Effects of Fenofibrate Therapy on Renal Function in Primary Gout Patients.
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ABSTRACT: Objective
To investigate the incidence and potential risk factors for development of fenofibrate-associated nephrotoxicity in gout patients.Methods
983 gout patients with fenofibrate treatment were retrospectively enrolled from the electronic record system who visited the dedicated Gout Clinic at the Affiliated Hospital of Qingdao University between September 2016 and June 2020. Fenofibrate-associated nephrotoxicity was defined as an increase in serum creatinine (SCr) ≥0.3 mg/dL within 6 months of fenofibrate initiation. The change trend of SCr and uric acid levels during treatment period were assessed by generalised additive mixed model (GAMM). Multivariate analysis was performed for risk factors affecting elevated SCr.Results
100 (10.2%) patients experienced an increase in SCr ≥0.3 mg/dL within 6 months after fenofibrate initiation. The median (quartile) change of SCr in the whole cohort was 0.11 (0.03-0.20) mg/dL, whereas it was 0.36 (0.33-0.45) mg/dL in the fenofibrate-associated nephrotoxicity group. In a multivariable regression model, chronic kidney disease (CKD) (OR, 2.39, 95% CI,1.48-3.86) and tophus (OR, 2.29, 95% CI, 1.39-3.78) were identified to be risk predictors, independent of measured covariates, of fenofibrate-associated nephrotoxicity. During the treatment period, although SCr temporarily elevated, serum urate and triglyceride concentrations decreased resulted from the interaction analysis of GAMM. Of those with fenofibrate withdrawal records, 65% of patients' SCr was reversible after an average of 49 days off the drug.Conclusions
This observational study implied that fenofibrate-associated nephrotoxicity occurs frequently in gout patients, especially in patients with tophi or CKD. The potential renal risks of fenofibrate usage in gout need additional focus.
SUBMITTER: Li X
PROVIDER: S-EPMC8566261 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Fibrates are widely used to treat hypertriglyceridemia, a risk factor for arteriosclerosis, but these compounds have been associated with renal dysfunction. This study aimed to investigate the effects of fibrates on renal function in relatively healthy adult subjects with no cardiovascular diseases.This retrospective study included 558 outpatients who were prescribed 160 mg fenofibrate (fenofibrate group) or 10 mg atorvastatin (control group) between August 2007 and October 2015. The groups were randomly matched using propensity scores at a 1:1 ratio. Serum creatinine levels and estimated glomerular filtration rates before and after treatment were compared between the two groups.Patients in the fenofibrate group showed greater changes in serum creatinine levels than those in the control group (9.73%±9.83% versus -0.89%±7.37%, P<0.001). Furthermore, 55.1% of patients in the fenofibrate group, but only 6.1% of those in the control group, exhibited a serum creatinine level increase ≥0.1 mg/dL (P<0.001). The fenofibrate group showed significantly greater declines in the estimated glomerular filtration rate than the control group (-10.1%±9.48% versus 1.42%±9.42%, P<0.001). Moreover, 34.7% of the fenofibrate group, but only 4.1% of the control group, exhibited an estimated glomerular filtration rate decrease ≥10 mL/min·1.73 m2 (P<0.001).Fenofibrate treatment resulted in increased serum creatinine levels and reduced estimated glomerular filtration rates in a primary care setting. Therefore, regular renal function monitoring should be considered essential during fibrate administration.
