scholarly journals A randomized, double-blind, positive-controlled, prospective, dose-response clinical study to evaluate the efficacy and tolerability of an aqueous extract of Terminalia bellerica in lowering uric acid and creatinine levels in chronic kidney disease subjects with hyperuricemia

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Usharani Pingali ◽  
Chandrasekhar Nutalapati ◽  
Niranjan Koilagundla ◽  
Gangadhar Taduri
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Clinical Study ◽  
Platelet Aggregation ◽  
Kidney Disease ◽  
Endothelial Function ◽  
Serum Uric Acid ◽  
Filtration Rate ◽  
Once Daily ◽  
Terminalia Bellerica

Abstract Background Hyperuricemia is an independent risk factor in chronic kidney disease (CKD). Allopurinol and febuxostat are prescription medicines used to treat hyperuricemia but suffer side-effects. Earlier clinical study has shown that an aqueous extract of Terminalia bellerica (TBE), significantly reduced uric acid levels with no serious adverse effects in hyperuricemic subjects. The objective of this study is to determine the efficacy and tolerability of TB in reducing uric acid and creatinine levels in CKD subjects. Methods 59-subjects were randomized to three groups-40 mg-once-daily febuxostat, 500 mg-twice-daily and 1000 mg-twice-daily of TBE. Serum uric acid, creatinine levels and estimated-glometular-filtration-rate were measured at baseline, 4, 8, 12, 16, 20, 24-weeks. Biomarkers of oxidative-stress, endothelial function, systemic inflammation, and platelet-aggregation were evaluated at baseline, 4, 8, 12, 24-weeks. Adverse drug reactions were recorded. Statistical analysis evaluated using GraphPadPrism4. Results 55-subjects completed 24-week study. Starting at 4-weeks, all treatment groups showed a significant decrease in serum uric acid levels from baseline (p ≤ 0.0001). At 24-weeks, febuxostat, T.bellerica 500 mg-twice-daily, and T.bellerica 1000 mg-twice-daily doses decreased mean-percentage serum uric acid by 63.70 ± 4.62, 19.84 ± 6.43 and 33.88% ± 4.95% respectively (p ≤ 0.0001). Significant decrease in serum creatinine with all the groups starting at 16-weeks was seen (p ≤ 0.005-p ≤ 0.0001). At 24-weeks, the mean-percentage change in creatinine levels was 23.71 ± 12.50, 11.70 ± 9.0, and 24.42 ± 8.14, respectively with febuxostat, T.bellerica 500 mg-twice-daily and T.bellerica 1000 mg-twice-daily. Statistically significant (p ≤ 0.05) increase in estimated glomerular filtration rate-(eGFR) was seen at 20 (p ≤ 0.05) and 24-weeks (p ≤ 0.01) for both febuxostat vs T.bellerica 500 mg-twice-daily and T.bellerica 1000 mg-twice-daily vs T.bellerica 500 mg-twice-daily. There was no statistically significant difference between febuxostat and T.bellerica 1000 mg-twice-daily, with an increase of eGFR of 41.38 and 40.39 ml/min/1.73m2 respectively, with the inference that T.bellerica at 1000 mg-twice-daily dose is as good as febuxostat 40 mg-once-daily. Positive improvements were made by all the groups in endothelial function and the related biomarkers and high-sensitivity C-reactive protein. None of the products showed effect on platelet aggregation. Conclusion In this 24-week study Febuxostat 40 mg, T. bellerica 500 mg-twice-daily and 1000 mg-twice-daily, significantly decreased the serum uric acid and creatinine levels, increased eGFR in CKD subjects. T. bellerica 500 mg-twice-daily and 1000 mg-twice-daily were one-third and more than half as effective at 24-weeks, respectively. T. bellerica extract may be considered a natural alternative for reducing serum uric acid levels. Trial registration This study was registered with the Clinical Trials Registry – India (CTRI) with the registration number: CTRI/2019/11/022093 [Registered on: 21/11/2019] Trial Registered Retrospectively.

