KIDNEY DISEASES

Developmental disorders

Glomerular diseases

Tubulo-interstitial diseases

Urinary stones

Obstructive uropathy

Tumors

LUPUS GLOMERULONEPHRITISGN-Common feature of SLE

Immune complex-deposition -in situ formationAssociated with deposits in

-blood vessels-tubular BM-interstitium

Complementinflammation

LUPUS GLOMERULONEPHRITIS

I: No lesion

II: Mesangial

III: Focal proliferative

IV: Diffuse proliferative

V: Membranous

VI: Chronic

PATHOLOGY OF SLE GNHighly variable

Immune complexes vary in/size/location

• Subendothelial

• Intramembranous

• Subepithelial

• Mesangial

Proliferation of Mes, End, Ep cells; PMN and MACROPHAGES

Fibrinoid necrosis

IF-”full house” (ML Ig)

KIDNEY ANATOMIC COMPARTMENTS

Glomerulus

Tubules

Blood vessels

Interstitium

Collecting system

(Callices & Pelvis)

COMPONENTS OF THE GLOMERULUS

Capillary basement membrane

Mesangium

Bowman capsule

Cells

• Endothelial

• Epithelial

• Mesangial

THE JUXTAGLOMERULAR APPARATUS

Afferent arteriole

Macula densa – ascending loop of Henle

Lacis cells - Renin

CONGENITAL RENAL ANOMALIES

Agenesis – Potter syndrome

Ectopia

Fusion

Dysplasia

Polycystic kidney disease

POLYCYSTIC KIDNEY DISEASE

Autosomal dominant (adult) (1:1,000)

Autosomal recessive (infantile (1:30,000)

Medullary cystic disease complex (1:10,000)

Medullary sponge kidney

Acquired cystic renal disease

AUTOSOMAL DOMINANT

POLYCYSTIC KIDNEY DISEASE

Common kidney disease (1:1,000)

10% of all transplant/dialysis patients

ADPKD-1 gene (polycystin) mutation 85%

Bilaterally enlarged kidneys (>3,000g)

Symptoms appear in adult life

Renal failure 5-10 years thereafter

ADPKD

Associated Conditions

Liver cysts (30%)

Splenic cysts (10%)

Pancreatic cysts (5%)

Cerebral aneurysms (20%)

Diverticulosis coli

GLOMERULAR DISEASES

Asymptomatic hematuria/proteinuria

Nephrotic syndrome

Nephritic syndrome

Rapidly progressive glomerulonephritis

Chronic nephritis

KIDNEY DISEASES

(MNEMONIC “ANNURIC”)A Asymptomatic hematuria/proteinuria

N Nephrotic syndrome

N Nephritic syndrome

U Urolithiasis

R Rapidly progressive glomerulonephritis

I Interstitial and tubular diseases

C Chronic renal disease

CHRONIC RENAL FAILURE

(UREMIA)General symptoms – weakness, fatigueCardiovascular – hypertension, pericarditisG.I. – nausea, vomiting, diarrheaCNS – lethargy, confusion, comaMuscles – twitching, weaknessBones – osteodystrophyMetabolic – acidosis, PK, BUN, Cr.Endocrine - parathyroids

NEPHROTIC SYNDROME

Proteinuria (“nephrotic range” >3.5g/24h)

Hypoalbumimenia

Edema

Hyperlipidemia

Lipiduria

CAUSES OF NEPHROTIC SYNDROME

Disease Children(%) Adults(%)

Minimal change GN 75 20

Membanous GN 5 40

MPGN I 5 5

Other GN 5 20

NEPHRITIC SYNDROME

Hematuria

Proteinuria

Hypoalbuminemia

Oliguria (GFR, Cr, BUN)

Edema (salt and water retention)

Hypertension

DIAGNOSTIC FEATURES OF GLOMERULAR DISEASES

Light microscopy

• Cellularity

• Extracellular matrix

Special stains

(PAS, amyloid)

Immunofluorescence microscopy

(Linear, granular, mesangial, irregular deposits)

Electron microscopy

(deposits of immune complexes, BM changes, amyloid)

MINIMAL CHANGE GLOMERULOPATHY

Most common cause of nephrotic syndrome in children

E/P: unknown (?immune)

Path: normal by LM and IF

EM: fusion of foot processes

CL: Nephrotic sy – responds to steroids

Dd: FGS

FOCAL SEGMENTAL GLOMERULOSCLEROSIS

Def: 15% of all nephrotic syndromes; heterogenous group of diseases

E/P: unknown-circulatory glomerular injury (?)

HIV, I-V drug abuse

CHD, obesity, sickle-cell disease

Path: focal and segmental glomerular hyalinosis

“Collapsing” pattern (e.g. HIV)

Trapping of serum proteins (IF and EM)

Clin: Nephrotic syndromeESKD (5-20y)

If HIV relatedESKD (1 year)

MEMBRANOUS NEPHROPATHYDef: Most common cause of nephrotic syndrome in adults (40%)

Immune complexBM thickening

E/P: Primary (unknown)

Secondary (SLE, HBV, drugs, cancer)

Path: Subepithelial deposits of immune complex

CL: Nephrotic syndrome

(25% recover, 50% persist, 25% progress)

DIABETIC GLOMERULOSCLEROSISDef: Diabetes caused BM thickening

Proteinuria renal failure (leading cause in US)

E/P: BM synthesis , nonenzymatic glycation (?)

