p-Cresyl sulphate and indoxyl sulphate predict progression of chronic kidney disease

Abstract

Background: Indoxyl sulphate (IS) and p-cresyl sulphate (PCS) are uraemic toxins that have similar protein binding, dialytic clearance and proinflammatory features. However, only a few prospective studies have evaluated possible associations between these two retained solutes and renal disease progression in chronic kidney disease (CKD) patients.

Methods: This prospective observational study evaluated independent associations between serum total IS and PCS with renal progression in a selected cohort of patients having different stages of CKD. Baseline PCS and IS were correlated with renal progression [defined as decrements in estimated glomerular filtration rate (eGFR) > 50% from baseline or progression to end-stage renal disease (ESRD)] and death during a follow-up period of 24 months.

Results: Of 268 patients, 35 (13.1%) had renal progression and 14 (5.2%) died after a mean follow-up of 21 ± 3 months. Univariate Cox regression analysis followed by multivariate analysis showed that high-serum PCS levels were associated with renal progression and all-cause mortality independent of age, gender, diabetes status, albumin levels, serum IS, serum creatinine, Ca × P product, intact parathyroid hormone, haemoglobin or high-sensitivity C-reactive protein level. Serum IS was only associated with renal progression; however, the predictive power of serum IS was weakened when serum PCS was also present in the analytical model.

Conclusions: In addition to traditional and uraemia-related risk factors such as renal function, serum IS and PCS levels may help in predicting the risk of renal progression in patients having different stages of CKD.

Fig. 1

Flow chart indicates patient enrollment.

Fig. 2

Kaplan–Meier survival curves in all patients according to serum PCS level (above and below the median of 7.16 mg/L); (A) cumulative renal survival (censored for death), log-rank, P < 0.001; (B) cumulative survival, log-rank, P = 0.002; (C) cumulative proportion of patients who did not reach composite endpoints, log-rank, P < 0.001.

Fig. 3

Kaplan–Meier survival curves in all patients according to serum IS level (above and below the median of 4.63 mg/L); (A) cumulative renal survival (censored for death), log-rank, P < 0.001; (B) cumulative survival, log-rank, P = 0.062; (C) cumulative proportion of patients who did not reach composite endpoints, log-rank, P < 0.001.