Inherited kidney diseases

Autosomal dominant polycystic kidney disease (ADPKD)

• Prevalence 1/1000
• Genes on Chr16 and Chr 4
• Causes renal enlargement with cysts, abdo pain, haematuria, cyst infection, renal calculi, raised BP and progressive renal failure
• Extra-renal associations
  • Liver cysts
  • Intracranial aneurysms – SAH
  • Mitral valve prolapse
• Treatment
  • Monitor U&Es
  • Control BP
  • Treat infections
  • Dialysis or transplantation for ESRF
  • Genetic counselling

Autosomal recessive polycystic kidney disease

• Prevalence is 1 in 40,000
• Gene on chromosome 6
• Causes renal cysts and congenital hepatic fibrosis in infants

Medullary cystic disease

• Inherited disorder with tubular loss and medullary cyst formation
• The juvenile (autosomal recessive) form accounts for 10-20% of ESRF in children
• The adult (autosomal dominant) form is rare
• Results in polyuria, polydipsia, FTT, renal impairment
• Extra-renal associations;
  • Retinal degeneration
  • Retinitis pigmentosum
  • Skeletal changes
  • Cerebellar ataxia
  • Liver fibrosis

Renal phakomatoses (neuroectodermal syndromes)

Tuberous sclerosis

• Autosomal dominant disorder caused by mutations on chr9 and 16
• Associated with hamartoma formation in skin, brain, eye, kidney and heart
• Signs;
  • Skin
    • Adenoma sebaceum
    • Angiofibromas
    • Ash leaf hypomelanic macules
    • Shegreen patch (sacral plaques of shark like skin)
    • Periungal fibroma
  • Reduced IQ
  • Epilepsy

Von Hippel-Lindau

• Autosomal dominant condition resulting from mutation of TSG on chromosome 3
• It predisposes to bilateral renal cell carcinoma, retinal and cerebellar haemangiolastomas and phaeochromocytomas
• It may present with visual impairment of cerebellar signs

Alport’s syndrome

• Variable inheritance (85% sex linked) – affected genes code for Type IV collagen
• Causes thickened GBM with splitting, the Goodpasteurs antigen is lacking so there is a risk of Goodpasteurs disease post transplant
• Signs;
  • Haematuric nephritis
  • Sensorineural deafness
  • Progressive renal failure
  • Lenticonus – bulging of the lens capsule seen via slit lamp examination

Hyperoxaluria

• Primary hyperoxaluria
  • Autosomal recessive inherited error of metabolism due to an enzyme defect
• Secondary hyperoxaluria
  • Due to;
    • Increased intake – rhubarb, spinach, tea
    • Increased intestinal reabsorption due to ileal disease
    • Low calcium intake
  • Signs;
    • Oxalate renal stones
    • Nephrocalcinosis
    • Progressive renal failure
    • Cardiac conduction defects
    • Arterial disease – oxalate crystalisation
    • Osteodystrophy
  • Treatment
    • High fluid intake
    • Reduce dietary oxalate
    • Calcium supplements (bind oxalate in the gut reducing absorption)
    • Pyridoxine (Vit B6) can be used to reduced endogenous oxalate production

Cystinuria

• This is the commonest aminoaciduria causing reduced tubular reabsorption of dibasic amino acids
• COAL – Cystine, Orthithine Arginine, Lysine
• Autosomal recessive defect
• Causes cystine renal stones
• Treatment
• Increase fluid intake
• Urine alkalinization with potassium citrate
• Penicillamine to bind cystine