Path: Diffuse global thickening of BM

Nodular sclerosis (K-W)

Arteriolosclerosis

Trapping of serum proteins

Clin: Proteinuria (in 50% diabetics)

ESKD (30% all in the US)

DIABETIC KIDNEY DISEASES

Glomerulosclerosis

Arteriolosclerosis Hypertension

Pyelonephritis

Papillary necrosis

AMYLOIDOSISAA amyloid – systemic disease

AL amyloid – multiple myeloma

Deposits of amyloid – glomeruli (mesangial)

- arterioles

- tulular BM

Nonselective proteinuria – nephrotic sydrome (60%)

renal failure (with large kidneys!)

ACUTE POSTINFECTIOUS GNDef: Acute nephritic syndrome 1-2 weeks after infection

E/P: immune response to A -hemolytic streptococci

(other infections Staph, malaria, HBV less common)

Path: Acute glomerulonephritis

Clin: Childhood nephritic syndrome

90% recover

9% presistent hematuria/proteirunria

1% chronic renal disease

PATHOLOGY OF ACUTE POSTINFECTIOUS GN

LM: hypercellularity (endo + MES + PMN)

IF: Irregular deposits of Ig, Compl.

EM: Deposits (mesang + BM)

“HUMPS”

MEMBRANOPROLIFERATIVE GLUMERULONEPHRITIS

Type I

Def: Immune mediated presistent GN

Mesangiocapillary cell proliferation and BM reduplication

E/P: Immune comples deposition in glomeruli

•Primary (unknown cause)

•Secondary (SBE, chronic infection, HCV, cryoglobulinemia, cancer)

Path: Lobular gromerulonephritis

Clin: Older children/young adults

Nephritic or nephrotic syndrome

Progressive – 50% ESKD (10 years)

MEMBRONOPROLIFERATIVE GLOMERULONEPHRITIS

Type II

Def: Immune mediated persistent GN

Dense deposits in GBM

E/P: C3 nephritic factor (IgG)

Stablizes the activated C3 convertase

Path: Similar by LM to MPGN-I

EM-shows linear dense deposits in GBM

RENAL BIOPSY IN SLETo determine

1. Category (class)

2. Activity

3. Extent

4. Chronicity

Note: Class IV-worst prognosis

Class V-no response to steroids

IgA NEPHROPATHY (BERGER)Most common form of GNYoung adults (15-30 years)Pathology: IgA deposits in mesangium

-varied severityClin: Protean manifestations

40% asymptomatic microscopic hematuria 40% bouts of macro hematuria 10% nephrotic syndrome 10% renal failure

ANTI-GBM ANTIBODY GNRPGN mediated by antibody

Antibody to collagen IV

Linear IF

Fibrinoid necrosis of GBM

Crescentic GN

Goodpasture syndrome

CRESCENTIC GLOMERULONEPHRITIS

1. Anti-GBM glomerulonephritis

(inc. Goodpasture syndrome)

2. ANCA granulonephritis

(inc. Wegener granulomatosis, micr. polyangitis, Churg-Strauss syndrome)

3. Immune complex glomerulonephritis

(inc. Henoch-Schonlein purpura, cryoglobulinemia)

4. Non-immune

ANCA GLOMERULONEPHRITIS

Necrotizing and crescentic

ANCA (PMN myeloperoxidase, proteinase 3)

No immune deposits in glomeruli

Respond to immunosuppresion (25% pregress)

Associated with small vessel polyangiitis (75%)

Pulmonary-renal vasculitic syndromes

SMALL VESSEL VASCULITIS

AFFECTING KIDNEYS

Henoch-Schonlein purpura-children, IgA

Cryoglobulinemic vasculitis-HCV, MPGN-I

Wegener GR.-upper slower respiratory tract

Churg-Strauss-eosinophilia, asthma

Microscopic polyangiitis-multiple organs, lungs (-)

NEPHROSCLEROSISBenign – sustained mild hypertension

– hyaline arteriolosclerosis

– arterial fibrosis

– glomerular hyalinization, tubular atrophy

Malignant-BP>125 mm/Hg, retinal hemorrhage, papilledema, renal dysfunction

– fibrinoid necrosis of arterioles

– myxoid intimal expansion of arteries

– microthrombi

THROMBOTIC MICROANGIOPATHY

Morphologic finding in several diseases

Assoc: microangiopathic hemolytic anemia

E/P: HUS

TTP

Malignant nephrosclerosis

Systemic sclerosis

RENAL INFARCTS

Thromboemboli

•Mural thrombi

(M.I., atrial fibrillation)

•Endocarditis

•Aortic thrombi (atherosclerosis)

