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American Journal of Nephrology 2023There were insufficient pieces of evidence regarding the effect of the two drugs (allopurinol and febuxostat) on patient survival in hemodialysis (HD) patients. Herein,... (Comparative Study)
Comparative Study
INTRODUCTION
There were insufficient pieces of evidence regarding the effect of the two drugs (allopurinol and febuxostat) on patient survival in hemodialysis (HD) patients. Herein, we aimed to compare the efficacy of uric acid-lowering drugs (ULDs) or the type of the drug on patient survival using a representative sample of maintenance HD patients in South Korea.
METHODS
This study used data from a national HD quality assessment program and the claims data. Use of ULDs was defined as more than one prescription during the 6 months of each HD quality assessment period. The patients were divided into three groups. Patients who were not prescribed allopurinol or febuxostat were included in group 1 (n = 43,251); patients who were prescribed allopurinol were included in group 2 (n = 9,987); and patients who were prescribed febuxostat were included in group 3 (n = 2,890).
RESULTS
Kaplan-Meier curves showed that the survival rate was greatest in group 3 and worst in group 1 among the three groups. Multivariable analysis showed that group 2 had better patient survival compared to group 1; however, there was no significant difference in patient survival between groups 2 and 3. In addition, patients with hyperuricemia or gout had better patient survival compared to those without these diseases.
CONCLUSIONS
Our study showed that survival in patients receiving ULDs was not inferior to that of those not receiving ULDs. Patient survival between patients on HD receiving allopurinol and those receiving febuxostat was similar.
Topics: Humans; Allopurinol; Febuxostat; Gout; Gout Suppressants; Hyperuricemia; Renal Dialysis; Treatment Outcome; Uric Acid
PubMed: 37231773
DOI: 10.1159/000530972 -
Allopurinol to reduce cardiovascular morbidity and mortality: A systematic review and meta-analysis.PloS One 2021To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients. (Meta-Analysis)
Meta-Analysis
AIMS
To compare the effectiveness of allopurinol with no treatment or placebo for the prevention of cardiovascular events in hyperuricemic patients.
METHODS AND RESULTS
Pubmed, Web of Science and Cochrane library were searched from inception until July 2020. Randomized controlled trials (RCT) and observational studies in hyperuricemic patients without significant renal disease and treated with allopurinol, versus placebo or no treatment were included. Outcome measures were cardiovascular mortality, myocardial infarction, stroke, or a combined endpoint (CM/MI/S). For RCT's a random effects meta-analysis was performed. For observational studies a narrative synthesis was performed. Of the original 1995 references we ultimately included 26 RCT's and 21 observational studies. We found a significantly reduced risk of combined endpoint (Risk Ratio 0.65 [95% CI] [0.46 to 0.91]; p = 0.012) and myocardial infarction (RR 0.47 [0.27 to 0.80]; p = 0.01) in the allopurinol group compared to controls. We found no significant effect of allopurinol on stroke or cardiovascular mortality. Of the 15 observational studies with sufficient quality, allopurinol was associated with reduced cardiovascular mortality in 1 out of 3 studies that reported this outcome, myocardial infarction in 6 out of 8, stroke in 4 out of 7, and combined end-point in 2 out of 2. Cardiovascular benefit was only observed when allopurinol therapy was prolonged for more than 6 months and when an appropriate allopurinol dose was administered (300 mg or more/day) or sufficient reduction of serum urate concentration was achieved (<0.36 mmol/l).
CONCLUSIONS
Data from RCT's and observational studies indicate that allopurinol treatment reduces cardiovascular risk in patients with hyperuricemia. However, the quality of evidence from RCTs is low to moderate. To establish whether allopurinol lowers the risk of cardiovascular events a well-designed and adequately powered randomized, placebo-controlled trial is needed in high-risk patients with hyperuricemia.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO registration CRD42018089744.
Topics: Allopurinol; Antimetabolites; Cardiovascular Diseases; Humans; Morbidity; Prognosis; Survival Rate
PubMed: 34855873
DOI: 10.1371/journal.pone.0260844 -
Advances in Kidney Disease and Health Mar 2023Calcium stones are common and recurrent in nature, yet few therapeutic tools are available for secondary prevention. Personalized approaches for stone prevention have... (Review)
Review
Calcium stones are common and recurrent in nature, yet few therapeutic tools are available for secondary prevention. Personalized approaches for stone prevention have been informed by 24-hour urine testing to guide dietary and medical interventions. However, current evidence is conflicting about whether an approach guided by 24-hour urine testing is more effective than a generic one. The available medications for stone prevention, namely thiazide diuretics, alkali, and allopurinol, are not always prescribed consistently, dosed correctly, or tolerated well by patients. New treatments on the horizon hold the promise of preventing calcium oxalate stones by degrading oxalate in the gut, reprogramming the gut microbiome to reduce oxalate absorption, or knocking down expression of enzymes involved in hepatic oxalate production. New treatments are also needed to target Randall's plaque, the root cause of calcium stone formation.
