Predialysis Systolic Blood Pressure and Risk of All-Cause Mortality Postdialysis

The incidence of end-stage renal disease (ESRD) among individuals with chronic kidney disease (CKD) is high, despite advances in the understanding of CKD progression. Patients with CKD not dependent on dialysis who transition to ESRD have the highest mortality within the first few months following the transition to dialysis therapy. Those patients also have exceptionally high healthcare costs and burden. Identifying modifiable risk factors and interventions during the period prior to the transition to dialysis could lessen the adverse outcomes in this vulnerable population.

In the general population, a common risk factor for cardiovascular disease and death is hypertension; however, low blood pressure has been associated with mortality in patients on dialysis therapy. Some studies have suggested a J-shaped association between systolic blood pressure and mortality in patients with non–dialysis-dependent CKD. Current clinical guidelines suggest a target blood pressure <140/90 or <130/80 mm Hg for patients with CKD, depending on age, severity of albuminuria, and comorbid conditions. However, there are few data on the association between blood pressure and mortality in patients with advanced non–dialysis-dependent CKD, including those transitioning to maintenance dialysis therapy.

Keiichi Sumida, MD, and colleagues conducted an observational study designed to examine the associations of systolic and diastolic blood pressure in the period of transition to dialysis therapy with postdialysis all-cause mortality in a large, nationally representative cohort of US veterans transitioning to dialysis therapy. The researchers reported results of the study in the American Journal of Kidney Diseases [2017;70(2):207-217].

The primary outcome of interest was all-cause mortality postdialysis, assessed over different follow-up periods: <3, 3 to <6, 6 to <12, and ≥12 months following initiation of dialysis therapy. Cox regression analyses adjusted for demographics, comorbid conditions, medications, cardiovascular medication adherence, body mass index, estimated glomerular filtration rate, and type of vascular access were conducted.
The data analyzed were from the TC-CKD (Transition of Care in CKD) study. TC-CKD was a retrospective cohort study that included veterans in the United States with CKD who transitioned to chronic kidney failure requiring renal replacement therapy; data from October 1, 2007, through September 30, 2011, were analyzed. The primary exposure of interest were systolic blood pressure and diastolic blood pressure averaged over the 1-year period prior to initiation of dialysis.

The cohort included 17,729 patients. Of those, 98% were men (n=17,388), mean age at baseline was 73.7 years, 31.4% were African American (n=5559), and 73% (n=12,941) had diabetes. Median estimated glomerular filtration rate (eGFR) prior to dialysis initiation was 11.0 mL/min/1.73 m2. There were a median of 10 outpatient blood pressure measurements per patient: mean systolic blood pressure was 141.2 mm Hg and mean diastolic blood pressure was 73.7 mm Hg.

Those with higher systolic blood pressure were younger, more likely to be African American, and had a higher prevalence of diabetes and lower prevalence of other comorbid conditions compared with patients with lower systolic blood pressure. Participants in the higher systolic blood pressure group were also more likely to be prescribed antihypertensive medications, less likely to be adherent to cardiovascular medications, and had lower levels of serum albumin, blood hemoglobin, and eGFR.

Median follow-up was 2.0 years. During that time, following initiation of dialysis therapy (total time at risk, 37.969 patient-years), there were 9064 all-cause deaths (crude incidence rate, 238.7; 95% confidence interval [CI], 233.9-243.7) per 1000 patient-years. Among the 9064 deaths, 1515 occurred in the first 3 months following initiation of dialysis therapy, 1097 in 3 to <6 months, 1529 in 6 to <15 months, and 4923 in ≥12 months after dialysis therapy initiation.

Following adjustment for possible confounders, there was an inverse association between category of systolic blood pressure and all-cause mortality: adjusted hazard ratios (HRs) of systolic blood pressure <120, 120 to <130, and 130 to <140 (compared with 140 to <150) mm Hg were 2.40 (95% CI, 1.96-2.93), 1.99 (95% CI, 1.66-2.40), and 1.35 (95% CI, 1.13-1.62), respectively. There was a nonsignificant lower risk for mortality associated with systolic blood pressure categories of ≥150 mm Hg. The highest risk of death was observed in patients with systolic blood pressure <120 mm Hg.

There was no consistent association seen between predialysis diastolic blood pressure and risk of mortality following initiation of dialysis therapy.

Limitations to the study cited by the authors included the observational design, which precluded the establishment of cause-effect relationships and created the inability to conclude that the mortality risk associated with various systolic blood pressures equals the risk associated with the same systolic blood pressures when they occur as a result of antihypertensive interventions in clinical practice. Further, because most of the participants were male US veterans, the results may not be generalizable to women or patients from other geographic areas.

The researchers said, “In this large national cohort of US veterans transitioning to dialysis therapy, we found a reverse J-shaped association of predialysis systolic blood pressure with all-cause mortality following dialysis therapy initiation, with significantly higher death risk seen with systolic blood pressures <140 mm Hg, but found no consistent association with predialysis diastolic blood pressure. Our findings suggest that pretransition low systolic blood pressure could be a useful predictor of early post-transition mortality, and also that physicians should be cautious when substantially lowering systolic blood pressure below the currently established targets in this unique patient population. Future clinical trials are needed to clarify the ideal predialysis systolic blood pressure and determine whether active interventions targeting predialysis systolic blood pressure could be applied to improve the high early mortality seen among incident dialysis patients.”

Takeaway Points

  • Researchers conducted an observational study among a cohort of US veterans with chronic kidney disease during the transition period to end-stage renal disease to examine the association between blood pressure prior to initiation of dialysis therapy and mortality following dialysis initiation.
  • There was a reverse J-shaped association between systolic blood pressure and post-dialysis mortality; the mortality risk was significantly higher with systolic blood pressure <140 mm Hg.
  • The mortality risks associated with lower systolic blood pressure were greatest in the first 3 months following initiation of dialysis therapy.