember: '''v'''isceral has '''v'''essels.


==Basic approach to renal biopsy==
===Glomerulus===
Comment on:
*A large [[autopsy]] series suggest it is: 223-292 micrometers.<ref name=pmid12864872>{{Cite journal  | last1 = Hoy | first1 = WE. | last2 = Douglas-Denton | first2 = RN. | last3 = Hughson | first3 = MD. | last4 = Cass | first4 = A. | last5 = Johnson | first5 = K. | last6 = Bertram | first6 = JF. | title = A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy. | journal = Kidney Int Suppl | volume =  | issue = 83 | pages = S31-7 | month = Feb | year = 2003 | doi =  | PMID = 12864872 | url = http://www.nature.com/ki/journal/v63/n83s/fig_tab/4493733t2.html#figure-title }}</ref>
**Another autopsy series suggests the mean diameter is: 225 micrometers.<ref>{{Cite journal  | last1 = Nyengaard | first1 = JR. | last2 = Bendtsen | first2 = TF. | title = Glomerular number and size in relation to age, kidney weight, and body surface in normal man. | journal = Anat Rec | volume = 232 | issue = 2 | pages = 194-201 | month = Feb | year = 1992 | doi = 10.1002/ar.1092320205 | PMID = 1546799 }}</ref>
 
Note:
*If the glomerulus fills half the field at 40x on a microscope with 22 mm diameter eye pieces it is ~ 0.275 mm or 275 micrometers.
====Glomerular basement membrane====
The glomerular basement membrane (GBM) should be thinner than the tubular basement membrane.
 
===Images===
<gallery>
Image: Benign kidney -- very low mag.jpg | Benign kidney - very low mag.
Image: Benign kidney -- low mag.jpg | Benign kidney - low mag.
Image: Benign kidney - alt -- low mag.jpg | Benign kidney - low mag.
Image: Benign kidney -- intermed mag.jpg | Benign kidney - intermed. mag.
</gallery>
 
=Basic approach to renal biopsy=
===Basic components===
*Glomeruli.
*Glomeruli.
*Tubules.
*Tubules.
*Interstitium.
*Interstitium.
*Vessels.
*Vessels.
Memory device ''GI TV'': glomeruli, interstitium, tubules, vessels.


===Glomeruli===
===Glomeruli===
#Mesangium
#Mesangium
#*Matrix should be: "1 cell thick" (expanded in diabetes mellitus).
#*Matrix should be: "one cell thick" (expanded in diabetes mellitus).
#*Cellularity of the mesangium - normal = '''upto 3 cells''' (don't count cell abutting the capillary lumen).
#*Cellularity of the mesangium - normal = '''upto 3 cells''' (don't count cell abutting the capillary lumen, don't count at the hilum).
#Capillary loops "open"
#Capillary loops "open"
#*Lumina patent? If ''not'' patent is it due to ''matrix'' or ''cells'' (endocapillary hypercellularity).
#*Lumina patent? If ''not'' patent is it due to ''matrix'' or ''cells'' (endocapillary hypercellularity).
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*Count the number of glomeruli.
*Count the number of glomeruli.
*Count number of the obsolete glomeruli.
*Count number of the obsolete glomeruli.
Notes:
*Endocapillary hypercellularity has a DDx - it includes: [[IgA nephropathy]],<ref name=pmid21258273>{{Cite journal  | last1 = Grcevska | first1 = L. | last2 = Ristovska | first2 = V. | last3 = Nikolov | first3 = V. | last4 = Petrusevska | first4 = G. | last5 = Milovanceva-Popovska | first5 = M. | last6 = Polenakovic | first6 = M. | title = The Oxford classification of IgA nephropathy: single centre experience. | journal = Prilozi | volume = 31 | issue = 2 | pages = 7-16 | month = Dec | year = 2010 | doi =  | PMID = 21258273 }}</ref> and [[lupus nephritis]].<ref name=pmid6975091>{{Cite journal  | last1 = Jothy | first1 = S. | last2 = Sawka | first2 = RJ. | title = Presence of monocytes in systemic lupus erythematosus-associated glomerulonephritis: marker study and significance. | journal = Arch Pathol Lab Med | volume = 105 | issue = 11 | pages = 590-3 | month = Nov | year = 1981 | doi =  | PMID = 6975091 }}</ref>


====Components of the glomeruli (anatomical)====
====Components of the glomeruli (anatomical)====
*Podocyte - rarely affect by disease  
*Podocyte - rarely affect by disease  
**One notable disease is ''collapsing glomerulopathy'' in [[HIV]].<ref>AH. 13 August 2009.</ref>
**One notable disease is ''[[collapsing glomerulopathy]]'' in [[HIV]].<ref>AH. 13 August 2009.</ref>
*Endothelial cell.
*Endothelial cell.
*Mesangial cell.
*Mesangial cell.
====Obsolete glomeruli====
*Completely sclerosed glomeruli are not important - unless present in larger numbers than expected for the age of the patient.
:Percent of sclerosed glomeruli = (age in years)/2 - 10%.<ref name=Ref_DARP16>{{Ref DARP|16}}</ref>
Example:
*It is normal for an 80 year-old to have 30% sclerosed glomeruli.
====Glomerular disease terms====
Number of glomeruli involved:<ref name=DARP7>{{Ref DARP|7}}</ref>
*Focal = some of the glomeruli.
**In practical terms, defined as: <50% of glomeruli.
*Diffuse = most of glomeruli.
How much of the glomerulus is involved:<ref name=DARP7>{{Ref DARP|7}}</ref>
*Global = most of the glomerulus.
**In practical terms, defined as: >80% of glomerulus.<ref>{{Cite journal  | last1 = Berden | first1 = AE. | last2 = Ferrario | first2 = F. | last3 = Hagen | first3 = EC. | last4 = Jayne | first4 = DR. | last5 = Jennette | first5 = JC. | last6 = Joh | first6 = K. | last7 = Neumann | first7 = I. | last8 = Noël | first8 = LH. | last9 = Pusey | first9 = CD. | title = Histopathologic classification of ANCA-associated glomerulonephritis. | journal = J Am Soc Nephrol | volume = 21 | issue = 10 | pages = 1628-36 | month = Oct | year = 2010 | doi = 10.1681/ASN.2010050477 | PMID = 20616173 |url=http://jasn.asnjournals.org/content/21/10/1628/T1.expansion.html}}</ref>
*Segmental = part of the glomerulus.


===Vessels===
===Vessels===
#Arteriolar hyalinosis - too much pink stuff???
#Arteriolar hyalinosis - too much glassy pink stuff?
#Intimal hyperplasia.
#Intimal hyperplasia (atherosclerosis).


Consider:
Consider:
*Vasculitis? - inflammatory cells in vessel wall.
*[[Vasculitis]]? - inflammatory cells in vessel wall.
*Amyloid? - pink.
*[[Amyloid]]? - pink.
*Rejection? - PMNs.
*Rejection? - [[PMN]]s.
*[[Cholesterol emboli]]?


===Tubules & interstitium===
====Arteriolar hyalinosis====
Microscopic:
*Small vessels (afferent +/- efferent arteriole) with:
**Glassy eosinophilic material in arteriolar wall.
***[[PAS stain]] +ve.
 
DDx:
*Aging.
*[[Diabetes mellitus]].
*[[Hypertension]].
*Drugs - [[calcineurin inhibitor toxicity|calcineurin inhibitors]] (tacrolimus, cyclosporine).
 
Note:
*Arteriolar hyalinosis - involves ''afferent'' and ''efferent'' arterioles in diabetes, in others it is only the afferent.
 
Memory device ''ADHD'':
*'''A'''ging, '''D'''iabetes, '''H'''ypertension, '''D'''rugs.
 
=====Image=====
<gallery>
Image:Renal_arterial_hyalinosis_-_he_-_very_high_mag.jpg | Arterial hyaline - HE - very high mag. (WC/Nephron)
Image:Renal_arterial_hyalinosis_-_pas_-_very_high_mag.jpg | Arterial hyaline - PAS - very high mag. (WC/Nephron)
Image:Renal_arterial_hyalinosis_-_hps_-_very_high_mag.jpg | Arterial hyaline - HPS - very high mag. (WC/Nephron)
</gallery>
 
====Atherosclerosis====
{{Main|Atherosclerosis}}
Microscopic:
*Intimal thickening of medium-sized vessels.
**Where is the intima/media interface?
***Internal elastic lamina - wavy band of eosinophilic material on H&E that is 1-2 micrometres thick.
 
Grading - based on the thickness of the media and intima:
*Mild: (tunica) media > (tunica) intima.
*Moderate: media = intima.
*Severe: media < intima.
 
===Tubules===
Tubules - proximal portion is the most important.
Tubules - proximal portion is the most important.
Consider:
*Casts?
*Casts?
*Degeneration, i.e. apoptosis.
*Necrosis?
*Necrosis?
*Regeneration, e.g. mitoses.


===Interstitium===
Interstitium
Interstitium
*Fibrosis - prognostically important.
*Fibrosis - prognostically important.
**Grading: mild = <25%, moderate 25-50%, severe >50%.
**Grading: mild = <25%, moderate 25-50%, severe >50%.
*Inflammation?


==Important terms/process related==
==Important terms/process related==
===Obsolete glomeruli===
*Completely sclerosed glomeruli are not important - unless present in larger numbers than expected for the age of the patient.
:Percent of sclerosed glomeruli = (age in years)/2 - 10%.<ref name=Ref_DARP16>{{Ref DARP|16}}</ref>
Example:
*It is normal for an 80 year-old to have 30% sclerosed glomeruli.
===Glomerular disease terms<ref name=Ref_FoRP>{{Ref FoRP|82}}</ref>===
*Global = >50% of glomeruli.
*Focal = <50% of glomeruli.
*Segmental = part of glomerulus.
*Diffuse = most of glomerulus.
===Staining===
===Staining===
The standard [[stain]] in kidney pathology is ''PAS''.
The standard [[stain]] in kidney pathology is ''PAS''.
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*IgA.
*IgA.
*IgM.
*IgM.
*C1q
*C3.
*C3.
*Fibrinogen.
*Fibrinogen.
*Albumin.


Optional:
Optional:
*Kappa.
*Kappa.
*Lambda.
*Lambda.
*C4d.
**Positive staining = peri-tubular capillaries stain.
====Negative immunofluorescence====
*Excludes all immune complex associated disease.
Seen in:
* [[Minimal change disease]].
* [[Focal segmental glomerulosclerosis]].
====Positive immunofluorescence====
*Positive immunofluorescence is usually diagnostic.
Basic patterns:
#Linear.
#Granular.
#Ring-like.
Examples:
*Linear IgG:
**[[Antiglomerular basement membrane disease]].
**[[Goodpasture syndrome]].
*Granular deposits:
**"Full house" - all present.
***[[Lupus nephritis]].
**Branching IgA.
***[[IgA nephropathy]].
**IgG, C3, kappa, lambda.
***[[Membranous glomerulonephritis]].
*Linear C3 with mesangial rings; IgG -ve, IgA -ve.
**[[Dense deposit disease]] (DDD).
Notes:
*Nonspecific linear IgG staining may be seen in [[diabetic nephropathy]].


===Immune complex-related disease===
===Immune complex-related disease===
Can be:
Can be:
*Subepithelial - distal to basement membrane (BM).
*Subepithelial - distal to basement membrane (BM), closer to the urinary space.
*Subendothelial - proximal to BM.
**[[Membranous nephropathy]], [[Post-infectious glomerulonephritis]] (hump-like), [[MPGN]].
*Subendothelial - proximal to BM, closer to the glomerular capillary.
**[[MPGN]] - classic location.


==Pathologic differential diagnosis==
===Tram-tracking of BM===
===Tram-tracking of BM===
DDx:<ref>AH. 17 July 2009.</ref>
DDx:<ref>AH. 17 July 2009.</ref>
#MPGN.
#[[MPGN]].
#Thrombotic microscopic angiopathy (TMA).
#[[Thrombotic microangiopathy]] (TMA).
#Transplant glomerulopathy (TG).
#[[Transplant glomerulopathy]] (TG).
 
===Mesangial hypercellularity===
DDx:
#[[Lupus nephritis]].
#[[IgA nephropathy]].
 
===Mesangial expansion===
*A patch of matrix can contain more than three mesangial cell nuclei.
**Highly subjective.


===Arteriolar hyalinosis===
DDx:
DDx:
*Diabetes mellitus.
*[[Diabetes mellitus]].<ref name=pmid17418688>{{cite journal |author=Fioretto P, Mauer M |title=Histopathology of diabetic nephropathy |journal=Semin. Nephrol. |volume=27 |issue=2 |pages=195-207 |year=2007 |month=March |pmid=17418688 |doi=10.1016/j.semnephrol.2007.01.012 |url=}}</ref>
*Hypertension.
*MPGN:
*Aging.
**[[IgA nephropathy]].
*Drugs - tarolimus, cyclosporine.
**[[Henoch-Schoenlein purpura]].
**[[Lupus nephritis]].
*[[Fibrillary glomerulopathy]].
*[[Immunotactoid glomerulopathy]].
*[[Renal amyloidosis]].
*Monoclonal immunoglobulin deposition disease.


*Image: [http://www.kidneypathology.com/Im%E1genes/Diabetes/DM.11.w.jpg Arteriolar hyalinosis (kidneypathology.com)]
===Glomerular crescents===
*[[AKA]] crescents.
====General====
*Indicates a rapidly progressive disease.
*Etiology/definition: break in the glomerular basement membrane (GBM).


Note:
====Microscopic====
*Arteriolar hyalinosis - involves ''afferent'' and ''efferent'' arterioles in diabetes, in others it is only tha afferent.
Features:
===Mesangial hypercellularity===
*Crescentic-shaped lesion in the urinary space of a glomerulus.
Think:
**Crescent = looks like the moon shortly after new moon.
# Lupus.
**Cells & cellular debris in the urinary space.
# IgA nephropathy.
***Crescents lack GBM -- thus PAS -ve and MPAS -ve.
*Break in the glomerular basement membrane - '''key feature'''.
**Best seen on a silver stain (e.g. [[Jones stain]]).
*Fibrin.
**Orange on [[HPS stain|HPS]].
**Pink on [[H&E stain|H&E]].


