ESPN 53rd Annual Meeting

ESPN 2021


 
Neutrophil gelatinase-associated lipocalin (NGAL) and Interleukine-18 (IL-18) in graft urine correlate with the rate of recovery of transplanted kidneys in children
DE JONG HUIB 1 TERPSTRA ANNIEK 1 MEYS KARLIJN 1 ZWIERS ALEXANDRA 2 SLOOTS CORNELIUS 2 CORNELISSEN ELISABETH 3 BOUTS ANTONIA 4 DE RIJKE YOLANDA 5 VAN ROSMALEN JOOST 6 CRANSBERG KARLIEN 1

1- DEPT. OF PEDIATRIC NEPHROLOGY, SOPHIA CHILDREN’S HOSPITAL, ERASMUS UNIVERSITYMC, ROTTERDAM, THE NETHERLANDS
2- DEPT. OF PEDIATRIC SURGERY, SOPHIA CHILDREN’S HOSPITAL, ERASMUS UNIVERSITY MC, ROTTERDAM, THE NETHERLANDS
3- DEPT. OF PEDIATRIC NEPHROLOGY, RADBOUDUMC AMALIA CHILDRENS HOSPITAL, NIJMEGEN, THE NETHERLANDS
4- DEPT. OF PEDIATRIC NEPHROLOGY, EMMA CHILDREN’S HOSPITAL, AMSTERDAM UNIVERSITY MEDICAL CENTER, AMSTERDAM, THE NETHERLANDS
5- DEPT. OF CLINICAL CHEMISTRY, ERASMUS UNIVERSITY MEDICAL CENTER ROTTERDAM, THE NETHERLANDS
6- DEPT. OF BIOSTATISTICS, ERASMUS UNIVERSITY MEDICAL CENTER ROTTERDAM, THE NETHERLANDS
 
Introduction:

Organ transplantation includes the procurement, preservation and implantation of an organ. During this process ischemia-reperfusion injury (IRI) of the graft is inevitable. Pediatric kidney transplantation carries a high risk of IRI, because most children receive an adult donor kidney mismatched in size. Considering the tubular pathogenesis of IRI, we hypothesize that specific biomarkers of tubular damage (neutrophil gelatinase-associated lipocalin (NGAL) and interleukin-18 (IL-18) better predict graft recovery then serum kreatinine.

Material and methods:

We performed a prospective multi-center trial in pediatric kidney transplantation recipients. We measured urinary neutrophil gelatinase-associated lipocalin (uNGAL) and interleukin-18 (uIL-18) concentrations in 82 recipients, in urine separately collected from graft and bladder within 3 days after transplantation. Concentrations at 3, 6 and 12 hours post-reperfusion were compared with the half-life of serum creatinine at reperfusion (T1/2Creat) as measure of graft recovery, and with the estimated glomerular filtration rate (eGFR) after 3 months. 

Results:

At all time-points post-transplantation, the median graft uNGAL concentration was lower than the bladder concentration, whereas the median graft uIL-18 concentration was structurally higher than the bladder concentration. After reperfusion, the graft uNGAL and uIL-18 concentrations peaked within 6 hours, then gradually declined. The graft uNGAL and uIL-18 concentrations at 3, 6 and 12 hours post-reperfusion correlated with the rate of graft recovery, and predicted slow graft function, with higher ROC-AUCs for uNGAL than for uIL-18. The graft function at 3 months post-transplant was only weakly predicted by the uNGAL and uIL-18 concentrations at the early time-points.

Conclusions:

uNGAL and uIL-18 concentrations in urine directly drained from the graft in the hours after reperfusion are associated with graft recovery after transplantation. Thus slow graft function can be anticipated by measuring these tubular injury markers and therefore prevent us to perform more invasive diagnostic interventions in pediatric kidney recipients.