Cholesterol emboli

RENAL CORTICAL NECROSISCortical ischemia: thrombi, vasospasm

Complication of shock

• Abruptio placentae

• Endotoxic shock

• Hypotensive shock

Cortex pale – medulla spared

Massive tubular necrosis

CAUSES OF ACUTE TUBULAR NECROSIS

Ischemia (hypoperfusion)• Hypovolemic shock (e.g. bleeding)• Sepsis• Burns• Prolonged surgical operations

Nephrotoxins• Toxic chemicals (e.g. CCl4)• Heavy metals (e.g. Hg)• Drugs (e.g. cisplatin)

Heme proteins• Myoglobin (e.g. rhabdomyolysis)• Hemoglobin (e.g. hemolysis)

PATHOLOGY OF ACUTE TUBULAR NECROSIS

Cortex> medulla

Necrotic tubular cells slough off

Intratubular cast in medulla

Regeneration of tubules occurs fast

CLINICAL ASPECTS OF ATNThe most common cause of acute renal failure

“Dirty” brown casts in urine

Oliguria anuria polyuria

• Azotemia

• Acidosis, K• Fluid retention

Recovery 1-2 weeks

ACUTE PYELONEPHRITIS

Bacterial infection (E. coli 80%)

Ascending > hematogenous

Lower UTI precedes renal infection

Fever, flank pain, neutrophilia

Leukocyte casts in urine

Healing - recurrence chronic pyelonephritis

PATHOLOGY OF ACUTE PYELONEPHRITIS

Unilateral> bilateral

Focal

PMNs in tubules interstitium

Abscesses with tissue destruction

PYELONEPHRITIS

PREDISPOSING CONDITIONSUrinary stonesHydronephrosisCystitisProstatic hyperplasiaTumorsPregnancyVesico-ureteric refluxExternal ureteric compression (e.g. fibrosis)

PREDISPOSITION TO PYELONEPHRITIS

(MNEMONIC URINE)

U Urolithiasis

R Reflux (vesico-ureteric)

I Infections of lower UT

N Neoplasms (e.g. ureteric, vesical, prostatic)

E External compression (e.g.) pregnancy

retroperitoneal fibrosis

CHRONIC PYELONEPHRITIS

PATHOLOGYDestruction of renal tissue and fibrosis

• Cortical scars• Loss of papillae• Ectasia of calices• Hydronephrosis

Irregularly shrunken small kidneyHistology: Chronic inflammatory infiltrates

•Tubular atrophy with casts (“thyroidization”)

DRUG INDUCED RENAL DISEASES

1. Acute tubular necrosis(toxic)

2. Acute tubulointerstitial nephritis (allergic)

3. Analgesic nepropathy (phenacetin

dose-related)

METABOLIC TUBULAR INJURY

Multiple myeloma – light chain casts

Hyperuricemia (gout) – urate nephropathy

Hypercalcemia – uric acid stones

Hypercalciuria – nephrocalcinosis

– calcium stones

CAUSES OF HYPERCALCEMIA – HYPERCALCIURIA

Primary (increased intestinal absorption of Ca)

• Idiopathic (most common)

• Milk-alkali syndrome

• Vitamin D excess

• Sarcoidosis

Secondary (release of Ca from bones)

• Renal osteodystrophy

• Hyperparathyroidism

• Osteolytic metastases (e.g. breast cancer)

• Paraneoplastic syndromes (PTrP)

RENAL STONES (NEPHRODITHIASIS)

1. Calcium oxalate or phosphate (75%)

2. Uric acid (15%)

3. Struvite (magnesium ammonium phosphate)

and calcium phosphate (8%)

4. Cystine (1%)

RENAL TUMORS

Benign – oncocytoma, angiomyolipoma, fibroma

(rare!)

Renal cell carcinoma (most common – adults)

Wilms tumor (childhood)

Transitional cell carcinoma of renal pelvis

RENAL CELL CARCINOMA

Most common renal tumor

Peak age – 60y M:F = 2:1

Incidence increasing world wide

Risk factors: Tobacco; genetics (vHL-gene, familial cases)

RENAL CELL CARCINOMA PATHOLOGY

Yellow orange on cut surface

Partially encapsulated

Extends into renal vein

Histology: tubular clear cell (77%)

papillary (15%)

granular, chromophobe, sarcomatoid (5%)

RENAL CELL CARCINOMA

CLINICAL ASPECTSClassical triad (hematuria, flank pain, mass) (<10%)

Hematuria (50%) most common symptom

Metastases-hematogenous and local abdominal

Paraneoplastic syndromes (PTH, Epo, amyloid)

5 year survival = 40%

WILMS TUMORChildhood tumor (peak age 2 years) 98%< 10 years

Most common abdominal solid tumor in childhood

Sporadic (90%)

Familial syndromic (5%)

(WAGR syndrome – WT1 tumor suppressor gene Beckwith – Wiedemann syndrome – WT2)

Familial nonsyndromic (5%)

Unilateral (90%)

Bilateral more common in familial cases (20%)

WILMS TUMOR

CLINICAL – PATHOLOGIC FEATURES

Lobulated tumors mass – usually encapsulated

Histology: mixture of immature cells metanephic, stromal, tubular

Chemotherapy + surgery = 5 years = 90%

Children< 2 years better prognosis