Dihydropyridine Calcium Channel Blockers and Kidney Outcomes

Matthew F Blum; Aditya Surapaneni; Alexander Chang; Lesley A Inker; Teresa K Chen; Lawrence J Appel; Jung-Im Shin; Morgan E Grams

doi:10.1007/s11606-024-08762-2

Dihydropyridine Calcium Channel Blockers and Kidney Outcomes

J Gen Intern Med. 2024 Apr 19. doi: 10.1007/s11606-024-08762-2. Online ahead of print.

Authors

Matthew F Blum¹, Aditya Surapaneni², Alexander Chang³, Lesley A Inker⁴, Teresa K Chen^{5

6}, Lawrence J Appel^{7

8}, Jung-Im Shin^{8

9}, Morgan E Grams^{2

8}

Affiliations

¹ Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. mblum@medicine.wisc.edu.
² Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA.
³ Medicine Institute, Geisinger Health, Danville, PA, USA.
⁴ Division of Nephrology, Tufts Medical Center, Boston, MA, USA.
⁵ Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
⁶ San Francisco VA Health Care System, San Francisco, CA, USA.
⁷ Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.
⁸ Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA.
⁹ Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

PMID: 38639831
DOI: 10.1007/s11606-024-08762-2

Abstract

Background: Early trials of dihydropyridine calcium channel blockers (DCCBs) suggest a detrimental effect on intraglomerular pressure and an association with albuminuria.

Objective: We sought to evaluate the associations of DCCB initiation with albuminuria and kidney failure with replacement therapy (KFRT) and to determine whether renin-angiotensin system (RAS) blockade modified these associations.

Design: We conducted a target trial emulation study using a new user, active comparator design and electronic health record data from Geisinger Health.

Participants: We included patients without severe albuminuria or KFRT who were initiated on a DCCB or thiazide (active comparator) between January 1, 2004, and December 31, 2019.

Main measures: Using inverse probability of treatment weighting, we performed doubly robust Cox proportional hazards regression to estimate the association of DCCB initiation with incident severe albuminuria (urine albumin to creatinine ratio > 300 mg/g) and KFRT, overall and stratified by RAS blocker use.

Key results: There were 11,747 and 26,758 eligible patients initiating a DCCB and thiazide, respectively, with a weighted baseline mean age of 60 years, systolic blood pressure of 143 mm Hg, and eGFR of 86 mL/min/1.73 m², and with a mean follow-up of 8 years. Compared with thiazides, DCCBs were significantly associated with the development of severe albuminuria (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.16-1.43), with attenuation of risk in the presence of RAS blockade (P for interaction < 0.001). The risk of KFRT was increased among patients without RAS blockade (HR, 1.66; 95% CI, 1.19-2.31), but not with RAS blockade (P for interaction = 0.005).

Conclusions: DCCBs were associated with increased risk of albuminuria and, in the absence of RAS blockade, KFRT. These findings suggest coupling DCCB therapy with RAS blockade may mitigate adverse kidney outcomes.

Keywords: albuminuria; calcium channel blockers; hypertension; kidney failure.

Abstract

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