Chapter 20- The Kidney 1. 2.

Glomerular diseases- immuno mediated; Tubular & Interstitial toxic or infection Azotemia: Increased BUN & creatinine- usually due to decreased glomerular filtration rate (GFR) IF EXTRARENAL1. Prerenal- hypoperfusion of kidneys- impaired fxn w/o parenchymal damage 2. Postrenal- urine flow obstruction beyond the kidney Uremia- azotemia a/w clinical signs and symptoms (metabolic and endocrine alterations and 2ndary involvement of GI, nerves, heart) Nephritic Syndrome- acute onset of hematuria, mild-mod proteinuria, and hypertension Nephrotic Syndrome- heavy proteinuria (3.5+ gm/day), hypoalbuminemia, severe edema, hyperlipidemia, and lipiduria (lipid in urine) Renal Tubular defects- polyuria (excessive urine formation), nocturia, and electrolyte disorders Rapidly Progressive Glomerulonephritis: nephritic syndrome w/ rapid (hrs/days) decrease in GFR Acute Renal Failure- Oliguria/Anuria and recent onset azotemia

3. 4. 5. 6. 7. 8.

Acute Chronic Renal Fxn Progression 1. 2. 3. 4. Dimished renal reserve: GFR is 50%; BUN and creatinine normal; asymptotic Renal Insufficiency : GFR is 20-50%; Azotemia (a/w anemia & HTN); Polyuria and nocturia Chronic Renal Failure: GFR is less than 20-25%; Edema, metabolic acidosis, hyperkalemia End-Stage Renal Disease: GFR is less than 5%; Uremia

Glomerular Diseases Secondary (a/w DM, SLE, vasculitis, amyloidosis, HTN, Fabry) vs Primary (Kidney predom organ effected) Glomerular capillary wall is the filtering membrane and consists of 1. 2. 3. Fenestrate endothelial cells Glomerular basement membrane (GBM) with electron-dense central layer (lamina densa) and electronlucent peripheral layers (lamina rara interna and externa); Consists of type IV collagen Visceral epithelial cells (podocytes)- foot processes (pedicels) separated by filtration slits 1. Podocytes- maintain barrier fxn and synthesize GBM components 2. Slit Diaphrgam proteins- Nephrin, podocin, CD2AP control glomerular permeability Mesangial cells lying between the capillaries support the entire glomerular tuft

4.

Glomerulophathies characterized by: 1. Hypercellularity : # of cells in glomerular tuft a/w inflammatory diseases 1. Cell prolif (mesangial or endothelial) 2. Leukocytic infiltration 3. Formation of crescents- if fibrin leaks into urinary spaces BM thickening: thickening of capillary walls best seen w/ PAS Hyalnosis: accumulation of homogeneous and eosinophilic material seen by light microscopy; Usually due to endothelial or capillary wall injury; common feature of focal segmental glomerulosclerosis Sclerosis: accumulations of extracellular collagenous matrix in mesangial area or capillary loops

2. 3. 4.

Immune Complex Deposition Injury can either by: antibodies reacting directly w/ intrinsic tissue antigen ( Ex is Good Pasture with antiGBM) or to antigens planted there OR by circulating immune complexes that deposit w/in golmeruli Circulating Immune Complex Glomerulonephritis o Ciruclating antigen-antibody complexes localize in glomeruli b/c of physiochemical and hemodynamic factors (BUT not immuno specific for glomeruli) o Complexes seen on EM as electron-dense deposits

