Inherited tubular disorders

Autosomal dominant PKD

• Systemic disorder beginning in utero with gradual cyst enlargement, separation from nephron, compression of surrounding renal parenchyma and progressive compromise of renal function
• 1/400 to 1/1000 individuals worldwide
• Often asymptomatic until 4thor 5^th decade
• Presenting symptoms include abdominal pain, haematuria, UTI, incidental HTN, abdominal mass, rising serum creatinine or cystic kidneys on imaging
• ESRD occurs in 60% of patients by age 70

ADPKD

• Cyst rupture or haemorrhage into a cyst may produce flank pain or localised peritonitis
• Nephrolithiasis occurs in 20% of patients
• Acute pyelo is more common
• Infection of a kidney or liver cyst is a serious complication and is usually due to Gram-negative bacteria
  • Urine culture may be negative as infected cysts DO NOT communicate with the collecting system
  • Difficult to differentiate from cyst haemorrhage and imaging is usually unhelpful

ADPKD

• Extra-renal manifestations
  • Fourfold increased risk of SAH or cerebral haemorrhage from ruptured intracranial aneurysm
  • Saccular aneurysms of anterior cerebral circulation are found in 10% of asymptomatic patients on MRA screening
  • Risk factors for haemorrhage include age <50, FHx of ICH, survivors of previous bleed, aneurysms >10mm and uncontrolled HTN
  • Aortic root and root annulus dilatation are also seen
  • Cardiac valvular abnormalities in 25% (mostly mitral valve prolapse and aortic regurgitation)
  • 40% of patients have hepatic cysts by age 60 which may bleed, become infected, rupture or cause pain
  • Colonic diverticular are more common
  • Abdominal wall hernias are more common

ADPKD

• Diagnostic criteria
  • 2 or more cysts in one kidney and at least one cyst in contralateral kidney in young patients
  • Need 4 or more cysts in older patients

Autosomal recessive PKD

• 1/20 000 live births
• 50% of affected neonates die from pulmonary hypoplasia as a result of oligohydramnios secondary to severe intrauterine kidney disease
• Often detected soon after birth as abdominal masses
• HTN occurs within first years of life
• Kidney function deteriorates rapidly into early adult life

Bartter’s syndrome

• Mutations in any of four ion transport proteins in the thick ascending loop of Henle
• Loss of lumen-positive electrical gradient that drives paracellular reabsortion of Na, Ca, Mg causes Na, Cl, calcium and magnesium wasting
• Mimics long-term loop diuretic use

Gietelman’s syndrome

• Due to mutations in thiazide-sensitive Na-Cl co-transporter in distal collecting tubule
• Impairs sodium and chloride reabsorption and resembles thiazide use
• In both Bartter’s and Gietelman’s syndromes, hypovolaemia triggers hyperaldosteronism with subsequent sodium retention and renal wasting of potassium and metabolic alkalosis

Liddle’s syndrome

• Mimics hyperaldosteronism with early/severe HTN, hypokalaemia and metabolic alkalosis
• Testing shows low aldosterone and renin levels
• Due to unregulated sodium reabsorption by overactive ENaC

Hereditary nephrogenic diabetes insipidus

• Presents in infancy with vasopressin-resistant severe polyuria, dehydration, failure to thrive and dilute urine despite hypernatraemia
• Hypernatraemia is simply due to loss of free water
• Very rare

Renal tubular acidosis

• Causes normal anion gap metabolic acidosis
• Type 1 (distal) RTA
  • Kidneys unable to acidify urine to pH <5.5 despite systemic metabolic acidosis due to impaired hydrogen ion secretion or bicarbonate reabsorption in distal nephron
  • Presents with hypokalaemia, hypercalciuria, nephrocalcinosis and/or nephrolithiasis
  • Alkali replacement corrects acidosis, hypokalaemia and maintains growth and bone density

Renal tubular acidosis

• Type 2 (proximal) RTA
  • Due to impaired bicarbonate reabsorption in proximal renal tubular
  • Presents with severe NAGMA not responsive to bicarbonate administration (as continue to waste bicarbonate and subsequently flooding distal nephron with bicarb and causing ongoing K loss
  • Need to continue bicarb + supplement K
• Type 4 RTA
  • Characterised by hyperkalaemia

Last Updated on October 9, 2020 by Andrew Crofton