scholarly journals The Role of Hyperuricemia in the Pathogenesis and Progressivity of Chronic Kidney Disease

2021 ◽  
Vol 9 (F) ◽  
pp. 428-435
Author(s):  
Gede Wira Mahadita ◽  
Ketut Suwitra
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Filtration Rate ◽  
Stage Iv ◽  
Review Of The Literature ◽  
The Relationship ◽  
Uric Acid Secretion

In humans, the end product of purine metabolism is uric acid. Over 70% of uric acid is excreted through the kidneys. When renal function is impaired, uric acid secretion is also impaired. This directly correlates the prevalence of hyperuricemia with the severity of chronic kidney disease (CKD). It has been reported that the prevalence of hyperuricemia in patients with Stage I-III CKD is 40–60% and up to 70% in patients with Stage IV-V CKD. Some studies found a link between serum uric acid levels and decreased glomerular filtration rate (GFR), an independent risk factor for CKD development. Because CKD and serum uric acid levels are related, the relationship between the two frequently generates controversy. As such, this review of the literature discusses the role of uric acid in the pathogenesis and progression of CKD.

scholarly journals Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function

2017 ◽  
Vol 14 (3) ◽  
pp. 221-225 ◽  
Author(s):  
Liubao Gu ◽  
Liji Huang ◽  
Haidi Wu ◽  
Qinglin Lou ◽  
Rongwen Bian
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Incident Chronic Kidney Disease

Background: Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. Methods: In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. Results: In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. Conclusion: serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.

scholarly journals Sex differences in the association between serum uric acid levels and cardiac hypertrophy in patients with chronic kidney disease

2013 ◽  
Vol 37 (3) ◽  
pp. 246-252 ◽  
Author(s):  
Ryota Yoshitomi ◽  
Akiko Fukui ◽  
Masaru Nakayama ◽  
Yoriko Ura ◽  
Hirofumi Ikeda ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Sex Differences ◽  
Uric Acid ◽  
Kidney Disease ◽  
Cardiac Hypertrophy ◽  
Serum Uric Acid

MO491ASSOCIATION BETWEEN SERUM URIC ACID LEVEL AND CHRONIC KIDNEY DISEASE INCIDENCE STRATIFIED BY SEX IN MIDDLE-AGED ADULTS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Shingo Nakayama ◽  
Michihiro Satoh ◽  
Takahisa Murakami ◽  
Yukako Tatsumi ◽  
Tomoko Muroya ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Health Check ◽  
Middle Aged ◽  
Men And Women ◽  
Increased Risk ◽  
The Mean ◽  
Middle Aged Adults

