|Year : 2012 | Volume
| Issue : 4 | Page : 235-238
Importance of assessment of microalbuminuria in β-thalassemia major patients
Parveen Doddamani1, MN Suma1, MD Ravi2, Akila Prashant1, Prashant Vishwanath1, CS Nagalakshmi1
1 Department of Biochemistry, JSS Medical College, JSS University, Mysore, India
2 Department of Paediatrics, JSS Medical College, JSS University, Mysore, India
|Date of Web Publication||27-Feb-2013|
House no 286, Near Government Primary School, Shivanand Nagar, Navanagar, Hubli - 25, Karnataka
Source of Support: None, Conflict of Interest: None
Introduction: β-thalassemia major is one of the most common hereditary hematologic disorders characterized by severely impaired β-globulin synthesis. Renal proximal tubular dysfunction may occur in children with β-thalassemia major without clinical manifestations of renal dysfunction or decrease in GFR. However, there is paucity of information about renal involvement in this disease and its early detection in patients with β-thalassemia major is rare. Aims and Objectives: The aim of the present study was to determine the levels of urinary microalbumin along with serum levels of urea, creatinine, uric acid, calcium and inorganic phosphate and to correlate the levels of urinary microalbumin with the above parameters in β-thalassemia major patients. Results: Serum urea, uric acid and phosphate increased ( P < 0.001, <0.05, <0.001 respectively) while serum calcium was decreased ( P < 0.001) in patients with β-thalassemia major patients when compared to healthy controls. Microalbuminuria ( P < 0.001) was seen in patients with β-thalassemia major patients indicating renal damage. Conclusion: Our study emphasizes the need to include microalbuminuria levels into the routine follow up of these patients. Thereby, impedance of disease progress will improve the patients' quality of life.
Keywords: β-thalassemia, microalbuminuria, renal damage
|How to cite this article:|
Doddamani P, Suma M N, Ravi M D, Prashant A, Vishwanath P, Nagalakshmi C S. Importance of assessment of microalbuminuria in β-thalassemia major patients. Int J Health Allied Sci 2012;1:235-8
|How to cite this URL:|
Doddamani P, Suma M N, Ravi M D, Prashant A, Vishwanath P, Nagalakshmi C S. Importance of assessment of microalbuminuria in β-thalassemia major patients. Int J Health Allied Sci [serial online] 2012 [cited 2022 Oct 2];1:235-8. Available from: https://www.ijhas.in/text.asp?2012/1/4/235/107864
| Introduction|| |
β-Thalassemia major is a common hereditary hematologic disorder characterized by severely impaired β-globulin synthesis.  Although the management and treatment of patients with thalassemia have greatly improved in recent decades with the use of modern newborn screening, blood transfusions and iron chelation therapy, multiorgan dysfunctions are still a major drawback. , Although involvement of other organs such as liver is common in patients with β-thalassemia major, involvement of the kidney is not well documented. Renal involvement may occur by three mechanisms: Deferoxamine desferoxamine side effects, deposition of iron in renal tissue in addition to lipid peroxidation, oxidative stress, free radical release and vascular thrombosis, resulting in renal infarction due to increased platelet aggregation and decreased serum level of protein S and antithrombin III. ,,
Renal proximal tubular dysfunction may occur in children with β-thalassemia major without clinical manifestations of renal dysfunction or a decrease in GFR.  However, there is paucity of information about renal involvement in this disease and its early detection in patients with β-thalassemia major. Recent studies on microalbuminuria have demonstrated that microalbuminuria is the early marker of kidney disease in which the damaged kidneys allow traces of albumin to spill into urine. , Microalbuminuria (microalbumin/creatinine ratio) is an early predictor of worse outcomes for both kidney and heart diseases. 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. ,
In the recent years, few studies have demonstrated early markers of renal dysfunction but these markers of renal tubular damage are not routinely used in the clinical laboratories and are relatively expensive when compared to the estimation of urinary microalbumin, thus adding up to the financial burden of managing β-thalassemia major patients. The aim of this study was to determine the levels of urinary microalbumin along with serum levels of urea, creatinine, uric acid, calcium, and inorganic phosphate and also to correlate the levels of urinary microalbumin with other parameters in β-thalassemia major.
