Efficacy and Tolerability of Probenecid as Urate-lowering Therapy in Gout; Clinical Experience in High-prevalence Population

2013 ◽  
Vol 40 (6) ◽  
pp. 872-876 ◽  
Author(s):  
Karen Pui ◽  
Peter J. Gow ◽  
Nicola Dalbeth
Keyword(s):  
Adverse Events ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Laboratory Data ◽  
Serum Urate ◽  
Rheumatology Clinic ◽  
Combination Treatment Group ◽  
Lowering Therapy ◽  
Xanthine Oxidase Inhibitors ◽  
High Prevalence

Objective.Probenecid is recommended as urate-lowering therapy (ULT) in patients with gout where xanthine oxidase inhibitors are ineffective, not tolerated, or contraindicated. The aim of our study was to determine the efficacy of probenecid to achieve serum urate (SU) targets (< 0.36 mmol/l) in clinical practice.Methods.We identified 57 patients prescribed with probenecid from a database of 521 rheumatology clinic attenders with gout. Demographic characteristics, indications for probenecid, probenecid doses, side effects, and laboratory data including estimated glomerular filtration rate (eGFR) and SU were recorded.Results.There were 30/57 (53%) patients treated with probenecid as monotherapy and 27/57 (47%) patients treated with probenecid in combination with allopurinol. Target SU concentrations (< 0.36 mmol/l) were achieved in 10/30 (33%) of the probenecid monotherapy group and 10/27 (37%) of the combination treatment group. Baseline SU concentrations, but not eGFR or probenecid dose, independently predicted achievement of target SU. Target SU was achieved in 5/15 (33%) patients with eGFR < 50 ml/min/1.73 m2. There was no difference in the percentage of patients achieving SU target in those with eGFR < 50 ml/min/1.73 m2 compared with those with eGFR ≥ 50 ml/min/1.73 m2. Adverse events attributed to probenecid were observed in 8/42 (19%) patients with eGFR ≥ 50 ml/min/1.73 m2 and in 2/15 (13%) patients with eGFR < 50 ml/min/1.73 m2.Conclusion.Probenecid has moderate efficacy as ULT in clinical management of patients with complex gout who have a lack of efficacy or intolerance to allopurinol. Patients with chronic kidney disease may respond to probenecid with similar rates of adverse events.

Pomalidomide Plus Low-Dose Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma and Renal Impairment: Results From a Phase II Trial

2018 ◽  
Vol 36 (20) ◽  
pp. 2035-2043 ◽  
Author(s):  
Meletios Dimopoulos ◽  
Katja Weisel ◽  
Niels W.C.J. van de Donk ◽  
Karthik Ramasamy ◽  
Barbara Gamberi ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Glomerular Filtration Rate ◽  
Adverse Events ◽  
Renal Impairment ◽  
Glomerular Filtration ◽  
Phase Ii ◽  
Filtration Rate ◽  
Low Dose ◽  
Estimated Glomerular Filtration Rate ◽  
Phase Ii Trial

Purpose Renal impairment (RI) limits treatment options in patients with relapsed/refractory multiple myeloma (RRMM). Here, we prospectively studied pomalidomide plus low-dose dexamethasone (LoDEX) in patients with RRMM and moderate or severe RI, including those receiving hemodialysis. Patients and Methods MM-013, a noncomparative, European phase II trial, enrolled three patient cohorts: moderate RI (cohort A; estimated glomerular filtration rate, 30 to < 45 mL/min/1.73 m2); severe RI (cohort B; estimated glomerular filtration rate, < 30 mL/min/1.73 m2); and severe RI that requires hemodialysis (cohort C). Patients received pomalidomide 4 mg/d on days 1 to 21 and LoDEX 20 or 40 mg once per week in 28-day cycles. The primary end point was overall response rate. Results Of 81 enrolled patients (33, 34, and 14 patients in cohorts A, B, and C, respectively), 13 were still receiving treatment at data cutoff (January 28, 2017). Overall response rates were 39.4%, 32.4%, and 14.3%, with a median duration of response of 14.7 months, 4.6 months, and not estimable, respectively. Of importance, 100%, 79.4%, and 78.6% of patients, respectively, achieved disease control. With a median follow-up of 8.6 months, median overall survival was 16.4 months, 11.8 months, and 5.2 months, respectively. Complete renal responses were observed only in cohort A (18.2%), and no patients in cohort C became hemodialysis independent. Grade 3 and 4 hematologic treatment-emergent adverse events and pomalidomide discontinuations as a result of treatment-emergent adverse events occurred more frequently in cohort C. Pomalidomide pharmacokinetics were comparable among the three renal cohorts. Conclusion Pomalidomide 4 mg/d plus LoDEX is efficacious in patients with RRMM with moderate or severe RI, including those who had more advanced disease and required hemodialysis. The safety profile was acceptable among the three groups, and no new safety signals were observed.

