Oral Supplements Delay ESRD

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Sodium bicarbonate supplements may delay progression of renal disease.
Sodium bicarbonate supplements may delay progression of renal disease.

CKD patients who took oral sodium bicarbonate supplements slowed their progression to end-stage renal disease (ESRD) and improved their nutritional status, according to a British study that researchers say is the first randomized, controlled trial to show these positive effects.

The researchers, led by Muhammad M. Yaqoob, MD, Professor of Nephrology at Barts and the London NHS Trust in London, recruited 134 adult CKD patients (creatinine clearance [CrCL] 15-30 mL/min/1.73 m2) and serum bicarbonate levels of 16-20 mmol/L.

They randomly assigned 67 patients to receive supplementation with oral sodium bicarbonate (600 mg tablets three times daily increased as needed to achieve and maintain a bicarbonate level of 23 mmol/L) and 67 patients to receive standard care for two years.

The primary end points were the rate of CrCL decline, the proportion of patients with rapid decline of CrCl (greater than 3 mL/min/1.73 m2/year), and ESRD (CrCl less than 10 mL/min/1.73 m2).

After two years of follow-up, the researchers found that the mean CrCl decline was significantly slower in the treatment group than the control arm (1.88 vs. 5.93 mL/min/1.73 m2), according to findings published in the Journal of the American Society of Nephrology (2009; published online ahead of print).

Furthermore, a rapid decline in CrCl occurred in 9% of the sodium bicarbonate group versus 45% of controls, which translated into a significant 85% reduction in relative risk. Only 6.5% of the sodium bicarbonate group progressed to ESRD requiring dialysis compared with 33% of controls.

Moreover, the investigators observed a significant increment in dietary protein intake (DPI) in the treatment group compared with controls.

In addition, normalized protein nitrogen appearance (nPNA) decreased in the bicarbonate group—suggesting reduced protein breakdown—and increased in the control arm, the investigators found. This increase in DPI and decrease in nPNA resulted in an increment in the lean body mass as assessed by mid-arm muscle circumference in the treatment group from 24.8 to 26.3 cm compared with no change (from 24.6 to 24.5 cm) in the control group, they noted.

Serum albunin levels increased in the sodium bicarbonate group but remained stable in the control group. At the end of the study, albumin levels were significantly higher in the sodium bicarbonate arm, the researchers reported.

They pointed out that the positive renal effects of sodium bicarbonate supplementation were observed in the absence of any effects on BP control or proteinuria, which are two important factors relevant to CKD progression. The finding is suggestive of a specific independent role of low plasma bicarbonate, they said.

“Absence of a deleterious effect on BP despite increased sodium intake is of particular interest but is consistent with the results of other studies suggest that sodium salts other than sodium chloride have a negligible effect on BP,” they wrote.

In an interview with Renal & Urology News, Dr. Yaqoob said the study's findings confirm experimental evidence from the 1980s suggesting that, in subtotal nephrectomy models of experimental uremia, bicarbonate supplementation led to an attenuation of tubulointerstitial fibrosis and progression of renal failure.

He said his study provides “conclusive proof of a significant beneficial effect of correction of acidosis both for progression of CKD and improvement of nutritional status of patients with stage IV/V CKD in the predialysis phase.”

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