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Project description:Gout is a chronic disease associated with deposition of monosodium urate crystals and accompanied by diabetes, hypertension, and dyslipidemia. Hypertriglyceridemia is common among patients with gout, and fenofibrate is usually used to reduce triglyceride levels. The aim of this study is to determine the effect of uric acid reduction by fenofibrate in patients with gout administered uric acid lowering agents (viz., the xanthine oxidase inhibitors allopurinol and febuxostat). Data from 863 patients with gout were collected from electronic medical records comprising information on underlying diseases, laboratory findings, and drug histories. Among all the patients, 70 (8.11%) took fenofibrate with allopurinol or febuxostat. Male and young patients took fenofibrate more frequently, and hypertension was less frequent in patients administered xanthine oxidase inhibitors and fenofibrate than in those administered only xanthine oxidase inhibitors. After the treatment, serum uric acid levels more significantly decreased (-1.81?±?2.41 vs. -2.40?±?2.28?mg/dL, p?=?0.043) in patients with fenofibrate cotreatment, than in those administered allopurinol or febuxostat alone. The effect of uric acid reduction was larger (b?=?-1.098, p?<?0.001) in patients taking glucocorticoids than in those administered other treatments. There was no difference in the levels of creatinine, blood urea nitrogen, and aminotransferases between patients treated with and without fenofibrate. Fenofibrate additionally reduced uric acid levels without showing any change in the results of renal or liver function tests, suggesting that the addition of fenofibrate is a reasonable option for treating gout in patients having high triglyceride levels.
| S-EPMC6233215 | biostudies-literature
Project description:BackgroundPatients with gout frequently have low urinary pH, which is associated with the nephrolithiasis. However, the specific distribution of urinary pH and potential relationship of acidic urine pH to broader manifestations of kidney disease in gout are still poorly understood.MethodsA 2016-2020 population-based cross-sectional study was conducted among 3565 gout patients in the dedicated gout clinic of the Affiliated Hospital of Qingdao University to investigate the association between low urinary pH and kidney disease. We studied patients that we defined to have "primary gout", based on the absence of > stage 2 CKD. All subjects underwent 14 days of medication washout and 3-day standardized metabolic diet. We obtained general medical information, blood and urine biochemistries, and renal ultrasound examination on the day of the visit. The primary readouts were urine pH, eGFR, nephrolithiasis, renal cysts, microhematuria, and proteinuria. Patients were assigned into 5 subgroups (urine pH ≤5.0, 5.0 <pH≤ 5.5, 5.5 <pH< 6.2, 6.2 ≤pH≤ 6.9, and pH >6.9), aligning with the clinical significance of urine pH.ResultsOverall, the median urine pH and eGFR of all patients was 5.63 (IQR 5.37~6.09), and 98.32 (IQR 86.03~110.6), with acidic urine in 46.5% of patients. The prevalence of nephrolithiasis, microhematuria, and proteinuria were 16.9%, 49.5%, and 6.9%, respectively. By univariate analysis, eGFR was significantly associated with age, sex, duration of gout, tophus, body mass index, systolic blood pressure, diastolic blood pressure, fasting blood glucose, total cholesterol, serum utare, hypertension, diabetes, and urine pH. On multivariable analysis, eGFR was associated with age, sex, diastolic blood pressure, serum uric acid, hypertension, diabetes, and urine pH. Acidic urine pH, especially urine pH < 5.0, was significantly associated with the prevalence of kidney disease, including > stage 1 CKD, nephrolithiasis, kidney cyst, and microhematuria. Patients with 6.2 ≤ urine pH ≤ 6.9 and SU ≤ 480 μmol/L had the highest eGFR with the lowest prevalence of nephrolithiasis, microhematuria, and proteinuria.ConclusionsApproximately half of gout subjects had acidic urine pH. Urine pH < 5.0 was associated with significantly increased nephrolithiasis, renal cyst, microhematuria, and proteinuria. The results support prospective clinical investigation of urinary alkalinization in selected gout patients with acidic urine pH.
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Project description:To determine the expression profile and clinical significance of circular RNAs (circRNAs) in peripheral blood mononuclear cells (PBMCs) of patients with primary gout and healthy control subjects. Human circRNA microarrays were used to identify the differentially expressed circRNAs in primary gout (Gout, n = 5) and healthy subjects (HC, n = 3). Bioinformatics analyses were performed to predict the roles of differently expressed circRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results in 90 gout patients, and 60 healthy control subjects (HC). Microarray analysis indicated that 238 circRNAs were up-regulated and 41 circRNAs were down-regulated in the Gout group (Fold change>1.5, p-value<0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout through a variety of different pathways. Significant association was observed between these circRNAs and lipid metabolism indicators. Our results provide novel insight into the mechanisms of primary gout, and reveal that hsa_circRNA_103657 could effectively discriminate the gout group and the healthy control groups.
