Dihydropyridine Calcium Channel Blockers and Kidney Outcomes

• Published in: Journal of general internal medicine : JGIM Vol. 39; no. 10; pp. 1880 - 1886
• Main Authors: Blum, Matthew F., Surapaneni, Aditya, Chang, Alexander, Inker, Lesley A., Chen, Teresa K., Appel, Lawrence J., Shin, Jung-Im, Grams, Morgan E.
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2024; Springer Nature B.V
• Subjects: Angiotensin; Antihypertensives; Blood pressure; Body mass index; Calcium channel blockers; Calcium channels; Cardiovascular disease; Clinical trials; Comparators; Confidence intervals; Creatinine; Dihydropyridine; Diuretics; Electronic health records; Electronic medical records; Endocrine system; Epidemiology; Hypertension; Internal Medicine; Kidney diseases; Kidneys; Medicine; Medicine & Public Health; Nephrology; Original Research; Patients; Pressure effects; Proteins; Public health; Renal failure; Renin; Risk; Statistical analysis; Thiazides; Urine; kidney failure; albuminuria; calcium channel blockers; hypertension
• ISSN: 0884-8734; 1525-1497; 1525-1497
• DOI: 10.1007/s11606-024-08762-2

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 m 2 , 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.