Topics: Humans; Calcium; Allopurinol; Alkalies; Body Fluids; Chronic Disease; Oxalates
PubMed: 36868731
DOI: 10.1053/j.akdh.2022.12.004 -
CMAJ : Canadian Medical Association... Apr 2023
Topics: Humans; Allopurinol; Drug Hypersensitivity Syndrome; Gout Suppressants; Disease Progression; Drug Hypersensitivity
PubMed: 37011932
DOI: 10.1503/cmaj.221575 -
Medicine Mar 2022The aim of the study was to investigate the risk of prostate cancer among people with gout and/or hyperuricemia who used allopurinol and who did not use allopurinol. (Meta-Analysis)
Meta-Analysis
OBJECTIVE:
The aim of the study was to investigate the risk of prostate cancer among people with gout and/or hyperuricemia who used allopurinol and who did not use allopurinol.
METHODS:
We conducted a meta-analysis to identify the cohort and case-control studies by searching PubMed and Web of Science. We used the random-effects model to calculate the pooled risk ratio with 95% confidence interval for the risk of prostate cancer associated with allopurinol treatment.
RESULTS:
There were 5 cohort studies and 2 case-control studies included in the meta-analysis. All 7 eligible studies were published between 2012 and 2021. The study period ranged from 8 to 13years. The number of study subjects ranged from 25,770 to 1,623,550. The age of study subjects ranged from 20 to 99years. Overall, allopurinol treatment was not associated with the risk of prostate cancer (risk ratio = 1.13, 95% confidence interval = 0.96-1.34 and = .13). The heterogeneity was high between studies (I = 93%).
CONCLUSIONS:
Our meta-analysis reveals that no association can be found between allopurinol treatment and the risk of prostate cancer among people with gout and/or hyperuricemia. We propose that the inhibition of xanthine oxidase and the reduction of serum uric acid via allopurinol treatment do not affect the probability of developing prostate cancer. Further studies are needed to confirm our findings.
KEY POINTS
No association can be found between allopurinol treatment and the risk of prostate cancer. The inhibition of xanthine oxidase and the reduction of serum uric acid via allopurinol treatment do not affect the probability of developing prostate cancer.
Topics: Allopurinol; Gout Suppressants; Humans; Male; Prostatic Neoplasms
PubMed: 35356907
DOI: 10.1097/MD.0000000000028998 -
BMC Medicine May 2017Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of... (Review)
Review
Over the last decade, there have been major advances in the understanding of the genetic basis of hyperuricaemia and gout as well as of the pharmacogenetics of urate-lowering therapy. Key findings include the reporting of 28 urate-associated loci, the discovery that ABCG2 plays a central role on extra-renal uric acid excretion, the identification of genes associated with development of gout in the context of hyperuricaemia, recognition that ABCG2 variants influence allopurinol response, and the impact of HLA-B*5801 testing in reducing the prevalence of allopurinol hypersensitivity in high-risk populations. These advances, together with the reducing cost of whole genome sequencing, mean that integrated personalised medicine approaches may soon be possible in clinical practice. Genetic data may inform assessment of disease prognosis in individuals with hyperuricaemia or established gout, personalised lifestyle advice, selection and dosing of urate-lowering therapy, and prevention of serious medication adverse effects. In this article, we summarise the discoveries from genome-wide association studies and discuss the potential for translation of these findings into clinical practice.
Topics: Allopurinol; Genome-Wide Association Study; Gout; Gout Suppressants; Humans; Hyperuricemia; Life Style; Precision Medicine; Prognosis; Uric Acid
PubMed: 28566086
DOI: 10.1186/s12916-017-0878-5 -
International Journal of... Jun 2016Sweet's syndrome, or acute febrile neutrophilic dermatosis, is an uncommon severe cutaneous condition, not previously associated with allopurinol therapy. We describe...
Sweet's syndrome, or acute febrile neutrophilic dermatosis, is an uncommon severe cutaneous condition, not previously associated with allopurinol therapy. We describe the case of an 87-year-old woman with hyperuricemia who developed classic Sweet's syndrome manifestations 8 days after being treated with allopurinol. Patient's symptoms included fever, painful edema in the hands and lower limbs with non-pruritic erythematous plaques topped by pus-filled skin blisters, right eye conjunctivitis, splenomegaly and joint pain. At the emergency department, blood tests showed neutrophilic leukocytosis, inflammatory state and altered liver function. During hospitalization, she received unsuccessful treatments with two different antibiotics (namely ceftriaxone and levofloxacin), while treatment with intravenous methylprednisolone produced a rapid clinical remission of symptoms, cutaneous lesion pain improvement, normalization of her body temperature and her blood values returned to normal. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient's development of Sweet's syndrome and allopurinol therapy. Because the signs and symptoms of Sweet's syndrome resemble an infectious process, the correct diagnosis may be delayed and inappropriate treatment regimen with antibiotics may often precede glucocorticoid therapy.
