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

Research Article

Ann Hematol Oncol. 2021; 8(5): 1342.

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

Sahithi A¹, Aggarwal R¹*, Prakash A¹, Jain SK¹, Jain A², Bansal P¹

1Department of Medicine, Lady Hardinge Medical College and Associated Hospitals, India

2Department of Biochemistry, Lady Hardinge Medical College and Associated Hospitals, India

*Corresponding author: Ramesh Aggarwal, Department of medicine, Lady Hardinge Medical College and Associated Hospitals, New Delhi, India

Received: March 09, 2021; Accepted: April 09, 2021; Published: April 16, 2021

Abstract

Background: In thalassemia patients erythrocyte turnover rate increases due to chronic hemolysis and ineffective erythropoiesis leading to increase in uric acid production. Hyperuricosuria is one of the marker of proximal tubular dysfunction. Splenectomy can increase the risk of hyperuricemia by increasing erythrocyte turnover rate in Transfusion Dependent Thalassemia (TDT). Deferasirox enhances uric acid excretion from renal tubules leading to low serum uric acid levels.

Methods: An institution based cross-sectional study was conducted from November 2018-March 2020 which included 60 adult TDT patients (≥18 years) attending Adult Thalassemia Day Care Centre at tertiary care hospital. Serum uric acid (mg/dl), 24 hour urinary uric acid (mg/dl), serum ferritin (ng/ml) were done.

Results: Hyperuricemia was present in 20%, hypouricemia in 3.33%. Hyperuricosuria was present in 80%. Mean SUA levels were higher in males than females which was statistically significant (5.77±1.66 vs 4.64±1.44, p=0.007). There was statistically significant positive correlation between serum uric acid and serum creatinine(p = 0.0036) and age (p=0.0129). Hyperuricemia was more in subjects with intact spleen but was not statistically significant(p=0.104). Hyperuricemia had negative association with deferasirox therapy [1 (3.03%) vs 11 (40.74%), p=0.0004] compared with normouricemia subjects.

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.

Keywords: Transfusion dependent thalassemia; Hyperuricemia; Hyperuricosuria; Splenectomy; Deferasirox

Introduction

Thalassemia is one of the most common inherited diseases worldwide which leads to chronic hemolytic anemia due to a partial or complete defect in the synthesis of a or β globin chains. The prevalence of β-thalassemia in India is 3-4 % and it is estimated that around 10,000-12,000 children were born every year with β-thalassemia major [1]. Thalassemia patients have enhanced erythrocyte turnover rate because of chronic haemolysis and ineffective erythropoiesis leading to increase in uric acid production. Therefore, hyperuricemia is anticipated. Uric acid has anti oxidant properties. Hyperuricemia is associated with increased risk of metabolic syndrome, iron overload, nephrolithiasis, renal dysfunction, gouty arthritis. In TDT patients proximal tubular dysfunction is common because of various reasons like chronic anemia, iron overload and chelation therapy. Proximal tubular dysfunction in TDT leads to hyperuricosuria due to the defective absorption of filtered uric acid, therefore hyperuricosuria is one of the marker of proximal tubular dysfunction [2-3]. However, there are scanty reports of uric acid abnormalities in TDT, especially adult subjects. Many patients undergo splenectomy to decrease transfusion requirement, to prevent growth retardation, symptomatic splenomegaly, leukopenia and thrombocytopenia. It has been observed that splenectomy can increase the risk of hyperuricemia by increasing erythrocyte turnover rate in thalasssemia patients [4]. Chelation therapy is an essential part of management of adult TDT. It has been observed that Deferasirox (DFX) enhances uric acid excretion from renal tubules leading to low serum uric acid levels [5]. Scanty data is available which highlights association of splenectomy and chelating agents with uric acid abnormalities. This study is an attempt to bridge the existing lacunae in knowledge with regard to uric acid abnormalities in adult TDT.

Materials and Methods

Our study was a descriptive cross-sectional study and included 60 adult TDT patients confirmed by High Performance Liquid Chromatography (HPLC) of age =18 years attending Adult Thalassemia Day Care Centre (TDCC) at tertiary care hospital. Subjects who were on medications affecting uric acid metabolism were excluded from the study. The study was approved by institutional research committee and ethical committee. The detailed clinical history was taken which included demographic data, dietary history, number of blood transfusions they receive every month, chelation therapy (dosage and duration of drug therapy), history of splenectomy, history of any other medications and menstrual history in females. General physical examination which include height, weight, body mass index (BMI) and systemic examination was done in all subjects.

Biochemical investigations

Serum Uric Acid (SUA), 24-hour Urinary Uric Acid (UUA), serum ferritin (ng/ml) and routine blood investigations were done. SUA and UUA were analysed by colorimetric method which uses uricase enzyme converting uric acid to allantoin and hydrogen peroxide. Hyperuricemia was defined as SUA of >7.0 mg/dL for men and >5.7 mg/dL for women and hypouricemia was defined as SUA<2 mg/dl [6]. Hyperuricosuria was defined as 24 hour UUA>750 mg/ day while on a normal, unrestricted purine diet [7,8]. The Estimated Glomerular Filtration Rate (eGFR) was calculated using the following formula Cockcroft-Gault formula ((140-age) × weight in kgs/ (72×serum creatinine) ×0.85 (if female)) [9]. Renal hyperfiltration was defined as eGFR>135 ml/min/m² [10].

Statistical analysis

Categorical variables were presented in number and percentage (%) and continuous variables as mean ± SD and median. Normality of data was tested by Kolmogorov-Smirnov test. If the normality was rejected then non parametric test was used. Quantitative variables were compared using independent t test/Mann-Whitney Test (as the data sets were not normally distributed) between the two groups and ANOVA test between more than two groups. Qualitative variables were correlated using Chi-Square test/Fisher’s test. Pearson correlation coefficient/Spearman rank correlation coefficient was used to assess the correlation of various parameters with SUA, 24 hr UUA. A p value of <0.05 was considered statistically significant. The data was entered in MS EXCEL spreadsheet and analysis was done.

Results

Our study comprised of 60 adult TDT 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%). In our study males were 58.33% (n=35) and females were 41.66% (n=25) (Table 1).