 Subendothelial (endothelial cells/GBM)- cationic Subepithelial (GBM/pdoctyes) anionic Mesangium- neutral Mediators of Glomerular Injury -Cells Neutrophils- release proteases, ROS, AA metabolites (reduce GFR) Mesangial cells Macrophages, T cells, Plateletes -Soluble Mediators C5b-C9 (MAC)- cause cell lysis and induce mesangial cell activation (causes proteinuria) Eicosanoids, NO, and endothelin- affect vascular flow Cytokines (IL-1 and TNF) and chemokines- inflammatory cell adhesion and recruitment PDGF (mesangial cell prolif); TGF- & FGF- matrix deposit; VEGF- endothelial integreity and capillary permeability Coagulartion proteins (esp fibrin) stimalte parietal epithelial cell proliferation (crescent formation) Mechanisms of Progression of Glomerular Diseases Focal Segmental Glomerulosclerosis (FSGS) o Initiated as compensatory hypertrophy and glomerular and systemic HTN that cause epithelial and endothelial injury proteinuria o Mesangial response to proteins accumulating in mesangial matrix causes glomerulosclerosis Tubulointerstitial Fibrosis o Tubular damage and interstitial inflammation o Renal fxn correlates w/ tubulointerstitial damage more than glomerular injury o Results from ischemia and inflammation in surrounding interstitium o Proteinuria- causes direct injury to and activation of tubular cells that produce cytokine and GFs that cause interstitial fibrosis Nephritic Syndrome Inflammation in glomeruli Hematuria, RBC casts in urine, azotemia, oliguria, mild/mod HTN, some proteinuria, edema Acute Proliferative (Poststreptococcal) Glomerulonephritis (PSGN) o 6-10 y.o. kid 1-4 weeks after pharyngeal or skin infection Only M 1,4, 12 of Grp A -hemolytic streptococci are nephritogenic o Presents w/ coco-cola urine (hematuria)/ nephritic syndrome o Enlarged, hypercellular glomeruli (due to diffuse leukocyte infiltration and cell proliferation) o IF- granular deposits (IgG, IgM, and C3) in mesangia and along GBM o EM- subepithelial, hump like deposits o Lab findings: antistrep antibody titers and serum C3 Rapidly Progressive (Crescentic) Glomerulonephritis (RPGN) Rapid, progressive loss of renal fxn w/ oliguria and signs of nephritic syndrome Kidney is enlarged, pale, w/ petechial hemorrhages Ruptures in GBM that allows for crescent formation (reach urinary space) w/ fibrin 3 types based on immunological findings o Anti-GBM antibody Good Pasture Anti-GBM (3 chain of type IV collagen) cross react w/ lung alveoli Linear deposits of IgG and C3 in GBM HLA-DRB1 prevalance Plasmapheresis helps rid of complexes o Immune Complex Mediated Complication of immune complex nephritides (i.e. IGA, lupus nephritis, etc) Glanular staining o Pauci-immune

NO Anti-GBM, instead anti-neutrophil cytoplasmic antibody (ANCA) with cytoplasmic (c) or perinuclear (p) staining Vasculitis association- Wegner granulomatosis (C-ANCA), Microscopic polyangitis (Panca) or idiopathic ( vasculitis limited to glomeruli)

Nephrotic Syndrome In kids <17 y.o.- usually due to primary kidney lesion while in adults usually a/w systemic disease Derangement in glomeruli capillary wall causes permeability to proteins Massive proteinuria (3.5+ gm/day) o Proteinuria can be high selective (albumin only) vs poorly selective (globulins and albumin) Loss of albumin through proteinuria causes hypoaluminemia and colloid osmotic pressure (causing pitting edema) Hyperlipidemia and lipiduria (oval fat bodies in urine) infections (staph and pneumococcal) due to loss of Ig in urine Thrombic/Thromboembolic complications (due to loss of serum anticoagulations and antiplasmins) o Renal vein thrombi due to this hypercoag state (esp membranous nephropathy) Types of Nephrotic Syndromes o Membranous Nephropathy (MGN) In adults; 85% idiopathic; 2ndary causes are drugs (esp RA tx), Lupus, Infections, (HBV, malaria, syphilis) and malignancy (lung, colon, melanoma) Accumulation of immune-complex Ig depostis (subepithelial) cause uniform, diffuse thickening of golmerular capillary wall Irregular spikes on GBM from deposits w/ silver stain eventually thicken to form domelike protrusions Nonselective proteinuria; corticosteroids not effective o Minimal- Change Disease Most freq cause of nephritic syndrome in kids (2-6 y.o.) Usually after respiration infection or immunization Diffuse effacement fusion of foot processes of visceral epithelial cells (podocytes) Glomeruli appear normal in light microscrope Proximal tubules laden w/ lipids and proteins DRAMATIC RESPONSE TO CORTICOSTEROIDS High slective proteinuria, NO HTN or hematuria o Focal Segmental Glomeruloscelrosis Most common nephritic syndrome in adults in US (esp Hispanics and blacks) Differs from min-change Hemturia, GFR, HTN, non-selective protienuria, poor response to steroids Progresses to chronic kidney disease Epithelial damage (focal and segmental) is hallmark Hyalonosis and lipid droplets in sclerotic areas Lesions at juxtamedullary glomeruli IF- IgM and C3 in sclerotic areas and mesangium Collapsing Glomerulopathy is HIV-associated (esp black ppl) variant Retraction/collapse of entire glomerular tuft Focal cystic dilation of tubule Lots of tubuloreticular inclusion w/ endothelial cells induced by IFN-alpha o Membranoproliferative Glomerulonephritis (MPGN) Teen- young adult presents w/ nephritic syndrome and hematuria Segmental thickening of GBM, proliferation of mesangial and capillary loop cells, and leukocyte infiltration Glomeruli have lobular appearance from mesengial prolif Glomeruli capillary wall double contour/tram-track appearance from splitting of BM Type I

