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