Saudi Journal of Kidney Diseases and Transplantation

ORIGINAL ARTICLE
Year
: 2011  |  Volume : 22  |  Issue : 3  |  Page : 497--500

Renal tubular dysfunction in pediatric patients with beta-thalassemia major


Ali Ahmadzadeh1, Amir Jalali2, Shiedeh Assar3, Hamid Khalilian3, Khamorad Zandian4, Mohammad Pedram4,  
1 Pediatric Nephrology Division, Abuzar Children's Hospital, Ahvaz, Iran
2 Pharmacy School, Ahvaz, Iran
3 Department of Pediatrics, Gholestan Hospital, Ahvaz, Iran
4 Department of Hematology-Oncology, Shafa Hospital and Hemoglubinopathies Research Center, Ahvaz Jondishapur University of Medical Sciences (AJUMS), Ahvaz, Iran

Correspondence Address:
Ali Ahmadzadeh
Pediatric Nephrology Division, Abuzar Children«SQ»s Hospital, Ahvaz
Iran

Abstract

To evaluate the prevalence of renal tubular dysfunction in children with β-thalassemia (β-T) major, we studied the glomerular and tubular function in 140 children with β-T major and compared them to a healthy control group at our center from May 2007 to April 2008. Fresh first morning samples were collected from each patient and analyzed for sodium, potassium, calcium (Ca), protein, uric acid (UA), creatinine (Cr), urine osmolality and urinary N-acetyl-β-D-glucosaminidase (UNAG) activity. Blood samples were also collected for complete blood count, blood urea nitrogen (BUN), fasting blood sugar, serum creatinine (SCr), electrolytes, and ferritin before transfusion. Among the study patients, 72 were males, and the mean age was 11.5 (ranging 7-16) years. SCr levels were all within normal limits and all of them had normal glomerular filtration rate (GFR). The mean UNAG was 17.8 IU/L in the study patients (normal 0.15-11.5 IU/L) and 3.2 IU/L in the control group (P < 0.001). Of the 82 study patients who had elevated level of UNAG, 58 (62.4%) had high blood levels of ferritin also (r = 0.2, P < 0.001) and 13 (15.9%) patients had hypercalciuria also (UCa/UCr > 0.21) (P = 0.006). Nine (6.4%) thalassemic patients with a mean age of 12 years had proteinuria (Upr/UCr > 0.2). Sixty-nine (49.3%) out of the 140 patients and 45 (65.2%) of the patients having UNAG had uricosuria also (UUA/UCr > 0.26). Ten (7%) patients had microscopic hematuria and 10 (7%) patients with a mean age of 13.5 years had glucosuria or diabetes mellitus. We conclude that tubular dysfunction is a relative common complication of the β-T major; UNAG and its index are the best to detect renal tubular dysfunction in these patients. Currently, periodic measurement of UCa/UCr and UUA/UCr ratios as well as urinalysis are recommended.



How to cite this article:
Ahmadzadeh A, Jalali A, Assar S, Khalilian H, Zandian K, Pedram M. Renal tubular dysfunction in pediatric patients with beta-thalassemia major.Saudi J Kidney Dis Transpl 2011;22:497-500


How to cite this URL:
Ahmadzadeh A, Jalali A, Assar S, Khalilian H, Zandian K, Pedram M. Renal tubular dysfunction in pediatric patients with beta-thalassemia major. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2019 Dec 14 ];22:497-500
Available from: http://www.sjkdt.org/text.asp?2011/22/3/497/80487


Full Text

 Introduction



Patients with beta-thalassemia (β-T) major are known to have severe cardiopulmonary, reticuloendothelial, and other major system dysfunction, but renal involvement has received little attention. Various glomerular pathologies have been sporadically reported, and it is still unknown whether these abnormalities are genuinely associated with thalassemia syndromes. [1],[2] Renal tubular acidosis has also been reported in patients with thalassemia. [3]

In recent years, there have been few published studies demonstrating proteinuria, aminoaciduria, low urine osmolarity and excess secretion of the proximal tubular damage markers such as N-acetyl-β-D-glucosaminidase (NAG) and β2 microglobulin in such patients.[4],[5],[6],[7] Although the main cause of tubular dysfunction in the patients remains unknown, renal damage can be attributed to chronic anemia, iron overload, and deferoxamine therapy. Excess free iron is known to be a catalyst of lipid peroxidation which damages cells. [6],[8] NAG is a proximal renal tubular protein that is excreted in the urine during tubular damage. [9] β-T is a well-known hereditary disease in Iran, particularly in the southwestern and northern provinces, and there are more than 20,000 beta-thalassemic patients and carriers in this country.[10]

The present study aims to evaluate the prevalence of renal tubular dysfunction in children with β-T major.

