Progress on Autosomal Dominant Polycystic Kidney Disease

Abstract

Introduction: Autosomal dominant polycystic kidney disease (ADPKD) is the most common life threatening hereditary disease of the kidney. It is a systemic disease characterized by multiple, bilateral renal cysts that result in massive renal enlargement and progressive functional impairment. This review discusses the current understanding of the epidemiology, genetics, clinical manifestations, natural history of the disease, the accuracy and reliability of diagnostic approaches, renal replacement therapy and emerging therapeutic strategies that are being evaluated in ADPKD.
Review: ADPKD is a genetically heterogeneous disease with significant inter-familial and intra-familial variability. The responsible genes were localized to separate loci on chromosome 16 (PKD1 gene) accounting for the majority of ADPKD cases, and chromosome 4 (PKD2 gene) accounting for the remainder. Each child of an affected parent has a 50% chance of inheriting the mutated gene, which is completely penetrant. Clinical manifestations include renal and cyst enlargement, impaired urine concentration capacity, hematuria, nephrolithiasis, proteinuria, hypertension, polycystic liver disease, abdominal wall hernia and intracranial aneurysms. The diagnosis of ADPKD usually relies on renal imaging. Ongoing research has engendered crucial insight into the disease’s underlying genetic, cellular and pathogenetic mechanisms and made possible the design and implementation of clinical trials testing promising treatments. Renin Angiotensin Aldosterone System (RAAS) blockade, vasopressin antagonists, somatostatin, rapamycin, sirolimus and everolimus are currently being evaluated for a potential therapeutic role in the management of ADPKD.
Conclusion: Current clinical trials investigating multiple therapeutic targets bring hope for treatments that may impede the progression of ADPKD.

Keywords: ADPKD, autosomal dominant polycystic kidney disease, kidney failure