Hypertension Guidelines Still Leave Room for Clinical Judgment

Guidelines for hypertension have converged on a blood pressure target of less than 140/90 mm Hg for most individuals with chronic kidney disease (CKD). However, studies still need to clarify optimal BPs for advanced disease and optimal cardiovascular prevention. Therefore, clinical judgment is still required, said Matthew Weir, MD, Director of the Division of Nephrology, University of Maryland Hospital and Professor of Medicine at the University of Maryland School of Medicine.

Weir’s presentation wrapped up an update of hypertension guidelines at Kidney Week on November 15, 2014, in Philadelphia. The overriding principle for lowering blood pressure (BP) in patients with CKD, he said, is the prevention of cardiovascular events. At the most basic level, this means kidney function and glomerular filtration rate (GFR) need to be protected.

Weir briefly reviewed the structure and function of the glomerulus: the afferent arteriole, he said functions as a gatekeeper, ensuring that the glomerulus receives 1/3 to 1/2 systemic BP. The efferent arteriole is responsible for maintaining adequate outflow, but its function may be affected by glomerulosclerosis.

Thus, determinants of hypertensive renal damage can include systemic BP load, intrarenal blood pressures, and BP-independent effects of antihypertensives. Hypertension’s effect on the kidney also has a number of endogenous mediators, such as the renin-angiotensin-aldosterone system and TGF-B. Specific antihypertensives may act on these mediators in addition to having direct BP-lowering properties, a factor to take into consideration when comparing findings from studies using different classes of medication.

Moving to a brief review of the three major studies supporting current hypertension guidelines, Weir began by sharing data from the large Modification of Diet in Renal Disease (MDRD) study, which also tracked the effect of BP on GFR and proteinuria. Lower BPs were associated with a slower overall rate of decline of GFR only for those patients who hadgreater proteinuria (>1 g/24 hrs),

The Ramipril Efficacy in Nephropathy (REIN-2) study specifically addressed BP control for renal protection in CKD, but excluded individuals with diabetes. All individuals in this relatively small (n=338) study received an angiotensin-converting enzyme inhibitor (ACEI), then therapy intensification with a calcium-channel blocker (CCB) if needed. Participants were randomized to “conventional” (diastolic <10 mm Hg) or “intensified” (systolic/diastolic <130/80 mm Hg) target BPs. After a mean 19 months, there was no difference in progression to end-stage renal disease (ESRD) between the two arms. Weir noted, however, that the study may not have been powered to detect a difference in outcomes.

Finally, the African-American Study of Kidney Disease and Hypertension (AASK) addressed the effect of medication choice and BP targets on the rate of GFR decline in those with CKD. AASK randomized 1,094 patients to either a CCB, an ACEI, or a beta blocker as first-line therapy, and then further randomized participants to one of two treatment groups: either a usual BP target (mean arterial pressure [MAP] ≤ 92 mm Hg), or a more aggressive target (MAP ≤ 102 mm Hg). Following up for a median 3.8 years, investigators found no significant difference in GFR decline or all-cause mortality between the two levels of treatment intensity.

Further key information from AASK, Weir said, is that the homozygous apoprotein L1 (APOL1) gene is a powerful factor for the progression of renal disease, and future therapy development in this population should target the effects of APOL1 polymorphism.

Summarizing recommendations from these studies and their meta-analyses — which all have limitations – Weir said that overall, he believes the evidence supports a lower blood pressure goal for individuals with more severe CKD. He cautioned providers to be careful interpreting currently available data and recommendations; looking forward, he noted that the ongoing Systolic Blood Pressure Intervention Trial (SPRINT) should provide the “gold standard” for answering the question of optimal BP control. This prospective, controlled trial plans to enroll more than 9,000 participants, who will be randomized to two levels of blood pressure control and followed for four to eight years.