scholarly journals Effects of canagliflozin on serum potassium in the CANagliflozin cardioVascular Assessment Study (CANVAS) Program

2020 ◽  
Author(s):  
Matthew R Weir ◽  
April Slee ◽  
Tao Sun ◽  
Dainius Balis ◽  
Richard Oh ◽  
...  
Keyword(s):  
Adverse Events ◽  
Serum Potassium ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
High Serum ◽  
Double Blind ◽  
Assessment Study ◽  
Sodium Glucose Cotransporter ◽  
Cardiovascular Assessment

Abstract Background The sodium-glucose cotransporter 2 inhibitor canagliflozin has been shown to reduce the risk of cardiovascular and renal events in patients with Type 2 diabetes mellitus and high risk. Pooled analyses of data from early studies and interim data from the CANagliflozin cardioVascular Assessment Study (CANVAS) suggested that canagliflozin might lead to increases in serum potassium, particularly the 300 mg dose in patients with renal impairment, which is important because high serum potassium is associated with increased cardiovascular and renal risk. We examined the effect of canagliflozin on serum potassium levels and hyperkalemia rates in the completed CANVAS Program. Methods The CANVAS Program (n = 10,142) was comprised of two comparable double-blind, randomized, placebo-controlled trials (CANVAS and CANVAS-Renal). Participants received canagliflozin 100 or 300 mg or placebo. Serum potassium measurements were performed in a central laboratory0 and assessed at ∼6-month intervals. Results In the CANVAS Program, mean potassium levels were generally consistent with canagliflozin and placebo, overall and by baseline estimated glomerular filtration rate (eGFR; ≥60, 45 to&lt;60 and &lt;45 mL/min/1.73 m2). The risk of increased or decreased potassium was similar with canagliflozin and placebo overall and by baseline eGFR (all P-heterogeneity ≥0.56) or use of renin–angiotensin–aldosterone system inhibitors (all P-heterogeneity ≥0.71); levels did not appear different by canagliflozin dose. Hyperkalemia {hazard ratio (HR) [95% confidence interval (CI)] 1.60 (0.92–2.81)} and serious hyperkalemia [HR (95% CI) 0.75 (0.27–2.11)] adverse events were not different across groups. Conclusions In the CANVAS Program, there were no meaningful effects of canagliflozin on serum potassium in the overall population or key subgroups. Hyperkalemia adverse events were uncommon and occurred at comparable rates with canagliflozin and placebo.

scholarly journals Elevated admission urinary N-acetyl-β-D-glucosamidase level is associated with worse long-term clinical outcomes in patients with acute heart failure

2020 ◽  
Vol 9 (5) ◽  
pp. 429-436 ◽  
Author(s):  
Sayaka Funabashi ◽  
Kazunori Omote ◽  
Toshiyuki Nagai ◽  
Yasuyuki Honda ◽  
Hiroki Nakano ◽  
...  
Keyword(s):  
Heart Failure ◽  
Glomerular Filtration Rate ◽  
Adverse Events ◽  
Glomerular Filtration ◽  
Clinical Outcomes ◽  
Acute Heart Failure ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Prognostic Significance ◽  
Heart Failure Patients

