VITAL: Paricalcitol reduced renal, CV risks in patients with diabetic nephropathy
Adding 2 mcg per day of paricalcitol to renin-angiotension-aldosterone system inhibition appears to be a novel approach to lower residual renal risk for patients with type 2 diabetes.
Paricalcitol effectively and significantly reduced urinary albumin-creatinine ratio in patients with diabetic nephropathy, ranging from 18% to 28%, compared with placebo (P=.014).
Previous research has demonstrated that lower concentrations of calcitriol, the natural activator of the vitamin D receptor, may lead to abnormalities in calcium metabolism and cardiovascular and renal disease progression. Paricalcitol had previously been associated with reduced albuminuria and slowed progression to kidney injury in animals; however, no clinical studies on renal disease progression had yet been performed in humans, according to the researchers.
With that in mind, Dick de Zeeuw, PhD, and colleagues examined the effectiveness of paricalcitol for the reduction of residual albuminuria in 281 patients with type 2 diabetic nephropathy. At the start of the study, all patients received stable treatment with an angiotensin-converting enzyme inhibitor or angiotensin-receptor blocker.
Researchers randomly assigned each patient to receive 24 weeks’ treatment with placebo (n=88), 1 mcg daily paricalcitol (n=92) or 2 mcg daily paricalcitol (n=92). The primary endpoint was the percentage change in geometric mean urinary albumin-to-creatinine ratio from baseline to last measurement during treatment for the combined paricalcitol groups vs. the placebo group.
Reductions in renal risk
According to the results, urinary albumin-creatinine ratio changed by –3% in the placebo group compared with –20% in the 2-mcg paricalcitol group. Further, the 1-mcg paricalcitol group recorded a change of –14% and the combined paricalcitol group recorded a change of –16%, but these results were not statistically significant.
“We have shown that 24 weeks’ treatment with 2 mcg 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 … Existing drug strategies have substantial limitations and have not been successful so far,” de Zeeuw and colleagues wrote. “However, paricalcitol could be an important adjunctive treatment.”
Potential addition to drug armamentarium
Results also showed that the incidence of hypercalcemia and other adverse events were similar between the paricalcitol and placebo groups.
The researchers further explained the importance of paricalcitol’s effects even when dietary sodium intake is high, as adherence to a low sodium diet may be difficult for patients with diabetic nephropathy who are on already restricted diets.
“Therefore, paricalcitol could be useful for kidney protection in the large number of people with type 2 diabetes that is resistant to ACE/ARB intervention and who have a high sodium diet,” the researchers wrote in the study.
In a related commentary, Merlin C. Thomas, MD, PhD, and Mark E. Cooper, MD, PhD, of Baker IDI Heart and Diabetes Institute, Melbourne, Australia, said, “Long-term and larger clinical trials in patients with diabetes should now test whether [these] analogues can ultimately improve mortality and CV outcomes, as suggested in studies of patients with end-stage renal disease.”
Paricalcitol has been used since 1998. It is associated with a good safety profile and increased survival in observational studies of long-term use.
For more information:
- De Zeeuw D. Lancet. 2010;doi:10.1016/S0140-6736(10)61032-X.
- Thomas MC. Lancet. 2010;doi:10.1016/S0140-6736(10)61301-3.
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