Acidosis in End-Stage Renal Failure

K.M.L. Leunissen, MD, PhD, University Hospital Maastricht, Department of Internal Medicine, PO Box 5800, NL-6202 AZ Maastricht (The Netherlands) Acidosis has been identified as one of the uremic toxins. Renal acidosis may contribute to renal osteodystrophy [1] and decreased myocardial contractility [2]. Furthermore, animal experimental studies proved that acidosis plays a pivotal role in the accelerated muscle proteolysis in chronic renal failure by activation of the ATP-ubiquitin proteasome-de-pendent pathway and will lead to stimulation of branched-chain ketoacid dehydrogenase activity causing degradation of branched-chain amino acids [3-5]. Correction of the acidosis could prevent this catabolism. Also, in clinical practice there is evidence for an impaired nitrogen utilisation and a change of amino acid and protein metabolism due to renal acidosis [6, 7]. It was shown that sodium bicarbonate supplementation improved significantly the nitrogen balance in nondialyzed uremic patients [8]. In another study, the urinary excretion of 3methylhistidine was used as an indicator of muscle turnover. When in addition to a restricted protein diet bicarbonate supplementation was given to correct acidosis, both excretion of nitrogen and of 3-methylhistidine was reduced, indicating a decrease of catabolism [9]. Reduced levels of branched-chain amino acids in uremic dia-lyzed patients have also been reported. The muscle valine level closely correlated with the plasma bicarbonate level [6]. Protein energy malnutrition in maintenance dialysis patients is very common and of multifactorial origin [10]. Low-protein diet and anorexia due to the uremic state are certainly important factors causing malnutrition, but apart from acidosis also the uremic state itself could directly stimulate protein catabolism. The question is: What is the role of renal acidosis and its degree of correction in malnutrition and clinical outcome of dialysis patients? Prospective studies are warranted to answer this question. Although the introduction of bicarbonate dialysis resulted in a better correction of the acidosis as compared to acetate dialysis, this correction is still not optimal [11]. Only a few studies showed a postdialysis bicarbonate level of 24-28 mmol/l, and in most studies the predialysis bicarbonate level was below 22 mmol/l [12,13]. Bicarbonate requirements in hemodialysis patients are dependent on acid production during the interdialytic period, the removal of organic anions during hemodialysis, and on the buffer deficit of the body [14]. When dialysis treatment is initiated, the endogenous buffer system is often exhausted by the long-existing positive hydro-