Abstract Background and Aims While previous studies have reported the association between serum uric acid (SUA) and chronic kidney disease (CKD) incidence, the sex differences in this association remain controversial. Therefore, we examined the association between SUA levels and CKD incidence in middle-aged adults stratified by sex using data from a large-scale health check-up. Method We analyzed information from the JMDC database, which included the annual health check-up data of Japanese employees and their dependents aged &lt;75 years. Among those individuals, we analyzed data from 138,511 individuals without CKD, kidney disease, or a history of cardiovascular disease at baseline. CKD was defined as an estimated glomerular filtration rate (eGFR) &lt;60 mL/min/1.73 m2 and/or proteinuria. We divided the participants into 9 and 7 groups according to SUA levels for men and women, respectively. A Cox model was applied to assess the adjusted hazard ratios (HRs) for CKD incidence in each SUA level group using an SUA concentration of 4.0–4.9 mg/dL as the reference after adjusting for age, body mass index, current or ex-smoker, current or ex-drinker, diabetes mellitus, dyslipidemia, systolic blood pressure, use of anti-hyperuricemic drugs, and baseline eGFR. Results The mean participant age was 44.1 years, and 29.6% were women. The mean SUA levels were 5.9 mg/dL and 4.1 mg/dL in men and women, respectively. During the mean follow-up period of 4.68 years, 12,589 participants developed CKD. The age-standardized incidence rates for CKD were 17.88/17.80 per 1000 person-years in men/women with SUA concentrations of 4.0–4.9 mg/dL, 209.76 per 1000 person-years in men with SUA ≥11.0 mg/dL, and 73.38 per 1000 person-years in women with SUA ≥ 9.0 mg/dL. The fully adjusted HRs (95% confidence interval [CI], P value) for CKD incidence in the groups with SUA concentrations of &lt;4.0, 10.0–10.9, and ≥11.0 mg/dL compared with those with SUA of 4.0–4.9 mg/dL among men were 1.13 (1.01–1.26, P=0.030), 1.98 (1.32–2.97, P=0.0010), and 3.74 (1.68–8.35, P=0.0013), respectively. In women, the fully adjusted HRs for CKD incidence in the groups with SUA concentrations of &lt;4.0, 8.0–8.9, and ≥9.0 mg/dL were 1.08 (1.01–1.16, P=0.032), 2.39 (1.07–5.35, P=0.034), and 3.20 (0.80–12.8, P=0.10), respectively. Similar results were observed when we performed the sensitivity analysis excluding 8,411 individuals with hypertensive treatment from the main analysis. The HRs for the outcomes caused by the onset of eGFR &lt;60 mL/min/1.73 m2 or proteinuria separately were similar to those for the main results. Conclusion The results of the present study demonstrated an increased risk of CKD in men with SUA concentrations of &lt;4.0 and ≥10.0 mg/dL and &lt;4.0 and ≥8.0 mg/dL in women compared to those with SUA concentrations of 4.0–4.9 mg/dL after adjusting for various covariates. Both high and low SUA levels were risk factors for CKD in middle-aged men and women. Hyperuricemia was demonstrated to cause renal injury due to the intraluminal deposition of uric acid crystals in the renal collecting duct. Hyperuricemia may also induce endothelial dysfunction, activation of the renin-angiotensin system, and induction of inflammation and stimulation of vascular smooth muscle cell proliferation by the induction of cyclooxygenase-2. However, as uric acid is one of the most important antioxidants in human plasma, low SUA levels may increase the risk of CKD incidence through decreased antioxidant activity. These mechanisms are implicated in the pathogenesis of CKD caused by high and low SUA levels. In addition, the SUA levels and ranges associated with increased risks of CKD incidence differed by sex.

scholarly journals The relationship between serum uric acid and chronic kidney disease among Appalachian adults

2010 ◽  
Vol 25 (11) ◽  
pp. 3593-3599 ◽  
Author(s):  
L. Cain ◽  
A. Shankar ◽  
A. M. Ducatman ◽  
K. Steenland
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
The Relationship

scholarly journals Study of Serum Uric Acid in Different Stages of Chronic Kidney Disease

2021 ◽  
pp. 70-79
Author(s):  
Shahida Akhter ◽  
A. S. M. Rizwan
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Creatinine ◽  
Serum Uric Acid ◽  
Uric Acid Level ◽  
Acid Level ◽  
Serum Uric Acid Level ◽  
Medical College ◽  
Bonferroni Test