More common; Activates booth classical and alternative complement Subendothelial electron-dense deposits of IgG, C3, and C1q and C4 Type II- Dense-Deposit Disease Activation of alternative complement pathway only (c1 and c4 unaffected) Lamina densa of GBM becomes ribbon-like and electron-dense C3 in mesangium causes mesangial rings Serum findings: o C3 Nephritic factor (C3NeF)- autoantibody to C3 convertase o C3 but normal C1 and C4

Isolated Urinary Abnormalities IgA Nephropathy (Berger Disease) o Most common glomerulonephritis worldwide o IgA deposits in mesangial regions (only IgA1 nephritogenic) o Frequent cause of recurrent hematuria esp in older kids/young adults after resp infection o Occurs often in pts w/ celiacs and 2nd in pts w/ liver disease Alport Syndrome o Microscopic hematuria that progresses to chronic renal failure o Nerve deafness and eye disorders (lens discoloration, post. Cataracts, and corneal dystrophy) o X-linked, abnormal chagins of type IV collagen o Basket-weave appearance of glomeruli- alternating thickening/thinning of GBM o Interstitial foam cells in tubular epithelial cells Chronic Glomerulonephritis End-stage glomerular disease Kidneys symmetrically contracted w/ diffuse granular cortical surface; cortex thinned w/ peripelvic fat Evntually obliteration of glomeruli Aterial and arteriolar sclerosis (HTN) Atrophy of tubules Dialysis Chagnes: o Arterial intimal thickening, o Extensive calcium oxalate crystals deposit in tubules and interstitium o Acquired cystic disease Uremic complications from chronic glomerulonephritis include pericarditis, 2ndary hyperparathyroidism and LV hypertrophy (due to HTN) Most pts are hypertensive, w/ cerebral or cardiovascular manifestations Glomerular Lesions Associated with Systemic Disease Lupus nephritis Henoch-Schonlein Purpura o Kids 3-8 y.o. with allergies (atopy) w/ onset after URT infection o Purpuric skin lesion on extensor of arms/legs and on butt Subepidermal hemorrages; necrotizing vasculitis o Abdominal manifestations- pain, vomiting, intestinal bleeding o Nonmigratory arthralgia o Renal Abnormalities- IgA deposits in mesangial regions Diabetic Nephropathy o Most commonly involves the glomeruli o Also affects aretrioles (hyalinizing arteriolar sclerosis), pyelonephritis suspectability, and papillary necrosis o Diabetic glomeruloscerosis casued by metabolic defect (insulin deficiency) o Glycosylation of proteins and hemodynamic changes a/w glomerular hypertrophy contribute to loss of podoctyes nephritic syndrome Amyloidosis o Deposits of AA or AL- stain congo red w/in mesangium or capillary walls

