Autosomal dominant polycystic kidney disease is an important cause of renal failure. It is inherited as an autosomal dominant trait with penetrance approaching 100% in those surviving until their seventh or eighth decade. The condition most usually presents in adult life but may develop at any time, including in utero.
Both kidneys are always affected. Cysts arise from the tubules throughout the nephrons but initially, involve only a portion of them
The diagnosis of ADPKD is based on family history and ultrasonographic evaluation
In up to 25% of patients with ADPKD, no family history is identified, which may be related to subclinical disease or a new genetic mutation in about 5% of cases
Patients with ADPKD typically progress to end-stage renal disease (ESRD) by the fifth or sixth decade of life. The rate of progression of ADPKD is related directly to kidney volume.
- cysts may arise in other organs, particularly the liver; intracranial berry aneurysms are found in up to 40% of patients, predisposing to subarachnoid haemorrhage
- ADPKD is the most common hereditary kidney disease in Western countries - ADPKD is the fourth most common renal disease requiring renal replacement therapy
- prevalence is between 2.4/10,000 and 3.9/10,000
- estimated that ADPKD affects 1 in every 400 to 1,000 live births
- mutations in two genes (PKD1 and PKD2) have been identified
- ADPKD is a multi-systemic disease characterized by the progressive development of bilateral renal cysts, resulting in enlargement of the kidney volume due to cystic formations, hypertension, haematuria, and loss of renal function
- patients with PKD1 mutations typically have a more severe phenotype than those with PKD2 mutations
- vasopressin and the associated cyclic adenosine monophosphate-related signalling pathways have been demonstrated to be important contributors to cyst growth in ADPKD
- supportive treatments are recommended with the aim of reducing morbidity and mortality associated with disease manifestations - therapies aim to slow the decline in renal volume to delay progression.
- besides lifestyle changes (low-salt diet, sufficient fluid intake, and no smoking), blood pressure control is the primary nonspecific treatment recommended by Kidney Disease -Improving Global Outcomes (KDIGO) for ADPKD patients
- tolvaptan (vasopressin V2 receptor antagonist) has demonstrated a slower decline than placebo in the eGFR over a one year period in patients with late-stage chronic kidney disease but is associated with elevations of bilirubin and alanine aminotransferase levels.
References:
- Bergmann C, Guay-Woodford LM, Harris PC, et al. Polycystic kidney disease. Nat Rev Dis Primers. 2018 Dec 6;4(1):50.
- Barnawi RA et al. Is the light at the end of the tunnel nigh? A review of ADPKD focusing on the burden of disease and tolvaptan as a new treatment. Int J Nephrol Renovasc Dis. 2018; 11: 53-67.