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