Effect Of Uric Acid Lowering Therapy Research Articles

Effects of uric acid-lowering therapy (ULT) on renal outcomes in CKD patients with asymptomatic hyperuricemia: a systematic review and meta-analysis

BackgroundIt is well known that asymptomatic hyperuricemia and gout play an important role in patients with chronic kidney disease (CKD). However, the effect of uric acid-lowering therapy (ULT) on the prognosis of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, we aim to investigate the influence of ULT on renal outcomes in these patients.MethodsComprehensive searches were conducted in PubMed, EMBASE, China National Knowledge Internet (CNKI), and the Cochrane Library, up until January 2024. We included randomized controlled trials (RCTs) that evaluated the effects of ULT on renal outcomes in CKD patients with asymptomatic hyperuricemia.ResultsA total of 17 studies were included in the meta-analysis. Compared with placebo or no treatment, ULT preserved the loss of estimated glomerular filtrating rate (eGFR) (Weighted mean difference [WMD] and its 95% confidence intercal(CI): 2.07 [0.15,3.98] mL/min/1.73m2) at long-term subgroup. At the same time, short-term subgroup also proved the preserved loss of eGFR (WMD 5.74[2.09, 9.39] mL/min/1.73m2). Compared with placebo or no treatment, ULT also reduced the increase in serum creatinine (Scr) at short-term (WMD -44.48[-84.03,-4.92]μmol/L) subgroup and long-term (WMD -46.13[-65.64,-26.62]μmol/L) subgroup. ULT was associated with lower incidence of the events of doubling of Scr without dialysis (relative risk (RR) 0.32 [0.21, 0.49], p < 0.001). However, no difference was found for lower incidence of acute kidney injury (AKI) (p = 0.943).ConclusionsAccording to our study, ULT is beneficial for slowing CKD progression both in short to long-term follow-ups. Additionally, in patients younger than 60 years old, the protective effect of ULT on renal outcome is more pronounced. However, it showed no significant difference in the incidence of AKI. These findings underscore the importance of considering ULT in clinical strategies for CKD patients with asymptomatic hyperuricemia.

#5341 EFFECTS OF URIC ACID-LOWERING THERAPY ON RENAL OUTCOMES IN CKD PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA: A SYSTEMATIC REVIEW AND META-ANALYSIS

Abstract Background and Aims It is well known that hyperuricemia and gout play an important role in the adverse cardiovascular and renal events both in patients with and without renal disease. However, the effect of uric acid-lowering therapy (ULT) on renal outcomes of CKD patients with asymptomatic hyperuricemia remains controversial. Therefore, our study summarized reliable results draw from published randomized controlled trials (RCTs) to evaluate the effects of ULT on renal and cardiovascular outcomes in CKD patients with asymptomatic hyperuricemia. Method Pubmed, EMBASE, China National Knowledge Internet (CNKI) and the Cochrane Library were searched systematically for trials up to October 2021. RCTs assessing the effects of uric acid-lowering agents on renal and/or cardiovascular outcomes in CKD patients complicated with asymptomatic hyperuricemia were included. Both the fixed-effect and the random-effect models were used. Results A total of 17 RCTs (one trial1 divided patients into two groups according to CKD stages). including CKD patients with asymptomatic hyperuricemia were included in this meta-analysis. Compared with placebo or no treatment group, ULT group showed a higher estimated glomerular filtration rate (eGFR) with a weighted mean difference (WMD) of 3.679 mL/min/1.73 m2, 95%CI [1.592, 5.766] (p = 0.001) and a lower serum creatinine (Scr) with a WMD of -46.131umol/L, 95% CI [-65.643, -26.619] (p&amp;lt;0.0001). Subgroup analysis demonstrated a significant benefit from ULT in patients with CKD stage 1-3 (p = 0.035), from Asian countries (p = 0.005) and those younger than 60 years (p = 0.002). At the same time, ULT was associated with lower incidence of events of doubling of Scr without dialysis (relative risk (RR) 0.314[0.203, 0.485] (p&amp;lt; 0.0001)). However, no difference was found for all-cause mortality, incidence of AKI, progression to end-stage kidney disease (ESKD), and cardiovascular events. In addition, ULT with allopurinol was associated with lower cardiovascular events (RR 0.678[0.473, 0.971] (p = 0.034)). Conclusion ULT could slow down the progression of renal impairment in CKD patients complicated with asymptomatic hyperuricemia, especially for patients under 60 years old, early CKD stage(1-3) and the Asian descent.