Background: The prognostic significance of urinary N-acetyl-β-D-glucosamidase in acute heart failure has not been fully elucidated. Accordingly, this study investigated whether urinary N-acetyl-β-D-glucosamidase could be associated with subsequent adverse events in acute heart failure patients. Methods: We studied 708 consecutive acute heart failure patients who had accessible N-acetyl-β-D-glucosamidase data on admission from the National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure registry. We assessed the relationship between the admission N-acetyl-β-D-glucosamidase level and the combined endpoint of all-cause death and worsening heart failure. Worsening heart failure was defined as worsening symptoms and signs of heart failure requiring intensification of intravenous therapy such as diuretics, vasodilators and inotropes or initiation of mechanical support after stabilisation with initial treatment during hospitalisation, or readmission due to heart failure after discharge. Results: During a median follow-up period of 763 (interquartile range 431–1028) days, higher urinary N-acetyl-β-D-glucosamidase was significantly related to increased events of all-cause death and worsening heart failure. In addition, patients with higher urinary N-acetyl-β-D-glucosamidase and lower estimated glomerular filtration rate on admission had the worst clinical outcomes. In multivariable Cox regression, urinary N-acetyl-β-D-glucosamidase on admission was independently associated with adverse events (hazard ratio 1.19, 95% confidence interval 1.04–1.35) even after adjustment by covariates including the baseline estimated glomerular filtration rate. Conclusions: Higher urinary N-acetyl-β-D-glucosamidase level on admission was independently associated with worse clinical outcomes. Our findings indicate the potential value of assessing urinary N-acetyl-β-D-glucosamidase on admission for further risk stratification in patients with acute heart failure.

scholarly journals Pegloticase in gout treatment - safety issues, latest evidence and clinical considerations

2017 ◽  
Vol 8 (12) ◽  
pp. 379-388 ◽  
Author(s):  
Allison Guttmann ◽  
Svetlana Krasnokutsky ◽  
Michael H. Pillinger ◽  
Adey Berhanu
Keyword(s):  
Serum Urate ◽  
Infusion Reaction ◽  
Lower Serum ◽  
Safety Issues ◽  
Lowering Therapy ◽  
Xanthine Oxidase Inhibitors ◽  
The Us ◽  
Infusion Reactions ◽  
Clinical Considerations ◽  
Treatment Safety

Gout is a common rheumatic condition, with increasing prevalence in recent decades. The mainstay of treatment for gout is oral urate-lowering therapy (ULT), typically with xanthine oxidase inhibitors (XOIs). Unfortunately, a proportion of patients have persistent gout that is refractory to ULT. Pegloticase, a recombinant pegylated uricase, has been approved by the US Food and Drug Administration for the treatment of refractory gout. However, concern has been raised regarding the risk of infusion reactions, which are now understood to be largely due to the development of antipegloticase antibodies. Discontinuation of pegloticase upon failure to lower serum urate has been shown to markedly reduce infusion reaction risk, but deprives patients of what, in many cases, is a last-resort treatment. In this manuscript, we review the rationale, mechanism of action, efficacy and safety of pegloticase. Additionally, we focus on potential strategies to reduce pegloticase immunogenicity and potentially make this important agent available to a wider group of patients requiring treatment.

scholarly journals A Phase 1 Randomized Dose-Escalation Study of a Human Monoclonal Antibody to IL-6 in CKD

Kidney360 ◽  
2020 ◽  
pp. 10.34067/KID.0005862020
Author(s):  
Kristen L. Nowak ◽  
Rahul Kakkar ◽  
Matt Devalaraja ◽  
Larry Lo ◽  
Wansu Park ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Glomerular Filtration Rate ◽  
Adverse Events ◽  
Chronic Inflammation ◽  
Dose Escalation ◽  
Interleukin 6 ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Human Monoclonal Antibody ◽  
50Mg Dose

