Kidney non-tumor
Last revised 8 July 2008
Copyright (c) 2002-2008, PathologyOutlines.com, Inc.
Bold and underlined topics are hypertext links within this document or to references
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
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
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
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
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
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; #3; A: light microscopy; B: fluorescence microscopy with Hollande’s fixative distinguishes proximal (heavy star) and distal (asterisk) convoluted tubules; fluorescence microscopy shows thin and delicate glomerular loops, smooth mesangial matrices
EM images: glomerular basement membrane and podocytes
References: Mod Path 2002;15:988
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)
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
Clearance: amount of plasma cleared of a substance per minute to appear in urine
Renal hormones
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
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:
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:
Abrupt anuria or oliguria with rapidly progressive azotemia identified by increase in BUN or ammonia
Azotemia:
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:
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:
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:
Acute glomerulonephritis with proteinuria and acute renal failure
Uremia:
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
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
Associated with monochorionic twinning or renal hypoperfusion
References: Hum Path 1991;22:147; Hum Path 1986;17:1259
Agenesis
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
Occurs in <1% of individuals
Usually asymptomatic; may be associated with obstruction
Gross images: bilateral duplication
Ectopic (displaced) kidneys
Usually at pelvic brim, may have kinking of ureters
Horseshoe kidney
1/500 autopsies, 90% are fused at lower pole
Associated with obstruction
Gross images: fusion at lower pole
Hypoplasia
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
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
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
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)
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)
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
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
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
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
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
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
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
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
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
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