===Mesangial expansion===
*Inflammatory cells (lymphocytes, plasma cells, eosinophils, macrophages) - extravascular - '''low power''' feature.
*Diabetes mellitus.<ref name=pmid17418688>{{cite journal |author=Fioretto P, Mauer M |title=Histopathology of diabetic nephropathy |journal=Semin. Nephrol. |volume=27 |issue=2 |pages=195-207 |year=2007 |month=March |pmid=17418688 |doi=10.1016/j.semnephrol.2007.01.012 |url=}}</ref>
*Immune complex mediated disease (e.g. IgA nephropathy).
*Henoch-Schoenlein disease.
*Lupus.


==Pathologic DDx==
DDx:
The clinical presentations suggest a pathologic DDx.<ref>URL: [http://www.emedicine.com/med/topic886.htm http://www.emedicine.com/med/topic886.htm] and [http://www.emedicine.com/ped/topic1564.htm http://www.emedicine.com/ped/topic1564.htm]. Accessed on: 8 November 2010.</ref>
*Glomerular sclerosis:
**GBM visible through-out glomerulus.
**No fibrin.
**Collagen deposition within the glomerular tuft.
***Seen with [[trichrome stain]].
**+/-Glomerular tuft-capsule adhesions.
**+/-Glomerular enlargement.
**Usu. no significant inflammation.


===Nephritic===
====Bland necrotic crescents====
*Post-infectious glomerulonephritis,
DDx:
**Classically streptococcal
*ANCA-related glomerulonephritis.
*Crescentic glomerulonephritis (AKA rapidly progressive glomerulonephritis (RPGN)),
*Anti-GBM disease.
**Anti-GBM disease,
**ANCA disease (e.g. Wegener's granulomatosis),
**Goodpasture's syndrome.


===Nephrotic===
Diseases with crescents - is a long list.<ref>URL: [http://path.upmc.edu/cases/case51/dx.html http://path.upmc.edu/cases/case51/dx.html]. Accessed on: 9 November 2010.</ref>
*Minimal segmental disease (MSD) - AKA ''minimal change disease'' (MCD),
*Focal segmental glomerulosclerosis (FSGS),
*Membranous nephropathy.


===Mixed presentation===
===Primary light microscopy patterns===
*IgA nephropathy,  
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Focal proliferative glomerulosclerosis (FPGS),  
! Pattern
*Membranoproliferative glomerulonephritis (MPGN).
! Key feature
! Other findings
! DDx of the pattern
! DDx
! Image
|-
|Normal light microscopy
| Normal histology
| none ''or'' few glomeruli in a biopsy of an under sampled FSGS
| [[membranous nephropathy]], [[focal segmental glomerulosclerosis]] (FSGS)
| normal kidney, [[minimal change disease]], [[thin glomerular basement membrane disease]], [[Alport syndrome]], early [[membranous nephropathy]]
| [[Image:Benign kidney -- intermed mag.jpg|thumb|center|150px|Benign kidney (WC)]]
|-
|Nodular mesangial expansion
| nodular mesangial matrix expansion, no mesangial hypercellularity
| GBM thickening, both afferent and efferent arteriole hyalinized
| diffuse proliferative GN, membranous nephropathy
| [[diabetic nephropathy]], [[idiopathic nodular glomerulosclerosis]], [[renal amyloidosis]], light chain deposition disease, [[fibrillary glomerulopathy]], [[immunotactoid glomerulopathy]]
| [[Image:Nodular_glomerulosclerosis.jpeg|thumb|center|150px|Nodular GS (WC)]]
|-
|[[Membranous nephropathy]] (MN)
| GBM spikes or pinholes with silver stain, GBM thickening on PAS
| +/-mesangial hypercellularity +/-tram-tracking/wireloop GBM
| normal light microscopy, light chain deposition disease
| [[hepatitis B]], [[hepatitis C]], carcinoma, NSAID toxicity, SLE, idiopathic (MN); light chain deposition disease ([[plasma cell neoplasm]])
| [[Image:Membranous_nephropathy_-_mpas_-_very_high_mag.jpg|thumb|center|150px|MN (WC)]]
|-
|[[Focal segmental glomerulosclerosis]]
| sclerosed glomeruli = mesangial expansion with collagen
| +/-glomerular enlargement, +/- tuft-capsule adhesions
| [[rapidly progressive glomerulonephritis]], nodular mesangial expansion
| primary FSGS, secondary FSGS ([[HIV]], [[IVDU]], [[obesity]], [[parvovirus B19]], [[Alport syndrome]]
| [[Image:Focal_segmental_glomerulosclerosis_-_high_mag.jpg|thumb|center|150px|FSGS (WC)]]
|-
|Diffuse proliferative glomerulonephritis
| mesangial hypercellularity
| +/-mesangial expansion, +/-interstitial inflammation
| nodular glomerulosclerosis
| [[post-infectious glomerulonephritis]], [[MPGN]], [[dense deposit disease]], diffuse proliferative [[lupus nephritis]] (class IV), cryoglobulinemic GN
| [[Image:Membranoproliferative_glomerulonephritis_-_very_high_mag.jpg|thumb|center|150px|MPGN (WC)]]
|-
|[[Rapidly progressive glomerulonephritis]]
| [[glomerular crescents]]
| +/-inflammation, +/-vasculitis
| [[FSGS]], diffuse proliferative glomerulonephritis
| [[AGBM]], [[post-infectious glomerulonephritis]], pauci-immune GN, immune complex diseases ([[lupus nephritis]], [[IgA nephropathy]], others)
| [[Image:Crescentic_glomerulonephritis_%282%29.jpg|thumb|center|150px|Crescentic GN (WC)]]
|-
|Tubular injury
| tubular degeneration (loss of cilia in proximal tubule, apoptosis, necrosis), regeneration (mitosis, nucleoli)
| +/-interstitial fibrosis
| normal light microscopy
| [[acute tubular necrosis]], [[chronic allograft nephropathy]]
| [[Image:Chronic_allograft_nephropathy_-_intermed_mag.jpg|thumb|center|150px|CAN (WC)]]
|-
|Small vessel pathology
| luminal narrowing; +/-thrombosis, +/-hyalinosis
| +/-onion-skinning
| none
| [[thrombotic microangiopathy]] (malignant hypertension, [[scleroderma]] renal crisis, DIC, HUS, TTP,
| [[Image:Renal_arterial_hyalinosis_-_pas_-_very_high_mag.jpg |thumb|center|150px| Hyalinosis (WC)]] [[Image:Thrombotic_microangiopathy_-_very_high_mag.jpg|thumb|center|150px| TMA (WC)]]
|-
|Large vessel pathology
| luminal narrowing ''or'' obstruction; +/-intimal thickening; +/-embolization
| +/-medial thinning
| none
| [[atherosclerosis]], [[cholesterol embolism]], other types of embolism, [[thrombosis]]
| [[Image:Cholesterol_embolus_-_intermed_mag.jpg |thumb|center|150px| Cholesterol embolus (WC)]]
|- <!--
| Pattern
| Key feature
| Other findings
| DDx of the pattern
| Pathol. DDx
| Image -->
|}


===Patterns - Table===
===Diagnoses - Table===
{| class="wikitable"
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
| '''Pattern'''
! Pattern
| '''Key feature'''
! Key feature
| '''Other findings'''
! Other findings
| '''EM'''
! IF & EM
| '''Clinical'''
! Presentation
| '''Pathol. DDx'''
! Clinical
| '''Image'''
! Pathol. DDx
! Image
|-
|-
|Nodular GS
|[[Nodular glomerulosclerosis]]
| Key feature?
| nodular mesangial matrix expansion
| Other findings?
| GBM thickening, both afferent and efferent arteriole hyalinized
| EM?
| EM?
| Clinical?
| proteinuria - typical presentation, nephrotic syndrome{{fact}}
| Pathol. DDx?
| [[diabetes mellitus]] (DM)
| [[amyloidosis]], [[idiopathic nodular glomerulosclerosis]] (nodular GS without DM)
| [[Image:Nodular_glomerulosclerosis.jpeg|thumb|center|150px|Nodular GS (WC)]]
|-
|[[Focal segmental glomerulosclerosis]] (FSGS)
| focal sclerosis of gloms
| +/-interstitial fibrosis
| IF: negative; EM: foot process loss
| nephrotic syndrome
| primary FSGS, secondary FSGS ([[HIV]], [[IVDU]], obesity, [[parvovirus B19]], [[Alport syndrome]]); unresponsive to steroids, worse prognosis than MCD
| [[minimal change disease]]
| [[Image:Focal_segmental_glomerulosclerosis_-_high_mag.jpg|thumb|center|150px|FSGS (WC)]]
|-
|[[Membranous nephropathy]]<br>(AKA membranous GN)
| spikes or pinholes with silver stain
| mesangial hypercellularity; +/-tram-tracking/wireloop GBM
| IF: diffuse granular capillary loop IgG, C3, kappa, lambda; EM: diffuse subepithelial deposits - spike forming
| nephrotic syndrome
| [[hepatitis B]], [[hepatitis C]], carcinoma, NSAID toxicity, SLE, idiopathic
| Nodular glomerulosclerosis (?)
| [[Image:Membranous_nephropathy_-_mpas_-_very_high_mag.jpg|thumb|center|150px|MN (WC)]]
|-
|[[Minimal change disease]] (MCD)
| foot process loss on [[EM]]
| usu. none
| EM: foot process loss
| [[nephrotic syndrome]]
| primary vs. secondary ([[lymphoproliferative disorder]], NSAIDs); idiopathic responds to steroids
| [[FSGS]], [[thin glomerular basement membrane disease]] (histologic DDx)
| Image?
| Image?
|-
|-
|Focal segmental GS (FSGS)
|[[IgA nephropathy]]
| Key feature?
| IgA branching pattern
| +/-mesangial hypercellularity, +/-crescents
| IF: IgA +ve (branching pattern); EM: dense mesangial deposits
| mixed nephrotic/nephritic
| primary vs. secondary (Henoch-Schoenlein purpura)
| [[RPGN]]
| [[Image:Henoch-Sch%C3%B6nlein_nephritis_IgA_immunostaining.jpg|thumb|center|150px|HSN - IgA IHC (WC)]]
|-
|[[Membranoproliferative glomerulonephritis]] (MPGN)
| thick GBM
| Other findings?
| Other findings?
| EM?
| subepithelial deposits
| Clinical?
| mixed nephrotic/nephritic
| [[SLE]], [[cryoglobulinemia]], [[hepatitis B]], [[hepatitis C]]
| Pathol. DDx?
| Pathol. DDx?
| Image?
| [[Image:Membranoproliferative_glomerulonephritis_-_very_high_mag.jpg|thumb|center|MPGN (WC)]]
|-
|-
|Minimal change disease (MCD)
|[[Focal proliferative glomerosclerosis|Focal proliferative<br> glomerosclerosis]] (FPGS)
| Key feature?
| <50% of glomeruli partially sclerosis
| Other findings?
| Other findings?
| EM?
| EM?
| mixed nephrotic/nephritic
| Clinical?
| Clinical?
| Pathol. DDx?
| Pathol. DDx?
| Image?
| Image?  
|-
|-
|Rapidly progressive GN (RPGN)
|Rapidly progressive GN (RPGN)
| Key feature?
| crescents
| Other findings?
| Other findings?
| EM?
| EM?
| Clinical?
| nephritic syndrome
| Pathol. DDx?
| [[AGBM]], ANCA-vasculitis
| [[IgA nephropathy]] with crescents
| Image?  
| Image?  
<!-- |-
|-
| [[Dense deposit disease]]
| IF: linear C3 with rings
| +/-thick GBM
| EM: GBM lamina densa thickening
| Presentation?
| mixed nephrotic/nephritic (???)
| [[MPGN]]
| [http://www.nature.com/modpathol/journal/v20/n6/fig_tab/3800773f1.html (nature.com)] 
|- <!--
| Pattern
| Pattern
| Key feature?
| Key feature?
| Other findings?
| Other findings?
| EM?
| EM?
| Presentation?
| Clinical?
| Clinical?
| Pathol. DDx?
| Pathol. DDx?
| Image? -->
| Image? -->
|}
|}


==Nephrotic syndrome==
===Diffuse proliferative glomerulonephritis===
A broad classification of nephrotic syndrome based on etiology:
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
<center>
! Pattern
{{familytree/start}}
! Key feature
{{familytree | | | |A11| | | | |A11 =Nephrotic<br>syndrome}}
! Clinical
{{familytree | |,|-|-|^|-|-|.|}}
|-
{{familytree | B11 | | | | B12 |B11=Primary|B12=Secondary}}
| [[Post-infectious glomerulonephritis]]
{{familytree/end}}
| IF: capillary loop +/- mesangial IgG/C3; EM: large infreq. hump-like subepithelial deposits
</center>
| post-infection
|-
| [[Membranoproliferative glomerulonephritis]] (MPGN)
| mesangial proliferation with thickening of the glomerular capillary loops<ref name=pmid11682680>{{Cite journal  | last1 = Smet | first1 = AD. | last2 = Kuypers | first2 = D. | last3 = Evenepoel | first3 = P. | last4 = Maes | first4 = B. | last5 = Messiaen | first5 = T. | last6 = Van Damme | first6 = B. | last7 = Vanrenterghem | first7 = Y. | title = 'Full house' positive immunohistochemical membranoproliferative glomerulonephritis in a patient with portosystemic shunt. | journal = Nephrol Dial Transplant | volume = 16 | issue = 11 | pages = 2258-62 | month = Nov | year = 2001 | doi =  | PMID = 11682680 | URL = http://ndt.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11682680 }}</ref>


In children nephrotic syndrome is assumed to be ''minimal change disease''.  Biopsies are done only there is no response to steriods.
| low C3, normal C4; primary vs. secondary (often hepatitis C)
|-
| [[Dense deposit disease]]
| IF: linear C3 with rings
|
|-
| [[Cryoglobulinemic glomerulonephritis]]
|
|
|-
| Diffuse proliferative lupus glomerulonephritis
|
| [[systemic lupus erythematosus]]; low C3, low C4
|-
| Diffuse proliferative [[IgA nephropathy]]
| IF: IgA +ve (branching pattern)
|
|-
|}


==Diabetes mellitus==
=Common diseases=
==Diabetic nephropathy==
===General===
===General===
*Most common cause of end stage renal disease (ESRD).
*Due to [[diabetes mellitus]] - '''key feature'''.
*Rarely biopsied.
**If there is no history of diabetes... it is ''[[idiopathic nodular glomerulosclerosis]]''.
*Most common cause of [[end-stage renal disease]] (ESRD).
*Biopsied only if the (clinical) features are atypical.


