|
Autosomal dominant medullary cystic kidney disease (ADMCKD) is a chronic tubulointerstitial nephropathy, which belongs, together with nephronophthisis (NPH), to a heterogeneous group of inherited tubulo-interstitial nephritis, termed NPH-MCKD complex. Less than 60 families affected by ADMCKD have been described. Prevalence is estimated to be 1/100 000. Clinical onset and course are insidious. Symptoms typically appear at an average age of 28 years, when the urinary concentrating ability is markedly reduced, producing polyuria and stable low urinary osmolality in the first morning urine and lack of any compensatory effect after endo nasal desmopressin (2 pushes). Later, anemia, metabolic acidosis and uremia reflect the progressive renal insufficiency. End-stage renal disease typically occurs in the third-fifth decade of life or even later. Two genes have been linked to the disease: MCKD1 (1q21) is associated with end-stage renal disease at the mean age of 62 years, and MCKD2 (in 16p12, where the gene UMOD, encoding uromodulin or Tamm-Horsfall protein, has been identified as responsible of the disease) with earlier end-stage renal disease (around 32 years) often with hyperuricemia and gout. The latter form is an allelic variant of FJHN type 1 (Familial juvenile hyperuricemic nephropathy type 1 - see this term), which is also due to mutations in UMOD. Candidate genes have been localised to 1q41 in families which did not show linkage to MCKD1 nor to MCKD2 and had, in addition to uricemia, calcium and uromodulin reduced urinary excretion. The presence of a positive family history consistent with ADMCKD, the classical findings of long-standing polyuria and renal insufficiency in an adult patient aged from 30 to 50 years old evoke the diagnosis, which can be confirmed histologically, the most important criteria being tubulo-interstitial changes. The differential diagnosis of ADMCKD should include diseases causing chronic progressive tubulointerstitial disease with minimal or no glomerular abnormalities. Genetic counselling is difficult, due to the incomplete penetrance and variable expression of the disease. There is no specific therapy for ADMCKD other than correction of water and electrolyte imbalances that may occur. Dialysis followed by renal transplantation is the preferred approach for end-stage renal failure. The tubular injury does not occur in the transplanted kidney. |