Insidious Renal Damage in Patients with Thalassemia Major: Is it More Serious than Appreciated?

Abstract

Aim: To investigate early renal injury in thalassemia major patients by using novel serum markers and demonstrate the factors leading to renal injury. Material and Methods: Seventy-one thalassemia major patients (37 males) who were on regular transfusion and chelation programme with deferasirox have been enrolled in this study. Thirty-five healthy children of the same age served as a control group. Serum urea-creatinine, electrolytes, cystatin C and glomerular filtration rate were all noted in our cohort and compared with the control group. Proteinuria was also investigated by calculating UPr/UCr ratio. Results: The median serum creatinine level was 0.4 mg/dL (range; 0.2-0.76 mg/dL) and the median glomerular filtration rate level was 192 mL/min/1.73 m 2 (range; 106-308 mL/min/1.73 m 2) in patients. More than half of the patients had glomerular hyperfiltration (n=48, 67.6%). Hyperfiltration was prominent in thalassemia group (66.2% vs. 19.4%) (p=0.0001). Mean serum cystatin C levels were found to be statistically elevated in patient group comparing with controls (p=0.0001). Serum cystatin C level was above >1 mg/L in 46 patients (64.7%) whereas only three in controls (p=0.0001). Sex, age, hemoglobin level and cardiac T2* MRI results were not related to the elevated cystatin C levels. On the other hand, liver iron burden and serum ferritin levels were noted to be statistically correlated to elevated cystatin C level (p=0.024 and p=0.04). Deferasirox dose below 25 mg/kg/day was also found in relation with elevated cystatin C levels. Conclusion: Renal injury is multifactorial, insidious but progressive in thalassemia patients. High index of suspicion and routine use of novel markers are required for detection of renal injury during the follow up of thalassemia patients.

Detection of Renal Insufficiency in a Cohort of Patients With Beta-thalassemia Major Using Cystatin-C

“…In the current study, 56 patients (59.6%) had elevated Cystatin-C. Similarly, in previous study done by Gokce et al, 16 mean serum Cystatin-C levels were elevated in 46 (64.7%) of the studied β-TM patients in Turkey.…”

“…The source of elevated serum AST among patients with β-TM having elevated Cystatin-C serum levels could be because of the pathology of hemolysis or of hepatic origin, secondary to increased iron deposition or of muscular origin. 16 In a study performed in Iran by Sadeghi-Bojd et al, 18 high urinary levels of protein, calcium, phosphorous, uric acid, magnesium, and β2-microglobin were common signs among βTM patients and concluded that the pathology of β-TM can affect both renal tubules and glomeruli.…”

Hyperferritinemia and Other Factors Related to Glomerular Injury in Beta-Thalassemia Major

“…Hemoglobin level should be maintained for a range of 9.5-10.5 g/dl in order to maintain growth and development in normal range until the age of 10-11, however over that age, a complication may occur due to iron overload and chronic anemia. Gokce et al [31] found that BTM patients with glomerular hyperfiltration had a median hemoglobin level of 8.6 g/dL (7,6-10,5 g/dL). This hemoglobin range cannot be extrapolated in all health facilities as it depends on individual health center protocol and availability of local resources.…”

Serum Neutrophil Gelatinase-Associated Lipocalin as a Biomarker for Early Renal Dysfunction in Adult Egyptian Patients with b-Thalassemia Major

“…Regarding renal injury, several factors might play role in patients with thalassemia. Chronic hypoxia, ongoing hemolysis, iron overload owing to transfusions and possible nephrotoxicity of chelators are well-known reasons of the deterioration in renal functions [9] .…”