Renal Dysfunction in Pediatric Thalassemia Major Patients and Evaluation of Urine NGAL Levels in Thalassemia
Authors: Ozek Gulcihan , Carti Özgür , Serdaroglu Erkin , Cuhadar Serap , Yaman Yöntem , Oymak Yesim , Gunes Burcak , Gözmen Salih , Vergin Canan 
Published: October 2019

Abstract
Aim: There are limited studies on renal involvement in beta-thalassemia patients. The aim of the present study was to investigate renal dysfunctions in pediatric patients with transfusion dependent beta thalassemia major (TD-βTM), using both conventional and early markers of glomerular and tubular dysfunctions and corralate findings to iron chelation therapy, deferasirox. Neutrofil-gelatinase associated lipocalin (NGAL) is an emerging biomarker in early diagnosis of acute kidney injury and also elevated urine NGAL is a good predictor of chronic kidney disease. We aimed to evaluate urine NGAL/creatinin ratio in thalassemia patients and corralate findings with normal controls.
Methods: Fifty-three TD-βTM patients (aged 5-19 years) and 47 healthy controls (aged 3.5-18 years) were enrolled in this study. All patients were regularly transfused and all of them were using oral chelator; deferasirox. In addition to conventional renal biochemistries, serum cystatin C were measured with immunoturbodimetric technique. Fresh second morning urine samples collected and analysed for sodium, potassium, calcium, protein, creatinine, glucose, phosphate, uric acid, β2-microglobulin and NGAL. NGAL was measured with immunosorbent assay (ELISA). We calculated glomerular filtration rate by Schwartz formula, fractional excretion of sodium, tubular phosphorus reabsorption and uric acid excretion. Serum ferritin concentration was also measured to asses iron overload.
Results: The mean age of our patients were 145±45 month, and controls were 158±140 month. A considerable number of patients demonstrated impaired renal functions. Glomerular hyperfiltration was detected in 9.5%, proteinuria in 40% , hypercalciuria in 60% increased urinary excretion of β-2 mikroglobulin in 62%, increased uric acid excretion in 58% of thalassemia patients. We detected renal tubular and glomerular dysfunctions is associated with especially pretransfusional low hemoglobine levels. We detected no relationship with deferasirox treatment doses and period with renal patologies. Mean levels of plasma cystatin C were elevated in the patient cohort compared to controls ( 0.9+0.2 and 0.78 + 0.06 mg/L, respectively, p<0.05) , Specificially ; 26/53 thalassemia patients (%49) presented with abnormally elevated serum cystatin C. Mean levels of urine NGAL/creatinin ratio was found to be elevated in patients compared to controls (85 + 88 and 31 + 38 ng/mg kreatinin, respectively, p<0.001). In thalassemia group negative significant correlation between ürine NGAL/creatinin ratio and pretransfusional hemoglobine levels was found (r=-0.35, p<0.01). And also we detected urine NGAL/creatinin ratio was corralate with other renal parametries; such as serum cystatin c/creatinin, urine β-2MG/creatinin, urine Ca/creatinin values.
Conclusions: Our data confirm high frequency of glomerular and tubular dysfunctions in TD-βTM pediatric patients, and renal patologies was associated especially pretransfusional low hemoglobine levels. Therefore routine use of early markers of renal dysfunction such as urine NGAL is recommended for all patients.

Disclosures
No relevant conflicts of interest to declare.