Uric acid-lowering therapy with benzbromarone in hypertension with asymptomatic hyperuricemia: a randomized study focusing left ventricular diastolic function

Background Both hypertension and hyperuricemia are closely associated with the morbidity and mortality of heart failure with preserved ejection fraction (HFpEF). However, there is limited evidence on the effect of uric acid-lowering therapy on left ventricular (LV) diastolic function in this population. In this randomized study, we prescribed benzbromarone, a uric acid-lowering drug, to those with hypertension and asymptomatic hyperuricemia to investigate its clinical benefits by evaluating LV diastolic function, incidence of HFpEF and hospitalization for heart failure and cardiovascular death. Methods 230 participants were randomly assigned into two groups: uric acid-lowering group (benzbromarone) and control groups (without uric acid-lowering drug). The primary endpoint was LV diastolic function evaluated by echocardiography. The secondary endpoint of composite endpoints is the combination of new-onset HFpEF, hospitalization for heart failure and cardiovascular death. Results After a median of 23.5 months’ follow-up (16–30 months), the primary endpoint reflected by E/e’ in benzbromarone group reached a significant improvement when compared to control group (p <.001). Composite endpoints occurred in 11 patients of the control group while only 3 patients occurred in the benzbromarone group (p = .027). We also presented the favorable trend of freedom from the composite endpoints or new-onset HFpEF using Kaplan–Meier curve by log-rank test in benzbromarone group (p = .037 and p = .054). Conclusions Our study demonstrated the efficiency of benzbromarone in hypertensive patients with concomitant asymptomatic hyperuricemia, including the benefits on ameliorating LV diastolic dysfunction as well as improving composite endpoints.

Effects of uric acid-lowering therapy in patients with essential arterial hypertension.

Asymptomatic hyperuricemia (AHU) is elevated serum uric acid (UA) without symptoms. This study aimed to determine the effects of AHU treatment with allopurinol on selected hypertension-mediated organ damage (HMOD) indices in patients with uncomplicated essential arterial hypertension (AH). Patients aged 30-70 years with AHU and AH grade 1-2 with adequate blood pressure (BP) control, without previous urate-lowering therapy (ULT), were divided into two groups: (a) ULT (receiving allopurinol) and (b) control (age- and sex-matched patients without ULT). Both received a UA-lowering diet. BP (office, 24 h and central), echocardiographic parameters, carotid intima-media thickness (IMT) and lab tests [high-sensitivity C-reactive protein (hs-CRP)] were measured at baseline and at 6 months follow-up. Of 100 participants, 87 (44 ULT, 43 controls) completed the study. At 6 months follow-up, there was a greater reduction in serum UA concentration in the ULT group than in the control group. Patients receiving allopurinol had significant reductions in office systolic and diastolic BP, central systolic BP, pulse pressure, IMT (0.773 ± 0.121 vs. 0.752 ± 0.13 mm, P = 0.044) and hs-CRP (3.36 ± 2.73 vs. 2.74 ± 1.91 mg/L, P = 0.028) compared to controls. Multivariate regression analysis revealed the independent relationship between reduction in IMT and UA lowering (P < 0.026). In patients with AH and AHU, treatment with allopurinol leads to improvement in BP control and reduction in HMOD intensity, in particular IMT. The decrease in hs-CRP concentration associated with ULT may have a beneficial effect on a patient's long-term prognosis.

Distinct Gut Microbiota in Patients with Asymptomatic Hyperuricemia: A Potential Protector against Gout Development.

PurposeHere, we aimed to elucidate the differences in microbiota composition between patients with gout and those with asymptomatic hyperuricemia (asHU) and determine the effect of uric acid-lowering therapy (ULT) on the gut microbiome.Materials and MethodsStool samples from patients with asHU (n=8) and three groups of gout patients, i.e., acute gout patients before ULT (0ULT, n=14), the same acute gout patients after 30-day ULT (30ULT, n=9), and chronic gout patients after ≥6-month ULT (cULT, n=18) were collected and analyzed using 16S rRNA gene-based pyrosequencing. The composition of microbial taxonomy and communities, species diversity, and relationships among microbial communities were elucidated by bioinformatic analysis.ResultsGout patients showed less diverse gut microbiota than asHU patients. The microbiota of the asHU group exhibited a higher Firmicutes-to-Bacteroidetes (F/B) ratio and lower Prevotella-to-Bacteroides (P/B) ratio than the gout group; significantly, the F/B ratio increased in gout patients after ULT. Moreover, a balanced enterotype populated asHU patients compared to gout patients. Notably, the gut microbiota in asHU patients had a higher proportion of taxa with potentially anti-inflammatory effects compared to the gut microbiota in gout patients.ConclusionWe found that microbial composition differs between asHU and gout patients. The differential gut microbiota in asHU patients may protect against gout development, whereas that in gout patients may have a role in gout provocation. ULT in gout patients altered the gut microbiota, and may help alleviate gout pathology and mitigate gout progression.

