Clinical trial NCT00888030: P-cresol: Correlation With Glomerular Filtration Rate and Outcome in Chronic Kidney Disease
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Risk Factors
Renal Progression
Death
Keywords: p-cresol
indoxyl sulfate
chronic kidney disease
outcome
Lead sponsor: Chang Gung Memorial Hospital
Sponsor class: OTHER
First posted: 2009-04-24
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: 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.

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: end stage renal disease, reduction of eGFR by 50% and death
timeFrame: 1 year
Secondary outcomes:
Other outcomes:
Locations:
city: Keelung
country: Taiwan
facility: Department of Nephrology,Chang Gung Memorial Hospital
Study officials:
affiliation: Chang Gung Memorial Hospital
name: Iwen Wu, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1038/ki.2008.31. Epub 2008 Feb 27.
citation: 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. doi: 10.1016/j.diabres.2008.09.053. Epub 2008 Nov 22.
citation: 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. doi: 10.1038/sj.ki.5001530. No abstract available.