SBP Visit-to-Visit Variability Associated with Kidney Disease Outcomes

GettyImages_460532755There is an independent association between variability visit-to-visit in systolic blood pressure (SBP) and hard kidney disease outcomes in diabetic patients with nephropathy. That was the primary finding of an observational analysis conducted recently by Ciaran J. McMullan, MD, MMSc, and colleagues. The researchers reported their findings in the American Journal of Kidney Diseases [2014;64(5):714-722].

It has been demonstrated that in populations without kidney disease a greater degree of temporal variability in the SBP measured at outpatient visits is a predictor of increased overall mortality and cardiovascular events. In patients with decreased kidney function, there appears to be greater SBP visit-to-visit variability.

There have been few studies designed to assess the association of visit-to-visit variability in SBP and clinically relevant kidney disease outcomes. This study was designed to determine whether SBP visit-to-visit variability had independent associations with renal and cardiovascular events in patients with nephropathy due to type 2 diabetes. The participants were enrolled in either IDNT (Irbesartan Diabetic Nephrology Trial) or the RENAAL (Reduction of End Points in Non—Insulin-Dependent Diabetes with the Angiotensin II Antagonist Losartan) study.

IDNT and RENAAL were large, randomized, placebo-controlled, double-blind trials to assess the efficacy of an angiotensin receptor blocker (ARB: irbesartan in IDNT and losarstan in RENAAL) in the prevention of hard kidney disease outcomes in patients with type 2 diabetes and nephropathy.

Of the 3228 adult patients with type 2 diabetes and nephropathy who participated in the two studies, the current analysis included 2739 individuals randomly assigned to the study. Inclusion criteria were complete blood pressure readings from follow-up visits at 3, 6, 9, and 12 months following randomization. Individuals with an event prior to the 12-month visit were excluded.

The analysis kidney disease outcome was defined as time to confirmed doubling of serum creatinine level, end-stage renal disease, or death. The cardiovascular outcome was defined as time to cardiovascular death, myocardial infarction, stroke, hospitalization for heart failure, or revascularization.

Mean SBP visit-to-visit variability in the placebo group was 12.4 mm Hg. In the ARB group, the mean was similar (12.2 mm Hg); among those receiving amlodipine, however, it was significantly lower (10.6 mm Hg; P<.001). There was minimal change in visit-to-visit SBP variability among individuals in the placebo group; it was markedly reduced in those receiving amlodipine. From 3 months onward, there was no substantial change in SBP visit-to-visit variability.

Participants in the RENAAL study had higher SBP visit-to-visit variability than those in IDNT. Higher baseline, 12-month, and mean SBPs also were associated with higher visit-to-visit variability. Higher baseline and 3- to 12-month mean but not 12-month urine albumin-creatinine ratios were also associated with higher SBP visit-to-visit variability.

Higher baseline, 12-month, and 3- to 12-month mean estimated glomerular filtration rates were associated with lower SBP visit-to-visit variability. There was a significant association between a greater number of antihypertensive medications used at baseline and higher SBP visit-to-visit variability.

Survival curves for low, moderate, and high tertiles of SBP visit-to-visit variability for kidney disease end points, both composite and individual), and all-cause mortality were significantly different (all log-rank P<.05). The cumulative incidence of events increased with increasing tertile. However, there was no difference among tertiles in the cumulative incidence of cardiovascular mortality and of the composite of cardiovascular outcome.

Following adjustment for potential confounders, every 1-standard deviation increment in SBP visit-to-visit variability was associated significantly with increased risk of composite kidney disease end points (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.01-1.16; P=.02). Of individual components of the composite kidney disease end points, ESRD (HR, 1.12; 95% CI, 1.02-1.22; P=.02) and all-cause mortality (HR, 1.16; 95% CI, 1.04-1.29; P=.007) showed a significant relation. Doubling of serum creatinine level was directionally similar but not significant (HR, 1.16; 95% CI, 1.00-1.19; P=.06).

The HR for the association of higher SBP visit-to-visit variability and cardiovascular mortality was 1.15, but the result was not statistically significant. There were no statistically significant associations between SBP visit-to-visit variability and stroke or the composite of all cardiovascular events.

The researchers cited the observational study design with the potential for confounding as a limitation to the analysis.

In conclusion, the researchers said, “Higher SBP visit-to-visit variability is associated with adverse kidney disease outcomes and overall mortality in patients with type 2 diabetes and nephropathy independent of antihypertensive medication and baseline kidney function. Further studies are required to elucidate whether modification of SBP visit-to-visit variability can reduce the progression of both kidney and cardiovascular disease.”

Takeaway Points

  1. This study was designed to determine whether SBP visit-to-visit variability had independent associations with renal and cardiovascular events in patients with nephropathy due to type 2 diabetes.
  2. Higher baseline and 3- to 12-month mean but not 12-month urine albumin-creatinine ratios were also associated with higher SBP visit-to-visit variability.
  3. Following adjustment for potential confounders, every 1-standard deviation increment in SBP visit-to-visit variability was associated significantly with increased risk of composite kidney disease end points.