Hypertension is common in most chronic progressive kidney diseases. However, the pathogenesis is somewhat different in autosomal dominant polycystic kidney disease (ADPKD).
Hypertension is a common early finding in ADPKD, occurring in 50 to 70 percent of cases before any significant reduction in glomerular filtration rate within an average age onset of 30 years of age [1-3]. However, the tendency to develop hypertension and its complications begins even earlier (eg, left ventricular hypertrophy) . Affected young adults have a higher ambulatory blood pressure and left ventricular mass index than age-matched controls, even though the values remain within the normal range [5,6]. This raises the possibility that treatment of normotensive ADPKD patients may be beneficial.
Increased activity of the renin-angiotensin system (RAS) and extracellular volume expansion are often present early in ADPKD (ie, prior to elevation in the serum creatinine) and may play an important role in the rise in blood pressure . It has been suggested that cyst expansion, leading to focal areas of renal ischemia and enhanced renin release, is largely responsible for at least the initial rise in blood pressure [1,2]. Two observations are compatible with this hypothesis:
- Renin-containing cells are present in the attenuated arteries in the walls of the cysts and in cells in the connective tissue surrounding cysts [8,9]. Renin can also be produced by the epithelial cells lining the cysts and active renin is often present within the cyst fluid . Renin may directly promote epithelial cell hyperplasia and cyst growth, since angiotensin II is a growth factor.
- The degree of early hypertension varies with the degree of structural change, as patients with normal serum creatinine with an elevated blood pressure tend to have a higher total cyst volume than those who are normotensive .
The role of sodium retention and vasoactive hormones in the genesis of hypertension are less clear. Although aldosterone and vasopressin levels may be elevated in hypertensive ADPKD patients, and patients with ADPKD may be slightly volume expanded, their plasma volume is similar to normotensive patients with ADPKD [1,7,11]. The circulating levels of prostaglandins and norepinephrine are not different between hypertensive and normotensive patients . Importantly, measurement of renal blood flow utilizing PAH clearance techniques or breath held MR angiography demonstrate a relative decline in total renal blood flow that correlates with cyst burden (kidney volume) that responds to inhibition of the renin angiotensin system. Renal blood flow, similar to hypertension, is a risk factor for progressive renal disease in ADPKD .