Autosomal dominant polycystic kidney disease: genetics, epidemiology, and treatment

Abstract

Abstract:Autosomal dominant polycystic kidney disease (ADPKD) is the most common potentially lethal genetic disorder, accounting for 2%-8% of end-stage renal disease worldwide. While development of renal cysts is the major characteristic of ADPKD, several disease-related complications contribute significantly to morbidity and mortality. Since introduction of renal replacement therapies, cardiovascular disease is the leading cause of death among ADPKD patients. Loss of renal function requiring renal replacement therapy occurs in 50% of patients by the age of 60 years. The results of recent large epidemiological studies in ADPKD have shown little progress in delaying onset of renal failure despite an improvement in patient mortality. Significant progress has been made over the past decade in elucidating the genetics of the disorder. Genetic testing is now available in most countries, and development of more reliable methods for prenatal diagnosis of ADPKD has increased the sensitivity of testing. While there are no approved drugs for treatment of ADPKD within the USA, the first agent targeting renal disease progression in this disorder was recently approved for clinical use in Japan. Furthermore, several additional drugs for treatment of ADPKD are currently under clinical investigation. Overall, this presents an optimistic future for new therapeutic interventions in this disease. This paper reviews the current knowledge related to the epidemiology, genetics, and treatment of ADPKD.

Hypertension in adult polycystic kidney disease: a narrative review

“…ADPKD is a genetic disease and mutations in the PKD1 (chromosome 16p13.3) and PKD2 genes (chromosome 4q21) are the chief determinants (8). Symptoms can differ, yet HTN occurs in more than half of the patients prior to the functional impairment (9).…”

“…Based on these facts, the management of progressive disease relies heavily on early detection and control of BP. The goals of antihypertensive agents are to decrease total kidney volume (TKV), block the RAAS, and delay the progression of renal failure (8). Based on pathophysiological considerations, RAAS inhibitors, including angiotensin-converting enzyme inhibitors (ACE-I), angiotensin II receptor blockers (ARBs), are known to be the first choice in preventative therapy and management as well (19).…”

Extensive Inter-Cyst DNA Methylation Variation in Autosomal Dominant Polycystic Kidney Disease Revealed by Genome Scale Sequencing

“…Ultimately, disease progression results in kidney enlargement, leading to end-stage kidney disease typically by the sixth decade (Braun, 2009). While ADPKD is the most common heritable renal disease in humans, affecting an estimated 1-5 in 10,000 patients (Solazzo et al, 2018), treatment options for this disease are limited as there is still little understanding about the underlying cause of cystogenesis (Tan et al, 2011;Reed-Gitomer, 2014).…”

“…However, in atypical presentations of ADPKD, disease-causing mutations have also been reported in GANAB (Porath et al, 2016) and DNAJB11 (Cornec-Le Gall et al, 2018). It is generally accepted that each ADPKD cyst arises by means of focal proliferation (Reed-Gitomer, 2014), where a single cell will acquire altered growth characteristics, rapidly proliferate and form a distinct cyst.…”