NephMadness 2014: Treatment of Metabolic Acidosis in CKD

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Jordan Weinstein, MD
Assistant Professor of Medicine at the University of Toronto

Dr. Jordan Weinstein is a nephrologist at St. Michael’s Hospital in Toronto and Assistant Professor of Medicine at the University of Toronto. He is the founder and administrator of

The treatment of metabolic acidosis whether acute or chronic has always been a controversial area. Over the years however, the role of bicarbonate supplementation in CKD has become increasingly important and is recommended in current clinical practice guidelines.

Metabolic acidosis has a number of potential consequences.  These include muscle catabolism, insulin resistance, bone resorption, and enhanced systemic inflammation. Furthermore, as CKD progresses, nephrons lose function and their ability to participate in ammoniogensis declines. The burden on remaining nephron to maintain bicarbonate production via ammonium excretion rises. Some have argued that this increase in single nephron ammoniogenesis leads to fibrosis and accelerated loss of these remaining nephrons. Indeed, it has been observed that patients with CKD and metabolic acidosis have a faster rate of decline in renal function than those with normal serum bicarbonate.

Nevertheless, merely showing the impact of metabolic acidosis on patients with CKD does not prove that bicarbonate supplementation – even if the metabolic acidosis improves – is safe or effective. One of the early efforts that have shown benefit is the RCT by Ione de Brito-Ashurst et al. They randomized 134 patients with CKD stage 4 (average CrCl 20 mL/min) and metabolic acidosis (bicarbonate between 16 and 20, average 19.9 mmol/L) to usual care or 1.8 g of sodium bicarbonate (600 mg TID). The results were compelling. With two years of follow-up the bicarbonate group lost 1.88 mL/min of CrCl while the control group lost 5.93 mL/min. Four patients randomized to bicarbonate required dialysis compered to 22 randomized to usual care.

Phisitkul et al showed similar results in a 2-year study using sodium citrate as the exogenous alkali. This, however, is not a randomized study as the control group was made up of patients who refused the sodium citrate.

The theory of neutralizing acid and decreasing single nephron ammoniagenesis can also be achieved through diet changes. Goraya at al showed this during a year long trial of fruit and vegetable supplementation was able to reduce potential renal acid load. The intervention involved providing patients with:

The 36 patients in the fruits and vegetables group received fruits and vegetables free of charge, prescribed by a dietitian and distributed from the food bank in amounts to reduce PRAL by half, as done previously (9). Prescriptions emphasized base-producing fruits and vegetables (14), such as apples, apricots, oranges, peaches, pears, raisins, strawberries, carrots, cauliflower, eggplant, lettuce, potatoes, spinach, tomatoes, and zucchini.

This intervention was able to increase serum bicarbonate (marginally), reduce blood pressure (by 4.3 mmHg systolic 6.4 mmHg diastolic versus sodium bicarbonate for alkalization), and reduce net ammonia production. There was increased potassium load and aldosterone levels but serum potassium remained unchanged at 4.1 mmol/L.

One intriguing line of study has been looking at lowering the potential renal acid load in the absence of metabolic alkalosis. Mahajan attempted this in a cohort of patients with CKD stage 2 (mean GFR 75 ml/min) and serum bicarbonate over 24.5 mmol/L. Patients were randomized to one of three arms: sodium bicarbonate, placebo, or sodium chloride. The GFR was better preserved with sodium bicarbonate than both alternatives after five years of follow-up.

In the studies of alkali, adverse effects such as hypertension and edema have been uncommon and manageable. Alkali therapy still awaits a large, multicenter trial with hard end-points but the clinical data is building and the science looks sound. Sodium bicarbonate (or sodium citrate) supplementation should be strongly considered in patients with CKD and metabolic acidosis.

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