A reduced sodium diet may improve residual albuminuria in chronic kidney disease (CKD) patients free of diabetes who are treated with a single renin-angiotensin-aldosterone system (RAAS) inhibitor.
By comparison, adding on the vitamin D receptor activator (VDRA) paricalcitol (2 µg daily) to standard therapy appeared to have a minimal effect. Combining paricalcitol and dietary sodium restriction resulted in the lowest albuminuria levels, but caution is warranted.
“What we found was that sodium restriction provided a relatively large beneficial effect, whereas the effect of paricalcitol was small. Thus, the impact of the combined intervention was largely due to the protective effect of sodium restriction,” lead investigator Martin H. de Borst, MD, PhD, of the Holland Nephrology Study (HONEST) Network in the Netherlands, stated in a press release. Moderate sodium restriction may increase the antiproteinuric effect of conventional RAAS blockade, the researchers explained, which has been linked with protection of the heart and kidneys.
For the ViRTUE-CKD trial (Vitamin D Receptor activator and sodium restriction for Treatment of Urinary albumin Excretion in Chronic Kidney Disease), the team investigated the effects of paricalcitol and dietary sodium restriction as separate and combined interventions. In a crossover design, investigators randomly assigned 45 stage 1 to 3 CKD patients with albuminuria (above 300 mg/24 hours) despite ramipril (10 mg) and blood pressure below 140/90 mmHg, to 1 of the following 4 interventions for 8-weeks each with no washout periods:
- paricalcitol with dietary sodium restriction (50 mmol daily)
- paricalcitol with regular sodium consumption (200 mmol daily)
- placebo with dietary sodium restriction
- placebo with regular sodium consumption
According to results published online ahead of print in the Journal of the American Society of Nephrology, regular sodium consumption alone was associated with albuminuria of 1060 mg/24 hours. The addition of paricalcitol to regular sodium intake slowed albuminuria to 990 mg/24 hours.
By comparison, a low sodium diet alone was associated with reduced albuminuria of 717 mg/24 hours. No significance difference emerged with the addition of paricalcitol. A separate analysis restricted to only medication-compliant patients also found that paricalcitol did not improve albuminuria any further.
Both sodium restriction and paricalcitol were well tolerated. The most common adverse effects were mild hypotension and hypercalcemia.
With regard to clinical implications, sodium restriction appeared beneficial. “In our study, patients consumed on average 4 grams of sodium per day, which is well in line with global trends in sodium consumption among CKD patients,” Dr de Borst explained. “Interestingly, following our intervention aimed at reduced sodium intake, patients consumed 2.5 grams per day, which is still above the recommended level. This moderate restriction resulted in a strong reduction in albuminuria and blood pressure, indicating that even a moderate reduction in sodium intake may provide serious health benefits.”
Add on paricalcitol might increase phosphate and fibroblast growth factor 23. The researchers suggested future studies investigate the relative harms and benefits of combining paricalcitol and dietary sodium restriction. Larger and longer studies comparing patients with and without diabetes are also warranted.
The pharmaceutical company AbbVie funded the medication used in this study.
1. 1. Keyzer CA, Fenna van Breda G, Vervloet MG, et al. Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial. JASN, November 17, 2016, doi: 10.1681/ASN.2016040407. [Epub ahead of print.]