Metabolic acidosis often accompanies low glomerular filtration rate and induces secretion
of endothelin, which in turn might mediate kidney injury. Here we tested whether treatment
of metabolic acidosis in patients with low glomerular filtration rate reduced the
progression of kidney disease. Fifty-nine patients with hypertensive nephropathy and
metabolic acidosis had their blood pressure reduced with regimens that included angiotensin-converting
enzyme inhibition. Thirty patients were then prescribed sodium citrate, and the remaining
29, unable or unwilling to take sodium citrate, served as controls. All were followed
for 24 months with maintenance of their blood pressure reduction. Urine endothelin-1
excretion, a surrogate of kidney endothelin production, and N-acetyl-beta-D-glucosaminidase,
a marker of kidney tubulointerstitial injury, were each significantly lower, while
the rate of estimated glomerular filtration rate decline was significantly slower.
The estimated glomerular filtration rate was statistically higher after 24 months
of sodium citrate treatment compared to the control group. Hence it appears that sodium
citrate is an effective kidney-protective adjunct to blood pressure reduction and
angiotensin-converting enzyme inhibition.