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Abstract
Background and Aims
Uremic toxins have been highlighted as serious risk factors for deterioration of renal function and onset/progression of cardiovascular diseases (CVD). Serum level of indoxyl sulphate (IS), a major uremic toxin, was demonstrated its significant association with vascular disease and mortality in a cohort of chronic kidney disease (CKD) patients, however, IS has not been available in clinical setting due to time consuming and expensive measurement cost. Recently epoch-making IS measurement method applicable for general auto analyzer has been developed, which could explore new therapeutic avenue in CKD from the view point of uremic toxin management.
In this study, clinical utility of new enzymatic IS measurement method was analyzed in association with renal function and CVD among CKD patients.
Method
Subjects were consecutive 150 CKD patients in Nagoya University Hospital whose serum samples were collected between 2009 and 2014. Serum IS levels were measured by “NIPRO” reagent and analyzed with eGFR, CVD events and renal outcomes defined by 30% decrease in eGFR.
Results
Characteristics of patients were 69 ± 10 years old, 29% female, eGFR: 44 ± 20 mL/min/1.73m2 (∼G3a: 43％, G3b: 29％, G4: 24％, Ｇ5: 4％), proteinuria 2.8 ± 3. 5ｇ/ｇCr (A1: 29％, A2: 29％, A3: 42％), HTN: 83％, and DM: 39％. Serum IS levels (μmol/L) were 10.5 ± 7.5 (∼G3a: 1.8 ± 0.6, G3b: 2.1 ± 0.6, G4: 15.8 ± 8.1, Ｇ5: 22.9 ± 13.5), and strongly correlated with eGFR (r =0.518, P<0.001). Among IS low (<6), middle and high (≥12) tertiles, significantly different factors were age, eGFR, Hb, iPTH and LDL-C. In multiple logistic regression analysis, only eGFR was significant associating factor with IS tertiles. IS levels in 2 patients prescribed AST-120 (Kremezin) were 8.1 and 10.3, which seems to be very low in comparison to their eGFR of 13.8 and 13.7. During observation period of 5.1 ± 1.0 years, 59 renal outcomes and 9 CVD events were observed. Kaplan-Meier survival curve analysis free from renal outcomes revealed better tendency in IS low group (p= 0.0617 in log-rank test). According to IS levels adjusted by eGFR, only 1 out of 9 CVD events occurred in low IS/eGFR tertile group.
Conclusion
Serum IS levels could be measured in new enzymatic method. Strong correlation between IS and eGFR was demonstrated, and AST-120 might be effective to improve IS. In renal and CVD outcome analysis, more sample size is needed for further study.