| Materials and Methods|| |
Study group included 30 diagnosed cases of β-thalassemia major by clinical examination and hemoglobin electrophoresis in the age group of 6 months to 14 years attending the outpatient department (OPD) and admitted in the pediatric ward of a tertiary care teaching hospital and 30 healthy age and sex matched controls. Exclusion criteria included patients with other hemoglobinopathies such as sickle cell anemia, type 1 diabetes mellitus and patients on diuretic therapy. Institutional ethical committee approval was obtained before the commencement of the study and written consent was obtained from parents/guardians before collection of blood and urine samples. The investigations included estimation of hemoglobin, serum urea, creatinine, uric acid, calcium, inorganic-phosphate and spot urinary microalbumin: creatinine ratio in urine. The same were compared with controls. Three milliliters of venous blood was collected using all aseptic precautions prior to blood transfusion, out of which one mL was collected in an EDTA vacutainer and used to estimate hemoglobin (Cyanmethemoglobin method) using Nihon Kohden 5 part Coulter and the rest two mL was allowed to clot and centrifuged at 5000 rpm for five minutes. The serum separated was then used for estimation of serum urea (Urease method), creatinine (Modified Jaffes method), calcium (Arsenazo III method), inorganic phosphate (Ammonium molybdate method) and uric acid (Enzymatic method) by a fully automated Randox Daytona Chemistry Analyzer. The first morning midstream urine samples (10 mL) were collected in sterile containers without preservative and assayed for urinary microalbumin (immunoturbidimetric method) and creatinine (Modified Jaffes method) by a fully automated Randox Daytona Chemistry Analyzer. GFR was calculated using the standard formula. 
Mean and standard deviation were worked out to assess the level of serum calcium, phosphate, urea, uric acid, creatinine, and urinary microalbuminuria in the study and control groups. Student's t-test was applied at 5% level, to test the significance of difference in the parameters under study in the study and control group. Pearson's correlation was applied among various parameters under study. The analysis of data was performed using SPSS 16 and a P value of < 0.05 was considered significant.
| Results|| |
The study was conducted on 30 patients with β-thalassemia major and 30 healthy controls. The cases and controls were age and sex matched. The age group was between 6 months to 14 years. The mean age in β-thalassemia major patients was 4.72 ± 2.96 years and in controls was 4.79 ± 3.34 years. Patients with β-thalassemia major (Cases) consisted of 17 males and 13 females. In the control group, there were 15 males and 15 females (Controls). GFR was >95 mL/min/1.72 m 2 in both cases and controls.
The details of the findings are elaborated in [Table 1]. As demonstrated in the table, mean hemoglobin levels were significantly decreased in β-thalassemia major patients when compared to controls. Serum urea levels were increased in β-thalassemia major patients when compared to controls. There was no statistical significant difference in the mean values of creatinine levels between study groups.
Mean serum uric acid levels were significantly increased in β-thalassemia major patients when compared to control. Mean serum calcium levels were significantly decreased and a compensatory increase in mean serum inorganic phosphate levels was observed in β-thalassemia major patients when compared to controls.
Mean values of spot urinary microalbumin to creatinine ratio (μg/mg of creatinine) in β-thalassemia major was significantly increased in patients with β-thalassemia major patients when compared to controls, suggesting the occurrence of microalbuminuria in patients with β-thalassemia major patients.
Microalbuminuria is positively correlated with age (r = 0.938; P < 0.05) as shown in [Figure 1]. Age is positively correlated with the duration of blood transfusion as the age increases number of transfusions increase ( r = 0.0856). Microalbuminuria is also positively correlated with duration of blood transfusions ( r = 0.866; P > 0.05). Further, there was no significant correlation among concentration of hemoglobin, serum urea, creatinine, uric acid, calcium, phosphorous and microalbuminuria levels.
|Figure 1: Correlation between microalbuminuria (μg/mg of creatinine) and age (months) in β-thalassemia major patients|
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| Discussion|| |
Management of thalassemia has improved greatly in the past few years. People who have moderate and severe thalassemia are now living longer and have better quality of life than before. However, complications from thalassemia and their treatments are frequent. 
