P-cresol: Correlation With Glomerular Filtration Rate and Outcome in Chronic Kidney Disease

End-stage renal disease is a global epidemia with an estimated incidence of 7% per year and high morbidity-mortality rate. Early detection of chronic kidney disease (CKD) and intervention for CKD complication is important to retard renal progression. However, "traditional uremic toxin" or "small water-soluble molecules" are poorly correlated with the renal function, uremic symptoms and outcomes of CKD patients.

Putative protein-bound solute, p-cresol, is accumulated in ESRD patients receiving dialysis therapy. This uremic solute was associated with endothelial dysfunction, immune dysregulation and can predict outcome in hemodialysis patient. P-cresol inhibits endothelial cell proliferation and endothelial response to inflammatory cytokines. In vitro, p-cresol decreases leukocyte transendotherliar migratory function and inhibit production of phagocyte reactive species. Clinically, p-cresol plays a pathophysiological role in the uremic toxicity. High free serum level of p-cresol is associated with mortality in hemodialysis patients.

Information of p-cresol in CKD patients is not available. The investigators hypothesized p-cresol can be accumulated in early CKD and have a positive correlation with the morbidity- mortality of CKD patients.

Value of p-cresol in different stages of CRF is still unknown. Information of p-cresol in CKD patients is not available. The investigators hypothesized p-cresol can be accumulated in early CKD and have a positive correlation with the morbidity- mortality of CKD patients.

The principal aim of this prospective cohort study is to investigate the association between total serum levels of p-cresol and the glomerular filtration rate. The correlation of level of p-cresol and morbidity-mortality in CKD patients will be also evaluated.

To determine the relationship, patients of nephrology clinic with a diagnosis of CKD were enrolled in this prospective study and follow-up for 1-year period. The association between total and free serum levels of p-cresol and the glomerular filtration rate were evaluated in CKD patients. The p-cresol level was correlated with other many inflammatory markers (white blood cell counts, ferritin, hs-crp, leptin) and also with the hospitalization rate secondary to cardiovascular and infectious event. The renal outcome and all-cause mortality was assessed. Determination of this relationship can help to establish an accurate marker for early detection of CKD and also its prognostic role in CKD patients.

All CKD patients attended at out-patient department of nephrology were included for analysis. The inclusion criteria were adults aged > 18 y/o or < 80 y/o; estimated GFR or CCR < 60 ml/min; no spontaneous renal improvement or progression in past 3 months.

• Risk Factors
• Renal Progression
• Death

• 2
  CKD patients with normal p-cresol
  Intervention: Other: there are no interventions currently listed for this study
• 3
  CKD patient with normal indoxyl sulfate
  Intervention: Other: there are no interventions currently listed for this study
• 4
  CKD patients with high indoxyl sulfate
  Intervention: Other: there are no interventions currently listed for this study
• 1
  CKD patients with high p cresol
  Intervention: Other: there are no interventions currently listed for this study

• Meijers BK, Bammens B, De Moor B, Verbeke K, Vanrenterghem Y, Evenepoel P. Free p-cresol is associated with cardiovascular disease in hemodialysis patients. Kidney Int. 2008 May;73(10):1174-80. Epub 2008 Feb 27.
• Atoh K, Itoh H, Haneda M. Serum indoxyl sulfate levels in patients with diabetic nephropathy: relation to renal function. Diabetes Res Clin Pract. 2009 Feb;83(2):220-6. Epub 2008 Nov 22.
• Meijers BK, de Loor H, Verbeke K, Evenepoel P. p-Cresol for better or worse: but what are we measuring? Kidney Int. 2006 Jul;70(1):232; author reply 232-3. No abstract available.

Inclusion Criteria:

• All CKD patients attended at out-patient department of nephrology were included for analysis.
• The inclusion criteria were adults aged > 18 y/o or < 80 y/o
• Estimated GFR or CCR < 60 ml/min
• No spontaneous renal improvement or progression in past 3 months.

Exclusion Criteria:

• Recent cardiovascular disease (Coronary artery disease, myocardial ischemia, cerebrovascular disease or peripheral artery disease) in past 3 months
• Recent infections requiring admission in past 3 months
• Uncontrolled hypertension
• Serum albumin level < 2.5mg/dL
• Unwilling to participate in the trial.