Fibillary glomerulonephritis o Fibillar deposits similar to amyloidisis but dont stain w/ congo red o IF- IgG4, C3, Igk and Ig

Tubular and Interstitial Diseases Acute Kidney Injury (AKI) Acute diminution of renal fxn and often tubular injury Most common cause of acute renal failure (rapid decline of renal fxn & urine flow (<400ml/day w/in 24 hr) Reversible lesions Caused by ischemia, direct toxic injury, acute tubulointerstitial nephritis ( drug rxn), urinary obstruction o Ischemic AKI- marked by hypotension and shock (from inadequate blood flow) o Nephrotoxic (due to drugs) o Combo of ischemic and nephrotoxic--> Mismatched blood transfusion/ hemolytic crises- hemoglobinuria and hemoglobin casts Skeletal muscle injury- myoglobinuria and myoglobin casts Pathogenesis o Tubule Cell Injury Ischemia Redistribution of membrane proteins (Na/K) loss of cell polarity of tubular cells (vulnerable to injury bc of high metabolic use) Abnormal ion transport Increase Na+ delivery to distal tubules Tubuloglomerular feedback to cause vasoconstriction (renin-angiotensin system) Injured cells detach from BM cause lumen obstruction, increased intratubular pressure, and decreased GFR o Disturbances of Blood flow Ischemia hemodynamic alterations (esp intrarenal vasoconstriction) decrease GFR Renin-angiotensis system (Tubuloglomerular feedback to increase Na+) Sublethal endothelial injury increase endothelin (vasoconstricter) and decrease NO and PGI2 (vasodilators) Ischemic AKI Morph o Patchy tubular necrosis (w/skip lesions) in proximal tubule and ascending thick limb of HL Nephrotoxic AKI Morph o Extensive necrosis (w/o skip lesions) along proximal convoluted tubule Both types have hyaline casts (made of Tamm-Horsfall protein) in distal tubules and collecting ducts Clinical course o Initiation phase- slight decline in urine output and increased BUN (due to ischemic event) o Maintenance phase- oliguria, hyperkalemia, metabolic acidosis o Recovery phase- increase in urine, HYPOkalemia is problem, increase vulnerability to infection o In nephrotoxic AKI often nonoliguric AKI0 Increased urine volume instead of oliguria

Tubulointerstitial nephritis Acute- interstitial edema, leukocytic infiltration, focal tubular necrosis Chronic- interstitial fibrosis, tubular atrophy No glomeruli injury (no nephritic/nephrotic syndrome) Tubular fxn defects- inability to concentrate urine (polyuria or nocturia), salt wasting, metabolic acidosis (due to inability to excrete acids), and defects in reabsorption/secretion

Causes of Tubulointerstitial nephritis Pyelonephritis and UTIs o Most common cause of UTI is E. Coli (gram neg bacilli) from own fecal flora

Ascending infection is most common cause of pyelonephritis Colozinization of distal urethra and introitus urthera to bladder (more common in females in absence of instrumentation b/c of shorter urthera) Urinary tract obstruction and stasis of urine cant clear Vesicoureteral reflux- incompentence of vesicoureteral valve allow bacteria to ascend into renal pelvis (reflux of urine into ureters) w/o it infection says in bladder Reflux most often due to congenital absence or shortening of intravesical part of ureter or can be acquired (spinal cord injury) Intrarenal reflux- infected urine propelled up to renal pelvis and deep into parenchyma Most common in upper and lower poles of kidney Acute pyelonephritis- caused by bacterial infection; renal lesion of UTI Hallmarks: patchy interstitial suppurative inflammation, intratubular aggregates of neurophils, and tubular necrosis Complications of acute pyelnephritis Papillary necrosiso Seen in pts w/ DM and urinary tract obstruction o Bilateral coagulative necrosis in tips (distal ) of pyramids o Can lead to acute renal failure Pyonephrosis- total obstruction high in urinary tract causes pevlis, calyces, and urter to fill w/ puss Perinephric abscess- suppurative inflammation extends thru renal capsule into perinephric tissue Healing: inflammatory foci replaced by pyelonephritic scars a/w inflammation, fibrosis and deformation of calyx and plevis Jigsaw, patchy pattern Clinical: pain at costovertebral angle and systemic evidence of infection Bladder/urethral irritation- dysuria, frequency, urgency Urine contain leukocytes (pyuria) Pus casts in urine indicate renal involvement Polyomavirus nephropathy Viral pathogen causing pyelonephritis in kidney allografts Nuclear enlargement and intranuclear crystalline-like lattices inclusions Chronic Pyelonephritis

