Medical kidney diseases

Micrograph showing a glomerulus with an 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, 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.

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.
• Conversion: 1.0 mg/dL = 88.4 umol/L.

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.

Urine protein to creatinine ratio

• Indicator of proteinuria.
• Predictor of glomerular filtration rate.

Cut points:

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

Complement

C3, C4 levels:

• Changed:
  • Systemic lupus erythematosus (SLE); levels decreased = increased disease activity.
  • Post-infectious GN - decreased.
  • MPGN - decreased. (???)
  • Infection.
  • Hemolytic anemia.
• Normal:
  • Minimal change disease.
  • Chronic pyelonephritis.
  • Renal vein thrombosis.
  • Amyloidosis.

ANCA

Types:

• 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 neoplasms.
  • Often done together with urine protein electrophoresis (UPEP).

Renal ultrasound

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

Urine dip

Findings:

• 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; implies glomerulonephritis.
  • Some include the above (RBCs, RBC casts) + WBCs & protein.

Urine crystals

Main article: Crystals in body fluids

Clinical presentations

Nephrotic syndrome

Features:

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

Nephritic syndrome

Features - mnemonic PHAROH:

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

Mixed

• 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.

Isolated hematuria

• IgA nephropathy.
• 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:

1. Linear immune deposits.
   • Antiglomerular basement membrane disease & Goodpasture's syndrome.
2. Granular immune deposits.
   • Immune complex diseases.
     • Systemic lupus erythematosus.
     • IgA nephropathy.
     • Others.
3. 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:

• 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.
  • Another autopsy series suggests the mean diameter is: 225 micrometers.

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

• 

  Benign kidney - very low mag.

• 

  Benign kidney - low mag.

• 

  Benign kidney - low mag.

• 

  Benign kidney - intermed. mag.

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:

• Endocapillary hypercellularity has a DDx - it includes: IgA nephropathy, and lupus nephritis.

Components of the glomeruli (anatomical)

• Podocyte - rarely affect by disease
  • One notable disease is collapsing glomerulopathy in HIV.
• Endothelial 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%.

Example:

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

Glomerular disease terms

Number of glomeruli involved:

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

How much of the glomerulus is involved:

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

Vessels

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

Consider:

• Vasculitis? - inflammatory cells in vessel wall.
• Amyloid? - pink.
• Rejection? - PMNs.
• 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 inhibitors (tacrolimus, cyclosporine).

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

• 

  Arterial hyaline - HE - very high mag. (WC/Nephron)

• 

  Arterial hyaline - PAS - very high mag. (WC/Nephron)

• 

  Arterial hyaline - HPS - very high mag. (WC/Nephron)

Atherosclerosis

Main article: 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:

• Minimal change disease.
• Focal segmental glomerulosclerosis.

Positive immunofluorescence

• Positive immunofluorescence is usually diagnostic.

Basic patterns:

1. Linear.
2. Granular.
3. 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

Can be:

• Subepithelial - distal to basement membrane (BM), closer to the urinary space.
  • 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

DDx:

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:

• Diabetes mellitus.
• MPGN:
  • IgA nephropathy.
  • 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).

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.
  • Pink on H&E.

• 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.
    • Seen with trichrome stain.
  • +/-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.

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	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

• Due to diabetes mellitus - key feature.
  • 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

Features:

• Thick glomerular basement membrane (GBM).
• Thickened (eosinophilic) tunica media in both the afferent and efferent arterioles.
• 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; not specific to diabetes mellitus.
• Capsular drop = hyaline material deposited in the Bowman's capsule.
• Fibrin cap = subendothelial deposition of hyaline material.

Other - with weak evidence:

• Extra efferent vessels.

Memory device:

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

Images

• 

  Diabetic glomerulosclerosis. (WC/KGH)

• 

  Diabetic glomerulosclerosis. (WC/KGH)

• 

  Diabetic glomerulosclerosis. (WC/KGH)

• 

  Nodular glomerulosclerosis. (WC)

www:

• Nodular GS (med.utah.edu).
• Armanni-Ebstein lesion (markwickmd.com).

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:

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 article: 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:

• 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

• 

  SLE nephritis - schematic. (WC)

• Membranous lupus:
  • H&E (flickr.com).
  • Jones (flickr.com).
  • PAS (flickr.com).

Nephrotic syndrome

Main article: Nephrotic syndrome

This classically includes the following:

• Minimal change disease.
• Focal segmental glomerulosclerosis.
• Membranous nephropathy.

It also includes:

• IgA nephropathy.
• Pre-eclampsia - uncommon.

Mixed nephrotic and nephritic

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.
• IgA nephropathy, in children, with a skin rash (leukocytoclastic vasculitis) = Henoch–Schönlein purpura.
• May present as nephrotic syndrome.
• May present as isolated hematuria.

Microscopic

Features:

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

Note:

• Diagnosis based on immunofluorescence (IgA+).

Images

• IgA nephropathy (med.utah.edu).
• HSP (upmc.edu).

• 

  HSP - IgA IHC (WC)

Scoring

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

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.

Secondary causes

• In adults most common cause: hepatitis C.

Other causes:

• HIV.
• SLE - usu. has "full house" on IF.
• Cryoglobulinemia.
• Hepatitis B.
• Portocaval shunt.

Microscopic

Features:

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

DDx:

• Nodular glomerulosclerosis.

Images

• 

  MPGN - intermed. mag. (WC/Nephron)

• 

  MPGN - very high mag. (WC/Nephron)

• MPGN - several images (upmc.edu).

