Blood Pressure, Chronic Kidney Disease Progression, and Kidney Allograft Failure in Kidney Transplant Recipients: A Secondary Analysis of the FAVORIT Trial.

BACKGROUND: In chronic kidney disease, intensive systolic blood pressure (SBP) control reduces mortality at a cost of greater acute kidney injury risk. Kidney transplantation involves implantation of denervated kidneys and immunosuppressive medications that increase acute kidney injury risk. The optimal blood pressure (BP) target in kidney transplant recipients (KTRs) is uncertain. Prior observational studies from the Folic Acid for Vascular Outcome Reduction in Transplantation (FAVORIT) trial demonstrate associations of lower SBP levels and reduced mortality risk, but the relationship of BP with kidney allograft function remains unknown. Thus, in FAVORIT, we investigated the relationship of SBP and diastolic blood pressure (DBP) with risk of kidney allograft failure and estimated glomerular filtration rate (eGFR) slope among stable KTRs. METHODS: Cox proportional hazards and multivariable linear regression models adjusted for demographics, transplant characteristics, comorbidities, baseline eGFR, and urine albumin-to-creatinine ratio were used to determine associations of SBP and DBP with time to a composite kidney outcome of ≥50% eGFR decline or dialysis dependence, and with annualized eGFR change, respectively. Multivariable restricted cubic spline plots were developed to evaluate the functional form of the relationships. RESULTS: Among 3,598 KTRs, mean age was 52 ± 9 years, SBP was 136 ± 20 mm Hg, DBP was 79 ± 12 mm Hg, and eGFR was 49 ± 18 ml/minute/1.73 m2. There were 369 events of ≥50% eGFR decline or dialysis dependence during a mean follow-up of 4.0 ± 1.5 years. There was no association of either SBP (compared with SBP 120 to <130 mm Hg, hazard ratio (HR) for the SBP < 110 was 1.01 (95% confidence interval (CI) 0.60 to 1.70) and 130 to <140 was 0.89 (0.64 to 1.24)) or DBP (compared with DBP 70 to <80 mm Hg, HR for the DBP 60 to <70 was 1.00 (95% CI 0.74 to 1.34) and 80 to <90 was 0.90 (0.68 to 1.18)) with the kidney failure outcome or annualized eGFR slope, and, when examined using restricted cubic splines, there was no evidence of "J"- or "U"-shaped relationships. CONCLUSIONS: In a large sample of stable KTRs, we found no evidence of thresholds at which lower BPs were related to higher risk of allograft failure or eGFR decline. In light of prior findings of mortality benefit at low SBP, these observational findings suggest lower BP may be beneficial in KTRs. This important question requires confirmation in future randomized trials in KTRs.

Association of arterial rigidity with incident kidney disease and kidney function decline: the Health ABC study.

BACKGROUND AND OBJECTIVE: The association of large arterial rigidity and kidney function decline in longitudinal analyses is not well established. This study evaluated the association of aortic pulse wave velocity (aPWV) and pulse pressure (PP) with rapid kidney function decline and incident CKD in the Health, Aging and Body Composition study. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants were 2129 older adults with a baseline measurement of aPWV, PP, and cystatin C and at least one additional measurement of cystatin C, either at year 3 or year 10. Outcomes were rapid kidney function decline (estimated GFRcysC loss of >3 ml/min per 1.73 m(2) per year) and incident CKD (eGFRcysC < 60 ml/min per 1.73 m(2) in participants with baseline estimated GFR > 60 ml/min per 1.73 m(2)). Multivariate regression models were used to evaluate association of aPWV and PP with each outcome. RESULTS: Mean (SD) baseline estimated GFRcysC was 79±29 ml/min per 1.73 m(2). Median follow-up duration was 8.9 years. In multivariable analyses, aPWV was not associated with rapid decline (odds ratio [OR], 95% confidence interval [CI] 1.16, 0.89-1.52) but was associated with incident CKD (incident rate ratio [IRR], 95% CI, 1.39, 1.09-1.77) and PP was associated with both rapid decline (OR, 95% CI 1.10, 1.04-1.16) and incident CKD (IRR, 95% CI, 1.06, 1.01-1.11). CONCLUSIONS: Large arterial stiffness assessed by aPWV and pulsatility assessed by PP were associated with incident CKD among older adults. Pulsatility assessed by PP was associated with rapid kidney function decline and incident CKD. Future research should determine whether interventions targeting arterial rigidity will prevent CKD development and progression.