Kidney tubular health biomarkers identify patients with impaired attainment of intensive blood pressure targets: results from the SPRINT trial

Background/Introduction Resistance to antihypertensive therapy is common, particularly among individuals with chronic kidney disease (CKD). Clinical assessment of treatment resistance relies largely on markers of glomerular function and injury, which do not adequately capture abnormalities in kidney tubular integrity and function—key determinants of blood pressure (BP) regulation and response to therapy. Purpose To determine whether biomarkers of kidney tubular health are associated with BP treatment response among participants with CKD randomized to a systolic BP (SBP) target <120 mm Hg in the Systolic Blood Pressure Intervention Trial (SPRINT). Methods Among 1,272 SPRINT participants with CKD, 19 plasma and urinary biomarkers reflecting distinct domains of kidney tubular health and two cardio-renal biomarkers were measured at baseline. Associations were examined with three BP treatment response outcomes at 12 months: achievement of SBP <120 mm Hg; proportion of follow-up time with SBP <120 mm Hg; and number of antihypertensive medication classes required to achieve SBP <120 mm Hg. Models were adjusted for demographic and clinical characteristics, baseline eGFR, and urine albumin-to-creatinine ratio. False discovery rate correction was applied to account for multiple comparisons. Results Overall, the mean age of the participants was 73 years and 40% were female. The mean eGFR and SBP at baseline was 48 mL/min/1.73 m² and 140 mm Hg, respectively. Seven biomarkers met a false discovery rate threshold of <0.10 on at least one of the evaluated outcomes (Figure). The most consistent associations were observed for the composite tubular secretion score and NT-proBNP. Each 1-SD higher score (indicating better tubular secretory function) was associated with higher odds of achieving SBP <120 mm Hg at 12 months (OR 1.12; 95% CI 1.00–1.25), greater time in the target SBP range (OR 1.11; 95% CI 1.02–1.21), and fewer antihypertensive medication classes required (−4.9%; 95% CI −7.1 to −2.5). Each 1-SD higher NT-proBNP was associated with lower odds of SBP target attainment (OR 0.89; 95% CI 0.80–1.00), less time in target range (OR 0.89; 95% CI 0.81–0.98), and greater medication burden (5.9%; 95% CI 3.3–8.6). Other biomarkers demonstrated less consistent associations across outcomes. Conclusions Among individuals with CKD undergoing intensive BP treatment in SPRINT, biomarkers reflecting impaired tubular secretory function and neurohormonal activation were consistently associated with reduced attainment, durability, and greater treatment intensity required to achieve intensive SBP targets, independent of eGFR and albuminuria. Kidney tubular health biomarkers may capture physiologic determinants of BP control not reflected by traditional measures of glomerular function and help identify patients at risk for apparent treatment resistance.