Background: Beta thalassemia syndromes are a group of hereditary disorders chara-cterized by a genetic deficiency in the synthesis of beta-globin chains. In β-thalassemia major, the production of beta-globin chains is severely impaired because both beta-globin genes are mutated. This imbalance of globin-chain synthesis results in ineffective erythropoiesis and severe microcytic hypochromic anemia. In β-thalassemia, profound anemia and severe hemosiderosis can cause functional and physiological abnormalities in various organ systems. There are limited studies on renal involvement in β-thalass-emia, mainly involving patients on iron chelation therapy, reporting both glomerular and tubular dysfunction. Although the main underlying cause of renal dysfunction in these patients remains unknown, the renal damage can be attributed to chronic anemia, disturbed circulation through the medullary capillaries, iron overload and iron chelation therapy. Early identification of patients at high risk of developing renal failure is of great importance as it may allow specific measures to delay the progression of renal damage and thus reduce the incidence of end- stage renal failure and mortality. This prospective study aimed to detect the early renal involvement in young patients with transfusion dependant and or independent beta-thalassemia major, using both conven-tional and early markers of glomerular and tubular dysfunctions with early identification of patients at high risk of developing renal failure and to correlate these findings to iron chelation therapy.
Patients and Methods: This case –control observational retrospective study was cond-ucted on forty two β-thalassemia patients (27 males and 15 females) ,their ages ranged 5 –40 years old (mean age 15.1±8.09 years), recruited from the Hematology Unit, Department of Internal Medicine, Assuit University Hospital and Pediatric Hematology Unit, Pediatric Assuit University Hospital, Egypt from July 2010- December 2012. In addition, twenty two apparently healthy persons (11 males and 11 females), their ages ranged 8 –35 years old (mean age 18.9±7.41 years) were included as a control group .The patients were classified into two groups according to chelation therapy into thirty eight patients on chelation therapy, their ages ranged 5–40 years old (mean age 15.6±8.2 years) and four patients without therapy, their ages ranged 7 –40 years old (mean age 10.8±6.2 years). For analysis purposes, the patients under chelation therapy were divided into 2 groups: 26 cases on deferioxamine (DFRA) and 12 cases on deferiprone (DFO) therapy. All were subjected to thorough history taking, full clinical examination, and anthropometric measurements. Peripheral hemogram, liver function tests, iron indi-ces, serum ferritin, kidney function tests, complete urine analysis, creatinine clearance using Schwartz formula for children up to 18 years and Cockcroft – Gault MDRD or CKD-EPI formula for adults above 18 years, protein in urine, serum cystatin C (Cys C), JESNT, 15(1) Jan., 2015
serum and urinary β2 microglobulin (β2 MG) were measured by ELISA for both patients and controls.
Results: A considerable number of patients demonstrated impaired renal function with elevated Cys C levels (57.1%), glomerular dysfunction with hyperfiltration (80.95%), proteinuria (33.3 %), and elevated excretion of β2 MG (35.7%). The serum cystatin C (Cys C), serum and urinary β2 microglobulin (β2 MG) showed a strong correlation with creatinine clearance and age. The inverse correlations were also shown between haemoglobin, serum creatinine, urinary albumin and Cys C, β2 microglobulin (β2 MG) levels. These results indicate that Cys C is an accurate marker of renal dysfunction and urinary β2- MG can be considered as a reliable index of the tubular toxicity, and a possible predictor of proteinuria and eventual renal impairment in β-thalassemia patients, therefore, routine use of early markers of renal dysfunction is recomm-ended.There were high significant statistically differences regarding cystatin C (Cys C),serum and urinary β2 microglobulin (β2 MG) between patients and controls. However, no statistically differences regarding the age, gender, increased heart rate and high blood pressure between them were reported. Between patients subgroups according to iron chelation therapy, no statistically difference regarding, the duration between splenectomy and 1st blood transfusion, iron indices, serum ferritin, serum creatinine, creatinine clearance, proteinuria , hemoglobin level and serum β2 microglobulin (β2 MG) were reported, however, there were high statistical significant differences in the duration of blood transfusion, high blood pressure, organomegaly, splenectomy, serum cystatin C (Cys C) and urinary β2 microglobulin (β2 MG) between subgroups. Our results illustrated that the frequency of given blood transfusion to thalassemic patients (either ≥ or < than 10 times per year) had no effect on renal dysfunction, however, we reported that the ferrittin level (either ≥ or < than 1000 ng\dl) had significant effect on renal dysfunction. Nevertheless, our study also showed the more deterioration of renal Function in transfusion β- thalassemia major patients under iron chelation therapy especially desferioxamine (DFRA) with no significant statistical difference.
Conclusion: Renal dysfunction is a relative common complication of the β- thalassemia major and it may increase in terms of frequency with age, increased duration of transfusion and deferoxamine usage .Early identification of patients at high risk of developing renal damage is of great importance as it may allow specific measures to be undertaken that will delay the progression of renal injury and thus reduce the incidence of renal impairment. Cystatin C is an accurate marker of renal dysfunction and urinary β2- miroglobulin can be considered as a reliable index of the tubular toxicity, and a possible predictor of proteinuria and eventual renal impairment in β-thalassemia patients, therefore, routine use of early markers of renal dysfunction is recommended. Based on the results of our study and those of others, meticulous monitoring of renal function is mandatory for patients undergoing treatment with DFRA and means of preventing these disturbances should be sought. The usefulness of alternative drugs, such as deferiprone instead of deferoxamine, should be studied further.