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July 17, 2023
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Diuretic with renin-angiotensin system inhibitor slows CKD progression

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Key takeaways:

  • Diuretics in combination with renin-angiotensin system inhibitors may slow chronic kidney disease on top of antihypertensive effects.
  • Researchers called for clearer guidelines for diuretic management.

Adding a diuretic to renin-angiotensin system inhibitor therapy lowered the risk for disease progression in patients with chronic kidney disease compared with using a calcium channel blocker, according to study data.

Patients also had similar risk for death and major cardiovascular events after starting either agent, according to results of the observational study published in Kidney International. The findings could help establish a second-line antihypertensive therapy for patients with CKD and justify a clinical trial comparing diuretics or calcium channel blockers (CCBs), researchers wrote.

Paper that says kidney failure
Diuretics with renin-angiotensin system inhibitors may slow CKD. Image: Adobe Stock

“Taken together with the strong differences worldwide in nephrology practices for diuretic prescription, this study highlights the need for clearer guidelines for diuretic management in patients with CKD,” Anne-Laure Faucon, MD, PhD, and colleagues wrote.

The researchers conducted a target trial emulation study using Swedish national registries – particularly the Swedish Renal Registry, which logs nationwide data on all-cause CKD patients attending routine nephrologist care in Sweden.

They selected 5,875 adults with CKD stages 3 to 5 (eGFR < 60 mL/min/1.73 m2) who showed good adherence to renin-angiotensin system (RAS) inhibitor therapy and started taking a diuretic (n = 3,165) or CCB (n = 2,710), but not both. Patients were excluded for history of kidney transplantation or dialysis, as well as CVD events in the previous 6 months. Median follow-up was 6.3 years.

Researchers found diuretic therapy was associated with lower risk of major adverse kidney events than CCBs (HR = 0.87; 95% CI, 0.77-0.97). Diuretics showed benefit over CCBs in initiation of kidney replacement therapy; a decline in eGFR greater than or equal to 40% from baseline; and eGFR less than 15 mL/min/1.73 m2.

There were no significant differences between diuretics and CCBs in mortality, cardiovascular and non-cardiovascular deaths and major adverse cardiovascular events. The researchers wrote that subgroup analyses of diuretics “might suggest somewhat stronger renoprotection” in older patients, those with higher blood pressure or those with eGFR less than 30 mL/min/1.73 m2.

Researchers described the results as consistent with “small-scale studies reporting a synergy between diuretics and [RAS inhibitors] in renoprotection,” but said previous diuretic studies were “most often conducted in patients with low risk for CKD progression, and investigated diuretic against no use, as the first-line therapy, or without co-treatment with [RAS inhibitors], and were not always consistent.”