===Microscopic===
===Microscopic===
Line 275: Line 679:
*Mesangial matrix expansion - leads to nodule formation ''Kimmelstiel-Wilson nodules'' (''nodular glomerulosclerosis'').
*Mesangial matrix expansion - leads to nodule formation ''Kimmelstiel-Wilson nodules'' (''nodular glomerulosclerosis'').


Other:
Others:
*Armanni-Ebstein change - cytoplasmic vacuolization of tubular cells (usu. loop of Henle) -- innermost cortex, outer medulla;<ref name=pmid13478656>{{cite journal |author=RITCHIE S, WAUGH D |title=The pathology of Armanni-Ebstein diabetic nephropathy |journal=Am. J. Pathol. |volume=33 |issue=6 |pages=1035–57 |year=1957 |pmid=13478656 |pmc=1934668 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934668/?page=1}}</ref> not specific to diabetes mellitus.<ref name=pmid20875709>{{cite journal |author=Zhou C, Byard RW |title=Armanni-Ebstein phenomenon and hypothermia |journal=Forensic Sci Int |volume= |issue= |pages= |year=2010 |month=September |pmid=20875709 |doi=10.1016/j.forsciint.2010.08.018 |url=}}</ref>
*Armanni-Ebstein change = cytoplasmic vacuolization of tubular cells (usu. loop of Henle) -- innermost cortex, outer medulla;<ref name=pmid13478656>{{cite journal |author=Ritchie S, Waugh D |title=The pathology of Armanni-Ebstein diabetic nephropathy |journal=Am. J. Pathol. |volume=33 |issue=6 |pages=1035–57 |year=1957 |pmid=13478656 |pmc=1934668 |doi= |url=http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934668/?page=1}}</ref> not specific to diabetes mellitus.<ref name=pmid20875709>{{cite journal |author=Zhou C, Byard RW |title=Armanni-Ebstein phenomenon and hypothermia |journal=Forensic Sci Int |volume= |issue= |pages= |year=2010 |month=September |pmid=20875709 |doi=10.1016/j.forsciint.2010.08.018 |url=}}</ref>
*Capsular drop = hyaline material deposited in the Bowman's capsule.<ref name=ndt-edu>URL: [http://www.ndt-educational.org/ferrariodiabete.asp http://www.ndt-educational.org/ferrariodiabete.asp]. Accessed on: 29 April 2012.</ref>
*Fibrin cap = subendothelial deposition of hyaline material.<ref name=ndt-edu/>


Other - with weak evidence:
Other - with weak evidence:
Line 282: Line 688:


Memory device:
Memory device:
*GBM = ''thick '''G'''BM'', '''''b'''oth afferent & efferent artiole thickened'', '''''m'''esangial matrix expansion''.
*GBM = ''thick '''G'''BM'', '''''b'''oth afferent & efferent arterioles thickened'', '''''m'''esangial matrix expansion''.


Images:  
====Images====
*[http://commons.wikimedia.org/wiki/File:Nodular_glomerulosclerosis.jpeg Nodular glomerulosclerosis (WC)].
<gallery>
Image:Diabetic_glomerulosclerosis_%281%29_HE.jpg | Diabetic glomerulosclerosis. (WC/KGH)
Image:Diabetic_glomerulosclerosis_(2)_HE.jpg | Diabetic glomerulosclerosis. (WC/KGH)
Image:Diabetic_glomerulosclerosis_%283%29_HE.jpg | Diabetic glomerulosclerosis. (WC/KGH)
Image:Nodular_glomerulosclerosis.jpeg | Nodular glomerulosclerosis. (WC)
</gallery>
www:
*[http://library.med.utah.edu/WebPath/jpeg1/RENAL027.jpg Nodular GS (med.utah.edu)].
*[http://library.med.utah.edu/WebPath/jpeg1/RENAL027.jpg Nodular GS (med.utah.edu)].
*[http://www.markwickmd.com/images/pages/armani_ebstein_lesion.jpg Armanni-Ebstein lesion (markwickmd.com)].
*[http://www.markwickmd.com/images/pages/armani_ebstein_lesion.jpg Armanni-Ebstein lesion (markwickmd.com)].
Line 292: Line 704:
*Hypertensive kidneys have changes only in the afferent arteriole, i.e. the efferent arteriole is spared (see ''[[hypertension]]'').
*Hypertensive kidneys have changes only in the afferent arteriole, i.e. the efferent arteriole is spared (see ''[[hypertension]]'').


====Grading====
The severity of changes can be indicated by the grade:<ref>{{Cite journal  | last1 = Tervaert | first1 = TW. | last2 = Mooyaart | first2 = AL. | last3 = Amann | first3 = K. | last4 = Cohen | first4 = AH. | last5 = Cook | first5 = HT. | last6 = Drachenberg | first6 = CB. | last7 = Ferrario | first7 = F. | last8 = Fogo | first8 = AB. | last9 = Haas | first9 = M. | title = Pathologic classification of diabetic nephropathy. | journal = J Am Soc Nephrol | volume = 21 | issue = 4 | pages = 556-63 | month = Apr | year = 2010 | doi = 10.1681/ASN.2010010010 | PMID = 20167701 | URL = http://jasn.asnjournals.org/content/21/4/556.full }}</ref>
{| class="wikitable sortable"
! Grade
! Criteria
|-
|Grade I
| GBM thickening on EM only
|-
|Grade II
| Mild-to-moderate mesangial expansion only on LM
|-
|Grade III
| Glomerulus with mesangial nodules (Kimmelstiel–Wilson nodules)
|-
|Grade IV
| Stage III + global sclerosis in >50% of glomeruli
|}
===IF===
*Negative.
*+/-Nonspecific linear IgG.
===EM===
*Severe thickening of GBM.
*Mesangial sclerosis.
==Lupus nephritis==
*Abbreviated ''LN''.
===General===
{{Main|Systemic lupus erythematosus}}
*Bread & butter of nephropathology.
*The biopsy is done to determine treatment, i.e. how much immunosuppression is needed.
===Immunofluorescence===
*"Full house" = all of 'em light up.
===Classification===
International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification:<ref>{{cite journal |author=Weening JJ, D'Agati VD, Schwartz MM, ''et al.'' |title=The classification of glomerulonephritis in systemic lupus erythematosus revisited |journal=J. Am. Soc. Nephrol. |volume=15 |issue=2 |pages=241–50 |year=2004 |month=February |pmid=14747370 |doi= |url=http://www.nature.com/ki/journal/v55/n2/full/4490631a.html}}</ref><ref>URL: [http://www.med.niigata-u.ac.jp/npa/Lectures/Lupus_Nephritis.htm http://www.med.niigata-u.ac.jp/npa/Lectures/Lupus_Nephritis.htm]. Accessed on: 9 November 2010.</ref>
*Class I - minimal mesangial LN.
*Class II - mesangial proliferative LN.
**Mesangial hypercellularity. (???)
*Class III - focal lupus nephritis; <50% of glomeruli.
**Mesangial hypercellularity. (???)
*Class VI-S - diffuse segmental LN;  >50% of glomeruli.
**Mesangial hypercellularity. (???)
*Class VI-G - global LN; >50% of glomeruli.
*Class V - Membranous lupus nephritis.
**[[Membranous nephropathy]] due to SLE.
*Class IV - Advanced sclerosing LN; essentially end-stage kidney.
Notes:
*Most of the action is in Class III and Class IV. 
**Class I is near normal - doesn't get biopsied.
**Class IV is essentially a dead kidney - doesn't get biopsied.
====Images====
<gallery>
Image:SLE_Nephritis_Pathology_Diagram.svg| SLE nephritis - schematic. (WC)
</gallery>
*Membranous lupus:
**[http://www.flickr.com/photos/jian-hua_qiao_md/3989875425/in/set-72157622411941607 H&E (flickr.com)].
**[http://www.flickr.com/photos/jian-hua_qiao_md/3989875091/in/set-72157622411941607/ Jones (flickr.com)].
**[http://www.flickr.com/photos/jian-hua_qiao_md/3990630972/in/set-72157622411941607/ PAS (flickr.com)].
=Nephrotic syndrome=
{{Main|Nephrotic syndrome}}
This classically includes the following:
*[[Minimal change disease]].
*[[Focal segmental glomerulosclerosis]].
*[[Membranous nephropathy]].
It also includes:
*[[IgA nephropathy]].
*Pre-eclampsia - uncommon.<ref name=pmid20033418>{{Cite journal  | last1 = Wei | first1 = Q. | last2 = Zhang | first2 = L. | last3 = Liu | first3 = X. | title = Outcome of severe preeclampsia manifested as nephrotic syndrome. | journal = Arch Gynecol Obstet | volume = 283 | issue = 2 | pages = 201-4 | month = Feb | year = 2011 | doi = 10.1007/s00404-009-1338-z | PMID = 20033418 }}</ref>
=Mixed nephrotic and nephritic=
==IgA nephropathy==
==IgA nephropathy==
*[[AKA]] Berger disease.
**Should '''not''' be confused with ''Buerger disease'' ([[thromboangiitis obliterans]]).
===General===
===General===
*[[AKA]] Berger disease.
*More common in Asians.
*Associated with an increased incidence of [[Celiac disease]].<ref name=pmid19332868>{{Cite journal  | last1 = Smerud | first1 = HK. | last2 = Fellström | first2 = B. | last3 = Hällgren | first3 = R. | last4 = Osagie | first4 = S. | last5 = Venge | first5 = P. | last6 = Kristjánsson | first6 = G. | title = Gluten sensitivity in patients with IgA nephropathy. | journal = Nephrol Dial Transplant | volume = 24 | issue = 8 | pages = 2476-81 | month = Aug | year = 2009 | doi = 10.1093/ndt/gfp133 | PMID = 19332868 }}</ref>
*''IgA nephropathy'', in children, with a skin rash ([[leukocytoclastic vasculitis]]) = [[Henoch–Schönlein purpura]].
*May present as [[nephrotic syndrome]].<ref name=pmid7849391>{{Cite journal  | last1 = Komatsuda | first1 = A. | last2 = Wakui | first2 = H. | last3 = Yasuda | first3 = T. | last4 = Imai | first4 = H. | last5 = Miura | first5 = AB. | last6 = Tsuda | first6 = A. | last7 = Nakamoto | first7 = Y. | title = Successful delivery in a pregnant women with crescentic IgA nephropathy. | journal = Intern Med | volume = 33 | issue = 11 | pages = 723-6 | month = Nov | year = 1994 | doi =  | PMID = 7849391 }}</ref><ref name=pmid22322610>{{Cite journal  | last1 = Kim | first1 = JK. | last2 = Kim | first2 = JH. | last3 = Lee | first3 = SC. | last4 = Kang | first4 = EW. | last5 = Chang | first5 = TI. | last6 = Moon | first6 = SJ. | last7 = Yoon | first7 = SY. | last8 = Yoo | first8 = TH. | last9 = Kang | first9 = SW. | title = Clinical features and outcomes of IgA nephropathy with nephrotic syndrome. | journal = Clin J Am Soc Nephrol | volume = 7 | issue = 3 | pages = 427-36 | month = Mar | year = 2012 | doi = 10.2215/CJN.04820511 | PMID = 22322610 }}</ref>
*May present as isolated hematuria.<ref name=pmid19949735>{{Cite journal  | last1 = Kim | first1 = BS. | last2 = Kim | first2 = YK. | last3 = Shin | first3 = YS. | last4 = Kim | first4 = YO. | last5 = Song | first5 = HC. | last6 = Kim | first6 = YS. | last7 = Choi | first7 = EJ. | title = Natural history and renal pathology in patients with isolated microscopic hematuria. | journal = Korean J Intern Med | volume = 24 | issue = 4 | pages = 356-61 | month = Dec | year = 2009 | doi = 10.3904/kjim.2009.24.4.356 | PMID = 19949735 }}</ref>


===Microscopic===
===Microscopic===
Features:
Features:
*Mesangial hypercellularity - may be only light microscopy finding.
*Variable:
**Mesangial hypercellularity - may be only light microscopy finding.
 
Note:
*Diagnosis based on immunofluorescence (IgA+).
*Diagnosis based on immunofluorescence (IgA+).


Image: [http://library.med.utah.edu/WebPath/jpeg2/RENAL096.jpg IgA nephropathy (med.utah.edu)].
====Images====
*[http://library.med.utah.edu/WebPath/jpeg2/RENAL096.jpg IgA nephropathy (med.utah.edu)].
*[http://path.upmc.edu/cases/case96.html HSP (upmc.edu)].
<gallery>
Image:Henoch-Sch%C3%B6nlein_nephritis_IgA_immunostaining.jpg | HSP - IgA IHC (WC)
</gallery>
====Scoring====
IgA nephropathy can be scored using an assessment of '''m'''esangial proliferation, '''e'''ndocapillary proliferation, glomerulo'''s'''clerosis and '''t'''ubular atrophy and interstitial fibrosis (abbreviated ''MEST'').<ref>{{Cite journal  | last1 = Coppo | first1 = R. | last2 = Cattran | first2 = D. | last3 = Roberts Ian | first3 = SD. | last4 = Troyanov | first4 = S. | last5 = Camilla | first5 = R. | last6 = Cook | first6 = T. | last7 = Feehally | first7 = J. | title = The new Oxford Clinico-Pathological Classification of IgA nephropathy. | journal = Prilozi | volume = 31 | issue = 1 | pages = 241-8 | month = Jul | year = 2010 | doi =  | PMID = 20693944 }}</ref>
 
===IF===
*IgA +ve in a branching pattern - '''diagnostic'''.
 