 Material and Methods



In a cross-sectional study, we assessed the glomerular and tubular function in 140 children (age 7-16 years) with β-T major and compared them with 140 normal children, from May 2007 to April 2008. These patients were referred to the thalassemia clinic of Shafa hospital, the only hematology and oncology center in south-western Iran. The diagnosis of β-T major was based on standard criteria. The control group was selected from healthy volunteers; all subjects of this group matched in age and gender with the study group. The results of the kidney and urinary tract ultrasonography were normal in all the patients. Demographic data, including age, sex, duration of transfusion therapy and deferoxomine therapy, were collected.

All the patients received blood transfusion with iron chelation. Packed red blood cells were transfused every 3-4 weeks. Deferoxamine was administered subcutaneously at 50 mg/kg body weight with a pump for 6 days per week.

Fresh first morning samples were collected from each patient and analyzed for sodium (Na), potassium (K), calcium (Ca), protein, uric acid (UA), creatinine (Cr), urine osmolality and urinary NAG activity. A colorimetric method was used to measure the NAG (Diazgme, General Atomics, La Jolla, CA, USA).

Blood samples were also collected for complete blood count, blood urea nitrogen (BUN), fasting blood sugar, serum creatinine (Scr), electrolytes, and ferritin before transfusion. Estimated glomerular filtration rate (GFR) was calculated according to the Schwartz formula [GFR (mL/min/1.73 m 2 ) = K × height (cm)/SCr].

Fractional excretion of sodium (FENa), fractional excretion of potassium (FEK), uric acid excretion (UAE) and urinary ratios of protein/ Cr, and Ca/Cr and NAG/Cr were calculated with standard formulas.

This study was approved by the ethics committee of Jondishapur University of Medical Sciences. Parental consent was also obtained for each patient.

 Statistical Analysis



Data were evaluated by SPSS software, chi-square and t-test. A P value <0.05 was considered to be significant.

 Results



Among the study patients, 72 (51.4%) were males and 68 (48.6%) were females. The mean age was 11.5 (ranging 7-16) years. BUN and SCr levels were all within normal limits, and according to the Schwartz's formula, all of them had normal GFR [129 (92%) had >100 mL/min/ 1.73 m 2 and the rest had between 90 and 100 mL/min/1.73 m 2 ]. Serum Na, Ca and uric acid levels were also within normal limits.

The mean UNAG activity was 17.8 IU/L in the patients' group (normal: 0.15-11.5 IU/L), and 3.2 IU/L in the control group (P < 0.001) [Table 1]. Nobody in the control group had an abnormal UNAG, whereas 82 (52.6%) study patients had an elevated UNAG. The mean age in patients with abnormal UNAG activity was 12.4 years, while in the patients who had normal UNAG it was 10.2 years (P < 0.001). Of the 82 patients having elevated level of UNAG, 58 (62.4%) had a high blood level of ferritin also (r = 0.2, P < 0.001) [Table 2] and 13 (15.9%) patients had hypercalciuria also (UCa/UCr > 0.21) (P = 0.006) [Table 3]. Nine (6.4%) thalassemic patients with the mean age of 12 years had proteinuria (urinary protein to creatinine ratio >0.2). Sixty-nine (49.3%) out of the 140 patients and 45 (65.2%) of the patients who had abnormal UNAG revealed uricosuria also (uric acid/UCr > 0.26) [Table 4]. FENa, FEK, and urine osmolality were within normal limits in all the study patients. Ten (7%) study patients had microscopic hematuria and 10 (7%) patients with the mean age of 13.5 years had glucosuria and diabetes mellitus, receiving daily insulin.{Table 1}{Table 2}{Table 3}{Table 4}

 Discussion



Although the main cause of tubular dysfunction in patients with β-T major remains unknown, [4],[8] renal damages can be attributed to chronic anemia, iron overload, and deferoxamine therapy. Glomerular damage can also occur in these patients due to the prolonged use of deferoxamine and recurrent infections, resulting in a decreased ability of the kidneys to clear immune complexes. [9] In the present study, we investigated the renal function in children with β-T major. The main findings in our study are as follows:

Elevated level of UNAG, a good and sensitive marker of proximal tubular damage. Accordingly, about 60% of our patients had some degree of renal tubular damage.Hypercalciuria was found in about 16% of the patients who had abnormal levels of UNAG, which is another reason for the presence of tubular damage in the patients.Uricosuria, another marker of proximal tubular dysfunction, was found in 58.6% of our patients.

