Hypertension in Autosomal Dominant Polycystic Kidney Disease

Abstract

Hypertension is common and occurs in a majority of autosomal dominant polycystic kidney disease (ADPKD) patients prior to loss of kidney function. Hypertension relates to progressive kidney enlargement, and is a significant independent risk factor for progression to end stage renal disease. The pathogenesis of hypertension in ADPKD is complex and dependent on many factors that influence each other. Pkd1 and Pkd2 expression levels are highest in the major vessels and are present in the cilia of endothelial cells and in vascular smooth muscle cells. Decreased or absent polycystin 1 or 2 expression is associated with abnormal vascular structure and function. Pkd1/Pkd2 deficiency results in reduced nitric oxide (NO) levels, altered endothelial response to shear stress with attenuation in vascular relaxation. 10–20% of ADPKD children demonstrate hypertension and the majority of adults are hypertensive before any loss of kidney function. Cardiac abnormalities such as left ventricular hypertrophy and carotid intimal wall thickening are present prior to the development of hypertension in ADPKD. Activation of the renin-angiotensin-aldosterone system occurs in ADPKD due to decreased NO production as well as bilateral cyst expansion and intra-renal ischemia. With increasing cyst size, further activation of the RAAS occurs, blood pressure increases and a vicious cycle ensues with enhanced cyst growth and hypertension ultimately leading to ESRD. Inhibition of the angiotensin aldosterone system is possible with angiotensin converting enzyme inhibitors and angiotensin receptor blockers. However, interventional studies have not yet demonstrated benefit in slowing progression to renal failure in ADPKD. Currently, large multicenter studies are being performed to determine the beneficial effects of RAAS inhibition both early and late in ADPKD.

Copeptin, a Surrogate Marker of Vasopressin, Is Associated with Disease Severity in Autosomal Dominant Polycystic Kidney Disease

“…A reduction of renal blood flow parallels the increase in TRV and, importantly, precedes GFR decline and predicts structural and functional disease progression (26). Several studies show that in ADPKD, albuminuria is associated with renal volume (27,28), mean arterial BP, filtration fraction (28), renal growth, and slope of GFR (26). In our study, the different markers for disease severity correlated reasonably well with each other.…”

Effect of Pravastatin on Total Kidney Volume, Left Ventricular Mass Index, and Microalbuminuria in Pediatric Autosomal Dominant Polycystic Kidney Disease

“…There has been a marked decrease in the prevalence of left ventricular hypertrophy in adults with ADPKD in the current era with improved control of hypertension and widespread use of ACEIs (46,47). There was no effect of pravastatin on UAE; with repeated study, this marker appears to have minimal predictive value in children with ADPKD compared with affected adults (4,48). There was no effect of pravastatin on CrCl or proteinuria in this research study.…”

Kidney Volume and Functional Outcomes in Autosomal Dominant Polycystic Kidney Disease

“…Blood and urine samples were obtained for determination of serum creatinine, electrolytes, PKD genotype, urinary albumin (27), monocyte chemotactic protein-1 (MCP-1) excretion (28), and iothalamate clearance. Serum creatinine values were validated by the Cleveland Clinic.…”