Six-month urinary CCL2 and CXCL10 levels predict long-term renal allograft outcome
P Hirt-Minkowski, DN Rush, A Gao, H Hopfer… - …, 2016 - journals.lww.com
Transplantation, 2016•journals.lww.com
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 …
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 …
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.
Lippincott Williams & Wilkins