Fifty-nine percent of the patients with an abnormal level of UNAG had a serum ferritin level more than 2000 ng/dL; this condition is correlated with proximal tubular damage secondary to toxic effect of iron load. UNAG is a lysosomal enzyme that plays a role in the breakdown of glycoproteins in proximal tubular cells. Increased concentrations of UNAG indicate a loss of lysosomal integrity of tubular epithelial cells and can be an indicator of tubular dysfunction in various diseases. [11],[12] Since UNAG activity has recently been shown to vary with age and diuresis, an UNAG index (UNAG/creatinine) is often used to minimize variability.

Our findings are in accordance with the study of Mohkam [7] who reported abnormal urinary ex-cretion of NAG in 36% and uricosuria in 52%, but we found proteinuria in only 6.4% instead of 89% reported in that study. Cianciuli [11] evaluated renal function in 19 beta-thalassemic patients in Italy and found evidence of renal tubular damage in 13 patients. Seven percent of our patients had microscopic hematuria which might be related to either hyperuricosuria or hy-percalciuria. However, further studies are re-quired to confirm this speculation. GFR was normal in all the patients, which means that renal failure is a terminal event in β-T major and it is probably due to heart failure and/or hepatic failure.

We conclude that tubular dysfunction is a re-latively common complication of β-T major; UNAG and its index are the best to detect renal tubular dysfunction in these patients. Currently, periodic measurement of UCa/Ucr and UUA/U Cr ratios as well as urinalysis are recommended.

 Acknowledgments



The authors would like to thank the Vice-chancellor for Research of Jondishapur University of Medical Sciences, Ahvaz, Iran, for his financial support and also Mr. Cheraghian for his help in statistical analysis of the results.

References

1Lapatsanis P, Sbyrakis S, Vertos C, Karaklis BA, Dosiadis S. Phosphaturia in thalassemia. Pediatrics 1976;58:855-92.
2Mastrangelo F, Lopez T, Rizzelli S, Manisco G, Corliano C, Alfonso L. Function of the kidney in adult patients with Cooley's disease. A preliminary report. Nephron 1975;14:229-36.
3Shahab M, Barakat AY. Thalassemia β with distal renal tubular acidosis: a previous undescribed association Int J Pediatr Nephrol 1985;6: 143-4.
4Ong-ajyooth L, Malasit P, Ong-ajyooth S, et al. Renal function in adult beta-thalassemia/HbE disease. Nephron 1998;78(2):156-61.
5Sumboonnanonda A, Malasit P, Tanphaichitr VS, et al. Renal tubular function in beta-thalassemia. Pediatr Nephrol 1998;12:280-3.
6Aldudak B, Karabay Bayazit A, Noyan A, et al. Renal function in pediatric patients with beta-thalassemia major. Pediatr Nephrol 2000;15: 109-12.
7Mohkam M, Shamsian BS, Gharib A, Nariman S, Arzanian MT. Early markers of renal dys-function in patients with beta-thalassemia. Pediatr Nephrol 2008; 23:971-6.
8Sumboonda A, Malasit P, Tanphaichitr VS, Ongajyooth S, Vongiirad A. Renal tubular dys-function in alpha-thalassemia. Pediatr Nephrol 2003;18:257-60.
9Hyman CB, Gonick HC, Agness C, Nadorra R, Landing B. Effect of deferoxamine on renal function in thalassemia. Birth defects Orig Arctic Ser 1988;2 3:135-40.
10Ministry of Health and Medical Education. A report on mass screening of minor thalassemia and prevention program in Iran. Undersecretary for health Affairs. Center for disease control. Suda Publ, Tehran, 2004.
11Cianciula P, Sollecito D, Sorrentino F, et al. Early detection of nephrotoxic effects in thalassemic patients receiving desferoxamine therapy. Kidney Int 1994;46:467-70.
12Derakhshan A, Karimi M, Ghadi-Moghaddam A. Comparative evaluation of renal findings in beta-thalassemia major and intermedia. Saudi J Kidney Dis Transpl 2008;19:206-9.