Glomerular Hyperfiltration and Proteinuria in Transfusion-Independent Patients with β-Thalassemia Intermedia

Abstract

Background/Aims: Renal manifestations have been described in β-thalassemia major and were attributed to transfusional iron overload and chelation therapy. Patients with the milder phenotype, β-thalassemia intermedia (TI), remain largely transfusion and iron chelation independent while enduring a chronic hemolytic anemia and primary iron overload. Data on renal function in patients with TI is lacking. Methods: In this cross-sectional study of 50 TI patients, we evaluated the association of estimated glomerular filtration rate (eGFR) and urinary protein to creatinine (UPr/UCr) ratio with relevant patient, disease and laboratory indices. Results: The median age of patients was 28 years (44% males). The eGFR was >90 ml/min/1.73 m² in all patients, with a median value of 142.3 ml/min/1.73 m². The median UPr/UCr ratio was 213.2 mg/g. There was a negative correlation between age and eGFR, while the UPr/UCr ratio correlated positively with markers of anemia, hemolysis and iron overload. A total of 24 (48%) patients had evidence of glomerular hyperfiltration, while 7 (14%) had proteinuria (UPr/UCr ratio >500 mg/g). Patients with proteinuria were characterized by elevated liver iron concentration (>7 mg Fe/g dry weight), non-transferrin-bound iron levels and nucleated red blood cell counts. Conclusions: A considerable proportion of TI patients show evidence of abnormally elevated eGFR, with a declining trend towards advancing age. The occurrence of proteinuria is associated with anemia, hemolysis and iron toxicity.

Subclinical renal abnormalities in young thalassemia major and intermedia patients and its relation to chelation therapy

“…The mean GFR in our study (done by Schwartz equation) was higher than the normal range in both TM and TI groups indicating glomerular hyperfiltration. This was in agreement with other studies [26], which found that a total of 24 thalassemia intermedia patients (48%) had evidence of glomerular hyperfiltration (>149 ml/min/1.73 m 2 ) for males and females. Other studies [9,18] however, found that the mean GFR (evaluated by Schwartz formula) was within the normal reference range (107.5 ± 1.27 ml/min/1.73 m 2 ), and was comparable in TM and TI patients.…”

“…Mohkam et al [9] reported that 89.3% of their patients had abnormal U pr/Cr ratio. Also, Ziyadeh et al [26] found that 30 of their patients (60%) had abnormal U pr/Cr ratio and it was positively correlated with serum ferritin (P = 0.04). In our study, unlike other studies there was no significant correlation between U pr/Cr ratio and serum ferritin (P = 0.9).…”

Non-transfusion-dependent thalassemias

“…54 An association between iron overload and renal tubular dysfunction, as evident from proteinuria, has also been recently reported in β-thalassemia intermedia patients. 55 …”

GFR in Patients with β-Thalassemia Major

“…Recently, Ziyadeh et al (35) described hyperfiltration in patients with thalassemia intermedia by using eGFR (CKD-EPI formula). However, their Scr level was 0.5 mg/dl, suggesting a possible overestimation of GFR.…”