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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE  
Year : 2011  |  Volume : 22  |  Issue : 5  |  Page : 963-968
Beta thalassemia major: The effect of age on glomerular filtration rate


1 Department of Pediatric Nephrology, Tabriz Children's Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Oncology and Hematology, Tabriz Children's Hospital, Tabriz University of Medical Sciences, Tabriz, Iran
3 Department of Thalassemia Clinic, Tabriz Children's Hospital, Tabriz University of Medical Sciences, Tabriz, Iran

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Date of Web Publication6-Sep-2011
 

   Abstract 

Thalassemia is a common hereditary hemoglobinopathy disorder that affects many organs in the body. Estimation of kidney function is important, as it is the vital organ that plays the major role in the elimination of accumulated iron as well as the chelating drugs that have to be used as therapy. Sixty- three patients aged 1-29 years, with a mean ± SD of 14 ± 6.7 years, affected with beta- thalassemia major in Tabriz Children's Hospital were evaluated for their renal function on the basis of their age, serum iron, serum ferritin and serum creatinine levels along with two methods of estimating glomerular filtration rate (GFR); by Schwartz method for those under 18 years old and using Modification of Diet in Renal Disease (MDRD) formula for those who were 18 years and above. Elevation of serum creatinine denoting renal dysfunction was not seen in our patients, but hyperfiltration was a common finding. An increasing GFR was observed, which corresponded to age, but no relationships were seen between serum iron, serum ferritin, regular blood transfusion, chelating therapy to GFR.

How to cite this article:
Malaki M, Sorkhabi RS, Shoaran M, Shafighe B. Beta thalassemia major: The effect of age on glomerular filtration rate. Saudi J Kidney Dis Transpl 2011;22:963-8

How to cite this URL:
Malaki M, Sorkhabi RS, Shoaran M, Shafighe B. Beta thalassemia major: The effect of age on glomerular filtration rate. Saudi J Kidney Dis Transpl [serial online] 2011 [cited 2020 Jul 15];22:963-8. Available from: http://www.sjkdt.org/text.asp?2011/22/5/963/84396

   Introduction Top


Thalassemia major is a common etiology of anemia due to hemoglobinopathy and ineffective erythropoesis, especially in some parts of the world like the Mediterranean region, north and west of Africa and the Middle East. Frequency of thalassemia gene in Iran is reported to be 4-10%. [1]

Although thalassemia as a chronic disorder has many complications despite using chelating therapy, renal dysfunction is an uncommon finding in these patients. [1],[2],[3],[4] Kidneys are an important site that can be injured in thalassemia due to the generation of oxidative lipid peroxide, iron deposition, renal hypoxia due to anemia and toxic effects of iron chelating drugs. [5],[6],[7] Prototype of this involvement is the renal tubular dysfunction, demonstrated by low molecular weight proteinuria, aminoaciduria and high levels of N- acetyl-ί- D- glucosaminidase (NAG). [8],[9] Another reason for renal involvement in thalassemia is related to deferoxamine, which causes reduction of GFR as shown by Koren, [10] but Koliakos and Sumboonnanonda did not find any detrimental effect of deferoxamine on renal function. [2],[5] Evaluation of glomerular injury from a similar mechanism was demonstrated in renal biopsy, and findings included segmental glomeruloscerosis interstitial fibrosis and tubular atrophy. [11] Because there are multiple reasons for renal injury in thalasemia, evaluation of renal function of the patients in this study was done by measuring their GFR and not by serum creatinine alone.


