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Dihydropyridine Calcium Channel Blockers and Kidney Outcomes

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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.

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Data Availability:

The datasets analyzed during the current study are not publicly available because they contain protected health information.

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Acknowledgements:

Dr. Blum was supported by NHLBI T32HL139426. Dr. Shin was supported by NIDDK K01DK121825. Dr. Grams was supported by NHLBI K24HL155861 and NIDDK R01DK115534.

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Authors and Affiliations

  1. Division of Nephrology, Department of Medicine, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA

    Matthew F. Blum MD, MHS

  2. Division of Precision Medicine, Department of Medicine, New York University Grossman School of Medicine, New York, NY, USA

    Aditya Surapaneni PhD & Morgan E. Grams MD, PhD

  3. Medicine Institute, Geisinger Health, Danville, PA, USA

    Alexander Chang MD, MSc

  4. Division of Nephrology, Tufts Medical Center, Boston, MA, USA

    Lesley A. Inker MD, MS

  5. Division of Nephrology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA

    Teresa K. Chen MD, MHS

  6. San Francisco VA Health Care System, San Francisco, CA, USA

    Teresa K. Chen MD, MHS

  7. Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA

    Lawrence J. Appel MD, MPH

  8. Welch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, MD, USA

    Lawrence J. Appel MD, MPH, Jung-Im Shin MD, PhD & Morgan E. Grams MD, PhD

  9. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Jung-Im Shin MD, PhD

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  1. Matthew F. Blum MD, MHS
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Corresponding author

Correspondence to Matthew F. Blum MD, MHS.

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Conflict of Interest:

Dr. Blum reports grants or contracts: National Kidney Foundation and Johns Hopkins University; meeting or travel support: American Society of Nephrology. Dr. Chang reports grants or contracts: Bayer, Novartis, Novo Nordisk; consulting fees: Novartis, Reata, Amgen; data safety monitoring board or advisory board: Occurrence of Dyskalemia with Treatment for Hypertension Study. Dr. Inker reports grants or contracts: National Kidney Foundation, National Institutes of Health, Omeros, Dialysis Clinics Inc., Reata; consulting fees: Tufts Medical Center; data safety monitoring board or advisor board: Dimerix, TMC, Tricida, Healthlogistics. Dr. Chen reports grants or contracts: National Institutes of Health, Yale University; payment or honoraria: American Society of Nephrology; meeting or travel support: CKD Biomarkers Consortium Meeting. Dr. Grams reports grants or contracts: National Institutes of Health and National Kidney Foundation; payment or honoraria: University of Pennsylvania, Columbia University Medical Center, American Society of Nephrology; meeting/travel support: Kidney Disease Improving Global Outcomes, European Renal Association, University of Pennsylvania, and Korean Society of Nephrology; leadership or fiduciary role: American Society of Nephrology, Kidney Disease: Improving Global Outcomes, National Kidney Foundation, United States Renal Data System, American Society of Clinical Investigation, Clinical Journal of American Society of Nephrology, American Journal of Kidney Diseases, and Journal of American Society of Nephrology. The remaining authors declare that they have no relevant financial interests.

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This study was presented as an abstract at the American Society of Nephrology Kidney Week, Orlando, Florida, November 4, 2022.

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Blum, M.F., Surapaneni, A., Chang, A. et al. Dihydropyridine Calcium Channel Blockers and Kidney Outcomes. J GEN INTERN MED (2024). https://doi.org/10.1007/s11606-024-08762-2

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