KIDNEY DISEASES
Developmental disorders
Glomerular diseases
Tubulo-interstitial diseases
Urinary stones
Obstructive uropathy
Tumors
LUPUS GLOMERULONEPHRITIS
GN-Common feature of SLE
Immune complex-deposition
-in situ formation
Associated with deposits in
-blood vessels
-tubular BM
-interstitium
Complementinflammation
LUPUS GLOMERULONEPHRITIS
I:
No lesion
II: Mesangial
III: Focal proliferative
IV: Diffuse proliferative
V: Membranous
VI: Chronic
PATHOLOGY OF SLE GN
Highly 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
N
N
U
R
I
C
Asymptomatic hematuria/proteinuria
Nephrotic syndrome
Nephritic syndrome
Urolithiasis
Rapidly progressive glomerulonephritis
Interstitial and tubular diseases
Chronic renal disease
CHRONIC RENAL FAILURE
(UREMIA)
General symptoms – weakness, fatigue
Cardiovascular – hypertension, pericarditis
G.I. – nausea, vomiting, diarrhea
CNS – lethargy, confusion, coma
Muscles – twitching, weakness
Bones – osteodystrophy
Metabolic – acidosis, PK, BUN, Cr.
Endocrine - parathyroids
NEPHROTIC SYNDROME
Proteinuria (“nephrotic range” >3.5g/24h)
Hypoalbumimenia
Edema
Hyperlipidemia
Lipiduria
CAUSES OF NEPHROTIC SYNDROME
Disease
Children(%)
Minimal change GN
Adults(%)
75
20
5
40
MPGN I
5
5
Other GN
5
20
Membanous
GN
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 syndromeESKD (5-20y)
If HIV relatedESKD (1 year)
MEMBRANOUS NEPHROPATHY
Def: Most common cause of nephrotic syndrome in
adults (40%)
Immune complexBM 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 GLOMERULOSCLEROSIS
Def: 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
AMYLOIDOSIS
AA 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 GN
Def: 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 SLE
To 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 GN
Young adults (15-30 years)
Pathology: IgA deposits in mesangium
-varied severity
Clin: Protean manifestations
40% asymptomatic microscopic hematuria
40% bouts of macro hematuria
10% nephrotic syndrome
10% renal failure
ANTI-GBM ANTIBODY GN
RPGN 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 (-)
NEPHROSCLEROSIS
Benign – 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 NECROSIS
Cortical 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 ATN
The 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 CONDITIONS
Urinary stones
Hydronephrosis
Cystitis
Prostatic hyperplasia
Tumors
Pregnancy
Vesico-ureteric reflux
External 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
PATHOLOGY
Destruction of renal tissue and fibrosis
• Cortical scars
• Loss of papillae
• Ectasia of calices
• Hydronephrosis
Irregularly shrunken small kidney
Histology: 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 ASPECTS
Classical 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 TUMOR
Childhood 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