Uric Acid Abnormalities and Its Correlation with Splenectomy in Adult Transfusion Dependent Thalassemia Subjects (TDT)

  

    
Characteristics
    
Hyperuricemia
    
Hypouricemia 
    
Normouricemia
    
P value
  
  

    
Intact spleen (n=48) 
    
12 (25%)
    
2    (4.17%) 
    
34 (70.83%)
    
0.104
  
  

    
Splenectomised (n=12) 
    
0% 
    
0% 
    
12    (100%) 
  
  

    
Deferasirox    (n=33) 
    
1    (3.03%) 
    
2    (6.06%) 
    
30    (90.91%) 
    
0.0004 
  
  

    
Non    deferasirox (n=27) 
    
11    (40.74%) 
    
0% 
    
16    (59.26%) 
  

Table 3: Association of SUA with different variables.

Discussion

Our study comprised of 60 transfusion dependent adult thalassemia subjects with mean age of 23.10±4.55 years (18-38). Majority of the subjects were in the age group of 21-30 years (58.33%). Chaloemwong et al. [11] studied 58 thalassemia patients with mean age of 23.5 years (16-41).

In our study, proportion of hyperuricemia was 20% (n=12) and hypouricemia was 3.33% (n=2). In a study done by Vassalle et al. [12] on 369 β-thalassemia major patients with mean age of 33±6 years reported that proportion of hyperuricemia was 5% (n=19) and mean SUA was 4.4±1.2 mg/dl. In a prospective study done by Hamed et al. [13] on 69 thalassemia major patients of age 1-16 years and 15 age and sex matched controls were taken, reported that SUA levels were increased in thalassemic subjects when compared to controls (p<0.002). Doddamani et al. [14] studied on 30 thalassemia major subjects with age group of 6 months-14 years and compared with 30 age and sex matched controls elucidated that SUA levels were significantly increased in β thalassemia major patients when compared to controls (p<0.05). Hypouricemia was seen in 2.33% (n=2) of subjects and both had hyperuricosuria. Cetin et al. [15] studied 41 thalassemia minor subjects with age group 19-40 years and compared with 20 age and sex matched controls reported that 14.6% (n=6) of subjects had hypouricemia because of increased fractional excretion of uric acid. The difference in proportion of hypouricemia could be because of the difference in study population included in their study, that is thalassemia minor. Mean SUA levels were higher in males than females and the difference was statistically significant (5.77±1.66 vs 4.64±1.44, p=0.007). In a study done by Vassalle et al. [12] on 369 β-thalassemia major patients with mean age of 33±6 years found that mean serum uric acid levels were significantly higher in male than in female patients (4.8±1.3 vs 4.0±1.0 mg/dl; p<0.001). Our study observed that mean value of SUA increased proportionately as the age of the subjects increased which was statistically significant (p=0.0129). Chaloemwong et al. [11] studied 58 thalassemia patients with mean age of 23.5 years observed that increasing age was a significant risk factor for hyperuricemia (p=0.046).

Hyperuricosuria was found in 80% (n=48) in our study and it is one of the marker of proximal tubular dysfunction. Similar results were found in study done by Smolkin et al. [16] on 37 thalassemia major subjects where hyperuricosuria was present in 82.4%. Study done by Ahmadzadeh et al. [17] reported that hyperuricosuria is a marker of proximal tubular dysfunction was found in 58.6% of patients. Renal hyperfiltration (eGFR ≥135 ml/min/m²) in TDT can occur because of chronic hypoxia or chronic anemia leading to hyperdynamic circulation resulting in increase in renal plasma flow and decrease in glomerular vascular resistance [18]. In our study hyperfiltration was present in 66.67% (n=32). In a study done by Deveci et al. [19] on 84 thalassemia major and 12 Thalassemia Intermedia (TI) patients reported renal hyperfiltration in 40% of patients.

We observed that proportion of hyperuricemia was more in subjects with intact spleen than splenectomised subjects, however, the difference was not statistically significant (p=0.104). In a cross sectional study done by Chaloemwong et al. [20] on 112 thalassemic patients and proportion of splenectomised patients was high - 59.8% (n=67). They observed that intact spleen was a risk factor for hyperuricemia (p=0.01). In a retrospective study done by Ricchi et al [4] on 89 TI patients and splenectomy was done in 48% of subjects. They found that splenectomy was a risk factor for hyperuricemia. The difference in the observations could be accounted for low proportion of splenectomy in our study which may be due to difference in the protocols for splenectomy in different centres. There was a statistically significant positive correlation between SUA and serum creatinine (p=0.0036). Similar observations was done by Chaloemwong et al. [11] on 58 thalassemia patients with mean age of 23.5 years observed that hyperuricemic patients had higher mean serum creatinine (p=0.03) and lower fractional excretion of uric acid than thalassemia patients who had normal uric acid level.

Hyperuricemia was found to have negative association with DFX therapy (p=0.0004) compared with normouricemia subjects. Chaloemwong et al. [19] studied 112 thalassemic patients with mean age of 29 years reported that subjects who were on DFX therapy had lower serum uric acid levels which is due to increase in excretion of uric acid from renal tubules leading to low serum uric acid levels. Vlachaki et al. [5] studied 53 beta thalassemia major subjects with mean age 22.4±14.7 years. They found statistically significant difference between the mean values of SUA before and after the start of DFX therapy and reported that DFX augments the excretion of uric acid from renal tubules. They concluded that uric acid can be used as predictor factor of response to DFX therapy.

In our study, there was no statistically significant correlation between SUA and serum ferritin levels (p=0.191). This is in concordance with the study done by Vassalle et al. [12] on 369 β-thalassemia major patients with mean age of 33±6 years found that serum uric acid levels didn’t have statistically significant correlation with serum ferritin levels.

Conclusion

Uric acid abnormalities were seen in 23.3% of patients. Hyperuricemia was present in one fourth of the patients and significant risk factors were increasing age, male gender, rising serum creatinine. Deferasirox therapy was negatively associated with hyperuricemia. Tubular dysfunction is relatively common in TDT as more than three fourth patients had hyperuricosuria. Regular monitoring of serum uric acid and urinary uric acid is recommended.

Author’s Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Dr Avva Sahithi, Dr Ramesh Aggarwal, Dr Anupam prakash, Dr S.K. Jain, Dr Anju jain and Dr Priya Bansal. The first draft of the manuscript was written by Dr Avva Sahithi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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