Effect of uric acid-lowering therapy on renal function in patients with chronic kidney disease: a systematic review and meta-analysis

BackgroundWhether uric acid (UA)-lowering therapy (ULT) is effective in reducing the progression of renal dysfunction in patients with chronic kidney disease (CKD) remains controversial. Since several advances have been made in therapies for hyperuricemia, including novel xanthine oxidoreductase (XOR) inhibitors, we conducted a systematic review to clarify the effectiveness of ULT in preserving renal function among CKD patients.MethodsIn this systematic review, the MEDLINE database was searched up to June 2019. We included complete randomized controlled trials comparing renal events between adult non-dialyzed CKD patients, defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, with and without ULTs. Changes in eGFR were expressed as the mean difference (MD). The incidence of dichotomous outcomes was expressed as a risk ratio. This review was performed using the predefined protocol published in PROSPERO (CRD 42019140346).ResultsEleven studies with 4277 CKD patients were included. Drugs used in the intervention groups of all studies were XOR inhibitors (allopurinol, febuxostat or topiroxostat). Although patients with ULT tended to show superior preservation of eGFR as compared to those without ULT, no significant differences were identified (MD, 2.52; 95% confidence interval, − 0.15 to 5.18). In subgroup analysis, the use of allopurinol was associated with superior preservation of eGFR, whereas the newer XOR inhibitors, febuxostat and topiroxostat, showed no significant effects on eGFR changes. Neither incidence of end-stage kidney disease nor treatment-emergent adverse events differed significantly between groups.ConclusionsThe present systematic review and meta-analysis suggested that CKD patients with ULT tend to show superior eGFR preservation as compared to patients without ULT, but further studies are needed to verify the renoprotective effects of ULT.

Effects of uric acid-lowering therapy on the progression of chronic kidney disease: a systematic review and meta-analysis

Objectives: Whether uric acid levels were associated with the progression of chronic kidney disease (CKD) remained controversial. This meta-analysis was aimed to assess the effect of lowering serum uric acid therapy on the progression of CKD to clarify the role of uric acid in the progression of CKD indirectly.Methods: Pubmed, Embase, the Cochrane library, CBM were searched for randomized controlled trials (RCTs) that assessed the efficiency of lowering serum uric acid therapy on the progression of CKD without language restriction. Summary estimates of weighted mean differences (WMDs) and relative risk (RR) were obtained by using random-effect or fixed-effect models. Sensitivity analyses were performed to identify the source of heterogeneity.Results: A total of 12 randomized controlled trials with 832 CKD participants were included in the analysis. Pooled estimate for eGFR was in favor of lowering serum uric acid therapy with a mean difference (MD) of 3.88 ml/min/1.73 m2, 95% CI 1.26–6.49 ml/min/1.73 m2, p = .004 and this was consistent with results for serum creatinine. The risk of worsening of kidney function or ESRD or death was significantly decreased in the treatment group compared to the control group (RR 0.39, 95% CI 0.28–0.52, p< .01).Conclusions: Uric acid-lowering therapy may be effective in retarding the progression of CKD. Further randomized controlled trials should be performed to confirm the effect of lowering serum uric acid therapy on the progression of CKD.

Effects of uric acid-lowering therapy in patients with chronic kidney disease: A meta-analysis