===EM===
*Mesangial deposits.
**These are electron dense, ergo dark on EM images.


==Membranous nephropathy==
==Membranoproliferative glomerulonephritis==
*Abbreviated ''MPGN''.
*Old name ''MPGN type 1''.
===General===
===General===
*Presents as nephrotic syndrome.
Clinical:
*Nephrotic syndrome or nephrotic/nephritic syndrome.
 
Pathology:
*May be primary, i.e. idiopathic, or secondary, i.e. a consequence of another pathologic process.<ref name=pmid11682680>{{Cite journal  | last1 = Smet | first1 = AD. | last2 = Kuypers | first2 = D. | last3 = Evenepoel | first3 = P. | last4 = Maes | first4 = B. | last5 = Messiaen | first5 = T. | last6 = Van Damme | first6 = B. | last7 = Vanrenterghem | first7 = Y. | title = 'Full house' positive immunohistochemical membranoproliferative glomerulonephritis in a patient with portosystemic shunt. | journal = Nephrol Dial Transplant | volume = 16 | issue = 11 | pages = 2258-62 | month = Nov | year = 2001 | doi =  | PMID = 11682680 | URL = http://ndt.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=11682680 }}</ref>
 
====Secondary causes====
*In adults most common cause: ''[[hepatitis C]]''.
 
Other causes:
*[[HIV]].<ref name=pmid21743226>{{Cite journal  | last1 = Pakasa | first1 = NM. | last2 = Binda | first2 = PM. | title = HIV-associated immune complex glomerulonephritis with lupus-like features. | journal = Saudi J Kidney Dis Transpl | volume = 22 | issue = 4 | pages = 769-73 | month = Jul | year = 2011 | doi =  | PMID = 21743226 }}</ref>
*[[SLE]] - usu. has "full house" on IF.<ref name=pmid11682680/>
*Cryoglobulinemia.
*[[Hepatitis B]].
*Portocaval shunt.<ref name=pmid21743226/>


===Microscopic===
===Microscopic===
Features:
Features:
*Subepithelial immunocomplex deposition, spike forming.
*Endothelial cell proliferation.
*Basement membrane double layering (tram-tracking).
*Mesangial hypercellularity.


==Focal segmental glomerulosclerosis==
DDx:
*[[Nodular glomerulosclerosis]].
 
====Images====
<gallery>
Image:Membranoproliferative_glomerulonephritis_-_intermed_mag.jpg | MPGN - intermed. mag. (WC/Nephron)
Image:Membranoproliferative_glomerulonephritis_-_very_high_mag.jpg | MPGN - very high mag. (WC/Nephron)
</gallery>
*[http://path.upmc.edu/cases/case593.html MPGN - several images (upmc.edu)].
 
===EM===
Features:
*Subendothelial immune deposits - classic finding.<ref name=pmid21839367>{{Cite journal  | last1 = Sethi | first1 = S. | last2 = Fervenza | first2 = FC. | title = Membranoproliferative glomerulonephritis: pathogenetic heterogeneity and proposal for a new classification. | journal = Semin Nephrol | volume = 31 | issue = 4 | pages = 341-8 | month = Jul | year = 2011 | doi = 10.1016/j.semnephrol.2011.06.005 | PMID = 21839367 }}</ref>
*Subepithelial immune deposits - historically considered uncommon.<ref name=pmid2263028>{{Cite journal  | last1 = Sato | first1 = H. | title = [Ultrastructural study on membranoproliferative glomerulonephritis with special reference to subepithelial deposits]. | journal = Nihon Jinzo Gakkai Shi | volume = 32 | issue = 9 | pages = 973-83 | month = Sep | year = 1990 | doi =  | PMID = 2263028 }}</ref>
 
==Dense deposit disease==
*Abbreviated ''DDD''.
*[[AKA]] ''MPGN type 2'' (old name).
===General===
===General===
*Abbreviated ''FSGS''.
*Usually children and young adults.
*Presents as nephrotic syndrome.
*No longer considered a type of MPGN.<ref name=pmid17396142/>
*Does not respond to steroids (unlike MCD).


===Microscopic===
===Microscopic===
Features:
Features:
*Partial sclerosis of some glomeruli.
*Variable - may be like MPGN.
**Four patterns:<ref name=pmid17396142>{{Cite journal  | last1 = Walker | first1 = PD. | last2 = Ferrario | first2 = F. | last3 = Joh | first3 = K. | last4 = Bonsib | first4 = SM. | title = Dense deposit disease is not a membranoproliferative glomerulonephritis. | journal = Mod Pathol | volume = 20 | issue = 6 | pages = 605-16 | month = Jun | year = 2007 | doi = 10.1038/modpathol.3800773 | PMID = 17396142 }}</ref>
**#Hypercellularity and lobular (membranoproliferative-like).
**#Mesangial proliferative.
**#Crescentic.
**#Acute proliferative and exudative.


Image:
Images:
*[http://library.med.utah.edu/WebPath/jpeg1/RENAL083.jpg FSGS (utah.edu)].
*[http://www.nature.com/modpathol/journal/v20/n6/fig_tab/3800773f1.html DDD - light microscopy (nature.com)].<ref name=pmid17396142/>
*[http://path.upmc.edu/cases/case148.html DDD - several images (upmc.edu)].
 
===IF===
*Linear C3 with mesangial rings (donut-like).
*IgG negative.
*IgA negative
 
Images:
*[http://www.nature.com/modpathol/journal/v20/n6/fig_tab/3800773f3.html#figure-title DDD - IF (nature.com)].
 
===EM===
*Electron dense transformation of GBM lamina densa - key feature.
**Dense = darker.
 
Images:
*[http://www.nature.com/modpathol/journal/v20/n6/fig_tab/3800773f4.html#figure-title DDD (nature.com)].


==Membranoproliferative glomerulonephritis==
=Nephritic syndrome=
==Rapidly progressive glomerulonephritis==
*Abbreviated ''RPGN''.
*[[AKA]] ''crescentic glomerulonephritis''.
===General===
===General===
*Abbreviated ''MPGN''.
*Acute renal dysfunction.
*In adults most common cause: ''hepatitis C''.
*Nephritic syndrome.
 
DDx:
#Linear immunofluorescence.
#*[[Antiglomerular basement membrane disease]], [[Goodpasture syndrome]].
#Granular immunofluorescence
#*[[Lupus nephritis]].
#*[[Post-infectious glomerulonephritis]].
#*[[IgA nephropathy]].
#Pauci-immune.
#*[[Wegener granulomatosis]].
#*[[Microscopic polyangiitis]].


===Microscopic===
===Microscopic===
Features:
Features:
*Endothelial cell proliferation.
*[[Glomerular crescents]].
*Basement membrane double layering (tram-tracking).
*Interstitial inflammation.
*Mesangial hypercellularity.
*+/-[[Vasculitis]].


==Lupus nephritis==
====Images====
Five classes:
<gallery>
*Diffuse mesangial 2 vs. 4.
Image:Crescentic_glomerulonephritis_%282%29.jpg | RPGN (WC/KGH)
*Focal patch mesangial 3.
Image:Crescentic_glomerulonephritis_%281%29.jpg | RPGN (WC/KGH)
*Membranous 5 ???
Image:Crescentic_glomerulonephritis_-_intermed_mag.jpg | RPGN - intermed. mag. (WC/Nephron)
Image:Crescentic_glomerulonephritis_-_high_mag.jpg | RPGN - high mag. (WC/Nephron)
</gallery>
==Post-infectious glomerulonephritis==
*Abbreviated ''PIGN''.
{{Main|Post-infectious glomerulonephritis}}


Notes:
=Rare diseases=
*A six class schema is described here: [http://www.med.niigata-u.ac.jp/npa/Lectures/Lupus_Nephritis.htm http://www.med.niigata-u.ac.jp/npa/Lectures/Lupus_Nephritis.htm].
==Antiglomerular basement membrane disease==
 
*Abbreviated ''AGBM''.
==Fabry disease==
===General===
===General===
*Rare X-linked genetic disease.
*Known as '''Goodpasture disease''' ([[AKA]] '''Goodpasture syndrome'''), if renal failure is accompanied by [[pulmonary hemorrhage]].<ref>{{cite journal | author=Goodpasture EW | title=The significance of certain pulmonary lesions in relation to the etiology of influenza | journal=Am J Med Sci | year=1919 | volume=158 | pages=863–870 | doi=10.1097/00000441-191911000-00012 | issue=6}}</ref>
**Caused by defect in ''alpha-galactosidase A gene''.
*Rare - estimated incidence 1/1-2 million.<ref name=pmid20962523/>
**Women partially affected
*[[Antibody mediated hypersensitivity]].
*Lysosomal storage disorder -- 2nd in prevalence only to [[Gaucher disease]].
*Thought to occur in genetically susceptible individuals.<ref name=pmid20962523>{{Cite journal  | last1 = Zhou | first1 = XJ. | last2 = Lv | first2 = JC. | last3 = Zhao | first3 = MH. | last4 = Zhang | first4 = H. | title = Advances in the genetics of anti-glomerular basement membrane disease. | journal = Am J Nephrol | volume = 32 | issue = 5 | pages = 482-90 | month =  | year = 2010 | doi = 10.1159/000321324 | PMID = 20962523 }}</ref>
*Multisystem disease affecting small vessels and kidney.
**Associated with a specific HLA type (HLA-DRB1*1501) and two gene families.
**Antibodies directed against COL4A3,<ref>{{OMIM|120070}}</ref> which is ''not'' mutated.
*Oligouria - poor prognosticator.{{fact}}


===Presentation===
Tx:
*Women: usually proteinuria.
*Immune suppression & plasma exchange.<ref name=pmid12597309>{{Cite journal  | last1 = Shah | first1 = MK. | last2 = Hugghins | first2 = SY. | title = Characteristics and outcomes of patients with Goodpasture's syndrome. | journal = South Med J | volume = 95 | issue = 12 | pages = 1411-8 | month = Dec | year = 2002 | doi =  | PMID = 12597309 }}</ref>
*Men: angiokeratomas (skin lesion), proteinuria.


===Microscopy===
Clinical DDx:
LM:<ref name=pmid16799480>{{cite journal |author=Fischer EG, Moore MJ, Lager DJ |title=Fabry disease: a morphologic study of 11 cases |journal=Mod. Pathol. |volume=19 |issue=10 |pages=1295-301 |year=2006 |month=October |pmid=16799480 |doi=10.1038/modpathol.3800634 |url=http://www.nature.com/modpathol/journal/v19/n10/abs/3800634a.html}}</ref>
*[[Wegener granulomatosis]].
*Foamy podocyte inclusions, best visualized with ''[[toluidine blue]]''.
*Azathioprine toxicity.<ref name=pmid8203372>{{Cite journal | last1 = Stetter | first1 = M. | last2 = Schmidl | first2 = M. | last3 = Krapf | first3 = R. | title = Azathioprine hypersensitivity mimicking Goodpasture's syndrome. | journal = Am J Kidney Dis | volume = 23 | issue = 6 | pages = 874-7 | month = Jun | year = 1994 | doi = | PMID = 8203372 }}</ref>
*Mild mesangial hypercellularity.


EM:<ref name=pmid16799480/>
===Microscopic===
*Myelin-like inclusions.
Features:
**Concentric bodies with an onion-skin-like appearance.
*[[RPGN]].
*Zebra bodies.
**Crescentic glomerulonephritis.
**Ovoid inclusions with striped pattern.  


Note:  
====Images====
*Myelin-like inclusion are not [http://en.wikipedia.org/wiki/Pathognomonic pathognomonic] for Fabry disease; they may result from drug use:<ref name=pmid16799480/>
<gallery>
**Amiodarone,
Image:Crescentic_glomerulonephritis_-_intermed_mag.jpg | RPGN - intermed. mag. (WC/Nephron)
**Aminoglycosides,
Image:Crescentic_glomerulonephritis_-_high_mag.jpg | RPGN - high mag. (WC/Nephron)
**Chloroquine.
</gallery>
www:
*[http://path.upmc.edu/cases/case541.html AGBM disease - several images (upmc.edu)].


===Tx===
===IF===
*Symptomatic treatment.
*Linear IgG deposits - '''diagnostic'''.
*Enzyme replacement - ''agalsidase alpha'' (Replagal) or ''agalsidase beta'' (Fabrazyme).  
*Fibrinogen in crescents.


==Acute tubular necrosis==
DDx:
*Best diagnosed clinically (using urine R&M) - hemegranular casts are diagnostic.
*Goodpasture syndrome with the pulmonary hemorrhage.
*Often abbreviated ''ATN''.


===Histopathology===
Image:
Features:<ref>PS April 2009.</ref>
*[http://path.upmc.edu/cases/case541/images/fig08.jpg Linear IgG in AGBM disease (upmc.edu)].
*Hemegranular casts in the lumen.
*Regenerative activity (mitoses).


==Hepatorenal syndrome==
==Thin glomerular basement membrane disease==
*Acute renal failure due secondary to cirrhosis or fulminant liver failure.
===General===
*Collagen IV mutation - the same protein is involved in ''[[Alport syndrome]]''.


===Clinical===
Clinical:
*Urine sodium is low,<ref name=pmid1261103>{{cite journal |author=Epstein M, Oster JR, de Velasco RE |title=Hepatorenal syndrome following hemihepatectomy |journal=Clin. Nephrol. |volume=5 |issue=3 |pages=129-33 |year=1976 |month=March |pmid=1261103 |doi= |url=}}</ref> unlike in ATN (the main DDx).
*Hematuria.
*FHx.
*Nonprogressive.


