HEREDITARY RENAL DISEASE

AUTOSOMAL DOMINANT / AD Chromosome(s) ADPKD PKD1 - 16 (Polycystic Kidney Disease)PKD2 – 4 Tuberous Sclerosus 9,11,12,16 Von Hippel-Lindau Ds 3 Medullary Cystic Ds -

Autosomal Resistant / AR ARPKD Medullary Cystic Ds Cystinosis Primary Hyperoxaluria – Enzyme defect Sickle Cell Ds Chrom 11

Sex Linked Ds – X Chrom Alport’s syndrome Fabry’s Ds

ADPKD Most common 1/500 – 1/1000 80%: detectable cysts at age < 30; bilateral Systemic Ds : Hepatic cysts F>M, ovarium, pancreas Colonic diverticula, hepatic fibrosis, Cardiac valve abnl – MVP (palpitation, chest pain ) Intracranial Aneurisms Hernias – umbilical, inguinal Renal concentrating defect / acidification defect Hypertension – RAAS Episodes of microscopic / gross Hematuria Cyst infection / hemorrhage Flank pain, proteinuria Nephrolithiasis (20%) – Citrate Adenoma, ESRD

ARPKD 1/10.000 – 1/50.000 Biliary disgenesis and Hepatic fibrosis Early in life – RENAL Later in life – more severe liver ds Hematuria, proteinuria Concentration defect Hypertension Portal hypertension

MULTICYSTIC KIDNEY Abnormal Metanephric differentiation Misshapen irregular cysts Lack of callyces, renal pelvis Sporadic, congenital > familial Most common cause of abdominal mass in neonates 50 % Bilateral

Medullary Cystic Ds (MCD) AR: Juvenile Nephronophthysis / JN age 10, concentrating defect, polyuria, polydipsia growth retardation renal failure by age 13 AD: MCD Nephronophthysis Complex less common larger cysts onset age 20’s ESRD < age 60

MCD cont. Usually small kidneys, small medulllary cysts Dx by USG Histopath: BM~ thickened and wrinkled ? Autoimmune interstitial nephritis Extrarenal: retinal degeneration retinitis pigmentosa AR: liver w/ portal fibrosis, cns, bone

Acquired Renal Cysts Simple cyst, most frequent, 50% adults Acquired Cystic Ds, ESRD /CRF , 7% - 22% pre HD 90% >10 Yrs HD Component of epithelial hyperplasia Asymptomatic, gross hematuria, flank pain, erythrocytosis, cyst infection, cyst rupture w/ retroperitoneal bleeding Malignant transformation, RCC (5Y survival 35%)

Medullary sponge kidneys Developmental abnl > hereditair Dilated intramedullary collecting ducts, that impart a sponge like appearance Usually asymptomatic Defect urine concentration and dilution Nephrolithiasis, hematuria, UTI’s High FeNa ,Hypercalciuria, hyperparathyroidism (2`?), parathyroid adenoma Renal insufficiency uncommon Dx: IVP: characteristic linear striation ~ bushlike pattern, bouquet like spherical cysts,

Tuberous Sclerosis, AD Epilepsi, mental retardation, skin lesion, hamartomas in many organs Any age, neonatal to elderly Flank pain, back pain, hematuria, hypertension, retroperitoneal bleeding Renal angiomyolipomas, cysts Dx: CT: intracranial paraventricular calcifications, intrarenal angiomyolipomas Renal ds most common cause of death in patients age > 30

Von Hippel-Lindau Ds / AD Childhood to old age CNS, Retinal hemangioblastomas, renal cysts, RCC, pancreas cysts, epididymal cysts, pheochromocytomas Usually multiple & bilateral renal cysts Renal failure is rare

Alport’s Syndrome /X 1/5000, M>F Microhematuria, later also proteinuria, hypertension Frequent sensorineural hearing loss, Ocular abnormalities, anterior lenticonus, perimacular pigment changes Leiomyomatosis, genital, oesophageal, upper GI Progressive loss of renal function Path: Irreg thinning, thickening, lamellation of GBM Alport gene, mutations: type IV Collagen, COL 4α5 Missing in GBM: Goodpasteur’s Ag: COL 4α3 (not on X-chrom) Post transplant: unusual anti GBM Ds

Sickle Cell Nephropathy Early: glomerular hyperfiltration Later: renal concentrating defect, impaired K and H ion excretion Proteinuria, 25% Path: FSGS and glomerular hypertraphy 4-7% ESRD, mean age 23Y, anemia, hypertension, proteinuria, NS, microscopic hematuria Sickle Cell Trait / SA, microinfarcts in renal medulla, w/ hematuria, isosthenuria

Congenital disorders Obstruction and hydronephrosis, ureteropelvic junction, posterior urethral valve, prune-belly syndrome, nonobstructive hn Reflux nephropathy, obstruction, neurogenic bladder congenital defect ureterovesical junction frequent UTI, hypertension, renal scarring, renal insufficiency Nephrotic Syndrome congenital infections, syphilis, toxoplasma, CMV Nail-patelle syndrome, AR Finnish type