Background: Hyperuricaemia is a metabolic marker of decreased renal function in chronic kidney disease (CKD). It increases cardiovascular, cerebrovascular and mortality risk in patients with CKD. Objectives: To estimate serum uric acid level in different stages of CKD. Methods: The present study was a cross sectional analytical study and was conducted in the Department of Physiology, Dhaka Medical College, Dhaka from July 2012 to June 2013 on 300 participants. They were divided into group A (150 control healthy participants) and group B (150 diagnosed cases of CKD). Serum creatinine and serum uric acid levels were measured by auto analyzer in Department of Pathology, Dhaka Medical College. Estimated glomerular filtration rate (eGFR) was calculated from serum creatinine level by Modification of Diet in Renal Disease (MDRD) equation. For statistical analysis unpaired Student “t” test, one way ANOVA test, Bonferroni test, Pearson’s correlation coefficient (r) test and Linear regression were performed using SPSS for windows version 20. Result: In this study, serum uric acid level was significantly (p<0.05) higher and eGFR were significantly lower in study groups than that of control group. There was gradual rise of serum uric acid level in CKD subjects from stage I to V. A significant inverse correlation was observed between serum uric acid level and eGFR. Serum uric acid level increased 0.048 mg/dl for each ml/min/1.73m2 decrease of eGFR. Conclusion: This study concludes that serum uric acid level increases gradually in accordance with the higher stages of CKD. There is a negative correlation of serum uric acid with eGFR in all stages of CKD which was statistically significant (p<0.05). Screening of serum uric acid level in different stages of CKD may be beneficial for assessing renal damage as well as prediction of co-morbidities associated with it.

Association between serum uric acid and chronic kidney disease in patients with hypertension: A multicenter nationwide cross‐sectional study

2019 ◽  
Vol 12 (4) ◽  
pp. 235-242 ◽  
Author(s):  
Wisit Kaewput ◽  
Charat Thongprayoon ◽  
Ram Rangsin ◽  
Prajej Ruangkanchanasetr ◽  
Tarun Bathini ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional

scholarly journals Effect of Allopurinol on Inflammatory Markers in Chronic Kidney Disease Patients with Asymptomatic Hyperuricaemia

2017 ◽  
Vol 26 (1) ◽  
pp. 12-24
Author(s):  
ASM Tanim Anwar ◽  
Md Nizamuddin Chowdhury ◽  
Md Nazrul Islam ◽  
Parvez Iftekher Ahmed ◽  
Sohely Ahmed Sweety ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Uric Acid ◽  
Treatment Group ◽  
Kidney Disease ◽  
Serum Uric Acid ◽  
Chronic Kidney Disease Stage ◽  
Disease Stage ◽  
Control Group ◽  
Base Line

This was a hospital based prospective, interventional study which included CKD stage 3- 5 patients with higher level of uric acid (male>7mg/dl, female>6mg/dl). The objective of the study was to evaluate the effect of allopurinol on inflammatory markers in patients with chronic kidney disease (stage 3-5) with asymptomatic hyperuricaemia. One hundred and twenty patients were distributed in two groups. Sixty patients were placed in treatment group and sixty in control group. Purposive sampling technique was followed. In the study mean age was 49 (±9) years in treatment group and 45 (±11) years in control groups. Male were predominant in both groups. There were no significant difference in baseline characteristics between treatment group and control group (p>0.05). Sixty patients of treatment group were administered a dose of 100 mg/d of allopurinol. Follow up assessment was done at basally, at 4 months and at 8 month after starting treatment. No significant differences were seen between baseline SBP, DBP, Hb and HbA1c with 4th month and 8th month follow up in both treatment group and control group, but mean Hb was significantly decreased in control group from the baseline after 8 month. No significant change was found in case of mean ESR at 4th and 8th month in any group. But base line mean CRP was significantly reduced in treatment group and increased in control group at 4th and 8th month of follow up. Serum uric acid was decreased in treatment group while it was significantly raised from the base line at 4th month and 8th month in control group. While comparing between two groups results showed means of serum uric acid and CRP were significantly decreased in treatment group compared to control group after 8th month. There was a positive correlation between Uric Acid with CRP level after 8 month of allopurinol treatment although this finding was not statistically significant. So, allopurinol may have a protective role in CKD by decreasing serum uric acid level and reduction of inflammatory response in patients with chronic kidney disease stage 3 - 5 with asymptomatic hyperuricaemia.J Dhaka Medical College, Vol. 26, No.1, April, 2017, Page 12-24

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