ESPN 50th Annual Meeting

ESPN 2017


 
Soluble Urokinase Plasminogen Activator Receptor (suPAR) Serum Levels Predict Progression of Kidney Disease in Children
FRANZ SCHAEFER 1 ELKE WÜHL 1 HOWARD TRACHTMAN 2 MARIETTA KIRCHNER 3 SALIM S. HAYEK 4 ALI ANARAT 5 ALI DUZOVA 6 SEVGI MIR 7 DUSAN PARIPOVIC 8 ALEV YILMAZ 9 FRANCESCA LUGANI 10 KLAUS ARBEITER 11 JOCHEN REISER 12 for the ESCAPE Trial Consortium and 4C Study Group 1

1- CENTER FOR PEDIATRICS AND ADOLESCENT MEDICINE, UNIVERSITY HOSPITAL HEIDELBERG, HEIDELBERG, GERMANY
2- DEPARTMENT OF PEDIATRICS, DIVISION OF NEPHROLOGY, NYU LANGONE MEDICAL CENTER; NEW YORK CITY, NY, USA
3- INSTITUTE OF MEDICAL BIOMETRY AND INFORMATICS, UNIVERSITY OF HEIDELBERG, HEIDELBERG, GERMANY
4- DIVISION OF CARDIOLOGY, EMORY UNIVERSITY, ATLANTA, GA, UNITED STATES
5- TIP FAKULTESI COCUK NEFROLOJISI BILIM DALI, CUKUROVA UNIVERSITESI, ADANA, TURKEY
6- PEDIATRIC NEPHROLOGY, HACETTEPE MEDICAL FACULTY, ANKARA, TURKEY
7- PEDIATRIC NEPHROLOGY, EGE UNIVERSITY FACULTY OF MEDICINE, IZMIR, TURKEY
8- UNIVERSITY CHILDRENS HOSPITAL BELGRADE, SERBIA
9- DEPT. OF PEDIATRIC NEPHROLOGY, ISTANBUL MEDICAL FACULTY, ISTANBUL, TURKEY
10- PEDIATRIC NEPHROLOGY, ISTITUTO GIANNINA GASLINI, GENOVA, ITALY
11- PEDIATRIC NEPHROLOGY, VIENNA UNIVERSITY CHILDRENS HOSPITAL, VIENNA, AUSTRIA
12- DEPARTMENT OF MEDICINE, RUSH UNIVERSITY MEDICAL CENTER, CHICAGO, IL, USA
 
Introduction:

Renal disease progression rate in CKD children is highly variable. Even within individual age and disease groups, progression rate varies widely, defining a need for informative prognostic biomarkers predicting disease progression and the need for early intervention in an individual patient. Recently, serum soluble urokinase plasminogen activator receptor (suPAR) has been shown to be a strong predictor of incident CKD stage 3 in adults. Here we aimed to determine whether elevated suPAR levels are associated with renal disease progression in children with CKD.

Material and methods:

Post-hoc analysis of two prospectively followed pediatric CKD cohorts (ESCAPE trial and 4C Study) including 898 children (mean age 11.9±3.5 years) with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. Renal diagnoses included CAKUT (70%), tubulointerstitial nephropathies (10.2%), glomerulopathies (7.7%), post-ischemic (4.7%), and other CKD (6.5%). Mean eGFR was 34±16 ml/min/1.73m2, median follow-up 3.1 (0 to 7.9) years. The primary renal endpoint was a composite of 50% eGFR loss, eGFR<10 ml/min/1.73 m2 or start of renal replacement therapy.

Results:

5-year endpoint-free renal survival was 64.5% (95%CI 57.4-71.7%) in children with suPAR in the lowest quartile as compared to 35.9% (95%CI 28.7-43.0%) in those with levels in the highest quartile (P<0.0001). In multivariable analysis, the risk of attaining the endpoint was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria and lower eGFR at baseline. In patients with baseline eGFR>40 ml/min/1.73 m2, higher log-transformed suPAR levels were independently associated with a higher risk of CKD progression (HR 5.12, 95% CI 1.56-16.7, P=0.007).

Conclusions:

Elevated suPAR levels are independently associated with disease progression in children with mild to moderate CKD. Further studies are warranted to determine whether suPAR measurements in pediatric CKD patients will facilitate the identification of children at need for early nephroprotective interventions.