On-Treatment Blood Pressure and Long-Term Outcomes in Chronic Kidney Disease

Hae Hyuk Jung

Disclosures

Nephrol Dial Transplant. 2022;37(6):1088-1098. 

In This Article

Abstract and Introduction

Abstract

Background: The treatment blood pressure (BP) target in chronic kidney disease (CKD) remains unclear, and whether the benefit of intensive BP-lowering is comparable between CKD and non-CKD patients is debated.

Methods: Using the Korean National Health Information Database, 359 492 CKD patients who had received antihypertensives regularly were identified from 12.1 million participants of nationwide health screening. The composite risk of major cardiovascular events, kidney failure and all-cause mortality was assessed according to time-averaged, on-treatment systolic BP.

Results: Over a 9-year follow-up, the composite outcome was noted in 18.4% of 239 700 participants with eGFR <60 mL/min/1.73 m2 and 18.9% of 155 004 with dipstick albuminuria. The thresholds of systolic BP, above which the composite risk increased significantly, in the reduced eGFR and the proteinuric population were 135 mmHg and 125 mmHg, respectively. For all-cause mortality, the respective thresholds were 145 mmHg and 135 mmHg. When comparing the composite risk between propensity score-matched groups, the hazard ratios of on-treatment BP of systolic 135–144 mmHg (reference, 115–124 mmHg) in the reduced eGFR and non-CKD pairs were 1.18 and 0.98, respectively (P = 0.13 for interaction), and those in the proteinuria and non-CKD pairs were 1.30 and 1.01, respectively (P = 0.003 for interaction).

Conclusions: The findings support the recommendation that, based on office BP, the systolic target in CKD with proteinuria is ≤130 mmHg, and the target in CKD with no proteinuria is ≤140 mmHg. The benefit of intensive BP-lowering may be greater in CKD patients, particularly those with proteinuria, than in their non-CKD counterparts.

Introduction

Chronic kidney disease (CKD) is a global health problem associated with high risk of mortality and cardiovascular disease and progression to end-stage kidney disease. Hypertension is common in CKD, and blood pressure (BP) lowering in hypertensive patients improves outcomes. However, the appropriate treatment target for BP in CKD populations remains unclear, and whether the benefit of intensive BP-lowering is comparable between CKD and non-CKD patients is debated.

Several randomized trials that compared intensive BP control with usual control in CKD failed to show a difference in clinical outcomes during the trial period.[1–3] However, in an extended follow-up study of the Modification of Diet in Renal Disease of 840 patients with a glomerular filtration rate (GFR) of 13–55 mL/min/1.73 m2, intensive control was associated with a lower risk of kidney failure and all-cause mortality.[4] In contrast, with extended follow-up of the African American Study of Kidney Disease and Hypertension of 1094 non-diabetic Black patients with a GFR of 20–65 mL/min, overall analyses showed no significant effect of intensive control on mortality or renal outcome, although subgroup analyses showed a benefit of intensive control among patients with a urine protein–creatinine ratio of >0.22.[5] The results of recent meta-analyses were also inconclusive for the clinical effects of intensive versus usual BP control in CKD.[6–8] Meanwhile, in the Systolic Blood Pressure Intervention Trial (SPRINT) of 9361 non-diabetic participants at high risk, intensive BP-lowering to a systolic target <120 mmHg versus <140 mmHg resulted in lower rates of all-cause death and cardiovascular events.[9] Of the SPRINT participants, 2646 (28.3%) had an estimated GFR (eGFR) of <60 mL/min/1.73 m2, and intensive control was associated with a similar or attenuated risk reduction among participants with reduced eGFR compared with those without the condition.[9–11] However, the subgroup analyses were underpowered to examine effect modification by CKD. Moreover, as clinical trials enrol participants who are not necessarily representative of the patient population, the generalizability of the results should be considered with caution.[12,13]

To investigate the risk thresholds of on-treatment BP in CKD populations and compare the thresholds between CKD and non-CKD patients, the risk of major cardiovascular events, kidney failure and all-cause death was assessed according to on-treatment BP levels and the presence of CKD in nationwide cohorts of CKD and general populations in Korea.

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