Bicarbonate Supplement Restores Urinary Klotho Excretion in Chronic Kidney Disease: A Pilot Study

OBJECTIVE: We tested the hypothesis that correcting acidosis may improve urinary Klotho excretion and serum alpha-Klotho. DESIGN: This is a prospective, interventional, nonrandomized, open-label trial study. In this study setting, metabolic acidosis is commonly observed during chronic kidney disease (CKD). We reported a positive relationship between serum bicarbonate (Sbicar) and serum alpha-Klotho in these patients. SUBJECTS: The study involved 20 patients with a known kidney disease referred for renal checkup. Inclusion criteria were age \textgreater/= 18 years, CKD stage 3-5 non dialysis, Sbicar \textless 22 mmol/L, and not receiving bicarbonate supplementation. INTERVENTION: Patients were then prescribed 1 g of oral sodium bicarbonate 3 times per day for 4 weeks. MAIN OUTCOME MEASURE: Patients were evaluated at two and 4 weeks by blood and urine measurements. RESULTS: Mean serum Klotho was 615 +/- 287 pg/mL, and mean serum Sbicar was 19.3 +/- 1.7 mmol/L at baseline. Sbicar increased from baseline at two (23.9 +/- 2.9 mmol/L, P \textless .001) and 4 weeks (23.4 +/- 1.9 mmol/L, P \textless .001). There was no change in serum Klotho at two (630 +/- 333 mmol/L) and 4 weeks (632 +/- 285 mmol/L). By contrast, urine Klotho/creatinine ratio, which was very low at baseline (34.6 +/- 31.6 pg/mmoL), increased by 320% at two weeks (P \textless .005) and by 280% at 4 weeks (P \textless .01). CONCLUSIONS: Correcting acidosis by oral administration of sodium bicarbonate rapidly increases the urine excretion of soluble alpha-Klotho in CKD patients. However, a 4-week bicarbonate treatment was not able to increase serum alpha-Klotho. A longer study may confirm this pilot observation and increase serum Klotho, which has been shown to exert a protective cardiovascular effect during CKD