Topics: Aged, 80 and over; Allopurinol; Anti-Bacterial Agents; Female; Humans; Hyperuricemia; Sweet Syndrome
PubMed: 26684631
DOI: 10.1177/0394632015599705 -
The Journal of Rheumatology Jun 2024Allopurinol is the most widely used urate-lowering medication worldwide. However, allopurinol failure is frequently observed in clinical practice. In this review, we... (Review)
Review
Allopurinol is the most widely used urate-lowering medication worldwide. However, allopurinol failure is frequently observed in clinical practice. In this review, we provide a framework for assessing allopurinol failure, which includes failure of allopurinol to control serum urate concentrations, failure of allopurinol to control clinical symptoms, and failure of allopurinol due to an adverse drug reaction. Understanding the causes of allopurinol failure underpins the approach required to turn failure into success in gout management.
Topics: Allopurinol; Humans; Gout; Gout Suppressants; Treatment Failure; Uric Acid
PubMed: 38490676
DOI: 10.3899/jrheum.2024-0144 -
Journal of Ethnopharmacology Dec 2023Traditional Chinese Medicine (TCM) Compound Shizhifang (SZF), consisting of the seeds of four Chinese herbs, has been used in Shanghai Shuguang Hospital in China for...
ETHNOPHARMACOLOGICAL RELEVANCE
Traditional Chinese Medicine (TCM) Compound Shizhifang (SZF), consisting of the seeds of four Chinese herbs, has been used in Shanghai Shuguang Hospital in China for more than 20 years and has proven its clinical safety and efficacy in lowering uric acid and protecting kidney function.
AIM OF THE STUDY
Hyperuricemia (HUA)-induced pyroptosis of renal tubular epithelial cells serves as a significant cause of tubular damage. SZF proves to be effective in alleviating renal tubular injury and inflammation infiltration of HUA. However, the inhibiting effect of SZF on pyroptosis in HUA still remains elusive. This study aims to verify whether SZF could ameliorate pyroptosis in tubular cells induced by uric acid (UA).
MATERIALS AND METHODS
Quality control analysis and chemical and metabolic identification for SZF and SZF drug serum were performed by using UPLC-Q-TOF-MS. In vitro, human renal tubular epithelial cells (HK-2) stimulated by UA were treated with SZF or NLRP3 inhibitor (MCC950). HUA mouse models were induced by intraperitoneal injection of potassium oxonate (PO). Mice were treated with SZF, allopurinol or MCC950. We focused on evaluated the effect of SZF on the NLRP3/Caspase-1/GSDMD pathway, renal function, pathologic structure and inflammation.
RESULTS
SZF significantly restrained the activation of the NLRP3/Caspase-1/GSDMD pathway in vitro and in vivo induced by UA. SZF was better than allopurinol and MCC950 in reducing pro-inflammatory cytokine levels, attenuating tubular inflammatory injury, inhibiting interstitial fibrosis and tubular dilation, maintaining tubular epithelial cell function, and protecting kidney. Furthermore, 49 chemical compounds of SZF and 30 metabolites in serum after oral administration were identified.
CONCLUSIONS
SZF inhibits UA-induced renal tubular epithelial cell pyroptosis via by targeting NLRP3 to inhibit tubular inflammatory and prevent the progression of HUA-induced renal injury effectively.
Topics: Humans; Mice; Animals; Inflammasomes; Hyperuricemia; NLR Family, Pyrin Domain-Containing 3 Protein; Pyroptosis; Allopurinol; Uric Acid; Signal Transduction; China; Inflammation; Caspases; Epithelial Cells
PubMed: 37311502
DOI: 10.1016/j.jep.2023.116777 -
Medicine Jul 2022This study aimed to compare the risk of dementia between exposed to allopurinol and not exposed to allopurinol in persons who had gout and/or hyperuricemia. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This study aimed to compare the risk of dementia between exposed to allopurinol and not exposed to allopurinol in persons who had gout and/or hyperuricemia.
METHODS
The meta-analysis was conducted to select case-control research written in English through the help of PubMed and Web of Science. The pooled odds ratio (OR) with 95% confidence interval based on the fixed-effect model was applied to compare the allopurinol exposure among cases (subjects with dementia) and controls (subjects without dementia).
RESULTS
A total of 4 case-control studies relating the allopurinol exposure to the risk of dementia were identified. The study duration was from 9 to 14 years. The number of study persons was from 3148 to 137,640. The male percentage of study subjects was from 36.9 to 62.5. The mean age of study persons was from 72.3 to 78.7 years. Overall, the odds of the allopurinol exposure among cases were lower than the odds of the allopurinol exposure among control subjects (OR = 0.91, 95% confidence interval = 0.87-0.95, P < .001). The heterogeneity between these eligible studies was low (I² = 0%). The sensitivity analysis revealed that after excluding the studies with concern, the pooled OR did not achieve statistical significance.
CONCLUSIONS
This is the first meta-analysis to report that there is a negative relationship between the allopurinol exposure and the risk of dementia. Although the results favor the hypothesis, currently it is unable to draw strong conclusions about the protective effect of allopurinol against dementia due to inclusion of only a few eligible studies. Randomized controlled trials are needed to explore the relationship between allopurinol exposure and the probability of dementia.
Topics: Aged; Allopurinol; Case-Control Studies; Dementia; Gout; Gout Suppressants; Humans; Male
PubMed: 35777042
DOI: 10.1097/MD.0000000000029827