===Pathophysiology===
===Microscopic===
*Renal vasoconstriction.<ref name=pmid18304678>{{cite journal |author=Angeli P, Merkel C |title=Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis |journal=J. Hepatol. |volume=48 Suppl 1 |issue= |pages=S93-103 |year=2008 |pmid=18304678 |doi=10.1016/j.jhep.2008.01.010 |url=}}</ref>
*Normal.


===Histology===
===IF===
*Normal.
*Normal.


===Treatment===
===EM===
Medical and surgical:<ref name=pmid18417039>{{cite journal |author=Wong F |title=Hepatorenal syndrome: current management |journal=Curr Gastroenterol Rep |volume=10 |issue=1 |pages=22-9 |year=2008 |month=February |pmid=18417039 |doi= |url=}}</ref>
*GBM thin <200-250 - '''key feature'''.  
*Vasoconstrictors (e.g. midodrine, terlipressin (counteracts splanchnic vasodilation), norepinephrine).
*Albumin.
*TIPS (transjugular intrahepatic portosystemic shunt).
*Liver transplantation.


Note:
Note:
*I suspect a ''portal vein pump'' would work... it reduces portal pressure and would likely increase hepatic function.
*Normal GBM: 300-350 nm.


==Alport disease==
==Alport syndrome==
===Clinical===
===General===


Clinical:
*Hearing loss (sensorineural).
*Hearing loss (sensorineural).
*Hematuria - usually preceeds hearing loss.<ref name=emedicine981126>[http://emedicine.medscape.com/article/981126-overview http://emedicine.medscape.com/article/981126-overview]</ref>  
*Hematuria - usually preceeds hearing loss.<ref name=emedicine981126>URL: [http://emedicine.medscape.com/article/981126-overview http://emedicine.medscape.com/article/981126-overview]</ref>  


*Can be thought of a pathologic form of ''thin basement membrane disease''.<ref>AM. 13 August 2009.</ref>
*Can be thought of a pathologic form of ''[[thin basement membrane disease]]''.<ref>AM. 13 August 2009.</ref>


===Etiology===
Etiology:
*Genetic defect - collagen type IV.
*Genetic defect - collagen type IV.


Line 424: Line 1,007:
*Autosomal dominant - 5%.
*Autosomal dominant - 5%.


==Polycystic kidney disease==
===Microscopic===
Types:
Features:<ref name=pmid9727383/>
*Adult onset - autosomal dominant polycystic kidney disease (ADPKD).
*Usu. normal.
*Childhood onset - autosomal recessive polycystic kidney disease (ARPKD).
*+/-Foamy appearing renal tubular cells.<ref name=Ref_Klatt246>{{Ref Klatt|246}}</ref>
 
===IF===
*Negative.


==Autosomal dominant polycystic kidney disease (ADPKD)==
===EM===
Features:<ref name=pmid9727383>{{Cite journal  | last1 = Kashtan | first1 = CE. | title = Alport syndrome and thin glomerular basement membrane disease. | journal = J Am Soc Nephrol | volume = 9 | issue = 9 | pages = 1736-50 | month = Sep | year = 1998 | doi =  | PMID = 9727383 | url=http://jasn.asnjournals.org/content/9/9/1736.long}}</ref>
*Abnormal glomerular basement membrane (GBM); thinning or thickening.
**Classically thinning with thick lamellation (splitting/multi-layering).
 
==Idiopathic nodular glomerulosclerosis==
===General===
===General===
====Etiology====
*Not [[diabetes mellitus|diabetic]] - '''key feature'''.
*Mutation in ''PKD1'' gene or ''PKD2'' gene.
 
*Is classified in a large group of diseases - ''ciliopathies''.
Associations:<ref name=pmid18701135/>
*[[Smoking]] - common; thought to be important in the etiology.<ref name=pmid21904413>{{Cite journal  | last1 = Costa | first1 = AF. | last2 = Gomes dos Santos | first2 = WA. | last3 = Filho | first3 = MA. | last4 = Farias | first4 = FT. | last5 = Modesto dos Santos | first5 = V. | title = Nodular glomerulosclerosis in a non-diabetic hypertensive smoker with dyslipidemia. | journal = An Sist Sanit Navar | volume = 34 | issue = 2 | pages = 301-8 | month =  | year =  | doi =  | PMID = 21904413 }}</ref>
*[[Hypertension]].
 
===Microscopic===
Features:<ref name=pmid18701135>{{Cite journal  | last1 = Li | first1 = W. | last2 = Verani | first2 = RR. | title = Idiopathic nodular glomerulosclerosis: a clinicopathologic study of 15 cases. | journal = Hum Pathol | volume = 39 | issue = 12 | pages = 1771-6 | month = Dec | year = 2008 | doi = 10.1016/j.humpath.2008.05.004 | PMID = 18701135 }}</ref>
*Looks like diabetic nodular glomerulosclerosis.
 
===IF===
Nonspecific.
 
===EM===
Nonspecific.
 
==Fabry disease==
{{Main|Fabry disease}}
 
==Myeloma==
:See: ''[[Haematopathology]]''.
*[[AKA]] ''myeloma kidney''.
 
===Myeloma cast nephropathy===
====General====
*Renal failure.


PKD1 related disease:<ref name=Ref_MacSween174-5>{{Ref MacSween|174-5}}</ref>  
====Microscopic====
*Encodes polycystin.
Features:<ref>URL: [http://www.kidneypathology.com/English_version/Amyloidosis_and_others.html http://www.kidneypathology.com/English_version/Amyloidosis_and_others.html]. Accessed on: 9 November 2010.</ref>
*Death at ~53 years.
*Crap in tubules, eosinophilic.
*Assoc. with cerebral aneurysms.
**Classically angulated.
**Refractile.
*Cast with cellular reaction - '''virtually diagnostic'''.
**Macrophages (CD68 +ve).


PKD2 related disease:<ref name=Ref_MacSween174-5>{{Ref MacSween|174-5}}</ref>  
=====Images=====
*Death at ~69 years.
www:
*Assoc. with colonic diverticula, aortic aneurysm, mitral valve prolapse.
*[http://www.kidneypathology.com/Imagenes/Amiloidosis%20y/MM.3.w.jpg Cast nephropathy in myeloma (kidneypathology.com)].
*[http://www.kidneypathology.com/Imagenes/Amiloidosis%20y/MM.5.w.jpg Cast nephropathy in myeloma - refractile crap (kidneypathology.com)].
<gallery>
Image:Cast_nephropathy_-_high_mag.jpg | Myeloma cast nephropathy - high mag. (WC/Nephron)
Image:Cast_nephropathy_-_2_cropped_-_very_high_mag.jpg | Myeloma cast nephropathy - cropped - very high mag. (WC/Nephron)
</gallery>
====Stains====
*Myeloma casts = PAS -ve.
**Hyaline casts = PAS +ve.


====Liver cysts and PKD====
===Amyloidosis===
=====General=====
{{Main|Amyloidosis}}
*Usually associated with lambda clone.
 
===Light chain deposition===
*Usually associated with kappa clone.
 
==Immunotactoid glomerulopathy==
===General===
*Uncommon.
*Thought to be a primary glomerulopathy.
**Must exclude [[lupus nephritis]], paraproteinemias, [[fibrillary glomerulopathy]], cryoglobulinemia, [[renal amyloidosis]].
*"Not universally" considered distinct from [[fibrillary glomerulopathy]].<ref name=pmid18045849>{{Cite journal  | last1 = Alpers | first1 = CE. | last2 = Kowalewska | first2 = J. | title = Fibrillary glomerulonephritis and immunotactoid glomerulopathy. | journal = J Am Soc Nephrol | volume = 19 | issue = 1 | pages = 34-7 | month = Jan | year = 2008 | doi = 10.1681/ASN.2007070757 | PMID = 18045849 | URL = http://jasn.asnjournals.org/content/19/1/34.full }}</ref>
 
Presentation:
*Nephrotic range proteinuria ~ 60% of cases.<ref name=pmid1996564>{{Cite journal  | last1 = Korbet | first1 = SM. | last2 = Schwartz | first2 = MM. | last3 = Lewis | first3 = EJ. | title = Immunotactoid glomerulopathy. | journal = Am J Kidney Dis | volume = 17 | issue = 3 | pages = 247-57 | month = Mar | year = 1991 | doi =  | PMID = 1996564 }}</ref>
*[[Hypertension]].
 
===Microscopic===
Features:
Features:
*Most common extra-renal manifestation of PKD; dependent on age, sex and renal function:<ref name=pmid9186898>{{cite journal |author=Perrone RD |title=Extrarenal manifestations of ADPKD |journal=Kidney Int. |volume=51 |issue=6 |pages=2022–36 |year=1997 |month=June |pmid=9186898 |doi= |url=http://www.nature.com/ki/journal/v51/n6/pdf/ki1997276a.pdf}}</ref>
*Mesangial expansion.
**Age dependence:
 
***10-17% <40 years old have liver cysts.
DDx:
***70-75% >60 years old have liver cysts.
*Other causes of mesangial expansion.
**Renal function:
 
***60-70% of patients with end-stage renal disease (ESRD) and near-ESRD.
===IHC===
**Females more often affected.
*[[Congo red stain]] -ve.
*Hepatic function usu. preserved.


Complications:<ref name=Ref_MacSween174-5>{{Ref MacSween|174-5}}</ref>
==Fibrillary glomerulonephritis==
#Infected cyst.
*[[AKA]] ''fibrillary glomerulopathy''.
#Cholangiocarcinoma.
===General===
*Rare ~ 1% native kidney biopsies.<ref name=pmid18045849>{{Cite journal  | last1 = Alpers | first1 = CE. | last2 = Kowalewska | first2 = J. | title = Fibrillary glomerulonephritis and immunotactoid glomerulopathy. | journal = J Am Soc Nephrol | volume = 19 | issue = 1 | pages = 34-7 | month = Jan | year = 2008 | doi = 10.1681/ASN.2007070757 | PMID = 18045849 | URL = http://jasn.asnjournals.org/content/19/1/34.full }}</ref>
*Presents as [[nephrotic syndrome]].
*Prognosis poor; large number progress to ESRD.


=====Microscopic=====
===Microscopic===
Features:
Features:
*''Von Meyenburg complexes'':
*Mesangial matrix expansion.
**Cluster of dilated ducts with "altered" bile.
*Thickened capillary walls.
**Surrounded by collagenous stroma.


Images:
*www:
**[http://jasn.asnjournals.org/content/19/1/34/F1.expansion.html FG (asnjournals.org)].<ref name=pmid18045849/>
**[http://path.upmc.edu/cases/case78.html Fibrillary glomerulopathy (upmc.edu)].


===IF===
*IgG predominant.<ref name=pmid18045849/>


See also: ''[[Medical liver disease]]''.
===Stains===
*[[Congo red stain]] -ve.
 
===EM===
*Fibrils:<ref name=pmid18045849/>
**Non-branching.
**Randomly arranged.
**Usu. 18-20 nm in diameter -- larger than amyloid (see below).
***Size range 12-24 nm.
 
Note:
*[[Amyloid]] between 8 and 15 nm (diameter), most often 8-12 nm.<ref name=pmid18045849>{{Cite journal  | last1 = Alpers | first1 = CE. | last2 = Kowalewska | first2 = J. | title = Fibrillary glomerulonephritis and immunotactoid glomerulopathy. | journal = J Am Soc Nephrol | volume = 19 | issue = 1 | pages = 34-7 | month = Jan | year = 2008 | doi = 10.1681/ASN.2007070757 | PMID = 18045849 | URL = http://jasn.asnjournals.org/content/19/1/34.full }}</ref>
 
==Aristolochic acid nephropathy==
*Abbreviated ''AAN''.
*[[AKA]] ''chinese herb nephropathy''.<ref>{{Cite journal  | last1 = Yang | first1 = L. | last2 = Su | first2 = T. | last3 = Li | first3 = XM. | last4 = Wang | first4 = X. | last5 = Cai | first5 = SQ. | last6 = Meng | first6 = LQ. | last7 = Zou | first7 = WZ. | last8 = Wang | first8 = HY. | title = Aristolochic acid nephropathy: variation in presentation and prognosis. | journal = Nephrol Dial Transplant | volume =  | issue =  | pages =  | month = Jun | year = 2011 | doi = 10.1093/ndt/gfr291 | PMID = 21719716 }}</ref><ref name=cin2003>URL: [http://www.uninet.edu/cin2003/conf/cosyns/cosyns.html http://www.uninet.edu/cin2003/conf/cosyns/cosyns.html]. Accessed on: 23 November 2011.</ref>
 
===General===
*Nephropathy due to chinese herbs for slimming.<ref name=pmid9027778>{{Cite journal  | last1 = Reginster | first1 = F. | last2 = Jadoul | first2 = M. | last3 = van Ypersele de Strihou | first3 = C. | title = Chinese herbs nephropathy presentation, natural history and fate after transplantation. | journal = Nephrol Dial Transplant | volume = 12 | issue = 1 | pages = 81-6 | month = Jan | year = 1997 | doi =  | PMID = 9027778 | url = http://ndt.oxfordjournals.org/content/12/1/81 }}</ref>
*Associated with urothelial atypia/urothelial carcinoma.
 
Clinical:
*Chinese herb use.
*Low-molecular weight proteinuria.
 
===Microscopic===
Features:<ref name=pmid9027778/>
*Extensive interstitial fibrosis.
*Tubular atrophy - typically greater in outer cortex than inner cortex.
*Glomeruli spared.
*+/-Nuclear atypia of the urothelium.
 
DDx:
*Balkan endemic nephropathy.
 
