Abstract: SA-PO165

Oral Alkali Supplementation to Reduce Uremic Toxin in Early Stage CKD Patients

Session Information

Category: Nutrition, Inflammation, and Metabolism

  • 1401 Nutrition, Inflammation, Metabolism

Authors

  • Abe, Michiaki, Tohoku University Hospital, Sendai, Japan
  • Souma, Tomokazu, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Sato, Hiroshi, Clinical Pharamacology and Therapeutics, Graduate School of pharmaceutical Sciences, Tohoku University, Sendai, Japan
  • Ito, Sadayoshi, Tohoku Graduate School of Medicine, Sendai Miyagi, Japan

Group or Team Name

  • CKOALA study group
Background

Patients with chronic kidney disease (CKD) has increased plasma uremic toxins (UTxs) and they develop metabolic acidosis and aciduria. These metaboic dsysregulations affects CKD progression and cardiovascular and bone complicaitons. Recently, oral alkali therapy has been suggested to slow the progression of CKD pathologies. To investigate the effects of alkali supplementation on UTx accumulation, we have initiated a double-blinded randomized control cohort study of “Estimating the efficacy of the Oral ALkAlizers in patients with CKD; CKOALA study.” Two types of alkalizers, Na/K citrate and Na bicarbonate, were used.

Methods

Total 47 CKD patients (CKD stage G2, G3a, G3b) were randomized to divide into 3 groups, control (n=15), Na bicarbonate (n=16) and Na/K citrate (n=16). The urine and plasma samples at 0, 6, 12 and 24 weeks after the intervention were collected and anonymized. Five UTxs including (Indoxyl sulfate (IS), p-cresyl sulfate (PCS), phenylacetyl L-glutamine (PAG), and argininosuccinate (ASA) and hippuric acid) were quantified by a quantitative-target LC-MS/MS. Individual change of UTx abundance were compared and Mann-Whitney test was used for statistical analysis. This research was approved as a secondary use of CKOALA study by Tohoku University Hospital Ethics Committee.

Results

%change of urinary concentrations of IS, PCS, PAG and ASA from was compared among groups. Urinary UTx levels in the Na/K citrate-treated group were significantly increased compared to the other two groups [IS; 93% (control) vs. 145% (bicarbonate), p=0.017; PCS, 116% (control) or 181% (bicarbonate) vs. 351% (citrate), p=0.001 or p=0.015; PAG, 94% (control) or 100% (bicarbonate) vs. 160% (citrate), p=0.016 or p=0.019; ASA, 87% (control) vs. 126 (citrate), p=0.003]. Furtheremore, plasma concentrations for IS was significantly reduced by Na/K citrate-treatment (control 1.2 µg/mL or bicarbonate 1.4 µg/mL vs. citrate 1.1 µg/mL, p=0.029 or p=0.035).

Conclusion

Our feasiblity study shows that an alkali therapy reduces some kinds of UTxs abundance in CKD patients and may represent a mechanism whereby oral alkali supplementation prevents CKD progression.

Funding

  • Other NIH Support