   Methods and Materials Top


This is a cross- sectional study involving 63 patients with history, clinical features and laboratory findings and diagnosis of beta thalassemia major. Their ages were between one and 29 years, with a mean ± SD of 14 ± 6.7 years, including 29 females and 34 males [Table 1], [Table 2], [Table 3], [Table 4] adn [Table 5]. They were under management for their beta thalasemia major and were chosen for evaluation of renal function on the basis of serum creatinine and glomerular filtration rate (GFR), measured by height, weight, sex by Schwartz formula for those under 18 years and Modified Diet Renal Disease (MDRD) formula for those above the age of 18. Hyperfiltration was considered as GFR above 130 mL/min/1.73 m 2 as defined by Brochner- Mortensen (B- M) on the basis of previous studies [12],[13],[14],[15],[16],[17] and normofiltration considered as GFR between 90 and 130 mL/min/1.73 m 2 , and low GFR was below 60 mL/min/1.73 m 2 . Patients aged over 40 years, those under the age of one year and those affected with overt diabetes, renal malformation and overt congestive heart failure were not included in the study. Splenectomy was done when requirement of blood transfusion exceeded 250 mL/kg/year to achieve target hemoglobin. A classical treatment was considered as the patients receiving blood regularly every three weeks to achieve the desired pre- transfusion hemoglobin (above 9.5 less than 10.5 g/dL) and deferoxamine (starting after receiving 10-15 units of blood) as a chelating drug in a dose of 20-60 mg/kg/ day over 8-12 hours every night for 5- 6 days a week. This was considered as satisfactory treatment. Their iron status was evaluated by doing serum iron in μg/dL and ferritin level in μg /L. All data were analyzed with the statistical package SPSS16 data collected and processed by the Pearson test for parametric linear regression between variables (age, GFR, ferritin, serum iron, Cr) and Student's "t" test for parametric numerical data between groups. With a power of 95%, P- value less than 0.05 was considered significant.
Table 1: Data on sixty-three study patients with major thalassemia, their age serum iron, serum ferritin, renal function indices and physical growth measured in mean, minimum and maximum.

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Table 2: Correlations between variables with each other (Defined age has significant correlation with creatinine, iron and glomerular filtration rate)

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Table 3: Mean of glomerular filtration rates in those who underwent and did not undergo splenectomy and those who who were managed on a regular and irregular basis as per history

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Table 4: Hyperfiltration based on eGFR measured by modification of diet in renal disease (MDRD) for 18 and above and Schwartz formula for under 18 years.

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Table 5: Comaparison of age and hyperfiltration (more than 130 mL/min/1.73 m2) in beta-thalassemia major.

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   Results Top


Sixty- three patients aged between one and 29 years, with a mean ± SD of 14 ± 6.7 years, were included in the study. There were 29 females and 34 males, and splenectomy had been performed on five patients. Thirty- nine patients were under regular management with blood transfusions and deferroxamine and 24 were irregular for their treatment.

Mean GFR (min, max) ± SD was 134 (61, 225) ± 35 mL/min/1.73 m 2 . There was no significant relationship between GFR and serum iron or ferritin level (P insignificant).

The overall measured serum creatinine was: mean (min, max) ± SD 0.61 (0.4, 1.0) ± 0.12 and GFR was mean (min, max) ± SD of 164 (61, 225) ± 35.5. There was a correlation between decrease of serum creatinine and increase of the measured GFR (P < 0.001) [Figure 1]. Serum creatinine increased with age, as can be expected (P < 0.001) [Figure 2]. This shows that, in thalasemic patients, increasing values of serum creatinine seen as the age advances, cannot predict the decrease in GFR but on the contrary GFR increases with aging [Figure 1], [Figure 2], [Figure 3] and [Figure 4]. Therefore, measurements of both indices are necessary for evaluation of renal function in these patients.
Figure 1. Graph showing inverse relationship between glomerular filtration rate(GFR) and serum creatinine(cr) (P = 0.001, R = -0.42).

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Figure 2: Graph showing relationship between serum creatinine and age (P < 0.001, R = 0.47).

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Figure 3: Graph showing relationship between glomerular filtration rate and age (in spite of increasing serum creatinine as shown in Figure 1, GFR increa-ses) P = 0.025, R = 0.28.

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Figure 4: Graph showing significant linear relationship between age with GFR, creatinine and serum iron (P < 0.05).

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Although all creatinine measured in this group was in the normal range, it does not indicate anything about glomerular filtration rate to physicians, but calculating eGFR from creatinine level using formulas (Schwartz and MDRD) on the basis of height, sex and age or race showed a significant number of patients affected having hyperfiltration: in Schwartz group, 41% and in MDRD group, 68%. There was a correlation between age and GFR even above an eGFR of 130 as well (P = 0.025).