Image:
*[http://www.uninet.edu/cin2003/conf/cosyns/fig1.jpg AAN (uninet.edu)].<ref name=cin2003/>
 
==Cystic kidney diseases==
{{Main|Cystic kidney diseases}}
These are discussed in a separate article and include:
*[[Autosomal dominant polycystic kidney disease]] (ADPKD).
*Adult-onset medullary cystic disease.
*[[Acquired renal cystic disease]].
*[[Autosomal recessive polycystic kidney disease]] (ARPKD).
*Medullary sponge kidney.
*Nephronophthisis.
*Cystic [[renal cell carcinoma]].
 
=Pyelonephritis=
''Pyelonephritis'' is a misnomer; it is ''not'' an inflammatory process affecting the renal pelvis, as the name suggests. ''Pyelonephritis'' actually refers to a ''nephritis'' or ''tubulointerstitial nephritis''.<ref name=Ref_Sternberg5_1725>{{Ref Sternberg5|1725}}</ref>
 
It can be subdivided into:
*[[Acute pyelonephritis]].
*[[Chronic pyelonephritis]].
**[[Xanthogranulomatous pyelonephritis]].
 
==Acute pyelonephritis==
*[[AKA]] ''acute infectious tubulointerstitial nephritis''.
*[[AKA]] ''diffuse suppurative nephritis''.
===General===
*Typically preceeded by a (lower) [[urinary tract infection]] (UTI).
*Usually diagnosed clinically:
**Urine C&S, urine R&M, +/-CT abdomen.
**Fever, costovertebral tenderness.


===Gross===
===Gross===
Features:
Features:
*Thin walled cysts.
*+/-[[Necrosis]] of renal papillae.<ref name=Ref_Klatt251>{{Ref Klatt|251}}</ref>
**Number of cysts:
 
***If you can count 'em it favours acquired renal cystic disease... if you can't it favours the genetic condition.
===Microscopic===
Features:
*[[Neutrophil]]s within the renal tubules and interstitium.<ref name=Ref_Sternberg5_1726>{{Ref Sternberg5|1726}}</ref>
 
====Images====
<gallery>
Image:Acute_pyelonephritis_-_intermed_mag.jpg | Acute pyelonephritis - intermed. mag. (WC/Nephron)
Image:Acute_pyelonephritis_-_2_-_high_mag.jpg | Acute pyelonephritis - high mag. (WC/Nephron)
Image:Acute_pyelonephritis_-_2_-_very_high_mag.jpg | Acute pyelonephritis - very high mag. (WC/Nephron)
</gallery>
==Chronic pyelonephritis==
*''Reflux nephropathy'' is considered synonym in some sources.<ref name=Ref_Sternberg5_1728>{{Ref Sternberg5|1728}}</ref>
===General===
*Inflammation of the kidney (''nephritis'') and renal pelvis (''pyelo-''<ref>URL: [http://medical-dictionary.thefreedictionary.com/pyelo- http://medical-dictionary.thefreedictionary.com/pyelo-]. Accessed on: 5 June 2015.</ref>).
*May be associated with vesicoureteral reflux.
*Chronic [[pyelonephritis]] may be a reason for nephrectomy.<ref>URL: [https://secure.health.utas.edu.au/intranet/cds/pathprac/Files/Cases/Renal/Case44/Case44.htm https://secure.health.utas.edu.au/intranet/cds/pathprac/Files/Cases/Renal/Case44/Case44.htm]. Accessed on: 26 July 2011.</ref>
 
===Gross===
*Dilated and distorted renal pelvis.<ref name=Ref_Sternberg5_1729>{{Ref Sternberg5|1729}}</ref>
*+/-[[Necrosis]] of renal papillae.<ref name=Ref_Klatt251>{{Ref Klatt|251}}</ref>


===Microscopic===
===Microscopic===
Features:<ref name=Ref_DARP426>{{Ref DARP|426}}</ref>
Features:<ref name=Ref_Sternberg5_1729>{{Ref Sternberg5|1729}}</ref>
*Cysts lined by simple flattened epithelium.
*Mononuclear tubulointerstitial infiltrate.
*Normal renal tubules interspersed between cysts.
**Usu. more dense at the pelvis.
*+/-Fibrosis (late-stage).
*Interstitial fibrosis.
*+/-Renal casts (PAS positive); may result in a thyroid-like apparance.


DDx:  
DDx:
*Acquired renal cystic disease - rarely.<ref name=pmid1819219>{{cite journal |author=Kessler M, Testevuide P, Aymard B, Huu TC |title=Acquired renal cystic disease mimicking adult polycystic kidney disease in a patient undergoing long-term hemodialysis |journal=Am. J. Nephrol. |volume=11 |issue=6 |pages=513–7 |year=1991 |pmid=1819219 |doi= |url=}}</ref>
*[[End-stage kidney]].
**Morphologically similar to acquired renal cystic disease.<ref>RJ. 20 October 2010.</ref>
*[[Myeloma cast nephropathy]].


==Acquired renal cystic disease==
===Stains===
*PAS +ve -- renal tubular casts.
 
=Disease that does not commonly get biopsied=
==End-stage kidney==
{{Main|End-stage kidney}}
 
==Malignant hypertension==
:''See: [[hyperplastic arteriolosclerosis]]''.
:''See: [[thrombotic microangiopathy]]''.
*May be seen in [[scleroderma]].
 
==Acute tubular necrosis==
*Often abbreviated ''ATN''.
===General===
===General===
*Thought to arise due to uremia,<ref name=pmid7861721>{{cite journal |author=Fick GM, Gabow PA |title=Hereditary and acquired cystic disease of the kidney |journal=Kidney Int. |volume=46 |issue=4 |pages=951–64 |year=1994 |month=October |pmid=7861721 |doi= |url=http://www.nature.com/ki/journal/v46/n4/pdf/ki1994354a.pdf}}</ref> not specific to the type of renal dialysis, i.e. hemodialysis vs. peritoneal dialysis.
Diagnosed clinically:
*Presence of cysts dependent on duration of dialysis:<ref name=pmid7861721/>
*Using urine R&M - hemegranular casts<ref name=pmid19921458>{{Cite journal | last1 = Kanbay | first1 = M. | last2 = Kasapoglu | first2 = B. | last3 = Perazella | first3 = MA. | title = Acute tubular necrosis and pre-renal acute kidney injury: utility of urine microscopy in their evaluation- a systematic review. | journal = Int Urol Nephrol | volume = 42 | issue = 2 | pages = 425-33 | month = Jun | year = 2010 | doi = 10.1007/s11255-009-9673-3 | PMID = 19921458 }}</ref> are diagnostic.
**< 3 years ~44%.
*Anuria or low urine output.
**>4 years ~80%.
 
**>10 years ~90%.
===Gross===
*Associated with [[renal cell carcinoma]] (papillary subtype).<ref>{{Ref DARP|438}}</ref>
*Poorly defined corticomedullary junction - soft finding.
*Slightly heavier ~ 180 grams.<ref name=pmid19207286/>


===Microscopic===
===Microscopic===
Features:<ref name=pmid1819219>{{cite journal |author=Kessler M, Testevuide P, Aymard B, Huu TC |title=Acquired renal cystic disease mimicking adult polycystic kidney disease in a patient undergoing long-term hemodialysis |journal=Am. J. Nephrol. |volume=11 |issue=6 |pages=513–7 |year=1991 |pmid=1819219 |doi= |url=}}</ref>
Features:<ref name=pmid19207286>{{Cite journal | last1 = Kocovski | first1 = L. | last2 = Duflou | first2 = J. | title = Can renal acute tubular necrosis be differentiated from autolysis at autopsy? | journal = J Forensic Sci | volume = 54 | issue = 2 | pages = 439-42 | month = Mar | year = 2009 | doi = 10.1111/j.1556-4029.2008.00956.x | PMID = 19207286 }}</ref>
*Cysts - location: cortex and medulla.
*Tubular epithelial whorls - present in approx. one third of cases - '''most important'''.
**Lined by simple flattened epithelium.
**Detached epithelium within the luminal space surrounded by epithelium.
***Similar to ''epithelial telescoping'' seen in endometrial biopsies.
*Tubulorrhexis - present in approx. one third of cases.
**Disruption of the tubular basement membrane.
*Interstitial edema - sensitive... but not specific.


==Transplant==
Notes - not particularily useful findings:
===Predictors===
*Mitoses.
*Associated with C4d+ IHC.<ref name=pmid1747954>Vascular deposition of complement-split products in kidney allografts with cell-mediated rejection. Feucht HE, Felber E, Gokel MJ, Hillebrand G, Nattermann U, Brockmeyer C, Held E, Riethmüller G, Land W, Albert E. Clin Exp Immunol. 1991 Dec;86(3):464-70. PMID 1747954.</ref>
*Casts in tubules.
*Mean graft survival is ~4 years for C4d+ interstitial capillaries vs. ~8 years for C4d- renal grafts.<ref name=pmid11135088>Impact of humoral alloreactivity early after transplantation on the long-term survival of renal allografts. Lederer SR, Kluth-Pepper B, Schneeberger H, Albert E, Land W, Feucht HE. Kidney Int. 2001 Jan;59(1):334-41. PMID 11135088.</ref>
 
===IHC===
*Ki-67 - focal nuclear staining of the tubular epithelium.<ref name=pmid19207286/>
 
==Hepatorenal syndrome==
===General===
*Acute renal failure secondary to liver failure (e.g. fulminant liver failure, [[cirrhosis]] with marginal liver function).
 
Clinical:
*Urine sodium is low,<ref name=pmid1261103>{{cite journal |author=Epstein M, Oster JR, de Velasco RE |title=Hepatorenal syndrome following hemihepatectomy |journal=Clin. Nephrol. |volume=5 |issue=3 |pages=129-33 |year=1976 |month=March |pmid=1261103 |doi= |url=}}</ref> unlike in ATN (the main DDx).
 
Pathophysiology:
*Renal vasoconstriction.<ref name=pmid18304678>{{cite journal |author=Angeli P, Merkel C |title=Pathogenesis and management of hepatorenal syndrome in patients with cirrhosis |journal=J. Hepatol. |volume=48 Suppl 1 |issue= |pages=S93-103 |year=2008 |pmid=18304678 |doi=10.1016/j.jhep.2008.01.010 |url=}}</ref>
 
Treatment:
Medical and surgical:<ref name=pmid18417039>{{cite journal |author=Wong F |title=Hepatorenal syndrome: current management |journal=Curr Gastroenterol Rep |volume=10 |issue=1 |pages=22-9 |year=2008 |month=February |pmid=18417039 |doi= |url=}}</ref>
*Vasoconstrictors (e.g. midodrine, terlipressin (counteracts splanchnic vasodilation), norepinephrine).
*Albumin.
*TIPS (transjugular intrahepatic portosystemic shunt).
*Liver transplantation.
 
Note:
*I suspect a ''portal vein pump'' would work... it reduces portal pressure and would likely increase hepatic function.
 
===Microscopic===
Features (kidney):
*Normal.
 
==Nephrocalcinosis==
===General===
*[[Hypercalcemia]].
 
===Microscopic===
Features:
*Calcification of the renal parenchyma - '''key feature'''.


===Polyomavirus===
Images:
*This bad-boy is associated with failure of transplanted kidneys.<ref name=pmid216990>{{cite journal |author=Mackenzie EF, Poulding JM, Harrison PR, Amer B |title=Human polyoma virus (HPV)--a significant pathogen in renal transplantation |journal=Proc Eur Dial Transplant Assoc |volume=15 |issue= |pages=352–60 |year=1978 |pmid=216990 |doi= |url=}}</ref>
*[http://path.upmc.edu/cases/case514.html Nephrocalcinosis (upmc.edu)].
*Treatment: reduce immunosuppression.<ref name=Nickeleit>Nickeleit, Volker; Singh, Harsharan K. Polyomavirus Allograft Nephropathy: Clinico-Pathological Correlations. URL: [http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A74503#A74539 http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=eurekah&part=A74503#A74539]. Accessed on: 8 November 2010.</ref>


Microscopic features:<ref name=Nickeleit/>
=Renal transplant pathology=
*Ground glass-like nuclear inclusions.
{{Main|Renal transplant pathology}}
*Nuclear enlargement.


===Calcineurin-inhibitor toxicity===
*Acute rejection.
*Calcineurin-inhibitors (e.g. cyclosporine,<ref name=pmid10354295>{{cite journal |author=Zarifian A, Meleg-Smith S, O'donovan R, Tesi RJ, Batuman V |title=Cyclosporine-associated thrombotic microangiopathy in renal allografts |journal=Kidney Int. |volume=55 |issue=6 |pages=2457–66 |year=1999 |month=June |pmid=10354295 |doi=10.1046/j.1523-1755.1999.00492.x |url=}}</ref>, tacrolimus<ref name=Ref_FoRP203>{{Ref FoRP|203}}</ref>) toxicity can induce a [[thrombotic microangiopathy]].
*Chronic rejection.
*[[Polyomavirus]].
*[[Transplant glomerulopathy]].
*Calcineurin-inhibitor toxicity.


==See also==
=See also=
*[[Kidney tumours]].
*[[Kidney tumours]].
*[[Urinary bladder]].
*[[Urinary bladder]].
*[[Genitourinary pathology]].
*[[Genitourinary pathology]].
*[[Thrombotic microangiopathy]].


==References==
=References=
{{reflist|2}}
{{reflist|2}}


==External links==
=External links=
*[http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/rnfrm.html Nephropathology quiz (med.utah.edu)].
*[http://library.med.utah.edu/WebPath/EXAM/IMGQUIZ/rnfrm.html Nephropathology quiz (med.utah.edu)].
*[http://www.fondazionedamico.org/biopsiarenale_atlas/seco/crio/crio.htm Cryoglobulinemic nephritis (fondazionedamico.org)].
*[http://www.fondazionedamico.org/biopsiarenale_atlas/seco/crio/crio.htm Cryoglobulinemic nephritis (fondazionedamico.org)].


[[Category: Genitourinary pathology]]
[[Category: Medical kidney pathology]]

Latest revision as of 03:21, 22 February 2017

This article describes medical renal disease or the medical kidney. Much in medical kidney depends on the clinical information. Most of the disease seen by pathologists is... glomerular disease. It is one of the few areas that routinely requires electron microscopy.

