Biomarkers for Diagnosis and Prediction of Outcomes in Contrast-Induced Nephropathy
Justor Banda, Raquel Duarte, Thérèse Dix‐Peek, Caroline Dickens, Pravin Manga, Saraladevi Naicker
Abstract
Background . Serum creatinine is suboptimal as a biomarker in the early diagnosis of contrast-induced nephropathy (CIN). In this study, we investigated a panel of novel biomarkers in the early diagnosis of CIN and in assessing patient outcomes. Methods . This single-centre, nested, prospective case-controlled study included 30 patients with CIN and 60 matched controls. Serum and urine samples were collected before contrast administration and at 24 hours, 48 hours, and ≥5 days after contrast administration. Concentrations of NGAL, cystatin C, β 2 M, IL18, IL10, KIM1, and TNF α were determined using Luminex and ELISA assays. Outcomes were biomarker diagnostic discrimination performance for CIN and mortality after generation of area under receiver operating characteristic curves (AUROCs). Results . Median serum levels for 24 h cystatin C (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.01</mml:mn></mml:mrow></mml:math>) and 48 h β 2 M levels (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:mrow></mml:math>) and baseline urine NGAL (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.02</mml:mn></mml:mrow></mml:math>) were higher in CIN patients compared to controls with AUROCs of 0.75, 0.78, and 0.74, respectively, for the early diagnosis of CIN. Serum β 2 M levels were higher in CIN patients at all time points. Elevated baseline serum concentrations of IL18 (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M4"><mml:mrow><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:mrow></mml:math>), β 2 M (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M5"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.04</mml:mn></mml:mrow></mml:math>), TNF α (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M6"><mml:mrow><mml:mi>p</mml:mi><mml:mo><</mml:mo><mml:mn>0.001</mml:mn></mml:mrow></mml:math>), and baseline urine KIM (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M7"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.01</mml:mn></mml:mrow></mml:math>) and 24 h urine NGAL (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M8"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.02</mml:mn></mml:mrow></mml:math>) were significantly associated with mortality. Baseline serum concentrations of IL18, β 2 M, and TNF α showed the best discrimination performance for mortality with AUROCs, all >0.80. Baseline NGAL was superior for excluding patients at risk for CIN, with positive and negative predictive ranges of 0.50–0.55 and 0.81–0.88, respectively. Cystatin C (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M9"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.003</mml:mn></mml:mrow></mml:math>) and β 2 M (<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M10"><mml:mrow><mml:mi>p</mml:mi><mml:mo>=</mml:mo><mml:mn>0.03</mml:mn></mml:mrow></mml:math>) at 24 h independently predicted CIN risk. β 2 M predicted increased mortality of 40% at baseline and 50% at 24 hours. Conclusion . Serum cystatin C at 24 h was the best biomarker for CIN diagnosis, while baseline levels of serum IL18, β 2 M, and TNF α were best for predicting prognosis.