About Autosomal Dominant Polycystic Kidney Disease

Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a life-threatening genetic progressive kidney disease affecting many individuals in all parts of the world. Cardiovascular disease is the leading cause of premature mortality in patients with ADPKD, with over 80% of deaths attributable to coronary artery diseases.

How Hyperuricemia and Hypertension Contribute to ADPKD

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 reduced kidney function. Hyperuricemia and hypertension are considered independent risk factors predicting poorer prognosis in ADPKD patients. Hypertension is present in about half of all patients ages 24-30, and in all patients who reach kidney failure.

The high prevalence of hypertension is considered to contribute to the excess risk of cardiovascular disease in ADPKD patients. Experimental data from animal studies suggest that processes such as inflammation, the renin-angiotensin-aldosterone system, insulin resistance, and endothelial dysfunction may be involved in the pathogenesis of the disease.

This combination of risk factors is not unlike those observed in models of hyperuricemia and may directly contribute to the vascular pathology seen in these patients, or may be pathway factors via which hypertension leads to kidney disease progression and further cardiovascular disease. Moreover, 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.

Providing ADPKD Patients with New Opportunities

The goals of our 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 stringent blood pressure control using various inhibitors of the renin-angiotensin-aldosterone system (RAAS) 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. Kidney transplantation or dialysis may be the only options available once end-stage renal disease develops. Insulin resistance and diabetes are also serious concerns for patients with ADPKD.