Kidney non-tumor

Last revised 8 July 2008

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Table of Contents-Kidney

Primary references, embryology, anatomy, glomeruli, tubules and interstitium, physiology, renal disease-general, congenital anomalies

Primary glomerular diseases: biopsy-general, glomerular disease-general, pathogenesis, C1q, chronic glomerulonephritis, congenital nephrotic syndrome, diffuse mesangial hypercellularity with nephrotic syndrome, fibrillary GN, focal proliferative and necrotizing GN, focal and segmental GS, idiopathic nodular GS, IgA, immunotactoid, membranoproliferative GN, membranous GN, minimal change, post-infectious GN, rapidly progressive (crescentic) GN

Hereditary renal disease: Alport’s syndrome, Bartter’s syndrome, collagen type III, Fabry’s disease, fibronectin, glutaric acidemia, glycogen storage disease, hereditary onycho-osteodysplasia, infantine nephropathic cystinosis, LCAT deficiency, lipoprotein, ochronosis, thin membrane disease

Infections/parasites: abscess, adenovirus, BK virus, CMV, Coccidioidomycosis, Dioctophyma renale, E coli, hantavirus, microsporidiosis

Drug related toxicity: adefovir, analgesics, chloroquine, cyclosporin A, gold, indinavir, NSAID, oxycodone, tacrolimus

Associated with systemic conditions: amyloidosis, bone marrow transplant nephropathy, cryoglobulinemia, diabetic glomerulosclerosis, Henoch-Schonlein purpura, heavy chain deposition disease, HUS/TTP, light chain deposition disease, microscopic polyangiitis, myeloma, polyarteritis nodosa, preeclampsia, sarcoidosis, SLE/lupus, systemic sclerosis, Wegener’s granulomatosis

Tubular and interstitial disease: general, acute allergic tubulointerstitial nephritis, acute pyelonephritis, acute tubular necrosis, chronic pyelonephritis, drug toxicity-general, granulomatous interstitial nephritis, karyomegalic nephropathy, lead, malakoplakia, nephrocalcinosis, urate nephropathy, xanthogranulomatous pyelonephritis

Blood vessel disorders: atherosclerotic, benign nephrosclerosis, diffuse cortical necrosis, emboli, infarct, malignant hypertension, renal artery stenosis, sickle cell, venous thrombi

Kidney transplantation: general, hyperacute rejection, acute rejection, chronic rejection, Banff classification

Miscellaneous: dialysis, obstructive uropathy, radiation nephropathy, urolithiasis

 

Go to Kidney tumors

 

Primary references

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AJCC Cancer Staging Manual (6th Ed)

American Journal of Surgical Pathology (AJSP), March 1977 to November 2004

Archives of Pathology and Laboratory Medicine (Archives), January 1976 to November 2004

Human Pathology (Hum Path), March 1970 to October 2004

Modern Pathology (Mod Path), January 1988 to November 2004

Rosai, J: Ackerman’s Surgical Pathology (9th Ed); 2004

Atlas of Renal Pathology

University of North Carolina

University of Pittsburgh case studies: #1 to #60

www.WebPathology.com - source of numerous beautiful GU images

Journal search terms: kidney, renal

 

Please refer to these primary references for more detailed discussions and photographs

 

Embryology

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Stages of kidney development: pronephros (based on Wolffian duct, kidneys nonfunctional), mesonephros (appear at week 4, form nephron-like tubules but degenerate), metanephros (form at week 5, function by week 11)

Metanephric blastema: forms glomerulus, proximal convoluted tubules, loops of Henle, distal convoluted tubules, connective tissue of renal interstitium

Ureteric bud: forms cortical and medullary collecting tubules and medullary collecting ducts

Gross images: fetal kidneys at 25 weeks gestation; infant kidney with fetal lobulations

 

Anatomy

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Posterior abdomen on either side of vertebral column, in retroperitoneum

Surrounded by fat and loose areolar tissue

Superior border is at T12, inferior border is at L3

11 cm long x 5-8 cm x 3 cm

Weighs 125-170 g in males, 115-155 g in females

Capsule: covers kidney, is surrounded by perirenal fat

Cortex: outer 1.2 cm of kidney, surrounds inner medulla containing pyramids and lacking glomeruli

Renal sinus: fatty compartment within confines of kidney not delineated from renal cortex by a fibrous capsule

