Intensive Blood Pressure Control and Kidney Injury Markers: ACCORD Trial Subset Analysis

The SPRINT (Systolic Blood Pressure Intervention Trial) found a reduction in cardiovascular events in participants randomly assigned to a systolic blood pressure <120 mm Hg compared with those randomly assigned to standard treatment (systolic blood pressure <140 mm Hg). Those findings have increased efforts across the healthcare spectrum for aggressive blood control. However, over time, aggressive blood pressure control may result in unintended negative consequences, such as higher risk for acute and chronic kidney disease.

Recent reports have highlighted the increased risk for incident chronic kidney disease (CKD) in SPRINT participants in the intensive arm versus the standard care arm. There has also been an association between the magnitude of reduction in mean arterial pressure in the intensive arm and the risk for incident CKD. However, the significance of the type of CKD is unclear, and the reduction in cardiovascular risk outweighs the risk of CKD progression.

There are no clear findings on the optimal level of blood pressure control in patients with CKD to prevent progression to end-stage renal disease. Further, there are few data available on intensive blood pressure control and progression of kidney disease in patients with diabetes. Diabetes was an exclusion criterion in SPRINT due to the overall null results in the ACCORD (Action to Control Cardiovascular Risk in Diabetes) study, leaving open the question whether more intensive blood pressure control in patients with type 2 diabetes leads to kidney injury.

Researchers, led by Girish N. Nadkarni, MD, MPH, CPH, recently conducted a longitudinal analysis of a subgroup of ACCORD (ACCORD-BP) participants to examine changes in estimated glomerular filtration rates (eGFR) in conjunction with four urinary biomarkers representing kidney injury: kidney injury molecule 1 (KIM-1) and interleukin 18 (IL-18), inflammation (monocyte chemoattractant protein 1 [MCP-1]), and fibrosis (human cartilage glycoprotein 39 (YKL-40). A fifth biomarker of inflammation (monocyte chemoattractant protein) was also included.  Results were reported in the American Journal of Kidney Diseases [2019;73(1):31-38].

There were 529 participants in the ACCORD-BP group. Of those, 260 had been randomly assigned to the intensive blood pressure arm (systolic blood pressure target, <120 mm Hg) and 269 to the standard blood pressure arm (systolic blood pressure target, <140 mm Hg). At baseline, mean age of the overall cohort was 62 years and mean estimated glomerular filtration rate (eGFR) was 90 mL/min/1.73 m².

In the intensive arm, mean eGFR declined by 17% from baseline to 2 years (from 85.9 to 70.7 mL/min/1.73 m²) and by 9% in the standard arm (from 85.4 to 79.7 mL/min/1.73 m²). In the intensive arm versus the standard arm, the albumin-creatinine ratio was 30% lower at year 2 (12.7 vs 18.1 mg/g; P=.004).

In the intensive arm versus the standard arm, the four urinary biomarkers were unchanged or lower at year 2. All four levels trended lower in the intensive arm compared with the standard arm; this finding reached statistical significance for IL-18 (decrease of 14%; P=.04). Among patients in the intensive arm who had larger declines in eGFR, there were significant trends for a larger reduction in IL-18 (P for trend=.01) and YKL-40 levels (P for trend=.07).

Seventy-six patients in the intensive arm experienced incident CKD, defined as sustained 30% decline in eGFR and eGFR <60 mL/min/1.73 m²; among those patients, there was a mean eGFR decrease of 31% (from 8.7 to 5.9 mL/min/1.73 m²). Despite now meeting the definition for incident CKD, none of the urinary biomarker levels increased over time in that subpopulation. There were 27 patients in the standard arm who developed incident CKD; those patients had a mean eGFR decrease of 35% and one of the five biomarker levels increased (IL-18 increased by 7.1%).

Limitations to the study cited by the researchers included the small proportion of participants with baseline CKD; a single measurement of serum creatinine and thus a single eGFR value, both at baseline and at 24 months; the possibility of selection bias; and the inability of determine whether there were intercurrent episodes of acute kidney injury in the study cohort.

In conclusion, the researchers said, “Among a subset of ACCORD-BP trial participants, intensive blood pressure control was associated with reductions in eGFRs, but not with an increase in injury marker levels. These findings support that eGFR decline observed with intensive blood pressure goals in ACCORD participants may predominantly reflect hemodynamic alterations.”

Takeaway Points

1. Patients assigned to intensive blood pressure control in the ACCORD-BP trial experienced more rapid decline in estimated glomerular filtration rate (eGFR); it is unknown whether the decline reflected hemodynamic effects or intrinsic kidney damage.
2. Researchers conducted a longitudinal analysis of a subgroup of 529 ACCORD-BP participants to examine changes in eGFR from baseline to 2 years.
3. There was an association between intensive blood pressure control and reductions in eGFRs; however, there was no association with an increase in injury marker levels, suggesting the decline in eGFR may predominately reflect hemodynamic alterations.