Common Hypertension Drugs Linked to Worse Kidney Outcomes in Type 2 Diabetes Patients Despite Modern Therapies
Key Insights
A large observational study of 31,031 adults with type 2 diabetes (search) found that dihydropyridine calcium-channel blockers (search) (DCCBs) were associated with a 33% higher risk of major adverse kidney events, even among patients already receiving RAS and SGLT2 inhibitors (search).
The increased risk persisted despite concomitant use of SGLT2 inhibitors (search), which researchers had initially hypothesized might counterbalance potential harms from DCCBs.
Researchers suggest DCCBs may preferentially relax afferent blood vessels in the kidney, increasing pressure within filtering units and contributing to ongoing kidney damage in patients with diabetic kidney disease (search).
New research presented at the 63rd ERA Congress in Glasgow, Scotland suggests that dihydropyridine calcium-channel blockers (search) (DCCBs), a widely prescribed class of blood pressure medications, may be associated with poorer kidney outcomes in people with type 2 diabetes (search) (T2D), even among those already receiving modern kidney-protective therapies.
The observational study, which analyzed data from 31,031 adults with T2D between 2016 and 2021, found that patients taking DCCBs alongside standard-of-care therapies had a significantly higher risk of major adverse kidney events compared with those receiving alternative blood pressure treatments. All patients in the analysis were receiving both renin-angiotensin system (RAS) inhibitors and sodium-glucose cotransporter-2 (SGLT2) inhibitors as part of their care.
A 33% Increase in Kidney Risk
Among the study participants, 12,172 (39.2%) were taking DCCBs, while 18,859 (60%) were receiving other antihypertensive treatments. Patients were followed for a median of approximately 3.5 years. After adjusting for differences in baseline clinical and demographic characteristics, researchers found that DCCB use was associated with a 33% higher risk of a major adverse kidney event (HR 1.33, 95% CI 1.03–1.73).
Major adverse kidney events were defined as either a substantial decline in kidney filtration capacity — a drop of 40% or more in estimated glomerular filtration rate (eGFR), the standard measure of kidney function — or progression to end-stage kidney disease (search) requiring dialysis or transplantation.
"DCCBs are widely used as second-line blood pressure treatments in patients with DKD," said Dr. Timna Agur, lead author of the study. "Our findings raise important questions about whether these medications are always the best option for patients already receiving modern kidney-protective therapies."
The Burden of Diabetic Kidney Disease (search)
Diabetic kidney disease (search) (DKD) is one of the leading causes of kidney failure worldwide. It develops when persistently high blood sugar damages the small blood vessels in the kidneys, gradually reducing their ability to filter waste from the blood. Controlling blood pressure is a cornerstone of treatment, as high blood pressure accelerates this damage.
In recent years, two classes of medication have transformed care for people with DKD: RAS inhibitors, which lower blood pressure and reduce pressure within the kidney's filtering units, and SGLT2 inhibitors (search), originally developed as diabetes drugs but now recognized for their kidney-protective effects and ability to reduce the risk of kidney failure. Together, these therapies now form part of the standard of care for most patients with DKD.
A Proposed Mechanism of Harm
The researchers believe the findings may be explained by the way DCCBs affect blood flow within the kidney. In DKD, the kidneys are already exposed to increased pressure and hyperfiltration, a state in which the filtering units are working under excessive strain. Researchers suggest DCCBs may preferentially relax the blood vessels carrying blood into the kidney's filtering units without having the same effect on vessels carrying blood out, potentially increasing pressure within these structures and contributing to ongoing kidney damage.
"We initially thought the kidney-protective effects of SGLT2 inhibitors (search) might counterbalance the potential harms associated with DCCBs," said Dr. Agur. "However, the increased risk of kidney disease progression appeared to persist even in this group."
Calls for Further Investigation
The researchers caution that the study was observational in nature and cannot establish direct causation. Nevertheless, they argue the results are clinically significant given how commonly DCCBs are prescribed in this patient population.
"Further prospective studies and randomized controlled trials are needed to confirm these observations and better define the safest blood pressure treatment strategies for patients with DKD," concluded Dr. Agur. "However, given how commonly these medications are prescribed, any increase in kidney risk could have important implications for large numbers of patients with DKD."