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Six-Month Urinary CCL2 and CXCL10 Levels Predict Long-term Renal Allograft Outcome
- Source :
- Transplantation. 100(9)
- Publication Year :
- 2016
-
Abstract
- BACKGROUND Early prognostic markers that identify high-risk patients could lead to increased surveillance, personalized immunosuppression, and improved long-term outcomes. The goal of this study was to validate 6-month urinary chemokine ligand 2 (CCL2) as a noninvasive predictor of long-term outcomes and compare it with 6-month urinary CXCL10. METHODS A prospective, observational renal transplant cohort (n = 185; minimum, 5-year follow-up) was evaluated. The primary composite outcome included 1 or more: allograft loss, renal function decline (>20% decrease estimated glomerular filtration rate between 6 months and last follow-up), and biopsy-proven rejection after 6 months. CCL2/CXCL10 are reported in relation to urine creatinine (ng/mmol). RESULTS Fifty-two patients (52/185, 28%) reached the primary outcome at a median 6.0 years, and their urinary CCL2:Cr was significantly higher compared with patients with stable allograft function (median [interquartile range], 38.6 ng/mmol [19.7-72.5] vs 25.9 ng/mmol [16.1-45.8], P = 0.009). Low urinary CCL2:Cr (≤70.0 ng/mmol) was associated with 88% 5-year event-free survival compared with 50% with high urinary CCL2:Cr (P < 0.0001). In a multivariate Cox-regression model, the only independent predictors of the primary outcome were high CCL2:Cr (hazard ratio [HR], 2.86; 95% confidence interval [95% CI], 1.33-5.73) and CXCL10:Cr (HR, 2.35; 95% CI, 1.23-4.88; both P = 0.009). Urinary CCL2:Cr/CXCL10:Cr area under the curves were 0.62 (P = 0.001)/0.63 (P = 0.03), respectively. Time-to-endpoint analysis according to combined high or low urinary chemokines demonstrates that endpoint-free survival depends on the overall early chemokine burden. CONCLUSIONS This study confirms that urinary CCL2:Cr is an independent predictor of long-term allograft outcomes. Urinary CCL2:Cr/CXCL10:Cr alone have similar prognostic performance, but when both are elevated, this suggests a worse prognosis. Therefore, urinary chemokines may be a useful tool for timely identification of high-risk patients.
- Subjects :
- Adult
Graft Rejection
Male
medicine.medical_specialty
Time Factors
medicine.medical_treatment
Urinary system
030232 urology & nephrology
Urology
Renal function
Kaplan-Meier Estimate
030230 surgery
Urinalysis
Disease-Free Survival
03 medical and health sciences
0302 clinical medicine
Interquartile range
Predictive Value of Tests
Risk Factors
medicine
CXCL10
Humans
Prospective Studies
Chemokine CCL2
Proportional Hazards Models
Transplantation
Chi-Square Distribution
business.industry
Hazard ratio
Graft Survival
Reproducibility of Results
Immunosuppression
Middle Aged
Allografts
Kidney Transplantation
Confidence interval
Surgery
Chemokine CXCL10
Treatment Outcome
ROC Curve
Area Under Curve
Creatinine
Cohort
Multivariate Analysis
Female
business
Biomarkers
Switzerland
Glomerular Filtration Rate
Subjects
Details
- ISSN :
- 15346080
- Volume :
- 100
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- Transplantation
- Accession number :
- edsair.doi.dedup.....8017549a9e306b3fb8e9353a376c8612