1. Metabolic acidosis invariably accompanies chronic renal failure, an
d short periods of metabolic acidosis cause renal growth and proteinur
ia in normal rats. Rates of ammoniagenesis are increased in chronic re
nal failure, and it has been suggested that this contributes to diseas
e progression. This study assessed (i) whether prolonged acidosis caus
es chronic renal injury in the normal kidney and (ii) whether abrogati
on of acidosis slows disease progression in the remnant kidney. 2. Met
abolic acidosis was induced in normal rats by dietary hydrochloric aci
d. Urinary excretion of total protein, lysozyme and albumin increased,
peaking at week 8 but returning to baseline by week 14. At killing af
ter 14 weeks, kidney weights, glomerular filtration rates and serum cr
eatinine were the same in both groups, but kidney/body weight and kidn
ey/heart weight ratios were greater in the acidotic group. All kidneys
were normal by light microscopy. 3. Rats subjected to five-sixths nep
hrectomy 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 p
ressure, histological injury and time to the development of terminal u
raemia were no better in bicarbonate-supplemented animals than in cont
rols. 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 pa
tients with chronic renal failure.