2021-06-25 | GSE178825 | GEO
Project description:To determine the expression profile and clinical significance of long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) of patients with primary gout and healthy control subjects. Human lncRNA microarrays were used to identify the differentially expressed lncRNAs and mRNAs in primary gout (n=6) and healthy subjects (n=6). Bioinformatics analyses were performed to predict the roles of differently expressed lncRNAs and mRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results in 64 gout patients, and 32 healthy control subjects (HC). The microarray analysis identified 1479 differentially expressed lncRNAs (879 up-regulated and 600 down-regulated), 862 differentially expressed mRNAs (390 up-regulated and 472 down-regulated) in primary gout (fold change>2, P<0.05), respectively. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of gout through several different pathways. Significant association was observed between these lncRNAs and the Clinical inflammation indicators and lipid metabolism indicators. Our results provide novel insight into the mechanisms of primary gout, and reveal that ENST00000566457 and NR-026756 could effectively discriminate the gout group and the healthy control groups.
2020-11-03 | GSE160170 | GEO
Project description:Fenofibrate (FF) has shown potential benefits in patients with primary biliary cholangitis (PBC) who have an incomplete response to ursodeoxycholic acid (UDCA). However, the efficacy and safety of FF in patients with cirrhosis remain unclear. To evaluate the efficacy and safety of additional FF therapy in patients with PBC-related cirrhosis with an incomplete response to UDCA, we conducted a retrospective analysis comparing the clinical results of additional FF therapy and continued UDCA monotherapy. A total of 59 patients were included; 27 cases underwent UDCA monotherapy and 32 cases underwent UDCA combined with FF therapy. A significant difference in alkaline phosphatase (ALP) normalization was achieved in the FF group compared to the UDCA group (37% vs. 11%, respectively; p = 0.020). Additional FF therapy was an independent risk factor for ALP normalization (hazard ratio, 7.679; 95% confidence interval, 2.059-28.633; p = 0.003). Hepatic deterioration was experienced by 40% versus 48% (p = 0.562) while 11% vs. 37% (p = 0.111) experienced liver-related mortality or liver transplantation in the FF and UDCA groups, respectively. Compared to UDCA monotherapy, additional FF therapy was associated with lower United Kingdom (UK)-PBC risk score and surrogate serum indices of liver fibrosis. After 12 months of add-on FF therapy, median ALP level and UK-PBC risk score decreased 35% and 52% from baseline (p = 0.001 and 0.210, respectively). Serum aminotransferase, triglyceride, and cholesterol decreased progressively, while total bilirubin, serum creatinine, blood urea, estimated glomerular filtration rate, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 index remained stable in FF-treated cirrhotic cases during follow-up. No significant adverse effects associated with additional FF therapy were observed in our cohort. Conclusion: Additional FF therapy was associated with higher ALP normalization rates and lower UK-PBC risk scores in patients with cirrhotic PBC with an incomplete response to UDCA. In addition, FF therapy seemed safe and well tolerated with a low frequency of adverse effects in patients with cirrhosis.
| S-EPMC9701475 | biostudies-literature
Project description:Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with a single-stranded covalently closed-loop structure, and their abnormal expression may participate in the pathogenesis of various human diseases. Currently, knowledge of circRNAs in gout is limited. In this case-control study, human circRNA microarrays were used to identify differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with primary gout (n = 5) and healthy controls (HC; n = 3). Bioinformatics methods were used to analyze significantly different circRNAs (fold change >1.5, p < 0.05). In addition, four significantly differentially expressed circRNAs were selected for quantitative real-time polymerase chain reaction to detect expression levels in 90 gout patients and 60 HC. Subsequently, circRNA-miRNA-mRNA network was established to predict the function of circRNAs of interest. Microarray analysis indicated that 238 circRNAs were upregulated and 41 circRNAs were down-regulated in the gout group (fold change >1.5, p < 0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout via various pathways. Moreover, the expression levels of hsa_circRNA_103657 and hsa_circRNA_000241 were significantly higher in the gout group than those in the HC group, and both correlated significantly with lipid metabolism parameters. Furthermore, the area under the curve of hsa_circRNA_103657 was 0.801 (95% confidence interval (CI): 0.730-0.871; p < 0.001). Our results provide novel insights into the pathogenesis of primary gout. Differentially expressed circRNAs were identified in the PBMCs of gout patients, and these differential circRNAs may play important roles in the development and progression of gout.