Gerota’s fascia: fibromembranous tissue surrounding the kidney that separates it from adjacent musculature

Ureter ascends into renal pelvis, divides into calyces (2-3 major, 12 minor total)

Related to a calyx are renal pyramids with apices called papillae

Vasculature: receives 25% of cardiac output, 90% goes to cortex, via interlobar, arcuate, interlobular, afferent arterioles, then into glomeruli, efferent arterioles, peritubular vascular network

Deeper juxtamedullary glomeruli give rise to vasa recta, which supply outer and inner medulla

Since arteries are end vessels, their occlusion causes infarction

Glomerular disease causes tubular disease, since efferent arterioles supply tubules

Regional lymph nodes: renal hilar, paracaval, aortic, retroperitoneal

Diagrams: vertical section; relation to other organs - #1; #2; #3; #4; #5

Gross images: normal adult kidney; kidney cross section; close-up

Micro images: renal capsule

Virtual slides: normal kidney

 

Glomeruli

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Tuft-like vascular structure composed of lobules of specialized capillaries that arise from afferent arteriole and rejoin to drain into efferent arteriole

200 microns in diameter, 20% larger in juxtamedullary area

Layers (inner to outer) are: fenestrated endothelium, then glomerular basement membrane (lamina rare interna, lamina densa and lamina rare externa), then podocytes (visceral epithelium with foot processes); also parietal epithelium which lines Bowman’s space

Glomerular basement membrane (GBM): normally 310-380 nm, composed of type IV collagen, laminin, polyanionic proteoglycans (mostly heparan sulfate), fibronectin, entactin

Type IV collagen forms suprastructure to which other glycoproteins attach; composed of 3 alpha chains

Each alpha chain has amino 7S domain, middle triple helical domain and a carboxyl noncollagenous (NC1) domain; NC1 domain is site of anti-GBM nephritis and dimer formation

Mesangial cells: type of myofibroblast that supports glomerular tuft, regulates capillary width and blood flow; are phagocytic and can proliferate

Podocytes (visceral epithelium): their foot processes embed in lamina rare externa of glomerular basement membrane; the distal diffusion barrier to filtration of proteins is a filtration slit diaphragm between foot processes

Glomerular filtration: highly permeable to water and solutes through fenestrated endothelium, but impermeable to large proteins like albumin (proteins are more permeable if smaller and more cationic)

Diagrams: normal glomerulus #1; #2; #3; vessels surrounding glomeruli and tubules

Micro: hypercellularity - the presence of more than 3 cells in an individual glomerular mesangial region away from the vascular pole

Micro images: normal glomerulus #1;  #2;  #3A: light microscopy; B: fluorescence microscopy with Hollande’s fixative distinguishes proximal (heavy star) and distal (asterisk) convoluted tubulesfluorescence microscopy shows thin and delicate glomerular loops, smooth mesangial matrices

EM images: glomerular basement membrane and podocytes

References: Mod Path 2002;15:988

 

Tubules and interstitium

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Medullary rays: in cortex, contain cortical collecting tubules and loops of Henle of superficial nephrons

Renal columns of Bertin: cortical tissue extending into spaces between pyramids

Proximal tubules: long microvilli, numerous mitochondria and extensive intercellular interdigitations assist in reabsorption of sodium, water, proteins, glucose, potassium, phosphate, amino acids; vulnerable to toxins and ischemic damage

Juxtaglomerular apparatus: close to glomerulus where afferent arteriole enters it; consists of juxtaglomerular cells (modified smooth muscle cells) plus macula densa (region of distal tubule as it returns to vascular pole of parent glomeruli) plus lacis cells (nongranular cells that reside near afferent arteriole, macula densa and glomerulus and resemble mesangial cells); produces renin

Interstitium: contains fibroblast like cells and peritubular capillaries; expands due to edema and inflammation

Diagrams: renal tubule and its vascular supply;  vessels surrounding glomeruli and tubules

Micro images: renal papillae;  brush border of collecting duct; medullary rays; macula densa #1;  #2;  macula densa and juxtaglomerular apparatus;  distal and proximal convoluted tubules;  cytology of glomeruli (1A), tubules (1B)

 

Physiology of kidney

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Filters 1700L of blood to 1L of urine per day

Excretes metabolic waste; regulates water, salt, pH; secretes renin, prostaglandins, erythropoietin