Medical kidney is niche area in pathology. In the context of exams for general pathologists, if in doubt... the answer to most questions is diabetes mellitus or systemic lupus erythematosus.

Kidney tumours are dealt with in the kidney tumours article, and pediatric kidney tumours article.

Clinical

Creatinine

  • The standard screening test for renal function.
  • 300 mmol/L is the general cut-point for referral to a nephrologist.[1]

Notes:

  • In some parts of the world they use the units mg/dL; normal with these units is: 0.8 to 1.4 mg/dL.[2]
  • Conversion: 1.0 mg/dL = 88.4 umol/L.[3][4]

Glomerular filtration rate

  • Abbreviated GFR.
  • Ultimate measure of renal function - usually estimated from the serum creatinine using a formula.
  • Declines with age.
  • Normal range (dependent on age): 116-75 mL/min/1.73m2.[5]

Urine protein to creatinine ratio

  • Indicator of proteinuria.
  • Predictor of glomerular filtration rate.[6]

Cut points:[7]

  • Normal (2 years and older): <0.2 g protein / g Creatinine
  • Nephrotic range: >3.5 g protein / g Creatinine.

Complement

C3, C4 levels:[8]

ANCA

Types:[12]

C4d

  • Suggests humoral immunity (antibody-mediated immunity) at play.
  • Important in monitoring of renal transplant recipients.
  • Immunostain also available - see below.

Other blood work

Renal ultrasound

  • Normal adult kidney size ~10.8+/-0.8 cm.[13]
  • Good for assessing the major vessels, drainage system and parenchymal lesions.
    • Renal artery stenosis?
    • Hydronephrosis?
    • Pelviectasis?
    • Renal cyst?
    • Renal mass?

Urine dip

Findings:[14]

  • RBC casts = acute bleed, e.g. nephritic syndrome.
  • WBC casts = interstitial nephritis, e.g. pylonephritis, parenchymal infection.
  • Hemegranular casts = acute tubular necrosis, transplant rejection.

Notes:

  • "Active sediment" = RBCs, RBC casts;[15] implies glomerulonephritis.
    • Some include the above (RBCs, RBC casts) + WBCs & protein.[16]

Urine crystals

Clinical presentations

Nephrotic syndrome

Features:

  • Anasarca (whole body - edema).
  • Proteinuria (>3.5 g/24h).
  • Hypercholesterolemia.
  • Hypoalbuminemia.

Nephritic syndrome

Features - mnemonic PHAROH:[17]

  • Proteinuria.
  • Hypertension.
  • Azotemia.
  • RBC casts.
  • Oliguria.
  • Hematuria.

Mixed

Clinical DDx

Renal failure 101

  • Prerenal.
    • Shock - cardiogenic, hypovolemic, neurogenic, septic, anaphylatic.
  • Renal.
    • What this article deals with.
  • Postrenal.

Renal causes

  • Isolated hematuria.
  • Isolated proteinuria.
  • Nephrotic syndrome.
  • Nephritis syndrome.
  • Rapidly progressive glomerulonephritis.
  • Chronic renal failure.
  • A combination of any of the above.

The clinical presentations suggest a pathologic DDx.[18]

Isolated hematuria

Proteinuria

Nephritic syndrome

Classic:

Others:

Rapidly progressive glomerulonephritis

Classification:[20]

  1. Linear immune deposits.
  2. Granular immune deposits.
  3. Pauci-immune.

Nephrotic syndrome

Mixed presentation

Normal kidney

Cells of the glomerulus

  • Podocytes.
  • Mesangial cells.
  • Endothelium.

Epithelium

Features:[21]

  • The glomeruli visceral epithelium is part of the capillary wall (part of the glomerular tuft).
  • The parietal epithelium is part of Bowman's capsule.

Remember: visceral has vessels.

Glomerulus

  • A large autopsy series suggest it is: 223-292 micrometers.[22]
    • Another autopsy series suggests the mean diameter is: 225 micrometers.[23]

Note:

  • If the glomerulus fills half the field at 40x on a microscope with 22 mm diameter eye pieces it is ~ 0.275 mm or 275 micrometers.

Glomerular basement membrane

The glomerular basement membrane (GBM) should be thinner than the tubular basement membrane.

Images

Basic approach to renal biopsy

Basic components

  • Glomeruli.
  • Tubules.
  • Interstitium.
  • Vessels.

Memory device GI TV: glomeruli, interstitium, tubules, vessels.

Glomeruli

  1. Mesangium
    • Matrix should be: "one cell thick" (expanded in diabetes mellitus).
    • Cellularity of the mesangium - normal = upto 3 cells (don't count cell abutting the capillary lumen, don't count at the hilum).
  2. Capillary loops "open"
    • Lumina patent? If not patent is it due to matrix or cells (endocapillary hypercellularity).
    • Capillary wall morphology - wavy thin is normal; hulla-hoop/wire-like abnormal (suggestive of immune complex deposition).
  3. Bowman's space (urinary space) - crescents present?
  • Count the number of glomeruli.
  • Count number of the obsolete glomeruli.

Notes:

Components of the glomeruli (anatomical)

Obsolete glomeruli

  • Completely sclerosed glomeruli are not important - unless present in larger numbers than expected for the age of the patient.
Percent of sclerosed glomeruli = (age in years)/2 - 10%.[27]

Example:

  • It is normal for an 80 year-old to have 30% sclerosed glomeruli.

Glomerular disease terms

Number of glomeruli involved:[28]

  • Focal = some of the glomeruli.
    • In practical terms, defined as: <50% of glomeruli.
  • Diffuse = most of glomeruli.

How much of the glomerulus is involved:[28]

  • Global = most of the glomerulus.
    • In practical terms, defined as: >80% of glomerulus.[29]
  • Segmental = part of the glomerulus.

Vessels

  1. Arteriolar hyalinosis - too much glassy pink stuff?
  2. Intimal hyperplasia (atherosclerosis).

Consider:

Arteriolar hyalinosis

Microscopic:

  • Small vessels (afferent +/- efferent arteriole) with:
    • Glassy eosinophilic material in arteriolar wall.

DDx:

Note:

  • Arteriolar hyalinosis - involves afferent and efferent arterioles in diabetes, in others it is only the afferent.

Memory device ADHD:

  • Aging, Diabetes, Hypertension, Drugs.
Image

Atherosclerosis

Microscopic:

  • Intimal thickening of medium-sized vessels.
    • Where is the intima/media interface?
      • Internal elastic lamina - wavy band of eosinophilic material on H&E that is 1-2 micrometres thick.

Grading - based on the thickness of the media and intima:

  • Mild: (tunica) media > (tunica) intima.
  • Moderate: media = intima.
  • Severe: media < intima.

Tubules

Tubules - proximal portion is the most important.

Consider:

  • Casts?
  • Degeneration, i.e. apoptosis.
  • Necrosis?
  • Regeneration, e.g. mitoses.

Interstitium

Interstitium

  • Fibrosis - prognostically important.
    • Grading: mild = <25%, moderate 25-50%, severe >50%.
  • Inflammation?

Important terms/process related

Staining

The standard stain in kidney pathology is PAS. Section are usually 1-2 micrometers, as opposed to 4-5 micrometers seen in rountine section of other organs.

Interpretation of medical renal disease more difficult or even impossible if the sections are thicker, as one does not see the glomerular structures well.

In kidney that is cut thick the glomeruli look more nodular and it is more difficult to find open capillary loops.

Immunofluorescence

Routinue (mnemonic GAM CF):

  • IgG.
  • IgA.
  • IgM.
  • C1q
  • C3.
  • Fibrinogen.
  • Albumin.

Optional:

  • Kappa.
  • Lambda.
  • C4d.
    • Positive staining = peri-tubular capillaries stain.

Negative immunofluorescence

  • Excludes all immune complex associated disease.

Seen in:

Positive immunofluorescence

  • Positive immunofluorescence is usually diagnostic.

Basic patterns:

  1. Linear.
  2. Granular.
  3. Ring-like.

Examples:

Notes:

Immune complex-related disease

Can be:

Pathologic differential diagnosis

Tram-tracking of BM

DDx:[30]

  1. MPGN.
  2. Thrombotic microangiopathy (TMA).
  3. Transplant glomerulopathy (TG).

Mesangial hypercellularity

DDx:

  1. Lupus nephritis.
  2. IgA nephropathy.

Mesangial expansion

  • A patch of matrix can contain more than three mesangial cell nuclei.
    • Highly subjective.

DDx:

Glomerular crescents

General

  • Indicates a rapidly progressive disease.
  • Etiology/definition: break in the glomerular basement membrane (GBM).

Microscopic

Features:

  • Crescentic-shaped lesion in the urinary space of a glomerulus.
    • Crescent = looks like the moon shortly after new moon.
    • Cells & cellular debris in the urinary space.
      • Crescents lack GBM -- thus PAS -ve and MPAS -ve.
  • Break in the glomerular basement membrane - key feature.
  • Fibrin.
  • Inflammatory cells (lymphocytes, plasma cells, eosinophils, macrophages) - extravascular - low power feature.

DDx:

  • Glomerular sclerosis:
    • GBM visible through-out glomerulus.
    • No fibrin.
    • Collagen deposition within the glomerular tuft.
    • +/-Glomerular tuft-capsule adhesions.
    • +/-Glomerular enlargement.
    • Usu. no significant inflammation.

Bland necrotic crescents

DDx:

  • ANCA-related glomerulonephritis.
  • Anti-GBM disease.

Diseases with crescents - is a long list.[32]

Primary light microscopy patterns

Pattern Key feature Other findings DDx of the pattern DDx Image
Normal light microscopy Normal histology none or few glomeruli in a biopsy of an under sampled FSGS membranous nephropathy, focal segmental glomerulosclerosis (FSGS) normal kidney, minimal change disease, thin glomerular basement membrane disease, Alport syndrome, early membranous nephropathy
Benign kidney (WC)
Nodular mesangial expansion nodular mesangial matrix expansion, no mesangial hypercellularity GBM thickening, both afferent and efferent arteriole hyalinized diffuse proliferative GN, membranous nephropathy diabetic nephropathy, idiopathic nodular glomerulosclerosis, renal amyloidosis, light chain deposition disease, fibrillary glomerulopathy, immunotactoid glomerulopathy
Nodular GS (WC)
Membranous nephropathy (MN) GBM spikes or pinholes with silver stain, GBM thickening on PAS +/-mesangial hypercellularity +/-tram-tracking/wireloop GBM normal light microscopy, light chain deposition disease hepatitis B, hepatitis C, carcinoma, NSAID toxicity, SLE, idiopathic (MN); light chain deposition disease (plasma cell neoplasm)
MN (WC)
Focal segmental glomerulosclerosis sclerosed glomeruli = mesangial expansion with collagen +/-glomerular enlargement, +/- tuft-capsule adhesions rapidly progressive glomerulonephritis, nodular mesangial expansion primary FSGS, secondary FSGS (HIV, IVDU, obesity, parvovirus B19, Alport syndrome
FSGS (WC)
Diffuse proliferative glomerulonephritis mesangial hypercellularity +/-mesangial expansion, +/-interstitial inflammation nodular glomerulosclerosis post-infectious glomerulonephritis, MPGN, dense deposit disease, diffuse proliferative lupus nephritis (class IV), cryoglobulinemic GN
MPGN (WC)
Rapidly progressive glomerulonephritis glomerular crescents +/-inflammation, +/-vasculitis FSGS, diffuse proliferative glomerulonephritis AGBM, post-infectious glomerulonephritis, pauci-immune GN, immune complex diseases (lupus nephritis, IgA nephropathy, others)
Crescentic GN (WC)
Tubular injury tubular degeneration (loss of cilia in proximal tubule, apoptosis, necrosis), regeneration (mitosis, nucleoli) +/-interstitial fibrosis normal light microscopy acute tubular necrosis, chronic allograft nephropathy
CAN (WC)
Small vessel pathology luminal narrowing; +/-thrombosis, +/-hyalinosis +/-onion-skinning none thrombotic microangiopathy (malignant hypertension, scleroderma renal crisis, DIC, HUS, TTP,
Hyalinosis (WC)
TMA (WC)
Large vessel pathology luminal narrowing or obstruction; +/-intimal thickening; +/-embolization +/-medial thinning none atherosclerosis, cholesterol embolism, other types of embolism, thrombosis
Cholesterol embolus (WC)

Diagnoses - Table

Pattern Key feature Other findings IF & EM Presentation Clinical Pathol. DDx Image
Nodular glomerulosclerosis nodular mesangial matrix expansion GBM thickening, both afferent and efferent arteriole hyalinized EM? proteinuria - typical presentation, nephrotic syndrome[citation needed] diabetes mellitus (DM) amyloidosis, idiopathic nodular glomerulosclerosis (nodular GS without DM)
Nodular GS (WC)
Focal segmental glomerulosclerosis (FSGS) focal sclerosis of gloms +/-interstitial fibrosis IF: negative; EM: foot process loss nephrotic syndrome primary FSGS, secondary FSGS (HIV, IVDU, obesity, parvovirus B19, Alport syndrome); unresponsive to steroids, worse prognosis than MCD minimal change disease
FSGS (WC)
Membranous nephropathy
(AKA membranous GN)
spikes or pinholes with silver stain mesangial hypercellularity; +/-tram-tracking/wireloop GBM IF: diffuse granular capillary loop IgG, C3, kappa, lambda; EM: diffuse subepithelial deposits - spike forming nephrotic syndrome hepatitis B, hepatitis C, carcinoma, NSAID toxicity, SLE, idiopathic Nodular glomerulosclerosis (?)
MN (WC)
Minimal change disease (MCD) foot process loss on EM usu. none EM: foot process loss nephrotic syndrome primary vs. secondary (lymphoproliferative disorder, NSAIDs); idiopathic responds to steroids FSGS, thin glomerular basement membrane disease (histologic DDx) Image?
IgA nephropathy IgA branching pattern +/-mesangial hypercellularity, +/-crescents IF: IgA +ve (branching pattern); EM: dense mesangial deposits mixed nephrotic/nephritic primary vs. secondary (Henoch-Schoenlein purpura) RPGN
HSN - IgA IHC (WC)
Membranoproliferative glomerulonephritis (MPGN) thick GBM Other findings? subepithelial deposits mixed nephrotic/nephritic SLE, cryoglobulinemia, hepatitis B, hepatitis C Pathol. DDx?
MPGN (WC)
Focal proliferative
glomerosclerosis
(FPGS)
<50% of glomeruli partially sclerosis Other findings? EM? mixed nephrotic/nephritic Clinical? Pathol. DDx? Image?
Rapidly progressive GN (RPGN) crescents Other findings? EM? nephritic syndrome AGBM, ANCA-vasculitis IgA nephropathy with crescents Image?
Dense deposit disease IF: linear C3 with rings +/-thick GBM EM: GBM lamina densa thickening Presentation? mixed nephrotic/nephritic (???) MPGN (nature.com)

Diffuse proliferative glomerulonephritis

Pattern Key feature Clinical
Post-infectious glomerulonephritis IF: capillary loop +/- mesangial IgG/C3; EM: large infreq. hump-like subepithelial deposits post-infection
Membranoproliferative glomerulonephritis (MPGN) mesangial proliferation with thickening of the glomerular capillary loops[33] low C3, normal C4; primary vs. secondary (often hepatitis C)
Dense deposit disease IF: linear C3 with rings
Cryoglobulinemic glomerulonephritis
Diffuse proliferative lupus glomerulonephritis systemic lupus erythematosus; low C3, low C4
Diffuse proliferative IgA nephropathy IF: IgA +ve (branching pattern)

Common diseases

Diabetic nephropathy

General

Microscopic

Features:[34]

  • Thick glomerular basement membrane (GBM).
  • Thickened (eosinophilic) tunica media in both the afferent and efferent arterioles.[35]
  • Mesangial matrix expansion - leads to nodule formation Kimmelstiel-Wilson nodules (nodular glomerulosclerosis).

