Urinary neutrophil gelatinase-associated lipocalin as a marker of kidney injury in Egyptian patients with thalassemia

Abstract

Background Renal disease is a long-term complication that should be recognized in thalassemia, especially with the rise in the average age of this population. Proper assessment of renal function abnormalities in thalassemia can be challenging because of the increased use of iron chelators, which themselves can affect renal function. There is a trend toward earlier detection of glomerular and tubular abnormalities, using early biomarkers of renal dysfunction. However, conflicting data make conclusive correlations difficult to achieve and strong diagnostic statistical parameters for these biomarkers are still lacking. Examples include albumin/creatinine ratio which can predict the initial signs of glomerular impairment, serum cystatin-C, and serum or urinary β-2 microglobulin have received attention as better tools to assess sensitive changes in glomerular filtration rate (GFR) and creatinine clearance in thalassemia as compared with serum creatinine and eGFR. Neutrophil gelatinase-associated lipocalin (NGAL) excretion in urine occurs when there is proximal tubular injury that disrupts NGAL reabsorption or increases NGAL synthesis. Significant correlations between the levels of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and the degree of proteinuria in patients with chronic renal disease from diverse etiologies have been reported. Aim The study was to assess the markers of renal injury in β-thalassemia (β-TM) patients and to detect the significance of urinary albumin/creatinine ratio and uNGAL levels, as markers of kidney injury in Egyptian patients with thalassemia. Materials and methods This case–control study was conducted on 40 β-TM patients and 45 age-matched and gender-matched healthy controls, 27 women and 13 men, with a mean age of 29±9 years and for controls 28±5 years. The majority of enrolled patients (22) were thalassemia intermediate. One-third of the patients were receiving iron chelation therapy, 78.6% on deferasirox, and 21.4% on deferiprone. All patients were subjected to through history taking, physical examination, and routine laboratory investigation. Tests were done for the diagnosis of thalassemia and to identify the type of thalassemia. Type and dose of Iron chelation therapy was recorded treatment: type and dose of chelation. Measurement of uNGAL and calculation of uNGAL/creatinine ratio were done. eGFR was calculated according to the original modification of diet in renal disease equation eGFR (ml/min/1.73 m2). Chronic kidney disease was defined and graded according to KDIGO 2012. Results The results show that there is a statistically significant difference between cases and controls regarding uNGAL level as median was 498.0 ng/ml for cases compared with controls 423.3 ng/ml with a P value of 0.034. There is a statistically significant difference between cases and controls regarding uNGAL/creatinine ratio as the median was 481.75 ng/mg for cases compared with 333.79 with a P value of 0.003. There is no significant correlation between uNGAL (ng/ml) and dose of iron chelator, duration of iron chelator, eGFR, hemoglobin (Hg) level, serum ferritin, and albumin/creatinine ratio. There is no significant correlation between uNGAL/creatinine ratio (ng/mg) and eGFR, Hg level, serum ferritin, and albumin/creatinine ratio. eGFR was significantly higher (hyperfiltration) in cases compared with controls, with a median of 169.8 ml/min/1.73 m3 compared with 119.6 ml/min/1.73 m3, with a P value of less than 0.001. There was a statistically significant difference between cases and controls regarding albumin/creatinine ratio (μg/mg creatinine) as the median was 29.4 μg/mg creatinine for cases compared with controls 10.0 μg/mg creatinine with a P value of less than 0.001. Conclusion This study showed that assessment of albumin/creatinine ratio, uNGAL, and uNGAL/creatinine ratio, can be regarded as potential early biomarkers of renal dysfunction in β-TM patients.

Keywords

• chelation therapy
• neutrophil gelatinase-associated lipocalin thalassemia
• renal disease