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Chronic kidney disease (CKD) is a progressive disease with no curative treatment. Urinary albumin and estimated glomerular filtration rate (eGFR), which are used for CKD diagnosis, reflect kidney damage and are not effective for early CKD detection. Indoxyl sulfate (IS) is a uremic toxin that promotes renal failure via renal sclerosis and is a potential biomarker of early CKD detection. This retrospective study of a large cohort of healthy subject aimed to evaluate factors associated with serum IS levels and to assess the utility of serum IS as a biomarker for early CKD detection.
This cross-sectional study included 562 subjects with normal renal function (eGFR > 60 mL/min/1.73 m2, urine albumin/creatinine ratio < 30 mg/gCr) who underwent lifestyle health checkups in Kanegasaki Town, Iwate Prefecture, Japan. Collected data included routine parameters as well as serum IS levels and a questionnaire on the frequency of defecation and dietary habits (intake of vegetables and fruits).
The median (interquartile range) age, eGFR, and serum IS level were 68.0 (64.0ｰ71.0) years, 72.4 (67.0–79.6) mL/min/1.73 m2, and 3.80 (2.60–5.00) µmol/L respectively. Serum IS levels were significantly higher in subjects with an eGFR < 75 mL/min/1.73 m2 than in those with an eGFR ≥ 75 mL/min/1.73 m2 (p = 0.04), suggesting that serum IS levels might have utility in detecting CKD at an early stage. IS is a putrefactive product derived from tryptophan by the intestinal microflora, but the amount of protein intake did not have an overt effect on serum IS levels. However, serum IS levels were significantly higher in subjects with a defecation frequency of less than once every two days than in those with a defecation frequency of more than one per day (p = 0.03), suggesting the effect of prolonged transit time of intestinal contents on serum IS levels. The same tendency was also observed in patients with normal renal function. Although protein intake could impact IS levels, no obvious effect was observed in the present study. Serum IS levels were significantly higher in subjects aged >70 years than in those aged <60 years (p = 0.03), suggesting the effect of age-related disruption of the intestinal microflora and increased constipation.
Serum IS levels might have utility in detecting decline in renal function earlier than that is possible using the current diagnostic criteria for CKD. Age and frequency of defecation were also associated with serum IS levels.