For patients with chronic kidney disease, treatment of metabolic acidosis with oral alkali supplementation or a reduction in dietary acid intake may slow the rate of kidney function decline, thus reducing the risk for ESKD, according to systematic review and meta-analysis of clinical trials.
“A previous systematic review of the effect of alkali therapy suggested a potential benefit of alkali therapy on preservation of GFR in patients with CKD,” Sankar D. Navaneethan, MD, of the section of nephrology in the department of medicine at Baylor College of Medicine in Houston, and colleagues wrote. “The small number of included trials in this earlier report, along with the limited number of patients, precluded definitive conclusions regarding the risks and benefits of oral alkali supplementation. Subsequently, longer-term prospective trials have examined the effect of intervention with oral alkali supplementation (eg, sodium bicarbonate or sodium citrate) or dietary intervention (eg, diets enriched with fruits and vegetables or very low-protein diets supplemented with ketoanalogues, both designed to reduce the intake of dietary acids) on kidney disease progression and other surrogate outcome measures.”
Researchers considered 14 clinical trials that examined the effect of oral alkali supplementation or dietary intervention on 1,394 patients with stage 3 to 5 CKD and metabolic acidosis (<22 mEq/L) and low-to-normal serum bicarbonate levels (22 mEq/L to 24 mEq/L). Eight of the trials compared patients given oral alkali supplementation (sodium bicarbonate or sodium citrate) with a control group, consisting of no treatment, usual care or placebo.
Five of the studies compared dietary intervention (ketoanalogue-supplemented very low-protein diet or low-protein diets) with control diets (low-protein diet or usual diet). One study compared both sodium bicarbonate and dietary intervention (fruits and vegetables) with usual care.
For patients with chronic kidney disease, treatment of metabolic acidosis with oral alkali supplementation or a reduction in dietary acid intake may slow the rate of kidney function decline.
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Researchers found oral alkali supplementation or dietary intervention increased serum bicarbonate levels (mean difference, 3.33 mEq/L) and reduced risk for progression to ESKD (relative risk = 0.32) compared with control groups. In addition, oral alkali supplementation and dietary intervention — separately or together — slowed eGFR decline (mean difference, -3.28 mL/min/1.73m2).
As for risks, researchers found oral alkali supplementation was associated with worsening hypertension and the need for increased antihypertensive therapy, as well as worsening edema. Treatment with dietary intervention resulted in a reduction systolic blood pressure.
“Current clinical trial evidence suggests that oral alkali supplementation or a reduction of dietary acid load improved serum bicarbonate levels and may slow the progression of kidney disease, on the basis of very low- to moderate-certainty clinical evidence,” the researchers wrote. “Further larger, long-term studies of better quality are warranted to establish the benefits (such as delaying initiation of kidney replacement therapy or slowing progression to ESKD) and risks of treatment with oral alkali and/or a reduction in dietary acid load in patients with CKD.” – by Melissa J. Webb
Disclosures: Navaneethan reports serving as a consultant for Tricida. Please see the study for all other authors’ relevant financial disclosures.