EM

Features:

• Subendothelial immune deposits - classic finding.
• Subepithelial immune deposits - historically considered uncommon.

Dense deposit disease

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

General

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

Microscopic

Features:

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

Images:

• DDD - light microscopy (nature.com).
• DDD - several images (upmc.edu).

IF

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

Images:

• DDD - IF (nature.com).

EM

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

Images:

• DDD (nature.com).

Nephritic syndrome

Rapidly progressive glomerulonephritis

• Abbreviated RPGN.
• AKA crescentic glomerulonephritis.

General

• Acute renal dysfunction.
• Nephritic syndrome.

DDx:

1. Linear immunofluorescence.
   • Antiglomerular basement membrane disease, Goodpasture syndrome.
2. Granular immunofluorescence
   • Lupus nephritis.
   • Post-infectious glomerulonephritis.
   • IgA nephropathy.
3. Pauci-immune.
   • Wegener granulomatosis.
   • Microscopic polyangiitis.

Microscopic

Features:

• Glomerular crescents.
• Interstitial inflammation.
• +/-Vasculitis.

Images

• 

  RPGN (WC/KGH)

• 

  RPGN (WC/KGH)

• 

  RPGN - intermed. mag. (WC/Nephron)

• 

  RPGN - high mag. (WC/Nephron)

Post-infectious glomerulonephritis

• Abbreviated PIGN.

Main article: Post-infectious glomerulonephritis

Rare diseases

Antiglomerular basement membrane disease

• Abbreviated AGBM.

General

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

Tx:

• Immune suppression & plasma exchange.

Clinical DDx:

• Wegener granulomatosis.
• Azathioprine toxicity.

Microscopic

Features:

• RPGN.
  • Crescentic glomerulonephritis.

Images

• 

  RPGN - intermed. mag. (WC/Nephron)

• 

  RPGN - high mag. (WC/Nephron)

www:

• AGBM disease - several images (upmc.edu).

IF

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

DDx:

• Goodpasture syndrome with the pulmonary hemorrhage.

Image:

• Linear IgG in AGBM disease (upmc.edu).

Thin glomerular basement membrane disease

General

• Collagen IV mutation - the same protein is involved in Alport syndrome.

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.

• Can be thought of a pathologic form of thin basement membrane disease.

Etiology:

• Genetic defect - collagen type IV.

Inheritance:

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

Microscopic

Features:

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

IF

• Negative.

EM

Features:

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

Idiopathic nodular glomerulosclerosis

General

• Not diabetic - key feature.

Associations:

• Smoking - common; thought to be important in the etiology.
• Hypertension.

Microscopic

Features:

• Looks like diabetic nodular glomerulosclerosis.

IF

Nonspecific.

EM

Nonspecific.

Fabry disease

Main article: Fabry disease

Myeloma

See: Haematopathology.

• AKA myeloma kidney.

Myeloma cast nephropathy

General

• Renal failure.

Microscopic

Features:

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

Images

www:

• Cast nephropathy in myeloma (kidneypathology.com).
• Cast nephropathy in myeloma - refractile crap (kidneypathology.com).

• 

  Myeloma cast nephropathy - high mag. (WC/Nephron)

• 

  Myeloma cast nephropathy - cropped - very high mag. (WC/Nephron)

Stains

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

Amyloidosis

Main article: 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.

Presentation:

• Nephrotic range proteinuria ~ 60% of cases.
• Hypertension.

Microscopic

Features:

• Mesangial expansion.

DDx:

• Other causes of mesangial expansion.

IHC

• Congo red stain -ve.

Fibrillary glomerulonephritis

• AKA fibrillary glomerulopathy.

General

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

Microscopic

Features:

• Mesangial matrix expansion.
• Thickened capillary walls.

Images:

• www:
  • FG (asnjournals.org).
  • Fibrillary glomerulopathy (upmc.edu).

IF

• IgG predominant.

Stains

• Congo red stain -ve.

EM

• Fibrils:
  • 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.

Aristolochic acid nephropathy

• Abbreviated AAN.
• AKA chinese herb nephropathy.

General

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

Clinical:

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

Microscopic

Features:

• 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:

• AAN (uninet.edu).

Cystic kidney diseases

Main article: 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.

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

Features:

• +/-Necrosis of renal papillae.

Microscopic

Features:

• Neutrophils within the renal tubules and interstitium.

Images

• 

  Acute pyelonephritis - intermed. mag. (WC/Nephron)

• 

  Acute pyelonephritis - high mag. (WC/Nephron)

• 

  Acute pyelonephritis - very high mag. (WC/Nephron)

Chronic pyelonephritis

• Reflux nephropathy is considered synonym in some sources.

General

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

Gross

• Dilated and distorted renal pelvis.
• +/-Necrosis of renal papillae.

Microscopic

Features:

• 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 article: 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 are diagnostic.
• Anuria or low urine output.

Gross

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

Microscopic

Features:

• 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.

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, unlike in ATN (the main DDx).

Pathophysiology:

• Renal vasoconstriction.

Treatment: Medical and surgical:

• 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.

Images:

• Nephrocalcinosis (upmc.edu).

Renal transplant pathology

Main article: Renal transplant pathology

• Acute rejection.
• Chronic rejection.
• Polyomavirus.
• Transplant glomerulopathy.
• Calcineurin-inhibitor toxicity.

See also

• Kidney tumours.
• Urinary bladder.
• Genitourinary pathology.
• Thrombotic microangiopathy.

External links

• Nephropathology quiz (med.utah.edu).
• Cryoglobulinemic nephritis (fondazionedamico.org).