Metabolic Acidosis Does Not Contribute to Chronic Renal Injury in the Rat

Abstract

1. Metabolic acidosis invariably accompanies chronic renal failure, and short periods of metabolic acidosis cause renal growth and proteinuria in normal rats. Rates of ammoniagenesis are increased in chronic renal failure, and it has been suggested that this contributes to disease progression. This study assessed (i) whether prolonged acidosis causes chronic renal injury in the normal kidney and (ii) whether abrogation of acidosis slows disease progression in the remnant kidney. 2. Metabolic acidosis was induced in normal rats by dietary hydrochloric acid. Urinary excretion of total protein, lysozyme and albumin increased, peaking at week 8 but returning to baseline by week 14. At killing after 14 weeks, kidney weights, glomerular filtration rates and serum creatinine were the same in both groups, but kidney/body weight and kidney/heart weight ratios were greater in the acidotic group. All kidneys were normal by light microscopy. 3. Rats subjected to five-sixths nephrectomy were given sufficient dietary bicarbonate to abolish uraemic acidosis, and their outcome was compared with that of non-alkalinized remnants (controls). Proteinuria, glomerular filtration rates, blood pressure, histological injury and time to the development of terminal uraemia were no better in bicarbonate-supplemented animals than in controls. 4. These data demonstrate that metabolic acidosis neither causes nor exacerbates chronic renal injury. We conclude that the treatment of uraemic acidosis is unlikely to influence disease progression in patients with chronic renal failure.

Bicarbonate Supplementation Slows Progression of CKD and Improves Nutritional Status

“…Rats with CKD produced by the 5/6 nephrectomy model failed to demonstrate a beneficial effect of sodium bicarbonate supplementation. 17 In rats that had CKD and were receiving a high-phosphate diet, MA actually prevented progression of renal failure, presumably as a result of inhibition of calcium phosphate deposition in the kidney. 18,19 Few studies have examined the effects of amelioration of MA on renal function in humans.…”

Tubular Peptide Hypermetabolism and Urinary Ammonia in Chronic Renal Failure in Man: A Maladaptive Response?

“…In remnant animal models new data have been put forward to challenge this hypothesis [22], but the experimental design was not comparable to the original experiments of Nath et al [7] where oral sodium bicarbonate suppressed renal vein ammonia and with histological evidence of tubular damage after 6 weeks. In the study by Throssell et al [22], food intake was greater, proteinuria heavier, and sodium bicarbonate treatment delayed.…”

“…In the study by Throssell et al [22], food intake was greater, proteinuria heavier, and sodium bicarbonate treatment delayed. Additionally, the end points of the two studies were different, since these authors examined the rate of progression to death in end-stage renal failure with no blood pressure control, and neither ammonia nor histology were examined.…”

Treatment of Acidosis in CKD

“…Some preclinical studies have indicated that the MA is associated with a worsening of proteinuria, tubulointerstitial fibrosis, and a more rapid decline in renal function (9)(10)(11)(12). However, other studies in rodents have been unable to reproduce these detrimental effects (13). Furthermore, in rodents with CKD receiving a high-phosphate diet, MA actually reduced the rate of progression of renal failure.…”