Dihydropyridine CCBs associated with poorer kidney outcomes in type 2 diabetes, new study shows

New research presented at the 63rd ERA Congress suggests that a widely used class of blood pressure medications may be associated with poorer kidney outcomes in people with type 2 diabetes (T2D), even among patients already receiving modern kidney-protective treatments.

Dihydropyridine calcium-channel blockers (DCCBs) are a commonly prescribed class of blood pressure medications that work by relaxing blood vessels and are frequently used as second-line therapies in people with diabetic kidney disease (DKD). Researchers found that patients taking DCCBs alongside standard therapies had a significantly higher risk of major adverse kidney events, compared with those receiving alternative blood pressure treatments.

DKD is one of the leading causes of kidney failure worldwide.2 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: renin-angiotensin system (RAS) inhibitors, which lower blood pressure and reduce pressure within the kidney’s filtering units, and sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed as diabetes drugs but now recognised 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.

The study analysed data from 31,031 adults with T2D between 2016 and 2021. All patients were receiving both RAS and SGLT2 inhibitors as part of their care. Among the participants, 12,172 (39.2%) were also 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 (R 1.33, 95%, CI 1.03-1.73). These 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 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 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 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."

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 randomised 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.”

Reference:

Common blood pressure medication associated with poorer kidney outcomes in type 2 diabetes, new study shows, Beyond, Meeting: 63rd ERA Congress