| S-EPMC8576385 | biostudies-literature
Project description:Background The relationship between intensive volume removal in acute decompensated heart failure patients with preexisting worsening renal function (WRF) and renal tubular injury, postdischarge renal function, and clinical outcomes is unknown. Methods and Results We used data from the multicenter CARRESS-HF trial (Cardiorenal Rescue Study in Acute Decompensated Heart Failure) that randomized patients with acute decompensated heart failure and preexisting WRF to intensive volume removal with stepped pharmacological therapy or fixed rate ultrafiltration. Patients in the urinary renal tubular injury biomarker substudy (NAG [N-acetyl-b-D-glucosaminidase], KIM-1 [kidney injury molecule-1], and NGAL [neutrophil gelatinase-associated lipocalin]) were evaluated (N=105). The severity of prerandomization WRF was unrelated to baseline renal tubular injury biomarkers ( r=0.14; P=0.17). During randomized intensive volume removal, creatinine further worsened in 53% of patients. Despite a small to moderate magnitude increase in creatinine in most of these patients, postrandomization WRF was strongly associated with worsening in renal tubular injury biomarkers (odds ratio, 12.6; P=0.004). This observation did not differ by mode of volume removal (stepped pharmacological therapy versus ultrafiltration, Pinteraction=0.46). Increase in renal tubular injury biomarkers was associated with a higher incidence of hemoconcentration (odds ratio, 3.1; P=0.015), and paradoxically, better recovery of creatinine at 60 days ( P=0.01). Conclusions In acute decompensated heart failure patients with preexisting WRF, intensive volume removal resulted in a further worsening of creatinine approximately half of the time, a finding associated with a rise in tubular injury biomarkers. However, decongestion and renal function recovery at 60 days were superior in patients with increased tubular injury markers. These data suggest that the benefits of decongestion may outweigh any modest or transient increases in serum creatinine or tubular injury markers that occur during intensive volume removal. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT00608491.
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Project description:Aims/introductionRenal dysfunction might quickly progress in patients with type 2 diabetes mellitus, when accompanied by hypertension. However, whether primary aldosteronism (PA), which autonomously over-secretes aldosterone, causes additional renal damage in patients with type 2 diabetes mellitus is unclear. We evaluated the impact of PA on renal function in patients with type 2 diabetes mellitus.Materials and methodsA retrospective review of all patients with type 2 diabetes mellitus who visited Yokohama Rosai Hospital's (Yokohama Japan) outpatient department between April 2017 and March 2018 was carried out. Records of patients with PA who underwent PA treatment by adrenalectomy or mineralocorticoid receptor antagonists (PA group) and those without PA (non-PA group) were extracted, and renal function was compared between the two groups. Untreated PA patients were excluded, as their renal function might be overestimated as a result of glomerular hyperfiltration.ResultsThere were 83 patients in the PA group and 1,580 patients in the non-PA group. The PA group had significantly lower estimated glomerular filtration rates than the non-PA group (66.3 [52.4-78.2] vs 70.5 [56.0-85.6] mL/min/1.73 m2 , P = 0.047). Multiple regression analysis showed that PA was a factor for decreased estimated glomerular filtration rate, independent of age, sex, glycated hemoglobin, diuretic use and hypertension (P = 0.025). PA induced a 3.7-mL/min/1.73 m2 (95% confidence interval 0.47-6.9) decrease in estimated glomerular filtration rate, equivalent to that induced by 4.4 years of aging.ConclusionsOur results show that in patients with type 2 diabetes mellitus, PA is an independent risk factor for renal dysfunction. To prevent the progression of renal failure, PA should not be overlooked.
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