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Bicarbonate Slows Chronic Kidney Disease
Posted: Wednesday, July 22, 2009
Sodium bicarbonate supplementation significantly slowed loss of kidney function and improved nutrition status in patients with advanced chronic kidney disease, data from a two-year study showed.
Creatinine clearance (CrCl) declined one third as quickly as it did for controls, and both rapid progression and progression to end-stage renal disease (ESRD) occurred significantly less often. Specifically, patients randomized to bicarbonate supplementation had a mean decline in CrCl of 1.88 ml/min 1.73 m2 compared with 5.98 ml/min 1.73 m2 among controls (P<0.0001).
Some 9% of patients in the bicarbonate group had rapid progression of kidney disease compared with 45% of the control group (P<0.0001).
The findings suggest that the simple, inexpensive therapy can slow progression of kidney disease in the large proportion of patients with metabolic acidosis, according to an online report in the Journal of the American Society of Nephrology.
"This cheap and simple strategy also improves patients' nutritional status and has the potential of translating into significant economic, quality of life, and clinical outcome benefits," Magdi Yaqoob, MD, of the Royal London Hospital, said in a statement.
"In fact, in patients taking sodium bicarbonate, the rate of decline in kidney function was similar to the normal age-related decline," he added.
The results confirmed findings from preclinical studies showing that bicarbonate supplementation preserved kidney function in models of chronic kidney disease.
Metabolic acidosis occurs frequently as a complication of advanced chronic kidney disease. However, evidence implicating the metabolic disturbance in progression of renal failure in humans had been lacking.
"The lack of long-term studies examining the impact of alleviation of metabolic acidosis on renal function in predialysis patients and on nutritional status was the particular stimulus to perform this study," Dr. Yaqoob and co-authors said.
"We proposed the hypothesis that oral bicarbonate supplementation in patients with acidosis . . . would be associated with attenuation of the rate of decline in creatinine clearance and a reduction in the number of patients with rapid progression of renal failure."
To test the hypothesis, investigators studied 134 patients with chronic kidney disease (CrCl 15 to 30 ml/min per 1.73 m2) and metabolic acidosis (serum HCO3- >16 to <20 mmol/L). The patients' mean age was about 55, and half had diabetes. About 40% of the patients had hypertension, which was well controlled, reflected in a population mean of about 124/75 mm Hg.
Excellent blood pressure control was a striking feature of the study and is a consideration in using sodium bicarbonate in patients with chronic kidney disease, Stanley Goldfarb, MD, of the University of Pennsylvania in Philadelphia, said in an interview.
"There is always the concern that when you increase sodium intake in patients with kidney disease that you are going to drive up blood pressure," said Dr. Goldfarb, a spokesperson for the American Society of Nephrology. "These patients were on multiple antihypertensive medications. They were absolutely normotensive to begin with."
The patients were randomized to usual care or to oral sodium bicarbonate supplementation (mean dose 1.82 g/d) in addition to usual care. Follow-up continued for two years. The primary endpoints were rate of CrCl decline, proportion of patients with a rapid decline in CrCl (defined as >3 ml/min per 1.732/yr), and progression to ESRD (CrCl <10 ml/min).
Five times as many patients in the control group progressed to ESRD, compared with patients who received bicarbonate supplementation (33% versus 6.5%, P<0.001).
"The study demonstrated that despite a larger number of patients who reached ESRD in the control group, the rate of decline in the remaining patients was still higher, suggesting that competing risks did not confound the results," the authors said.
Bicarbonate supplementation also was associated with significant improvement in patients' nutrition status, including dietary protein intake (P<0.05), normalized protein nitrogen appearance (P<0.05), mid-arm muscle circumference (P<0.0001), plasma albumin (P<0.001), and serum potassium (P<0.05).
The authors noted that, "This study can be criticized for a lack of placebo use and absence of a double-blind design. Like any other single-center study, reproducibility and generalizability of this report will require further validation by a double-blind, placebo-controlled, multicenter trial."
Practice Pearl: Explain to patients that treatment with sodium bicarbonate slowed the rate of progression of kidney disease.
Source: Diabetes In Control: De Brito-Ashurst I, et al "Bicarbonate supplementation slows progression of CKD and improves nutritional status" J Am Soc Nephrol 2009; DOI: 10.1681/ASN.2008111205.
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