Review: Autosomal Dominant Polycystic Kidney Disease: Role of the Renin-Angiotensin System in Raised Blood Pressure in Progression of Renal and Cardiovascular Disease

Abstract

Raised blood pressure (BP) is extremely common in individuals with autosomal dominant polycystic kidney disease (ADPKD) and is almost invariably raised once they develop renal failure. The underlying mechanisms for the rise in BP in individuals with ADPKD are unclear. The progressive number and enlargement of renal cysts, causing structural damage to the kidneys and, thereby, affecting tubular function as well as causing distortion of the glomeruli and renal ischaemia, is likely to be of primary importance.There is some evidence from animal models that there may be over-activity of the intra-renal renin-angiotensin system (RAS) that could account for the rise in BP. Studies in man have shown conflicting results, but a recent more carefully controlled study using both measurements of activity and pharmacological blockade of the RAS clearly demonstrated no evidence of over-activity of the circulating RAS in ADPKD compared to matched individuals with essential hypertension.A more likely explanation for the rise in BP that occurs in ADPKD is retention of sodium and water due to tubular damage. Disappointingly, in spite of good evidence that RAS blocking drugs slow the progression of other renal, particularly glomerular, diseases, there is little evidence to suggest this is true for patients with ADPKD. Nevertheless, there is no doubt that lowering BP in ADPKD is just as important, if not more important, as in essential hypertension to prevent cardiovascular disease and strokes, with a recommended BP target of < 120/80 mmHg.

Improved Prognosis in Patients with Autosomal Dominant Polycystic Kidney Disease in Denmark

“…With the introduction of newer antihypertensive treatments such as the ACEIs, it seems that more patients with ADPKD reach BP control (24), and this may influence the age at onset of ESRD in these patients (15). Whether treatment with either an ACEI or angiotensin receptor blocker is superior to other antihypertensive drugs in slowing disease progression in ADPKD has not been clearly demonstrated (25,26).…”

A metabolomics approach using juvenile cystic mice to identify urinary biomarkers and altered pathways in polycystic kidney disease

“…Elevated levels of adenosine, which we consider a potential PKD biomarker, may be indicative of either a baseline increase in cAMP synthesis, rapid turnover of cAMP, or both. In addition, individuals with PKD show increased activity of the renin-angiotensin-aldosterone system (25). Aldosterone regulates sodium transport in part by stimulating S-adenosyl-homocysteine-hydrolase.…”

Molecular Pathways and Therapies in Autosomal-Dominant Polycystic Kidney Disease

“…Greater than 60% of PKD patients develop early HTN, which promotes cardiovascular disease and is a predictor for ESRD and increased mortality (17, 34). The mechanism for early onset HTN in PKD is unknown, but activation of the intrarenal renin-angiotensin-system (RAS) is considered to play an important role (57,67,138). In a pkd1-deficient mouse that has preserved GFR, the presence of cyst growth was essential for the development of early HTN in PKD mediated by activation of the intrarenal RAS (33).…”