NEW YORK (Reuters Health) – In patients with hypertensive nephropathy and metabolic acidosis, alkali treatment reduces tubulointerstitial injury and slows the decline in glomerular filtration rate (GFR), a prospective study suggests.

In hypertensive nephropathy, tubulointerstitial injury can persist even after blood pressure comes under control, the researchers note in a January 13 online paper in Kidney International.

The researchers also point out that endothelins are known to mediate tubulointerstitial injury – and that the metabolic acidosis that often accompanies low GFR is known to induce endothelin secretion.

Therefore, senior author Dr. Donald E. Wesson, from Texas A&M College of Medicine in Temple and his colleagues conducted a study to see whether reducing acidosis with sodium citrate would slow GFR decline in a cohort patients with hypertensive nephropathy.

“Ours is the first to examine the effects of alkali treatment on patients whose exclusive cause of reduced kidney function is hypertensive nephropathy, the second leading U.S. cause of complete kidney failure after diabetes,” Dr. Wesson told Reuters Health by email.

Their study included 59 adults (mean age, 54 years) with estimated GFR between 20 and 60 mL/min, and venous total CO2 less than 22 mmol/L. None of the subjects had primary kidney disease, diabetes or cardiovascular disease.

All patients were put on a blood pressure lowering regimen that included an ACE inhibitor. Six months later, 30 patients were prescribed sodium citrate (1 meq/kg HCO3 equivalent daily in 3 divided doses), and 29 who were unable or unwilling to take sodium citrate served as controls. Follow-up continued for a total of 30 months.

Urine endothelin-1 excretion – a marker of kidney endothelin production — was similar in the two groups at baseline. By the end of follow-up, however, it was significantly lower in the citrate group (4.83 vs 6.92 ng/g creatinine, p < 0.0001). Findings were similar for levels of N-acetyl-beta-D-glucosaminidase, a marker of kidney tubulointerstitial injury (7.72 vs 10.37 ng/g Cr, respectively, p = 0.0004). The same was true for urinary albumin excretion (107.1 vs 146.9 mg/g CR, p = 0.002). Furthermore, all three markers increased significantly from baseline in the no-citrate group. The rate of estimated GFR decline was also significantly slower in the citrate group (-1.60 vs -3.79 mL/min per year, p < 0.0001). “Our studies tell us that metabolic acidosis that commonly accompanies reduced kidney function contributes to the progressive kidney function decline (in) hypertensive nephropathy” and that the damage is mediated at least partially by endothelin production, Dr. Wesson said. Furthermore, he continued, “Our studies support that sodium citrate therapy is a kidney protective intervention and that treatment of metabolic acidosis with sodium citrate can help delay the onset of complete kidney failure…caused by hypertension and possibly other causes.” Dr. Wesson and his associates recommend further study of sodium citrate as an adjunct to blood pressure reduction and ACE inhibition in this population. Reference:
Kidney Int 2010.