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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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*WBC casts = interstitial nephritis, e.g. pylonephritis, parenchymal infection.
*WBC casts = interstitial nephritis, e.g. pylonephritis, parenchymal infection.
*Hemegranular casts = acute tubular necrosis, transplant rejection.
*Hemegranular casts = acute tubular necrosis, transplant rejection.
Notes:
*"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.
**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>


====Urine crystals====
====Urine crystals====
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====Mixed====
====Mixed====
*Features of nephritic syndrome and nephrotic syndrome.
*Features of nephritic syndrome and [[nephrotic syndrome]].


==Normal==
=Clinical DDx=
===Epithelium<ref name=Ref_PBoD956>{{Ref PBoD|956}}</ref>===
==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 kidney=
===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]]?
 
====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.


===Tubules & interstitium===
=====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.
 
===Glomerular crescents===
*[[AKA]] crescents.
====General====
*Indicates a rapidly progressive disease.
*Etiology/definition: break in the glomerular basement membrane (GBM).


*Image: [http://www.kidneypathology.com/Im%E1genes/Diabetes/DM.11.w.jpg Arteriolar hyalinosis (kidneypathology.com)]
====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'''.
**Best seen on a silver stain (e.g. [[Jones stain]]).
*Fibrin.
**Orange on [[HPS stain|HPS]].
**Pink on [[H&E stain|H&E]].


Note:
*Inflammatory cells (lymphocytes, plasma cells, eosinophils, macrophages) - extravascular - '''low power''' feature.
*Arteriolar hyalinosis - involves ''afferent'' and ''efferent'' arterioles in diabetes, in others it is only tha afferent.
===Mesangial hypercellularity===
Think:
# Lupus.
# IgA nephropathy.


===Mesangial expansion===
DDx:
*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>
*Glomerular sclerosis:
*Immune complex mediated disease (e.g. IgA nephropathy).
**GBM visible through-out glomerulus.
*Henoch-Schoenlein disease.
**No fibrin.
*Lupus.
**Collagen deposition within the glomerular tuft.
***Seen with [[trichrome stain]].
**+/-Glomerular tuft-capsule adhesions.
**+/-Glomerular enlargement.
**Usu. no significant inflammation.


==Pathologic DDx==
====Bland necrotic crescents====
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>
DDx:
*ANCA-related glomerulonephritis.
*Anti-GBM disease.


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


===Nephrotic===
===Primary light microscopy patterns===
*Minimal segmental disease (MSD) - AKA ''minimal change disease'' (MCD),  
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Focal segmental glomerulosclerosis (FSGS),  
! Pattern
*Membranous nephropathy.
! 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 -->
|}


===Mixed presentation===
===Diagnoses - Table===
*IgA nephropathy,  
{| class="wikitable sortable" style="margin-left:auto;margin-right:auto"
*Focal proliferative glomerulosclerosis (FPGS),  
! Pattern
*Membranoproliferative glomerulonephritis (MPGN).
! 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{{fact}}
| [[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?
|-
|[[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]]
| [[Image:Henoch-Sch%C3%B6nlein_nephritis_IgA_immunostaining.jpg|thumb|center|150px|HSN - IgA IHC (WC)]]
|-
|[[Membranoproliferative glomerulonephritis]] (MPGN)
| thick GBM
| Other findings?
| subepithelial deposits
| mixed nephrotic/nephritic
| [[SLE]], [[cryoglobulinemia]], [[hepatitis B]], [[hepatitis C]]
| Pathol. DDx?
| [[Image:Membranoproliferative_glomerulonephritis_-_very_high_mag.jpg|thumb|center|MPGN (WC)]]
|-
|[[Focal proliferative glomerosclerosis|Focal proliferative<br> 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]]
| [http://www.nature.com/modpathol/journal/v20/n6/fig_tab/3800773f1.html (nature.com)] 
|- <!--
| Pattern
| Key feature?
| Other findings?
| EM?
| Presentation?
| Clinical?
| Pathol. DDx?
| 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 216: 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 223: 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://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 232: 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===
*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===
Features:
*Variable:
**Mesangial hypercellularity - may be only light microscopy finding.
Note:
*Diagnosis based on immunofluorescence (IgA+).
*Diagnosis based on immunofluorescence (IgA+).


===Histology===
====Images====
*Mesangial hypercellularity - may be only light microscopy finding.
*[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>


==Membranous nephropathy==
===IF===
*Presents as nephrotic syndrome.
*IgA +ve in a branching pattern - '''diagnostic'''.


===Histology===
===EM===
*Subepithelial immunocomplex deposition, spike forming.
*Mesangial deposits.
**These are electron dense, ergo dark on EM images.


==Membranoproliferative glomerulonephritis==
==Membranoproliferative glomerulonephritis==
*Abbrev. ''MPGN''.
*Abbreviated ''MPGN''.
*In adults most common cause: ''hepatitis C''.
*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.<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]]''.


===Histology===
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===
Features:
*Endothelial cell proliferation.
*Endothelial cell proliferation.
*Basement membrane double layering (tram-tracking).
*Basement membrane double layering (tram-tracking).
*Mesangial hypercellularity.
*Mesangial hypercellularity.


==Lupus nephritis==
DDx:
Five classes:
*[[Nodular glomerulosclerosis]].
*Diffuse mesangial 2 vs. 4.
 
