Pathology 955-963 The Kidney
Congenital Anomalies
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CAKUT = congenital abnormalities of kidney and urinary tract
o Structural
Genetics effect tubular transport
Bilateral Agenesis = incompatible with life (stillborn)
Unilateral Agenesis = compatible without other abnormalities; compensatory hypertrophy with
progressive glomerular sclerosis
Hypoplasia = bilateral leads to early failure, more common unilateral; true hypoplasia has no
scars but reduced # (<6) of renal lobes and pyramids
o Oligomeganephronia -> hypoplastic, few nephrons that are hypertrophied
Ectopic Kidney = lie above pelvic brim or in pelvis, unremarkable
o abnormal position kinks ureters -> bacterial infection
Horseshoe Kidney = anterior to great vessels, 90% fused at lower pole
Multicystic renal dysplasia = histologic persistence in kidney of abnormal structures (cartilage,
undifferentiated mesenchyme, immature collecting ducts) and abnormal lobar organization
o Associated with other lower UT anomalies
o many nephrons have immature collecting ducts
o unilateral -> flank mass leading to nephrectomy; good prognosis
o Bilateral -> renal failure
Cystic Diseases of the Kidney
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Autosomal-dominant (Adult) Polycystic Kidney Disease = multiple expanding cysts of both
kidnes destroying renal parenchyma and causing renal failure; bilateral
o Mutations of both alleles of PKD gene
 PKD1 mutation = 85% and more severe; PKD2 mutation in rest
o Renal function retained until 40-50
o Systemic (cysts in other organs)
o Genetics and Pathogenesis:
 PKD1 encodes polycystin-1 localised in distal nephron
 PKD2 encodes polycystin-2 (Ca permeable cation channel) localized in all
segments
 Both polycystin’s localized in primary cilium
 Change in intracellular Ca level -> change in cell proliferation, apoptosis,
ECM interaction, and secretory function of epithelia
o Cyst enlargement results
 Affected Cilia-centrosome complex regulating ion flux of tubular epithelium
underlies cyst formation
o Morphology:
 Kidneys bilaterally enlarged with cysts externally
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 Functioning nephrons between (clear or red/brown fluid-filled) cysts
o Clinical:
 Asymptomatic until renal insufficiency; hemorrhage or dilation may have pain
 Onset of hematuria then proteinuria, polyuria and hypertension
 Accelerated in blacks (sickle-cell trait), males, and hypertensives
 40% have asymptomatic cysts in liver
 Other anomalies = intracranial berry aneurysms in circle of Willis, mitral valve
prolapse
 Azotemia and uremia for many years
 Most die from coronary/hypertensive heart disease, infection or ruptured
aneurysm/hemorrhage
Autosomal-Recessive (Childhood) Polycystic Kidney Disease = perinatal and neonatal most
common
o Mutation of PKHD1 gene encoding fibrocystin -> localized to primary cilium of tubular
cells
o Morphology:
 Enlarged kidney with smooth external appearance
 Spongelike appearance inside
 Dilation of collecting ducts
 Liver has cysts
o Clinical:
 Survivors develop congenital hepatic fibrosis
Cystic Disease of Renal Medulla =
o Medullary Sponge Kidney = lesions of multiple cystic dilations of collecting ducts in
medulla
 adults, incidental finding or secondary complications
 dilated papillary ducts
o Nephronophthisis and Adult-Onset Medullary Cystic Disease = cysts in medulla,
concentrated at corticomedullary junction
 cortical tubulointerstitial damage causes renal insufficiency
 3 variants: sporadic/nonfamilial, familial juvenile nephronophthisis (most
common) and renal-retinal dysplasia
 Most common genetic cause of ESRD in children/young adults
 Present with polyuria and polydipsia, sodium and tubular acidosis
 Pathogenesis:
 NPH1, 2, 3 (produce nephrocystins) mutated in juvenile
nephronophthisis
 MCKD1, 2 cause medullary cystic disease
 Morphology:
 Small kidney
 Cortical atrophy and thickened basement membrane
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Clinical:
 Strongly consider in kids with unexplained chronic renal failure, family
history and chronic tubulointerstitial nephritis
Acquired (Dialysis-Associated) Cystic Disease = cysts with clear fluid and calcium
oxalate crystals
 Complication -> renal cell carcinoma in cyst walls
Simple Cysts = translucent, smooth membrane, clear fluid
 No clinical significance unless hemorrhage into them (pain)
 Mistaken for tumors
 Cysts have smooth contour, avascular and fluid signals on US
Urinary Tract Obstruction (Obstructive Uropathy)
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Obstruction increases susceptibility to infection and stone and unrelieved leads to permanent
renal atrophy (hydronephrosis or obstructive uropathy)
Common causes:
o Congenital anomalies, calculi, benign prostatic hypertrophy, tumors, inflammation,
sloughed papillae/blood clots, pregnancy, uterine proplase and cystocele, functional
disorders
Hydronephrosis = dilation of renal pelvis and calyces with atrophy of kidney from obstruction
o Diminution in inner medullary blood flow
Obstruction triggers interstitial inflammatory reaction -> interstitial fibrosis
Morphology:
o Sudden, complete obstruction -> reduced glomerular filtration -> dilation of
pelvis/calyces
o Subtotal, intermittent obstruction -> normal filtration -> progressive dilation
o Interstitial inflammation
o Cortical tubular atrophy with interstitial fibrosis
o Blunting of pyramid apices and thinning of renal parenchyma
Clinical:
o Acute obstruction -> pain
o Unilateral complete or partial hydronephrosis may remain silent for long
 Ultrasound good for diagnosis
o Bilateral partial obstruction -> polyuria and nocturia, hyposthenuria; typical picture of
chronic tubulointerstitial nephritis, hypertension
o Complete bilateral obstruction -> oliguria/anuria, must relieve; postobstuctive diuresis
Urolithiasis (Rneal Calculi, Stones)
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Men > women, 20-30
Gout, cystinuria, primary hyperoxaluria = hereditary diseases associated
Cause and Pathogenesis:
o Four types (all have mucoprotein matrix)
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calcium stones (70%) -> radiopaque; hypercalcemia with hypercalciuria
(hyperparathyroidism, bone disease, sarcoidosis) or without hypercalciuria
(hyperabsorption), increased uric acid secretion (hyperuricosuric calcium
nephrolithiasis), hyperoxaluria (vegetarians), hyypocitraturia (acidosis, chronic
diarrhea)
 triple/struvite stones (15%; magnesium ammonium phosphate)-> after bacterial
infection (convert urea to ammonia), large stones (staghorn calculi)
 uric acid stones (5-10%) -> hyperuricemia (gout), leukemia, > ½ have neither
hyperuricemia nor increased uric acid excretion; radiolucent
 cysteine (1-2%)-> genetic defect in AA reabsorption, low pH
o most important determinant is increased urinary concentration of stones’ constituents
(exceeds solubility); also low urine volume
o formation enhanced by deficiency in inhibitors of crystal formation
Morphology
o Unilateral (80%)
o Favored within renal calyces/pelves or bladder
Clinical:
o May damage kidney
o Smaller are more hazardous (pass into ureters -> colic)
o Large stones -> hematuria