Autosomal Dominant Polycystic Kidney Disease


Autosomal Dominant Polycystic Kidney Disease (ADPKD) is one of the most common life-threatening genetic diseases, affecting many individuals in all parts of the world. ADPKD is a progressive kidney and cardiovascular disease. Cardiovascular disease is the leading cause of premature mortality in patients with ADPKD, with over 80% of deaths attributable to coronary artery diseases (1, 2). Patients at greatest risk are those who have high serum uric acid (hyperuricemia) and high blood pressure (hypertension).

Hyperuricemia and hypertension are frequently early events in the progression of ADPKD and accompany the development of kidney cyst growth and kidney volume expansion. Together these precede the development of reduce kidney function. Hypertension is present in about half of all patients ages 24-30, and in all patients who reach kidney failure (3). The high prevalence of hypertension is considered to contribute to the excess risk of cardiovascular disease in ADPKD patients (4-6). Experimental data from animal studies suggests that process such as inflammation, renin-angiotensin-aldosterone system, insulin resistance and endothelial dysfunction may be involved in the pathogenesis of the disease (7, 8). This combination of risk factors is not unlike those observed in models of hyperuricemia and may directly contribute to vascular pathology seen in these patients or may be pathway factors via which hypertension leads to kidney disease progression and cardiovascular disease (9-13). Recently, the causative effect of high serum uric acid on high blood pressure in new onset hypertension has been reported, in the peer reviewed journal, ‘Hypertension’, by Feig et al.

The goals of treatment of ADPKD are to slow the progression of kidney damage and control related complications. Varied therapeutic strategies targeting ADPKD have been explored such as tight blood pressure control (14) using various inhibitors of the renin angiotensin aldosterone system (RAAS) (15) as well as preventing the progressive decline of glomerular filtration rate (GFR) – HALT trial. None of these therapies so far appear to slow the progression of kidney disease due to ADPKD. Transplantation or dialysis my be the only options available once end-stage renal disease develops. Insulin resistance and diabetes are also serious concerns for patients with ADPKD.