Nephron: glomerulus filters blood, filtrate enters Bowman’s space, filtrate enters proximal convoluted tubule, to pars recta of proximal tubule, to thin descending limp of loop of Henle, to thick ascending limb of loop of Henle, to macula densa (adjacent to glomerulus), to distal convoluted tubule, to collecting tubule, to collecting duct of Bellini, to calyx

Nephrons: production ceases at birth, are 1.3 million/kidney

Details on physiology

Clearance: amount of plasma cleared of a substance per minute to appear in urine

 

Renal hormones

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Aldosterone: causes increased reabsorption of NaCl to increase blood volume

Antidiuretic hormone (vasopressin): stimulates water reabsorption by stimulating insertion of "water channels" or aquaporins into the membranes of kidney tubules; these channels transport solute-free water through tubular cells and back into blood, leading to a decrease in plasma osmolarity and an increased osmolarity of urine; in diabetes insipidus (without ADH), kidney tubules are virtually impermeable to water, which flows out as urine (up to 10 liters of dilute urine/day)

Erythropoietin: secreted in response to low serum pO2, promotes red blood cell production

Natriuretic hormones: cause increase in glomerular filtration rate after nephron destruction

Renin: produced by juxtaglomerular apparatus in response to hypotension, converts angiotensinogen to angiotensin I, which is converted to angiotensin II in the lung by angiotensin converting enzyme (ACE); angiotensin II increases aldosterone production and promotes vasoconstriction

 

Renal disease-general

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20% of women get urinary tract infections

1% of Americans develop renal stones

Divided for analytical purposes into diseases of glomeruli, tubules, interstitium and vessels

Glomerular diseases tend to be immunologically mediated; tubular and interstitial disorders are often due to toxins/infections

Glomerular and tubular disease affect each other, because glomerular disease impairs the tubular blood supply and increases tubular toxins, and tubular disease causes increased intraglomerular pressure

 

Acute nephritic syndrome:

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Grossly visible hematuria, hypertension, azotemia, oliguria, mild edema, red blood cell casts, variable proteinuria

Associated with postinfectious, diffuse crescentic and membranoproliferative glomerulonephritis

 

Acute renal failure:

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Abrupt anuria or oliguria with rapidly progressive azotemia identified by increase in BUN or ammonia

 

Azotemia:

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Increased serum BUN (blood urea nitrogen) and creatinine, due to reduced glomerular filtration rate (GFR); causes are prerenal (hemorrhage, shock, congestive heart failure, volume depletion), renal and postrenal (obstruction)

 

Chronic renal failure:

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Azotemia progressing to uremia over a period of years

Stages of chronic renal failure: (1) diminished renal reserve (GFR 50% normal) with normal BUN/Cr, (2) renal insufficiency (azotemia, anemia, hypertension, polyuria, nocturia, (3) renal failure: GFR < 20% normal, kidneys cannot regulate volume of solutes and patient develops edema, metabolic acidosis and hypocalcemia, (4) end stage renal disease: GFR <5% normal

Represents the end stage of various renal diseases

 

Nephrotic syndrome:

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Proteinuria > 3.5 g/day, hypoalbuminemia (serum level <3 g/dl), hyperlipidemia, lipiduria, severe edema (anasarca)

Due to derangement in glomerular capillary walls which leads to increased permeability to plasma proteins, causing massive proteinuria, hypoalbuminemia and generalized edema (pitting, periorbital and dependent edema)

Hyperlipidemia is due to increased lipoprotein synthesis and decreased catabolism

Lipiduria is due to leakage of lipoproteins with albumin

Patients are prone to staphylococcus and pneumococcal infections due to loss of immunoglobulins and factor B of complement; thrombosis and thromboemboli are due to loss of anticoagulants such as antithrombin III and antiplasmin

Associated with minimal change disease (more common in children), focal and segmental glomerulosclerosis, membranous glomerulonephritis (more common in adults), systemic disease (SLE, diabetes, amyloidosis), congenital nephrotic syndrome

 

Rapidly progressive glomerulonephritis:

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Acute glomerulonephritis with proteinuria and acute renal failure

 

Uremia:

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Azotemia plus clinical signs/symptoms (gastroenteritis, peripheral neuropathy, fibrinous pericarditis, secondary hyperparathyroidism); associated with chronic renal failure