With an increase of age, the GFR also increased. Thirty- one (50%) patients with mean age ± SD of 16.3 ± 6.1 years had an eGFR above 130 (hyperfiltration) and 32 with mean age ± SD of 12.5 ± 6.8 years had an eGFR below 130 (P significant = 0.025).

There was no relation between age and ferritin level (P = 0.059), but we noticed an increasing level of serum iron with age (P = 0.008) and, also, there was a correlation of serum iron with serum ferritin (P = 0.021).


   Discussion Top


Thalassemia has deleterious affects on many organs by iron overload due to ineffective erythropoesis and repeated transfusions that are given for these patients and release of toxic free radicals and accentuation of oxidation process at the cellular level. [3],[4],[5]

Kidney is a vital organ that may be affected by thalassemia major at the glomerular level by lobular and segmental sclerosis and in the tubules by atrophy and interstitial fibrosis. [1] The kidney is also as a target of iron chelating drugs like deferroxamine that binds with iron and is excreted in the urine. Renal dysfunction has been reported as a common side- effect of this drug, [7],[8],[9] although this finding is refuted by Koliakos and Sumboonnanonda. [2],[5]

Among our patients, there was no case of renal insufficiency and GFR between those receiving regular treatment with deferroxamine and those who had irregular therapy was not different significantly (P insignificant), but GFR was higher in those who had undergone splenectomy compared with others who were not operated. However, we cannot comment on this difference because of the small number of patients in the group.

In a recent study of renal function in thalassemia intermedia and thalassemia major, renal dysfunction was an uncommon finding in thalassemia based on serum creatinine level but not by eGFR, which depends on factors like height, age, weight, race and sex variables.

Renal function evaluated by Marouf et al in 59 patients who had sickle cell anemia found that hyperfiltration measured on the basis of serum creatinine in MDRD and Cockcroft- Gault formula were 30.5% (MDRD) and 44.1% (Cockroft- Gault). [18]

In this study, eGFR measured based on serum creatinine in the age group 18 and above using MDRD formula showed hyperfiltration in 68% whereas in patients under 18 using Schwartz method, it was 41%. This observed difference from Marouf et al may be because they considered hyper- filtration as above 140 mL/min/ 1.73 m 2 , but in our study it was 130. Our study was performed in beta thalassemia major, and there was no patient in the age group two years and above with renal failure (eGFR below 60 mL/min/1.73m 2 ).

eGFR has correlated with patient age and increased with aging despite a rise in creatinine values (P < 0.001), and 31 patients out of 63 (49%) with mean age ± SD 16.3 ± 6.2 years had eGFR above 130 that denoted hyperfiltration but those who had eGFR below 130 were aged 12.5 ± 6.8 years. This difference was statistically significant (P = 0.025).

These showed that with increasing duration of the disease (in our patient is 16.3 years on average), we found hyperfiltration as a maladaptation of renal glomerular hemodynamic function to the insults to the kidney in general. Therefore, serum creatinine alone cannot yield this information for evaluation of patients having renal dysfunction.

In our study, there is no correlation between serum ferritin or iron with eGFR or serum creatinine. Deferoxamine as a chelating drug for iron in standard doses apparently was not harmful. Iron that causes dysfunction in many organs by its deposition has a correlation with aging but not with eGFR in our study. However, the role of iron causing insidious insult over a prolonged period of disease duration resulting in renal involvement or with advancing age needs more broad- based study.

Thalassemia is a chronic disease that affects many organs in many ways. But, in our study, its effect on renal function did not cause a reduction in the eGFR but showed increased eGFR due to hyperfiltration in our patients aged 16.3 ± 6.2 years. Although creatinine is correlated with eGFR, it alone does not reflect eGFR values that are critical for our decision, especially in patients who have decreased muscle mass and nutritional problems. Serum ferritin and iron level did not correlate with eGFR.


   Acknowledgment Top


No body or institute helped us in this study. We appreciate the authors and patients that came to us.

