Evaluation of Early Glomerulopathy and Tubulopathy in Patients with Transfusion Dependent Thalassemia

Background: We have less information about renal injury in patients with transfusion dependent ß thalassemia (TDT).Cystatin C (Cys-C) is a marker to predict glomerular dysfunction with higher sensitivity and specificity than serum creatinine. Asymptomatic renal tubular dysfunction demonstrated in patients with Beta-thalassaemia who receive deferasirox although age and dose-dependent toxicity profile could not be fully understood.

Aim: The aim of this study was to evaluate renal tubular and glomeruler functions and the etiology of early glomerulopathy and tubulopathy in patients with TDT.

Patients and methods: Fifty TDT patients (2-45years, 28 F and 22 M, mean age:18.4±11.8 years), were evaluated for glomerulopatrhy and tubulopathy by using standard hematology and biochemistry, urine pH, blood pH, urine ca/crea ratio and meanFractional Na excretion (FENe) and compared to reference values. Thirthy healthy volunteer (18 F and 12 M, mean age: 21,6 ± 11, age ranged 3-44 years) were evaluated as control group. Thirthy-eight (75.5%) patients were receiving Deferasirox (DFX), 8 (16.3%) were Deferipron (DFP), 4 small children (8%) were none. Serum Cys-C and urine β-2MG were measured using a latex particle-enhanced nephelometric immunoassay. Patients with known renal disease were excluded.

Results: The main results of the study for tubulopathy were: a. Mean Na, K, Ca, P, urine and blood pH were within normal ranged. b. Eight older patients (16%) had high FENe. 7/8 of these patients received long term DFX therapy (mean 6,1±2.3 years) with 20-30mg/kg/day dose, c. Mean Ca/crea ratio (0.22 ± 0.11)and mean urine pH were found higher than normal level e. Eighteen percent (n=9) of patients had high urine β-2 MG (p<0.01). For glomerulopaty; a. No patient had increased serum Crea according to age. b. Mean urea, creatinin and albumin level determined within normal ranged b. eGFR was determinated above normal reference values according to age. c. 25/50 patients (50%) had higher serum Cys-C values compared with controls (p<0.001).When we evaluated the etiology of early glomerulopathy and tubulopathy,we found that; a. There were no statistically significant differences between pretransfusion Hb, liver iron overload, cardiac iron overload, and sistatin C, β-2 MG, FENa, Ca/Kreatinin, and GFR. b. Cys- C, urea, creatinine increases with the age, β-2 MG and FENe does not change with age. c. There was no statistically significant difference between Cys-C and β-2 MG levels in patients used DFP and control groups' but statistically difference was found between DFX and control group(Table 1). d. B-2 MG level significantly increased who received high dose DFX (20-30 and 30-40 mg/kg/day compared to 15-20 mg/kg/day dose and controls (Table 2). e. β-2MG level were higher in patients with ferritin level <500 ng/ml and >1000 ng/ mL than in control group (p<0.000). Low and high ferritin level were risk for tubulopathy in TDT patients (Table 3). f. There was positive correlation between Cys-C and age. g. Cys- C is significantly higher than the control group in all patients and not related to DFX dose. h. Cys C were detected significantly higher than the control group in all patients not related to ferrtin levels.

Conclusion: Early identification of subclinical renal glomerular and tubular ýnjury in TDT patients had great importance and it may allow specific measures to delay the progression of renal damage.We suggest to evaluate intermittently early marker of glomerulopathy and tubulopathy in addition to routine renal function tests to prevent major renal injury in TDT patients.