Chronic - bacterial infection+ vesicouretreal reflux and obstruction Vesicoureteral reflux is most often due to congenital absence or shortening of intravesical portion of ureter Reflux nephropathy is most common form of chronic pyelonpehritic scaring and occurs in early childhood (discovered when investigating hypertension in kids) o Often inability to concentrate urine (polyuria) Intrarenal reflux- infected bladder urine propelled up to renal pelvis Seen on radiograph: bladder filled with radiopaque dye Involves the calyces and pelvis Hallmark: coarse, discrete, corticomedullary scars overlying dilated, blunted, or deformed calyces and flattening of the papillae Most scars in upper and lower poles Xanthogranulomatous pyelonephritis form of chronic foamy macrophages mid w/ plasma cells, giant cells, etc associated w/ Proteus infection and obstruction orange nodules (can be mistaken for renal carcinoma Can develop secondary focal segmental glomerulosclerosis w/ proteinuria

Tubulointerstitial Nephritis Induced by Drugs

Acute Drug-induced interstitial nephritis o Occurs from synthetic antibiotics, NSAIDs, sulfonamides o Begins about 15 days after drug exposure o Fever, eosinophilia, rash, renal abnormalties o Rising serum creatinine level or acute renal fever w/ oliguria esp elderly o Tubulitis- infiltration of tubules by lymphocytes Analgesic Nephropathy o Chronic renal disease caused by excess analgesic (phenacetin-containing) mix o Papillary necrosis occurs first, cortical tubulointerstitial nephritis follows as a consequence o Early on- patchy necrosis but advance- entire papilla necrotic ghosts of tubules and foci of dystrophic calcification Cortical columns of Bertin are spared from atrophy o Usually stopping the drug intake stabilizes or improves renal fxn but some develop transitional papillary carcinoma of renal pelvis Nephropathy Associated w/ NSAIDs o Hemodynamically induced acute renal failure (b/c decreaed vasodilatory prostaglandings secereted) o Acute ypersensitivity interstitial neprhitis inducing acute renal failure o Acute interstitial nephritis and minimal-change disease o Membranous nephropathy (w/ nephrotic syndrome)

Other Tubulointerstitial Diseases Urate Nephropathy o Acute Urate nephropathy Uric acid crystal precipitate in collecting ducts causing obstruction Occurs b/c of tumor cell lysis after chemo for hematologic malignancy o Chronic Urate Nephropathy Monosodium urate crystals in distal tubules and collecting ducts Birefrigent needle-like crystals in tubular lumen or interstitium Obstruct tubles or form tophi (foreign body giant cells and fibrosis) Occurs in pts w/ gout esp after ingesting lead (i.e. moonshine) Hypercalcemia and nephrocalcinosis o Disorders of hypercalcemia induce renal calcium deposit (nephrocalcinosis) and calcium stone formation obstruct tubule Light-Chain Cast Nephropathy (Myeloma Kindey) o Pts w/ multiple myeloma have renal insufficiency due to Bence Jones proteinuria (light chain casts) Bence Jones proteins combine w/ Tamm-Horsfall proteins to form large casts that obstruct tubular lumen and induce peritubular inflammatory rxn Bence Jones casts appear pink-blue amorphous mass; often fractured Amyloidosis, light-chain deposition disease, Hypercalcemia, hyperuricemia