Tubular defects cause polyuria, nocturia, electrolyte disorders; due to diseases directly or indirectly affecting tubular function

 

Congenital anomalies

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10% of individuals have urinary tract malformations, although many are asymptomatic

15% of congenital urogenital anomalies are secondary to an underlying chromosomal disorder

In children, 20% of chronic renal failure is due to renal dysplasia or hypoplasia

In adults, 10% of chronic renal failure is due to adult polycystic kidney disease

 

Absence of normal appearing proximal tubules

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Associated with monochorionic twinning or renal hypoperfusion

References: Hum Path 1991;22:147; Hum Path 1986;17:1259

 

Agenesis

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Bilateral agenesis is incompatible with life and is associated with pulmonary hypoplasia and limb defects

Incidence is 0.03% of newborns but 0.3% of stillborns

Unilateral renal agenesis is uncommon, not fatal

Compensatory hypertrophy in other kidney may cause glomerulosclerosis in adults

Case reports: associated with Klinefelter’s (47, XXY) syndrome (Archives 2004;128:e44)

Gross images: 1: posterior view of stillborn with no kidneys and downwardly displaced adrenal glands (arrows); 2: 47,XXY

 

Duplication of ureters

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Occurs in <1% of individuals

Usually asymptomatic; may be associated with obstruction

Gross images: bilateral duplication

 

Ectopic (displaced) kidneys

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Usually at pelvic brim, may have kinking of ureters

 

Horseshoe kidney

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1/500 autopsies, 90% are fused at lower pole

Associated with obstruction

Gross images: fusion at lower pole

 

Hypoplasia

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Failure of kidney to develop to normal size without scarring

Usually unilateral, with a reduced number of pyramids (6 or less)

Oligomeganephronia: a type of hypoplasia with a small kidney but hypertrophied nephrons

Gross images: hypoplastic and hypertrophic kidneys

 

 

PRIMARY GLOMERULAR DISEASES

Biopsy-general

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Helps establish diagnosis and determine prognostic factors for renal disorders and transplant recipients

Needle core or open biopsies are relatively safe, and only rarely cause morbidity or mortality

Pathology should correlate complete clinical and laboratory information (using a clinical form is recommended) with light microscopy, immunofluorescence and electron microscopy; cannot diagnose certain diseases without immunofluorescence or EM

Must carefully evaluate glomeruli, tubules, interstitium, vessels

Specimen must be handled gently

Don’t: use forceps, pull or stretch tissue, place tissue on dry gauze or water-soaked gauze, freeze entire sample or place on ice-cold saline

Do: transport with tissue culture medium on saline-moistened gauze; cut with fresh scalpel

Dissecting microscope helps assess adequacy of glomeruli; place sample on glass slide with saline

Two cores recommended

Core #1: take samples 0.5 to 1.0 mm thick from each end with razor/scalpel and put in glutaraldehyde for EM; place remainder in saline, then fixative for light microscopy

Core #2: take samples for EM, snap freeze the remainder for immunofluorescence

Wrap light microscopy specimens in lens paper prewetted with fixative (avoid sponges or plastic embedding bags)

If only one core or a small specimen is obtained, use tissue for EM and immunofluorescence, because EM semi-thin sections can also provide light microscopic information

Fixative: mercury fixatives (Zenker’s, Bouin’s, other) provide optimal architectural and cytologic detail; ethanol fixation helps find glycogen or crystals of urate/uric acid

Recommended to section through entire specimen, put 3-4 sections on each slide; for every batch of 5 slides, stain 1 with H&E, 1 with PAS and keep 3 unstained slides for possible future use

Can detect immune complexes with antibodies or using fluorescence microscopy of H & E stained sections fixed in Hollande’s fixative (Mod Path 2002;15:988)

Immunofixation: best performed on unfixed, frozen sections; examine for IgG, IgM, IgA, C3, C1q, C4, fibrin, kappa, lambda; should include positive and negative controls for each run; immunoperoxidase may be a substitute (cheaper, can correlate with H&E, doesn’t fade), but complement antigens are difficult to detect, may have higher background staining

Gross images: (1) a: renal cortex with round red glomeruli; b: renal medulla without glomeruli; (2) diagram about dividing up core tissue if no dissecting microscope is present

