Work

Dihydropyridine Calcium Channel Blocker Therapy and Risk of CKD Progression in Type 2 Diabetes Treated With Renin Angiotensin System Inhibitors and SGLT2 Inhibitors: A Real-World Retrospective Cohort Study

Year: 2026

Type: article

Abstract: Rationale & Objective Optimal anti-hypertensive therapy with reno-protective effects is essential to slow diabetic kidney disease progression. We evaluated the impact of dihydropyridine calcium-channel-blockers on kidney outcomes in patients with type-2 diabetes receiving guideline-directed renin–angiotensin inhibitors and sodium–glucose cotransporter-2 inhibitors Study Design, Participants &; Settings A retrospective cohort study using Clalit Health Services (2016-2021). Exposure Adults with type-2 diabetes treated with both renin–angiotensin inhibitors and sodium–glucose cotransporter-2 inhibitors were categorized into dihydropyridine calcium-channel-blockers group (renin–angiotensin inhibitors + dihydropyridine calcium-channel-blockers, with or without other agents) or a dihydropyridine calcium-channel-blockers-free group, (renin–angiotensin inhibitors ± other antihypertensives excluding dihydropyridine calcium-channel-blockers). Outcomes: The primary outcome was a major adverse kidney event (MAKE; ≥40% eGFR decline or progression to kidney failure). Secondary outcomes included initiation of renal replacement therapy and all-cause mortality; Safety outcomes included hospitalizations and acute kidney injury. Analytical Approach Inverse probability of treatment weighting was applied to balance baseline characteristics. Results We included 31,031 patients with type 2 diabetes treated with both sodium–glucose cotransporter-2 inhibitors and renin–angiotensin inhibitors 12,172 (60.8%) received dihydropyridine calcium-channel-blockers, and 18,859 (39.2 %) received dihydropyridine calcium-channel-blockers -free therapy. Median follow-up was 1,260 days. Overall, 482 patients experienced major adverse kidney event, and 2064 patients died. dihydropyridine calcium-channel-blockers use was associated with a higher risk of major adverse kidney event compared with dihydropyridine calcium-channel-blocker-free therapy (weighted HR 1.33 95%CI 1.03-1.73, P =0.03), which remained significant after accounting for competing risk of death (HR 1.39, 95%CI 1.13-1.7, P =0.002). dihydropyridine calcium-channel-blocker use was not significantly associated with all-cause mortality or safety outcomes. Limitations The observational design is subject to residual confounding and did not allow for full characterization of medication exposure. Conclusions In patients with type 2 diabetes treated with renin–angiotensin system inhibitors and sodium–glucose cotransporter-2 inhibitors, concomitant therapy with dihydropyridine calcium channel blockers was associated with a higher risk of adverse kidney outcomes. These findings may help inform clinicians when weighing the potential risks and benefits of second-line antihypertensive therapy in this population. Plain-Language Summary We studied 31,031 adults with type 2 diabetes taking both renin–angiotensin inhibitors and sodium–glucose cotransporter-2 inhibitors. We compared those also using dihydropyridine calcium-channel blockers with those using other blood-pressure medicines. Over a median follow-up of 3.5 years, major kidney events (kidney failure or a sustained ≥40% eGFR drop) were uncommon but occurred more often in the dihydropyridine calcium-channel blockers group. After adjusting for baseline differences, dihydropyridine calcium-channel blockers use was associated with a 33% higher risk of major kidney events but not with a higher risk of overall mortality. In conclusion, adding a dihydropyridine calcium channel blocker to renin–angiotensin system inhibitor and sodium–glucose cotransporter-2 inhibitor therapy may be associated with worse kidney outcomes, and these findings may help clinicians weigh the risks and benefits of second-line blood pressure treatment in this population.

Source: Kidney Medicine

DOI: 10.1016/j.xkme.2026.101394