Lancet: Paricalcitol + RAAS inhibitors VITAL for curbing renal risk

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Adding a 2 ug/day dose of paricalcitol to a renin-angiotensin-aldosterone system (RAAS) inhibitor can safely reduce albuminuria in patients diagnosed with diabetic nephropathy, and could potentially reduce renal risk for diabetic patients, according to the VITAL trial published online Nov. 3 in the Lancet.

“Drugs that intervene in the RAAS, such as angiotensin receptor blockers (ARBs), can retard both cardiovascular and renal morbidity and mortality,” the authors wrote. However, residual cardiovascular and renal risk are high in patients receiving this treatment and renal risk is linked to residual albuminuria.

To understand whether the addition of paricalcitol (Zemplar, Abbott Laboratories) could reduce albuminuria in diabetic nephrophathy patients, Dick de Zeeuw, MD, PhD, University Medical Center Groningen, the Netherlands, and colleagues enrolled 281 type 2 diabetic patients with albuminuria between February 2007 and October 2008 to receive either placebo (n=93), 1 µg/day of paricalcitol (n-93) or 2 µg/day paricalcitol (n=95). The patients were also receiving angiotensin-converting enzyme (ACE) inhibitors or ARBs at the time of enrollment.

The primary endpoint of the study was the percentage change in geometric mean urinary albumin-to-creatinine ratio (UACR) from baseline to the last measurement during treatment for the combined paricalcitol groups versus the placebo group.

The researchers found a change in UACR of 3 percent in the placebo group (61 to 60 mg/mmol) and a change of 16 percent in the combined paricalcitol groups (62 to 51 mg/mmol). The UACR change in the 1 µg/day paricalcitol arm went from 63 to 54 mm/mmol—a 14 percent  change—while the UACR changes in the 2 µg/day paricalcitol arm changed by 20 percent, from 61 to 40 mg/mmol.

Patients in the 2 µg/day paricalcitol arm saw reductions in UACR that ranged from 18 to 28 percent.

Additionally, the incidences of hyperglycemia, adverse events and serious adverse events were similar between the patients who received paricalcitol and placebo. Forty-four patients reported treatment-emergent serious adverse events: 13 percent administered placebo, 14 percent for those administered 1 µg/day and 20 percent of patients administered 2 µg/day.

Three deaths occurred during the duration of the study and all three were patients in the 2 µg/day arm.

“We have shown that 24 weeks of treatment with 2 ?g paricalcitol daily reduced residual albuminuria in patients with type 2 diabetic nephropathy who were on stable doses of ACE inhibitors or ARBs, particularly in those with high dietary sodium intake,” the authors wrote.

“Existing drug strategies have substantial limitations and have not been successful so far. However, paricalcitol could be an important adjunctive treatment, providing optimum management of renal osteodystrophy, with little hyperglycemia, and lowering residual albuminuria.

“Therefore, paricalcitol could be useful for renoprotection in the large number of people with type 2 diabetes that is resistant to RAAS intervention and who have a high sodium diet,” the authors concluded.