Minimum glomeruli: 5-10 in general; 10 for crescentic disorders; 1 may be sufficient for diffuse lesions such as membranous glomerulonephritis

Immunohistochemistry: IgG, IgA, IgM, C1q, C3, C4, fibrinogen, fibrin

EM: uses osmium tetroxide or glutaraldehyde for fixation (cannot perform if tissue exposed to B5, Zenker’s or other mercury-based fixatives, can reprocess tissue from paraffin block); embed in epoxy resin, stain semi-thin (one micron thick) sections with toluidine blue or methylene blue; obtain thin sections for EM, stained with uranyl acetate and lead citrate

Frozen section: requested to determine adequacy (% sclerotic glomeruli) in donor kidney for transplant

Transplant biopsies: performed to assess rejection

References: Mod Path 2004;17:1555

 

Glomerular disease-general

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Glomerulonephritis: inflammation of glomerulus

Glomerulopathy: any disorder affecting glomerulus

Primary: kidney is only or predominant organ involved

Changes can be diffuse (all glomeruli) or focal; global (entire glomerulus) or segmental (part of glomerulus) or mesangial

Minimal change disease, diffuse mesangial hypercellularity and focal and segmental glomerulosclerosis may be a continuum of the same disease.

Micro:

Hypercellularity: due to cellular proliferation (mesangial, endothelial, parietal epithelial cells); white blood cells (acute and chronic) or crescents (white blood cells and epithelial cells)

Basement membrane thickening is highlighted by PAS stain and electron microscopy; EM also shows electron-dense deposits (usually immune complexes) in or adjacent to basement membrane (subepithelial is most common)

Hyalinization and sclerosis of glomeruli are the end result of glomerular damage from various causes

 

Pathogenesis of glomerular injury

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Usually immune mediated via antibody deposition, cell-mediated injury or activation of alternative complement pathway

Antibodies deposited are either to in situ antigen (intrinsic or planted) or are circulating immune complexes

Intrinsic: Goodpasture’s disease-antigens are in basement membrane; Heymann nephritis-antigens are on visceral epithelial cells; produce linear immunofluorescence patterns

Planted antigens are deposited in basement membrane; may be exogenous (drugs, infectious agents) or endogenous (DNA, immunoglobulin, immune complexes); their cationic proteins bind to glomerular anionic sites and produce granular lumpy staining by immunofluorescence

Circulating immune complexes may be endogenous (DNA, tumors) or exogenous (infectious products); they usually localize within glomeruli and activate complement; deposits are usually mesangial or subendothelial and resolve by macrophage phagocytosis, unless there are repeated cycles of formation (Hepatitis B/C, lupus)

Cell-mediated immune injury is by sensitized nephritogenic T cells

Progression to end stage renal disease occurs when the glomerular filtration rate (GFR) is 30-50% of normal, due to compensatory hypertrophy of remaining glomeruli and systemic hypertension (inhibited by angiotensin converting enzyme inhibitors), eventually causing glomerulosclerosis

Micro: injured epithelial cells have vacuoles, retract and detach from basement membrane, lose foot processes

Immunofluorescence patterns: granular deposits represent immune complexes that settle out of blood or form in situ; linear deposits are due to anti-basement membrane antibodies or light chain nephropathy

Can detect via fluorescent antibodies or using fluorescence microscopy of H & E stained sections fixed in Hollande’s fixative (Mod Path 2002;15:988)

 

C1q nephropathy

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Rare; causes proteinuria that responds poorly to steroids

Teenagers and young adults, higher incidence among blacks and males

Slow progression to renal failure

Micro: variable mesangial hypercellularity with increase in mesangial matrix; variable segmental glomerulopathy

Micro images: various images including EM

Immunofluorescence: prominent mesangial C1q deposition; also IgG, IgM, IgA and C3

EM: mesangial immune complex deposits

DD: lupus nephritis (may have prominent deposition of C1q, C3, immunoglobulins)

 

Chronic glomerulonephritis

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An end stage disease due to progression of various types of glomerulonephritis; occasionally is no prior history of kidney disease

Rates of progression: rapidly progressive (90%), post-streptococcal (1% kids, 5% adults), focal and segmental glomerulosclerosis (50-80%, rapid), membranous (50%), membranoproliferative (50%), IgA nephropathy (30-50%, slow)

