Achievement and Safety of a Low Blood Pressure Goal in Chronic Renal Disease

Abstract

The Modification of Diet in Renal Disease Study showed a beneficial effect of a lower-than-usual blood pressure (BP) goal on the progression of renal disease in patients with proteinuria. The purpose of the present analyses was to examine the achieved BP, baseline characteristics that helped or hindered achievement of the BP goals, and safety of the BP interventions. Five hundred eighty-five patients with baseline glomerular filtration rate between 13 and 55 mL/min per 1.73 m2 (0.22 to 0.92 mL/s per 1.73 m2) were randomly assigned to either a usual or low BP goal (mean arterial pressure < or = 107 or < or = 92 mm Hg, respectively). Few patients had a history of cardiovascular disease. All antihypertensive agents were permitted, but angiotensin-converting enzyme inhibitors (with or without diuretics) followed by calcium channel blockers were preferred. The mean (+/- SD) of the mean arterial pressures during follow-up in the low and usual BP groups was 93.0 +/- 7.3 and 97.7 +/- 7.7 mm Hg, respectively. Follow-up BP was significantly higher in subgroups of patients with preexisting hypertension, baseline mean arterial pressure > 92 mm Hg, a diagnosis of polycystic kidney disease or glomerular diseases, baseline urinary protein excretion > 1 g/d, age > or = 61 years, and black race. The frequency of medication changes and incidence of symptoms of low BP were greater in the low BP group, but there were no significant differences between BP groups in stop points, hospitalizations, or death. When data from both groups were combined, each 1-mm Hg increase in follow-up systolic BP was associated with a 1.35-times greater risk of hospitalization for cardiovascular or cerebrovascular disease. Lower BP than usually recommended for the prevention of cardiovascular disease is achievable by several medication regimens without serious adverse effects in patients with chronic renal disease without cardiovascular disease. For patients with urinary protein excretion > 1 g/d, target BP should be a mean arterial pressure of < or = 92 mm Hg, equivalent to 125/75 mm Hg.

Treatment of stage I hypertension and development of renal dysfunction

“…Adapted from Bakris et al 16 Modification of Dietary Protein in Renal Disease (MDRD) trial, clearly demonstrated that those with 1 gram or more of proteinuria and/or AfricanAmericans had slower rates of decline in GFR at blood pressure levels of Ͻ125/75 mm Hg as compared to Ͻ140/90 mm Hg. 13 In this and other trials that achieved a separation of at least 5 mm Hg in diastolic blood pressure levels, the rates of decline in renal function were slower, Figure 1. 16 Additionally, the number of antihypertensive medications needed to achieve these lower goals averaged 3.2 different medications, Figure 2.…”

“…2,12 African-American patients and those with diabetes have a higher likelihood of developing progressive renal disease than the general population. [12][13] Often end-stage renal disease (ESRD) in African-Americans is attributed to hypertensive nephrosclerosis. This might be due to poor hypertension control related to limited access to health care or some other factors.…”

“…17 Trials with primary renal endpoints in people with established renal disease such as the Ramipril Efficacy in Nephropathy (REIN), Angiotensin Converting Enzyme Inhibitor and Progressive Renal Insufficiency (AIPRI) and Modification of Dietary Protein in Renal Disease (MDRD) trials, as well as other smaller trials, establish the ability of antihypertensive therapy to slow the progression of nondiabetic renal disease. 13,16,18,19 Two separate studies and a meta-analysis in patients with non-diabetic renal disease further emphasise the point that the level of blood pressure reduction rather than the antihypertensive agent used determines renal protection. [20][21][22] A doubleblind, prospective trial in patients with non-diabetic renal disease followed for an average of 3. years demonstrated no difference in the slope of GFR decline between ACE inhibitor and beta-blocker treatment despite comparable blood pressure control.…”

Prevention of Hypertension and Its Complications

“…An important study in this regard is the Modification of Diet in Renal Disease Study (MDRD) in 585 persons with directly measured GFR between 13 to 55 ml/min per 1.73 m 2 aged 18 to 70 yr who were randomized to either a low goal BP (mean arterial pressure [MAP] Յ92 mmHg) or a usual goal BP (Յ107 mmHg); these respective goals were adjusted upward for persons Ն61 yr of age to MAP Յ98 mmHg or Յ113 mmHg (34,61). Actual attained MAP in the low and usual BP groups was 93 and 97.7 mmHg, respectively, over the mean follow-up of 2.2 yr. No particular hypertension drugs were emphasized.…”

“…Other strategies to lower urinary protein excretion include dietary sodium restriction (66,67) as well cessation of cigarette smoking (68,69) and weight loss (70,71). Reductions in urinary protein excretion correlate with slower loss of kidney function (32,34,63). The clinician should be aware that attainment of low target BP levels (Ͻ130 to 135/80 to 85 mmHg) will be accomplished only with prescription of multiple (typically 3 to 4), not solitary, antihypertensive drugs (72).…”