Vascular Diseases Benign Nephrosclerosis o Associated w/ renal arteriolar sclerosis Arteriolar lumen stenosed by wall thickening and hyalinization Large muscular arteries show fibroelastic hyperplasia (w/ medial and intimal thickening) o Vascular lesions cause diffuse ischemic atrophy of nephrons- kidneys become small and exhibit diffuse granular surfaces (grain leather) o Causes mild proteinuria but rarely renal failure but can occur if hypertensive, diabetic, or black (increased risk)

Malignant Hypertension and Accelerated Nephrosclerosis o Usually occurs w/ preexisting condition- frequent cause of death in scleroderma o Affects mostly younger black men o Fibrinoid necrosis of arterioles (acute event) o Onion-skinning- interlobular arteries and arterioles intimal thickening o Systolic pressure >200 , diastolic >120 o Papilledema, retinal petechial hemorrhages (flea -bitten appearance), encephalopathy, cardiovascular abnormalities, and renal failure o Earliest symptoms due to increased intracranial pressure=- scotomas or spots before the eyes o Elevated plasma renin o At onset- proteinuria and hematuria- MEDICAL EMERGENCY Renal Artery Stenosis o Unilateral stenosis is uncommon cause of hypertension; treatable w/ surgery o Elevated plasma or renal vein rennin lvls- BP decreases w/ Angiotensin II block o Most common cause is artheromatous plaque occlusion at origin of renal artery Older men w/ DM o 30% fibromuscular dysplasia usually medial Women, younger (30-40) o Hypertension w/ audible bruit Thrombotic Microangiopathies o Microangiopathic hemolytic anemia, thrombocytopenia, renal failure (often) o Schistocytes (fragmented RBC) in peripheral blood smears o Normal coag time, normal fibrin split products o Morph: Basement membrane- tram tracks; artery walls- onion skinning o Hemolytic-Uremic Syndrome (HUS) Typical- shiga-like toxin from E. Coli in contaminated ground meat causes endothelial injury which causes platelet activation and thrombi Most effects kids- main cause of acute renal failure in them Flu-like or diarrheal symptoms then sudden onset of bleeding manifestation (hematemesis, melena), oliguria, hematuria, Atypical- deficiency of factor H causes inappropriate, excessive activation of complement which causes endothelial injury thrombi Usually effects adults Causes: antiphospholipid syndrome in Lupus, postpartum renal failure, vascular disease of kidney Worse prognosis then typical HUS o Thrombotic thrombocytopenic Purpura (TTP) Pentad: fever, neuro symptoms, microangiopathic hemolytic anemia, thrombocytopenia, renal failure (CNS involment is dominant feature, renal failure only 50%) ADAMTS13 deficient due to inhibitory autoantibodies (women under 40) Microthrombi in arterioles throughout body Other Vascular Disorders o Atheroembolic Renal Disease Cholesteral crystals emoblize from atheromatous plaques after manipulation of diseased aorta into intraparenchymal renal vessels Appear as rhomboid clefts in arteriol wall or lumen Can rarely cause renal failure in elderly pts w/ compromised renal fxn o Renal Infarcts LA or LV mural thrombi after MI emboli white anemic variety, wedge-shaped Usually silent but can casue pain and hematuria

Cystic Diseases of the Kidney Autosomal-Dominant (Adult) Polycystic Kidney Disease (ADPKD)

Bilat large kidneys composed solely of mass of cysts filled with turbid, red to brown fluid Initially involves only parts of nephrons so kidney fxn retained until 40-50s (die at 53) Mutation of both alleles of PKD (usually PKD1) Clinical: enlarged kidney felt on palpation; dragging sensation; insidious onset of hematuria; flank pain Progression is accelerated in black males with hypertension 40% have polycystic liver disease BERRY ANEURYSMS & mitral valve prolapse Autosomal-Recessive (Childhoold) Polycystic Kidney Disease (ARPKD) Mutation of PKHD1 encoding fibrocystin (expressed in kidney, liver, pancreas) Large kidney w/ smooth exterior but spongelike due to many small cysts on cross section Congenital hepatic fibrosis Liver has cysts (bland periportal fibrosis) and proliferation of portal bile ducts Cystic Diseases of Renal Medulla Medullary Sponge Kidney (common) o Multiple cystic dilations of the collecting ducts in the medulla; o Discovered radiographically; Renal fxn usually normal Familial Juvenile Nephronophthisis (auto recessive) o Cysts in corticomedullary junction; shrunken kidneys o Consider in kids w/ unexplained chronic renal failure o Polyuria, Na+ wasting, and tubular acidosis o Tubulointerstitial nephritis on biopsy Acquired (Dialysis-Associated) Cystic Disease Prolonged dialysis cortical and medullary cysts filled w/ clear fluid and contain calcium oxalate crystals Can cause renal cell carcinoma Simple cysts (cortical) Must differentiate from renal tumors on radiographs o Smooth contours, avascular, give fluid rather solid signals