Paradoxically, nephrotic syndrome decreases as glomeruli disappear

Gross: symmetrically small kidneys with thin granular cortex and increased peripelvic fat

Gross images: bilaterally small kidneys #1; #2; #3; #4 (cut surface)

Micro: glomerulosclerosis, tubular atrophy and thyroidization, interstitial fibrosis and lymphocytic inflammation; arterial and arteriolar sclerosis

Micro images: end stage kidney with sclerotic glomeruli, tubular thyroidization, interstitial fibrosis and thickened arterial walls #1; #2

Virtual slides: chronic glomerulonephritis

 

Congenital nephrotic syndrome

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Heterogenous conditions with nephrotic syndrome in first 3 months of life

No response to steroids or immunosuppressive therapy

Treatment: renal transplant

DD: membranous glomerulonephritis (associated with congenital syphilis, mercury poisoning), toxoplasmosis, HIV, malaria, CMV, minimal change glomerulopathy

References: OMIM #600995

 

Finnish type

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Autosomal recessive

Occurs in 1 per 10,000 newborns in Finland, lower incidence elsewhere

1.5% of cases of nephrotic syndrome in childhood

Nephrin protein at 19q13.1, normally at slit diaphragm of glomerular podocyte, is missing in patients with Finnish-type syndrome of gene mutations

Can diagnose in utero via genetic testing

Heavy proteinuria in utero

At birth, large placentas, proteinuria, edema, infections, premature birth, mild facial/limb abnormalities, poor development

Disease progresses to death without kidney transplant; dramatic improvement with transplant, but 20% have recurrence of nephrotic syndrome

Micro: proximal and distal tubular ectasia with flattening of tubular epithelium, microcysts, glomerulosclerosis, immature glomeruli

Immunofluorescence: nonspecific IgM and C3 in mesangium and capillaries

EM: obliteration of foot processes

References: OMIM #256300

 

Diffuse mesangial sclerosis

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Early onset of severe proteinuria (within first 6 months of life), with rapid progression to end stage renal disease by age 3 years

May be associated with Denys-Drash syndrome (nephrotic syndrome, male pseudohermaphroditism, Wilms’ tumor) or be isolated

Normal placenta, no premature births, but is associated with cataracts and corneal clouding, aniridia, microencephaly, mental retardation, hypertelorism

Does not recur after transplantation

Micro: diffuse mesangial sclerosis; tubular atrophy and interstitial fibrosis

Immunofluorescence: mesangial deposits of IgM, C3, C1q

EM: obliteration of foot processes, basement membrane thickening, increase in mesangial matrix

References: OMIM #256370

 

Diffuse mesangial hypercellularity with nephrotic syndrome

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2-10% of renal biopsies from patients with idiopathic nephrotic syndrome

Associated with steroid resistant or steroid dependent minimal change glomerulopathy, focal and segmental glomerulosclerosis

Note: minimal change disease, diffuse mesangial hypercellularity and focal and segmental glomerulosclerosis may be a continuum of the same disease.

Micro: mild mesangial hypercellularity

Immunofluorescence: IgM, variable C3

EM: obliteration of foot processes, sparse mesangial deposits

 

Fibrillary glomerulonephritis

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Deposition of extracellular nonamyloid fibrillary material in glomeruli and tubular basement membranes (“nephropathy” better term than glomerulonephritis)

Rare, <1% of renal biopsies

More common in whites and females

Patients present with heavy proteinuria, hematuria, and systemic hypertension

50% eventually develop end-stage kidney disease within 2 to 4 years from diagnosis

Associated with membranoproliferative glomerulonephritis

7% also have lymphoproliferative disorders

No evidence of extrarenal fibrillary deposits

Features overlap with hepatitis C virus induced cryoglobulinemic glomerulonephritis

Not a disease, but the morphologic expression of a diverse group of diseases incompletely defined (Hum Path 2001;32:660)

Diagnosis: based on ultrastructural (EM) findings; some authors require exclusion of cryoglobulins

Case reports: crescentic glomerulonephritis with linear IgG staining (Archives 2001;125:534), polyclonal gammopathy but IgG1 deposits (Mod Path 1998;11:103)

Micro: mesangial expansion with PAS-positive material, diffuse thickening of the glomerular basement membrane; variable proliferative lesions, 25% have crescents