Background and objectivesThe effects of uric acid-lowering therapy in patients with chronic kidney disease (CKD) remain uncertain. Therefore, we undertook a systematic review and meta-analysis to investigate the effects of uric acid-lowering agents on major clinical outcomes of CKD.Design, setting, participants, and measurementsAccording to the pre-specified protocol that was registered with PROSPERO (No. CRD42016038030), we searched systematically in MEDLINE, EMBASE, and the Cochrane Library for trials up to February 2016. Prospective, randomized, controlled trials assessing the effects of uric acid-lowering agents on cardiovascular and kidney outcomes in patients with CKD were included. Random-effects analytical methods were used.ResultsSixteen eligible trials were identified, providing data for 1,211 patients with CKD, including 146 kidney failure events and 69 cardiovascular events. Uric acid-lowering therapy produced a 55% relative risk (RR) reduction (95% confidence interval [95% CI], 31–64) for kidney failure events (P < 0.001), and a 60% RR reduction (95% CI, 17–62) for cardiovascular events (P < 0.001), but had no significant effect on the risk of all-cause death (RR, 0.86; 95% CI, 0.50–1.46). The mean differences in rate of decline in the estimated glomerular filtration rate (4.10 mL/min/1.73 m2 per year slower in uric acid-lowering therapy recipients, 95% CI, 1.86–6.35) and the standardized mean differences in the change in proteinuria or albuminuria (−0.23 units of standard deviation greater in uric acid-lowering therapy recipients; 95% CI, −0.43 to −0.04) were also statistically significant.ConclusionsUric acid-lowering therapy seemed to improve kidney outcomes and reduce the risk of cardiovascular events in adults with CKD.

Effect of uric acid-lowering therapy on blood pressure: systematic review and meta-analysis

Background: The purpose of this meta-analysis was to determine if uric acid-lowering therapy is associated with a decrease in blood pressure (BP) and serum creatinine levels.Materials and methods: Medline, Cochrane, EMBASE, and Google Scholar databases were searched until 29 June 2016, with keywords: uric-acid-lowering therapy, allopurinol, febuxostat, uricosuric, and BP. Only randomized controlled trials were included. The primary outcomes were reduction in systolic BP (SBP) and diastolic BP (DBP), and secondary was reduction in serum creatinine level.Results: Patients treated with allopurinol had greater reduction in SBP (standardized difference in means [SDM] = 0.321, 95% confidence interval [CI]: 0.145–0.497, p < 0.001), DBP (SDM = 0.260, 95% CI: 0.102 to 0.417, p = 0.001), and creatinine level (SDM = 0.312, 95% CI: 0.008 to 0.615, p = 0.044) than control patients. Subgroup analysis showed that allopurinol significantly decreased SBP whether or not antihypertensive drugs were being administered; a decrease in DBP was only seen in patients receiving antihypertensive drugs. Low-dose allopurinol (≤300 mg/day) was more effective at reducing SBP than high-dose (>300 mg/day) in patients receiving antihypertensive drugs.Conclusions: These results support that allopurinol decreases BP and creatinine levels in patients with hyperuricemia.KEY MESSAGESAllopurinol decreases SBP and DPB, and creatinine levels in patients with hyperuricemia.Allopurinol resulted in a significant decrease in SBP in patients with or without treatment of antihypertensive drugs.A dose of allopurinol of ≤300 mg per day might be more effective than a higher dose.

Effects of uric acid-lowering therapy on renal outcomes: a systematic review and meta-analysis

Non-randomized studies suggest an association between serum uric acid levels and progression of chronic kidney disease (CKD). The aim of this systematic review is to summarize evidence from randomized controlled trials (RCTs) concerning the benefits and risks of uric acid-lowering therapy on renal outcomes. Medline, Excerpta Medical Database and Cochrane Central Register of Controlled Trials were searched with English language restriction for RCTs comparing the effect of uric acid-lowering therapy with placebo/no treatment on renal outcomes. Treatment effects were summarized using random-effects meta-analysis. Eight trials (476 participants) evaluating allopurinol treatment were eligible for inclusion. There was substantial heterogeneity in baseline kidney function, cause of CKD and duration of follow-up across these studies. In five trials, there was no significant difference in change in glomerular filtration rate from baseline between the allopurinol and control arms [mean difference (MD) 3.1 mL/min/1.73 m2, 95% confidence intervals (CI) -0.9, 7.1; heterogeneity χ2=1.9, I2=0%, P=0.75]. In three trials, allopurinol treatment abrogated increases in serum creatinine from baseline (MD -0.4 mg/dL, 95% CI -0.8, -0.0 mg/dL; heterogeneity χ2=3, I2=34%, P=0.22). Allopurinol had no effect on proteinuria and blood pressure. Data for effects of allopurinol therapy on progression to end-stage kidney disease and death were scant. Allopurinol had uncertain effects on the risks of adverse events. Uric acid-lowering therapy with allopurinol may retard the progression of CKD. However, adequately powered randomized trials are required to evaluate the benefits and risks of uric acid-lowering therapy in CKD.