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

Abstract

Background: Limited data are available about renal involvement in thalassemia patients. Renal dysfunction in these patients seems to be multifactorial attributed mainly to long standing anemia, chronic hypoxia, iron overload and toxicity of iron chelators.Objective: To assess the frequency of subclinical glomerular and tubular dysfunctions in children and adolescents with b-thalassemia major and intermedia, and to correlate these findings with the degree of iron overload and type of chelation therapy.Methods: The study included 40 thalassemia major and 20 thalassemia intermedia pediatric patients recruited from the Pediatric hematology clinic, Ain Shams University. Serum sodium, potassium, phosphorous and creatinine, and urinary sodium, potassium, phosphorous, protein/creatinine ratio and urinary b2 microglobulin were measured. Fractional excretion of sodium and potassium was calculated.Results: The mean level of serum creatinine in all patients was within the normal range and comparable in both TM and TI groups (0.17 ± 0.06 and 0.18 ± 0.07 mg/dl, respectively, P > 0.05). The mean eGFR was higher than normal range in both TM and TI groups (552.65 ± 231.73 and 472.15 ± 272.99 ml/min, respectively). Mean level of urinary b2 microglobulin was within the normal range (0.13 ± 0.05 and 0.10 ± 0.03 lg/ml) in TM and TI patients, however, it was significantly higher in TM patients (P = 0.009). Urinary b2 microglobulin was positively correlated to Abbreviations: A/C, albumin/creatinine ratio; b2MG, urinary b2 microglobulin; CBC, complete blood count; FENa, fractional excretion of sodium; FEK, fractional excretion of potassium; Hb, hemoglobin; HPLC, high-performance liquid chromatography; NAG, N-acetyl-b-dglucosaminidase; TM, thalassemia major; TI, thalassemia intermedia; U pr/Cr ratio, urinary protein/creatinine ratio * Corresponding author. E-mail addresses: amiradiabetes@yahoo.com (A.A.M. Adly), dtoaima@yahoo.com (D.N. Toaima). Production and hosting by Elsevier B.V. on behalf of Ain Shams University. both transfusion index and serum ferritin level (P < 0.05). Tubular reabsorption of phosphorus (TRP) was significantly higher among TM patients (P = 0.037). The mean height and height percentile were lower in the poorly chelated group (serum ferritin P2500 ng/ml) than the well chelated group. In addition, the mean serum sodium and urinary protein/creatinine ratio were significantly higher in the poorly chelated group (P < 0.05).Conclusion: Subclinical renal affection can start earlier in TM patients compared to TI. Poor chelation is associated with early signs of renal affection. Periodic renal assessment of those patients is mandatory as they may be affected by hidden renal dysfunction.Ó 2014 Production and hosting by Elsevier B.V. on behalf of Ain Shams University.

Evaluasi Fungsi Ginjal pada Penyandang Talasemia-β Mayor Anak

“…1,12,13 Beberapa penelitian mengenai keterlibatan ginjal pada penyandang talasemia-β mayor dewasa telah dilaporkan, tetapi data pada anak belum banyak didapatkan. 3 Pada penelitian ditemukan kadar rata-rata kreatinin serum yang rendah 0,38 (0,08) mg/ dL, dan didapatkan 32% subjek berstatus nutrisi kurang serta stunted sebanyak 80%. Hasil ini sesuai dengan penelitian di India tahun 2007 tentang pengaruh malnutrisi dan stunted terhadap kadar kreatinin serum.…”

“…14 Hal ini serupa dengan penelitian di Kairo pada 40 penyandang talasemia-β mayor anak dengan status gizi kurang sebanyak 32,5% didapatkan kadar kreatinin serum berada dalam nilai yang sama. 3 Sementara hasil penelitian di Iran melaporkan hanya 2% dari 208 penyandang talasemia dewasa yang menunjukkan peningkatan kadar kreatinin serum. 15 8-63 tahun tidak menunjukkan adanya korelasi kadar NGAL serum dan feritin.…”

“…Penyebab pasti disfungsi ginjal pada talasemia-β mayor belum diketahui sepenuhnya, tetapi dipastikan bahwa penyebabnya bersifat multifaktorial. [1][2][3] Saat ini, penanda kerusakan ginjal yang digunakan adalah kadar kreatinin serum. Pemeriksaan kreatinin tidak dapat digunakan untuk mendeteksi gangguan fungsi ginjal secara dini karena peningkatan kadar kreatinin serum mulai muncul ketika telah terjadi penurunan fungsi ginjal yang signifikan.…”

Fungsi Ginjal Pasien Thalassemia Mayor yang Mendapatkan Kelasi Besi Oral

“…Apabila kondisi penumpukan besi makin berat akan terjadi kerusakan sel tubular, dan pada akhirnya mencetuskan sitokin dan growth factor interstitial sehingga menyebabkan skar dan sklerosis glomerular. 19,20 Penelitian kami mendapatkan 9 (32,1%) pasien pengguna DFP dan 8 (30,8%) pasien pengguna DFX yang memiliki nilai LFG >140 ml/menit/1,73 m 2 .…”

Cystatin C an early marker of Glomerular dysfunction in thalassemia major.

“…6 Less is known about the effects of thalassemia on kidneys, however, anemia, chronic hypoxia, oxidative stress, iron excess and harmful effects of iron chelators can influence the normal functioning of the kidneys. 7 Hyperdynamic circulation due to chronic anemia may increase renal plasma flow and glomerular filtration rate (GFR), however, longstanding anemia and hypoxia can also cause epithelial and endothelial injury with transudation of macromolecules into the mesangium thus contributing to progressive glomerular injury and decrease in GFR. 3 GFR is measured by the plasma clearance of a substance in a unit of time by the kidney.…”