 
   References Top

1.Derakhshan A, Karimi M, Abdolkarim GM. Comparative evaluation of renal function in beta thalassemia major and intermedia. Saudi J Kidney Dis Transpl 2008;19:206- 9.  Back to cited text no. 1
    
2.Koliakos G, Papachristou F, Koussi A, et al. Urine biochemical markers of early renal dysfunction are associated with iron overload in beta thalassemia. Clin Lab Heamatol 2003;25: 105- 9.  Back to cited text no. 2
    
3.Miichelakakis H, Dimitriou E, Georgakis H, et al. Iron overload and urinary lysosomal enzyme levels in beta thalassemia major. Eur J Ped 1997;156:602- 4.  Back to cited text no. 3
    
4.Aldudk B, Karaby Bayazit A, Noyan A, et al. Renal function in pediatric patients with beta thalassemia major. Pediatric Nephrol 2000;15: 109- 12.  Back to cited text no. 4
    
5.Sumbooonamonda A. Renal tubular dysfunction in a thalassemia. Pedaitr Nephrol 2003; 30:137- 40.  Back to cited text no. 5
    
6.Cianciulli P, Sorrentino F, Forte L, et al. Acute renal failure occurring during intravenous deferroxamine therapy recovery after haemodialysis. Haematologica 1992;77:514- 5.  Back to cited text no. 6
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7.Prassannan L, Flynn JT, Levine JE. Acute renal failure following deferroxamine overdose. Pediatr Nephrol 2003;18:283- 5.  Back to cited text no. 7
    
8.Mohkam M, Shamsian BS, Gharib A, et al. Early markers of renal dysfunction in patients with beta- thalassemia major. Pediatr Nephrol 2008;23:971- 6.  Back to cited text no. 8
[PUBMED]  [FULLTEXT]  
9.Voskaridou E, Terpos E, Michail S, et al. Early markers of renal dysfunction in patients with sickle cell/beta- thalassemia. Kidney Int 2006;69:2037- 42.  Back to cited text no. 9
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10.Koren G, Kochavi- Atiya Y, Bentur Y, Olivieri NF. The effects of subcutaneous deferoxamine administration on renal function in thlassemia major. Int J Hematol 1991;54:371- 5.  Back to cited text no. 10
    
11.Benjamin H, Lavding MD. Renal lesion and clinical finding in thalassemia major and othe chronic anemia with hemosidrosis. Pediatr Pathol 1989;9:470- 500.  Back to cited text no. 11
    
12.Chaiken RL, Eckert- Norton M, Bard M, et al. Hyperfiltrartion in African- American patients with type 2 diabetes. Diabetes Care 1998;21: 2129- 34.  Back to cited text no. 12
    
13.Rudberg S, Persson B, Dahliquist G. Increased glomerular filtration rate as a predictor of diabetic nephropathy 8- year prospective study. Kidney Int 1992;41:822- 5.  Back to cited text no. 13
    
14.Grangoli G, Signorini AM, Tranganelli I, et al. Prevalence of glomerular hyperfiltration and nephromegaly in normo in normo and microalbuminuric type2 diabetes patients. Nephron 1993;65:206- 11.  Back to cited text no. 14
    
15.Silvero S, Friedman R, Gross J. Glomerular hyperfiltration in NIDDM patients without overt proteinuria. Diabetes Care 1993;16:115- 9.  Back to cited text no. 15
    
16.Keller CK, Bergis KH, Fliser D, Ritze E. Renal finding in patients with short- time type 2 Diabetes. J Am Soc Nephrol 1996;12:2627- 35.  Back to cited text no. 16
    
17.Sunder- Plassmann G, Horl WH. A critical appraisal for definition of hyperfiltration. Am J Kidney Dis 2003;43:396- 7.  Back to cited text no. 17
    
18.Marouf R, Mojiminiyi O, Abdella N, et al. Comparison of renal function markers in Kuwaiti patients with sickle cell disease. J Clin Pathol 2006;59:345- 51.  Back to cited text no. 18
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Correspondence Address:
Majid Malaki
Department of Pediatric Nephrology, Tabriz Children's Hospital, Tabriz University of Medical Sciences, Tabriz
Iran
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