Others:

  • Armanni-Ebstein change = cytoplasmic vacuolization of tubular cells (usu. loop of Henle) -- innermost cortex, outer medulla;[36] not specific to diabetes mellitus.[37]
  • Capsular drop = hyaline material deposited in the Bowman's capsule.[38]
  • Fibrin cap = subendothelial deposition of hyaline material.[38]

Other - with weak evidence:

  • Extra efferent vessels.[39]

Memory device:

  • GBM = thick GBM, both afferent & efferent arterioles thickened, mesangial matrix expansion.

Images

www:

Notes:

  • Hypertensive kidneys have changes only in the afferent arteriole, i.e. the efferent arteriole is spared (see hypertension).

Grading

The severity of changes can be indicated by the grade:[40]

Grade Criteria
Grade I GBM thickening on EM only
Grade II Mild-to-moderate mesangial expansion only on LM
Grade III Glomerulus with mesangial nodules (Kimmelstiel–Wilson nodules)
Grade IV Stage III + global sclerosis in >50% of glomeruli

IF

  • Negative.
  • +/-Nonspecific linear IgG.

EM

  • Severe thickening of GBM.
  • Mesangial sclerosis.

Lupus nephritis

  • Abbreviated LN.

General

  • Bread & butter of nephropathology.
  • The biopsy is done to determine treatment, i.e. how much immunosuppression is needed.

Immunofluorescence

  • "Full house" = all of 'em light up.

Classification

International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification:[41][42]

  • Class I - minimal mesangial LN.
  • Class II - mesangial proliferative LN.
    • Mesangial hypercellularity. (???)
  • Class III - focal lupus nephritis; <50% of glomeruli.
    • Mesangial hypercellularity. (???)
  • Class VI-S - diffuse segmental LN; >50% of glomeruli.
    • Mesangial hypercellularity. (???)
  • Class VI-G - global LN; >50% of glomeruli.
  • Class V - Membranous lupus nephritis.
  • Class IV - Advanced sclerosing LN; essentially end-stage kidney.

Notes:

  • Most of the action is in Class III and Class IV.
    • Class I is near normal - doesn't get biopsied.
    • Class IV is essentially a dead kidney - doesn't get biopsied.

Images

Nephrotic syndrome

This classically includes the following:

It also includes:

Mixed nephrotic and nephritic

IgA nephropathy

General

Microscopic

Features:

  • Variable:
    • Mesangial hypercellularity - may be only light microscopy finding.

Note:

  • Diagnosis based on immunofluorescence (IgA+).

Images

Scoring

IgA nephropathy can be scored using an assessment of mesangial proliferation, endocapillary proliferation, glomerulosclerosis and tubular atrophy and interstitial fibrosis (abbreviated MEST).[47]

IF

  • IgA +ve in a branching pattern - diagnostic.

EM

  • Mesangial deposits.
    • These are electron dense, ergo dark on EM images.

Membranoproliferative glomerulonephritis

  • Abbreviated MPGN.
  • Old name MPGN type 1.

General

Clinical:

  • Nephrotic syndrome or nephrotic/nephritic syndrome.

Pathology:

  • May be primary, i.e. idiopathic, or secondary, i.e. a consequence of another pathologic process.[33]

Secondary causes

Other causes:

Microscopic

Features:

  • Endothelial cell proliferation.
  • Basement membrane double layering (tram-tracking).
  • Mesangial hypercellularity.

DDx:

Images

EM

Features:

  • Subendothelial immune deposits - classic finding.[49]
  • Subepithelial immune deposits - historically considered uncommon.[50]

Dense deposit disease

  • Abbreviated DDD.
  • AKA MPGN type 2 (old name).

General

  • Usually children and young adults.
  • No longer considered a type of MPGN.[51]

Microscopic

Features:

  • Variable - may be like MPGN.
    • Four patterns:[51]
      1. Hypercellularity and lobular (membranoproliferative-like).
      2. Mesangial proliferative.
      3. Crescentic.
      4. Acute proliferative and exudative.

Images:

IF

  • Linear C3 with mesangial rings (donut-like).
  • IgG negative.
  • IgA negative

Images:

EM

  • Electron dense transformation of GBM lamina densa - key feature.
    • Dense = darker.

Images:

Nephritic syndrome

Rapidly progressive glomerulonephritis

  • Abbreviated RPGN.
  • AKA crescentic glomerulonephritis.

General

  • Acute renal dysfunction.
  • Nephritic syndrome.

DDx:

  1. Linear immunofluorescence.
  2. Granular immunofluorescence
  3. Pauci-immune.

Microscopic

Features:

Images

Post-infectious glomerulonephritis

  • Abbreviated PIGN.

Rare diseases

Antiglomerular basement membrane disease

  • Abbreviated AGBM.

General

  • Known as Goodpasture disease (AKA Goodpasture syndrome), if renal failure is accompanied by pulmonary hemorrhage.[52]
  • Rare - estimated incidence 1/1-2 million.[53]
  • Antibody mediated hypersensitivity.
  • Thought to occur in genetically susceptible individuals.[53]
    • Associated with a specific HLA type (HLA-DRB1*1501) and two gene families.
    • Antibodies directed against COL4A3,[54] which is not mutated.
  • Oligouria - poor prognosticator.[citation needed]

Tx:

  • Immune suppression & plasma exchange.[55]

Clinical DDx:

Microscopic

Features:

  • RPGN.
    • Crescentic glomerulonephritis.

Images

www:

IF

  • Linear IgG deposits - diagnostic.
  • Fibrinogen in crescents.

DDx:

  • Goodpasture syndrome with the pulmonary hemorrhage.

Image:

Thin glomerular basement membrane disease

General

Clinical:

  • Hematuria.
  • FHx.
  • Nonprogressive.

Microscopic

  • Normal.

IF

  • Normal.

EM

  • GBM thin <200-250 - key feature.

Note:

  • Normal GBM: 300-350 nm.

Alport syndrome

General

Clinical:

  • Hearing loss (sensorineural).
  • Hematuria - usually preceeds hearing loss.[57]

Etiology:

  • Genetic defect - collagen type IV.

Inheritance:[57]

  • X-linked - 80%.
  • Autosomal recessive - 15%.
  • Autosomal dominant - 5%.

Microscopic

Features:[59]

  • Usu. normal.
  • +/-Foamy appearing renal tubular cells.[60]

IF

  • Negative.

EM

Features:[59]

  • Abnormal glomerular basement membrane (GBM); thinning or thickening.
    • Classically thinning with thick lamellation (splitting/multi-layering).

Idiopathic nodular glomerulosclerosis

General

Associations:[61]

Microscopic

Features:[61]

  • Looks like diabetic nodular glomerulosclerosis.

IF

Nonspecific.

EM

Nonspecific.

Fabry disease

Myeloma

See: Haematopathology.
  • AKA myeloma kidney.

Myeloma cast nephropathy

General

  • Renal failure.

Microscopic

Features:[63]

  • Crap in tubules, eosinophilic.
    • Classically angulated.
    • Refractile.
  • Cast with cellular reaction - virtually diagnostic.
    • Macrophages (CD68 +ve).
Images

www:

Stains

  • Myeloma casts = PAS -ve.
    • Hyaline casts = PAS +ve.

Amyloidosis

  • Usually associated with lambda clone.

Light chain deposition

  • Usually associated with kappa clone.

Immunotactoid glomerulopathy

General

Presentation:

Microscopic

Features:

  • Mesangial expansion.

DDx:

  • Other causes of mesangial expansion.

IHC

Fibrillary glomerulonephritis

  • AKA fibrillary glomerulopathy.

General

  • Rare ~ 1% native kidney biopsies.[64]
  • Presents as nephrotic syndrome.
  • Prognosis poor; large number progress to ESRD.

Microscopic

Features:

  • Mesangial matrix expansion.
  • Thickened capillary walls.

Images:

IF

  • IgG predominant.[64]

Stains

EM

  • Fibrils:[64]
    • Non-branching.
    • Randomly arranged.
    • Usu. 18-20 nm in diameter -- larger than amyloid (see below).
      • Size range 12-24 nm.

Note:

  • Amyloid between 8 and 15 nm (diameter), most often 8-12 nm.[64]

Aristolochic acid nephropathy

General

  • Nephropathy due to chinese herbs for slimming.[68]
  • Associated with urothelial atypia/urothelial carcinoma.

Clinical:

  • Chinese herb use.
  • Low-molecular weight proteinuria.

Microscopic

Features:[68]

  • Extensive interstitial fibrosis.
  • Tubular atrophy - typically greater in outer cortex than inner cortex.
  • Glomeruli spared.
  • +/-Nuclear atypia of the urothelium.

DDx:

  • Balkan endemic nephropathy.

Image:

Cystic kidney diseases

These are discussed in a separate article and include:

Pyelonephritis

Pyelonephritis is a misnomer; it is not an inflammatory process affecting the renal pelvis, as the name suggests. Pyelonephritis actually refers to a nephritis or tubulointerstitial nephritis.[69]

It can be subdivided into:

Acute pyelonephritis

  • AKA acute infectious tubulointerstitial nephritis.
  • AKA diffuse suppurative nephritis.

General

  • Typically preceeded by a (lower) urinary tract infection (UTI).
  • Usually diagnosed clinically:
    • Urine C&S, urine R&M, +/-CT abdomen.
    • Fever, costovertebral tenderness.

Gross

Features:

Microscopic

Features:

Images

Chronic pyelonephritis

  • Reflux nephropathy is considered synonym in some sources.[72]

General

  • Inflammation of the kidney (nephritis) and renal pelvis (pyelo-[73]).
  • May be associated with vesicoureteral reflux.
  • Chronic pyelonephritis may be a reason for nephrectomy.[74]

Gross

Microscopic

Features:[75]

  • Mononuclear tubulointerstitial infiltrate.
    • Usu. more dense at the pelvis.
  • Interstitial fibrosis.
  • +/-Renal casts (PAS positive); may result in a thyroid-like apparance.

DDx:

Stains

  • PAS +ve -- renal tubular casts.

Disease that does not commonly get biopsied

End-stage kidney

Malignant hypertension

See: hyperplastic arteriolosclerosis.
See: thrombotic microangiopathy.

Acute tubular necrosis

  • Often abbreviated ATN.

General

Diagnosed clinically:

  • Using urine R&M - hemegranular casts[76] are diagnostic.
  • Anuria or low urine output.

Gross

  • Poorly defined corticomedullary junction - soft finding.
  • Slightly heavier ~ 180 grams.[77]

Microscopic

Features:[77]

  • Tubular epithelial whorls - present in approx. one third of cases - most important.
    • Detached epithelium within the luminal space surrounded by epithelium.
      • Similar to epithelial telescoping seen in endometrial biopsies.
  • Tubulorrhexis - present in approx. one third of cases.
    • Disruption of the tubular basement membrane.
  • Interstitial edema - sensitive... but not specific.

Notes - not particularily useful findings:

  • Mitoses.
  • Casts in tubules.

IHC

  • Ki-67 - focal nuclear staining of the tubular epithelium.[77]

Hepatorenal syndrome

General

  • Acute renal failure secondary to liver failure (e.g. fulminant liver failure, cirrhosis with marginal liver function).

Clinical:

  • Urine sodium is low,[78] unlike in ATN (the main DDx).

Pathophysiology:

  • Renal vasoconstriction.[79]

Treatment: Medical and surgical:[80]

  • Vasoconstrictors (e.g. midodrine, terlipressin (counteracts splanchnic vasodilation), norepinephrine).
  • Albumin.
  • TIPS (transjugular intrahepatic portosystemic shunt).
  • Liver transplantation.

Note:

  • I suspect a portal vein pump would work... it reduces portal pressure and would likely increase hepatic function.

Microscopic

Features (kidney):

  • Normal.

Nephrocalcinosis

General

Microscopic

Features:

  • Calcification of the renal parenchyma - key feature.

Images:

Renal transplant pathology

See also

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