Micro images: crescentic glomerulonephritis; various image including EM

Negative stains: Congo red, thioflavin T

Immunofluorescence: deposition of IgG4, C3, kappa and lambda light chains

EM: randomly arranged non-amyloid fibrils in the mesangium and glomerular capillary walls, 18-22 nm thick vs. 10 nm for amyloid and 30-50 nm thick and organized for immunotactoid glomerulopathy; usually extensive effacement of epithelial foot processes

EM images: randomly oriented subepithelial fibrils; 20 nm fibrils; series of images

References: AJSP 1991;15:632

 

Focal proliferative and necrotizing glomerulonephritis

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Only parts of some glomeruli affected; proliferative, not sclerotic; also necrosis and fibrin deposition

Microscopic to gross hematuria, occasionally with nephrotic syndrome

Seen early in systemic diseases (SLE, polyarteritis nodosa, Henoch-Schonlein purpura, Goodpasture’s syndrome, endocarditis, Wegener’s granulomatosis); may be part of IgA nephropathy or idiopathic

Micro images: focal necrotizing and crescentic glomerulonephritis

 

Focal and segmental glomerulosclerosis

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A histologic pattern of glomerulosclerosis (some glomeruli, part of capillary tuft) associated with heavy proteinuria and progressive renal failure

In normal adults ages 55 or less at autopsy, glomerulosclerosis affects <3% of glomeruli (Archives 1989;113:1253)

Primary (idiopathic) form: causes 10% of nephrotic syndrome in children (usually <5 years), 20% in adults (20-39 years); associated with hematuria, hypertension, nonselective proteinuria; rarely is familial

Secondary forms: heroin addiction, HIV, IgA nephropathy, renal ablation nephropathy, unilateral renal agenesis, hypertension, sickle cell disease, morbid obesity, obstruction, reflux, congenital (associated with 19q13 or nephrin alterations), glycogen storage disease, congenital heart disease, healed focal proliferative and necrotizing glomerulonephritis; have similar glomerular lesions as idiopathic forms

May be due to circulating mediator (proteinuria may recur with allografts in 24 hours, overall in 25-50% of allografts)

Children have better prognosis than adults, who often progress to renal failure (40-60% overall within 10-20 years)

Note: minimal change disease, diffuse mesangial hypercellularity and focal segmental glomerulosclerosis may be a continuum of the same disease.

Micro: focal and segmental glomerulosclerosis and mesangial sclerosis in lobules that appear to adhere to Bowman’s capsule (begins in corticomedullary region), hyaline deposits and foam cells or lipoid droplets in focal glomeruli, initially mild mesangial hypercellularity that becomes hypocellular in advanced lesions; focal tubular atrophy with interstitial fibrosis, hyaline thickening of afferent arterioles

Micro images: focal sclerosis of glomeruli #1; #2 (various images); focal sclerosis his highlighted by trichrome staining; increased glomerular size (left vs. right); perihilar sclerosis with hyalinosis, lipid vacuolization and adhesion to Bowman’s capsule; series of images; diffuse IgM staining

Immunofluorescence: IgM and C3 in sclerotic segments

EM: epithelial cell detachment from glomerular basement membrane; extensive foot process obliteration (even in non-sclerotic glomeruli), mesangial sclerosis with increased matrix, collapsed glomerular loops

EM images: series of images

 

Special form in IV drug abuse and AIDS

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Rapid progression to end stage renal failure in AIDS (3-4 months) and IV drug abuse (2-4 years)

Note: HIV also causes acute renal failure, postinfectious, membranous or membranoproliferative glomerulonephritis (Hum Path 1987;18:1293)

Micro: often collapse and sclerosis of entire glomerular tuft with hypertrophic podocytes filling Bowman’s space; large tubular hyaline casts, flattened epithelium; also manifestations of severe tubulointerstitial injury such as epithelial degenerative changes, microcystic dilation of tubules, interstitial inflammatory infiltrate (primarily activated T cells)

Micro images: various images including EM

EM: tubuloreticular structures in endothelium (non specific for infection), induced by interferon alpha

EM images: tubuloreticular inclusions

References: Hum Path 1988;19:1060 (tubuloreticular inclusions)

 

Collapsing glomerulopathy

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Resembles special form in IV drug abuse and AIDS (rapid progression to renal failure with severe proteinuria, poor response to treatment and similar microscopic changes), but HIV negative

Usually bl