Despite the increased iron deposition and the consequence of its possible oxidative stress on the renal parenchyma of these patients, many workers have also reported normal serum creatinine and creatinine clearance in patients with β-thalassemia major.  In the recent years, few studies have demonstrated early markers of renal dysfunction such as excess urinary secretion of N-acetyl-D-glucosaminidase and β2-microglobulin in patients with β-thalassemia major. ,,, These markers of renal tubular damage are not routinely used in the clinical laboratories and are relatively expensive thus adding up to the financial burden of managing β-thalassemia major patients. The urinary microalbumin-creatinine ratio is considered to be one of the early indicators of kidney disease and a predictor of outcome.  Hence, in this study we evaluated the levels of urinary microalbumin-creatinine ratio in β-thalassemia major patients and correlated the levels with other renal markers.
In our study, we found significant increase in levels of the spot urinary microalbumin-creatinine ratio in patients with β-thalassemia major when compared to normal controls, indicating increase in free radical production and lipid peroxidation due to deposition of iron in renal parenchyma leading to dysfunction mainly in glomerular mesangium and proximal renal tubular cells. One of the recent studies has indicated the absence of microalbuminuria in patients with β-thalassemia major, the cause of this may be better management of β-thalassemia major in relation to adequate blood transfusion and a well-monitored chelation therapy. 
We observed increased levels of serum urea in patients with β-thalassemia major as shown in [Table 1]. Studies have found significant higher blood urea levels in β-thalassemia major patients  and at the same time another study contradicts these findings.  The probable mechanism of increase in serum urea levels in our study is proximal renal tubular damage due to higher iron deposition in the kidneys. 
In this study, we have found no significant difference in mean serum creatinine levels in β-thalassemia major patients when compared to controls as shown in [Table 1]. Studies have reported that there was no significant difference between serum creatinine values between β-thalassemia major patients and healthy controls. , One of the studies has concluded that we cannot rely on GFR and serum creatinine levels to assess renal dysfunctions in β-thalassemia major patients. 
In this study, we have observed that mean serum uric acid levels were significantly increased in β-thalassemia major patients when compared to controls as shown in [Table 1]. The mechanism of increased serum uric acid levels in β-thalassemia major patients is due to rapid erythrocyte turnover and excess of urinary excretion of uric acid.  This excess increase in excretion is due to proximal renal tubular damage. This renal tubular damage is secondary to oxidative lipid peroxidation mediated by the iron overload. ,
The serum levels of calcium were significantly decreased in β-thalassemia major patients when compared to controls as shown in [Table 1]. Our findings are comparable with the observations of some of the other studies where they have found that there is decreased level of serum calcium in β-thalassemia major patients when compared to controls. ,
There are many probable mechanisms for this decrease in serum calcium levels: as a result of defective membrane transport in red cell membrane of these patients which causes increased calcium ions influx that is more calcium shifts from extracellular to intracellular fluid,  or it may be due to hypercalciuria which is again due to proximal renal tubular damage that may be secondary to oxidative lipid peroxidation mediated by the iron overload,  and finally low levels of serum calcium may also be due to parathyroid involvement (hypoparathyroidism). 
In this study, we found that serum levels of inorganic phosphate is significantly increased in β-thalassemia major patients when compared to controls as shown in [Table 1]. Our findings are comparable with previous studies. The probable mechanism of this increase in serum inorganic phosphate is due to increased erythrocyte turnover, liver involvement, or may be due to iron deposition in parathyroid (hypoparathyroidism). ,,
Microalbuminuria is positively correlated with age and duration of blood transfusion in our study, which may be due to increased iron overload with each transfusion. Studies have shown that the renal disorders in β-thalassemia major patients increase in terms of frequency with age, increased duration of blood transfusion and Deferoxamine usage. , Renal complications are not routinely encountered in β-thalassemia major patients, but it can be easily detected when present by a more cost-effective method such as urinary microalbumin. Hence our study emphasizes the need to include microalbuminuria levels into the routine follow-up of these patients. Thereby, impedance of disease progress will improve the patients' quality of life. The urinary microalbumin-creatinine ratio should be thus incorporated in the routine follow-up of these patients so as to detect any renal dysfunction at an early stage. Limitations of our study were as follows: It involves a smaller study group and the study would be more applicable if urinary microalbumin was correlated with serum ferritin levels with a long-term follow-up.
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