*Focal patch mesangial 3.
====Images====
*Membranous 5 ???
<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===
*Usually children and young adults.
*No longer considered a type of MPGN.<ref name=pmid17396142/>
 
===Microscopic===
Features:
*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.
 
Images:
*[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)].
 
=Nephritic syndrome=
==Rapidly progressive glomerulonephritis==
*Abbreviated ''RPGN''.
*[[AKA]] ''crescentic glomerulonephritis''.
===General===
*Acute renal dysfunction.
*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===
Features:
*[[Glomerular crescents]].
*Interstitial inflammation.
*+/-[[Vasculitis]].


Notes:
====Images====
*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].
<gallery>
Image:Crescentic_glomerulonephritis_%282%29.jpg | RPGN (WC/KGH)
Image:Crescentic_glomerulonephritis_%281%29.jpg | RPGN (WC/KGH)
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}}


==Fabry disease==
=Rare diseases=
==Antiglomerular basement membrane disease==
*Abbreviated ''AGBM''.
===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 342: 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.
 
===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).


==Autosomal dominant polycystic kidney disease (ADPKD)==
==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.
 
====Microscopic====
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>
*Crap in tubules, eosinophilic.
**Classically angulated.
**Refractile.
*Cast with cellular reaction - '''virtually diagnostic'''.
**Macrophages (CD68 +ve).
 
=====Images=====
www:
*[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.


PKD1 related disease:<ref name=Ref_MacSween174-5>{{Ref MacSween|174-5}}</ref>
===Amyloidosis===
*Encodes polycystin.
{{Main|Amyloidosis}}
*Death at ~53 years.
*Usually associated with lambda clone.
*Assoc. with cerebral aneurysms.


PKD2 related disease:<ref name=Ref_MacSween174-5>{{Ref MacSween|174-5}}</ref>
===Light chain deposition===
*Death at ~69 years.
*Usually associated with kappa clone.
*Assoc. with colonic diverticula, aortic aneurysm, mitral valve prolapse.


====Liver cysts and PKD====
==Immunotactoid glomerulopathy==
=====General=====
===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.
***70-75% >60 years old have liver cysts.
**Renal function:
***60-70% of patients with end-stage renal disease (ESRD) and near-ESRD.
**Females more often affected.
*Hepatic function usu. preserved.


Complications:<ref name=Ref_MacSween174-5>{{Ref MacSween|174-5}}</ref>
DDx:
#Infected cyst.
*Other causes of mesangial expansion.
#Cholangiocarcinoma.
 
===IHC===
*[[Congo red stain]] -ve.
 
==Fibrillary glomerulonephritis==
*[[AKA]] ''fibrillary glomerulopathy''.
===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/>
 
===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]].


See also: ''[[Medical liver disease]]''.
==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===
Features:<ref name=Ref_Sternberg5_1729>{{Ref Sternberg5|1729}}</ref>
*Mononuclear tubulointerstitial infiltrate.
**Usu. more dense at the pelvis.
*Interstitial fibrosis.
*+/-Renal casts (PAS positive); may result in a thyroid-like apparance.
 
DDx:
*[[End-stage kidney]].
*[[Myeloma cast nephropathy]].
 
===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===
Diagnosed clinically:
*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.
*Anuria or low urine output.
 
===Gross===
*Poorly defined corticomedullary junction - soft finding.
*Slightly heavier ~ 180 grams.<ref name=pmid19207286/>


===Microscopic===
===Microscopic===
Features:<ref name=Ref_DARP426>{{Ref DARP|426}}</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 lined by simple flattened epithelium.
*Tubular epithelial whorls - present in approx. one third of cases - '''most important'''.
*Normal renal tubules interspersed between cysts.
**Detached epithelium within the luminal space surrounded by epithelium.
*+/-Fibrosis (late-stage).
***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.<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>


DDx:  
Treatment:
*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>
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>
**Morphologically similar to acquired renal cystic disease.<ref>RJ. 20 October 2010.</ref>
*Vasoconstrictors (e.g. midodrine, terlipressin (counteracts splanchnic vasodilation), norepinephrine).
*Albumin.
*TIPS (transjugular intrahepatic portosystemic shunt).
*Liver transplantation.


==Acquired renal cystic disease==
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===
===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.
*[[Hypercalcemia]].
*Presence of cysts dependent on duration of dialysis:<ref name=pmid7861721/>
**< 3 years ~44%.
**>4 years ~80%.
**>10 years ~90%.
*Associated with [[renal cell carcinoma]] (papillary subtype).<ref>{{Ref DARP|438}}</ref>


===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:
*Cysts - location: cortex and medulla.
*Calcification of the renal parenchyma - '''key feature'''.
**Lined by simple flattened epithelium.


==Transplant==
Images:
===Predictors===
*[http://path.upmc.edu/cases/case514.html Nephrocalcinosis (upmc.edu)].
*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>
*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>


===Polyomavirus===
=Renal transplant pathology=
*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>
{{Main|Renal transplant pathology}}
*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/>
*Acute rejection.
*Ground glass-like nuclear inclusions.
*Chronic rejection.
*Nuclear enlargement.
*[[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}}


[[Category: Genitourinary pathology]]
=External links=
*[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)].
 
[[Category: Medical kidney pathology]]
Michael
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