Urinary Tract Obstruction (Obstructive Uropathy) Hydronephrosis: pelvis and calyceal dilation associated with progressive renal atrophy of the kidney following outflow obstruction Obstruction triggers interstitial inflammatory rxn leads to interstitial fibrosis Progressive blunting of apices of pyramids causes them to become cupped

Urolithiasis (Renal Calculi, Stones) Men, 20-30s, usually arise in kidney Four types o Calcium stone (70%)- hypercalciuria w/o hypercalcemia (55%); Radiopaque

Triple phosphate/struvite stones- largest stones; ALKALINE URINE staghorn caluli- always due to infection o Uric acid stones- hyperuricemia (gout) and leukemia (rapid cell turnover) Urine of pH below 5.5; Radiolucent o Cystine stone: genetic defect in renal absorption of cystine; form at pH Stones are usually unilateral and form in renal calyces, pelves, or in bladder

Tumors of the Kidney Benign Tumors Renal Papillary Adenoma o Within the cortex, pale, yellow-gray, discrete, well-circumscribe nodules o Cut off of 3 cm between benign and those that metastasize Angiomyolipoma o Presents in patients with tuberous sclerosis o Consists of vessels, smooth muscle, and fat o Presents as lesions of cerebral cortex (epilepsy and mental retardation) and skin abnormalities o Can spontaneously hemorrhage Oncocytoma o Epithelial tumor composed of eosinophilc cells; On EM cells packed with MT Malignant Tumors Renal Cell Carcinoma (adenocarcinoma of the kidney)- 85% of adult renal cancer o 60-70 y.o. male; Smoker, obese, asbestos exposure, hypertensive, estrogen o Arise from tubular epithelium and have gross yellow color o Most are sporadic but 4% are auto dominant familial- VHL or MET mutation o Tendency to invade the renal vein and grow as solid column of cells w/in it o 3 classiac features: costovertebral pain, palpable mass, and hematuria o Produce paraneoplastic syndromes (abnormal hormone production)- polycythemia, hypercalcemia, hypertension, hepatic dysfxn, fem or masculinization, Cushing syndrome, eosinophilia, leukemomid rxn, amyloidosis o Mestasize to lungs and bone o Nephrectomy is tx of choice o Classification Clear Cell Carcinoma- NONPAPILLARY (VHL mutation) Solitary, unilateral, large (3cm+), spherical, bright yellow-gray masses that distort renal outline Ischemic opaque, gray-white necrosis, foci of hemorrhagic discoloration, and areas of softening Individual cells are polygonal w/ clear cytoplasm; vasculature Arise from proximal tubular epithelium Papillary Carncinoma (MET mutation) Multifocal and bilateral Hemorrhagic and cystic Arise from distal convulated tubules

Common in dialysis-associated cystic disease Interstitial foam cells in papillary cores w/ psammoma bodies Chromphobe Renal Carcinoma Arise from collecting duct intercalated cells Pale, eosinophilic cells w/ preinuclear halos arranged in sheets around blood vessels Collecting Duct (Bellini duct) Carcinoma Arise from collecting ducts in medulla Atypical epithelium w/ hobnail pattern

Urothelial Carcinomas of the Renal Pelvis By fragmentation produce hematuria Pre-existing or concomitant bladder urothelial tumor; Infiltration of wall of pelvis and calyces is common