Background: Chronic systemic inflammation is highly prevalent in patients with chronic kidney disease (CKD; measured as an elevated high-sensitivity C-reactive protein [hsCRP]) and independently associated with cardiovascular events and all-cause mortality. An interleukin-6 blocker to suppress inflammation represents a potential novel paradigm to reduce cardiovascular risk in CKD. Methods: A phase I trial of Ziltivekimab, a fully human monoclonal antibody against interleukin-6, was conducted in patients with moderate-to-severe non-dialysis dependent CKD (estimated glomerular filtration rate of 20-60 ml/min/1.73m^2) and evidence of chronic inflammation (hsCRP level >2 mg/L over two consecutive measurements). Three cohorts of n=4 (3:1 active:placebo) were blindly randomized to a single dose of Ziltivekimab (5mg, 15mg, and 50mg subcutaneous injection) and followed for 12 weeks for safety and pharmacokinetic/pharmacodynamic assessments, and an additional 20 weeks for safety and anti-drug antibody assessments. Results: Participants were 67+/-11 years; baseline estimated glomerular filtration rate: 40+/-13 ml/min/1.73m2; baseline hsCRP: 5.0+/-2.5 mg/L. Dose escalation was approved and all adverse events were within the expected range for a CKD population with chronic inflammation. No serious adverse events were reported in any active cohort. hsCRP levels were substantially reduced with Ziltivekimab. 100% of participants achieved suppression of hsCRP to <2mg/L with the 15mg and 50mg dose, and several subjects had undetectable levels of hsCRP with the 50mg dose. The mean half-life ranged from of 45-65 days. Conclusions: In adults with moderate-to-severe CKD and evidence of chronic inflammation, a single-injection of the interleukin-6 inhibitor Ziltivekimab was safe and highly effective at suppressing hsCRP over 12 weeks.

Antimicrobial stewardship: The influence of behavioral nudging on renal-function–based appropriateness of dosing

2020 ◽  
Vol 41 (9) ◽  
pp. 1077-1079
Author(s):  
Rodrigo P. dos Santos ◽  
Caroline Deutschendorf ◽  
Hellena G. Vido ◽  
Rafaela B. Gerson ◽  
Fabiane Marson ◽  
...  
Keyword(s):  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Adverse Events ◽  
Glomerular Filtration ◽  
Antimicrobial Stewardship ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Prescription Behavior ◽  
Antimicrobial Prescription

AbstractFailure to adjust doses may contribute to adverse events. We evaluated the effectiveness of providing the estimated glomerular filtration rate on appropriateness of dosing for antimicrobials. The approach increased appropriateness of dosing from 33.9% to 41.4% (P < .001). Nudging prescription behavior can boost strategies for adequate antimicrobial prescription.

scholarly journals Embedded Catheters: Minimizing Excessive Embedment Time and Futile Placement While Maintaining Procedure Benefits

2015 ◽  
Vol 35 (5) ◽  
pp. 545-551 ◽  
Author(s):  
John H. Crabtree ◽  
Raoul J. Burchette ◽  
Rukhsana A. Siddiqi
Keyword(s):  
Regression Analysis ◽  
Central Venous Catheter ◽  
Serum Albumin ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Laboratory Data ◽  
Venous Catheter ◽  
Central Venous ◽  
Lower Serum ◽  
Diabetic Status

BackgroundEmbedding peritoneal catheters far in advance of anticipated need may successfully commit patients to their modality choice and reduce central venous catheter use but can be complicated by excessive embedment periods and futile catheter placement.ObjectiveEmbedded catheter outcomes were studied to identify factors that minimize inordinate embedment time and futile placement while maintaining procedure benefits.MethodsClinical and laboratory data were examined in 107 patients with embedded catheters that were either externalized, remained embedded, or were futilely placed.ResultsExternalization of 84 catheters was performed after a median embedment period of 9.4 months. Flow dysfunction occurred in 14.3% of externalized catheters. Overall function rate was 98.8% after laparoscopic revision. One patient changed their mind about modality choice. Except for 1 patient hospitalized acutely in a facility unfamiliar with embedded catheters, none remaining on a peritoneal dialysis pathway initiated dialysis with a central venous catheter. Including catheters with extremely long embedment periods, the incidence of futile placement was 13.1%. Multiple regression analysis identified estimated glomerular filtration rate (eGFR) and serum albumin as the 2 variables best associated with catheter embedment duration (r2= 0.44, p < 0.0001). Diabetic nephropathy was statistically more likely to be associated with lower serum albumin values ( p < 0.0001); however, no association was noted between diabetic status and embedment duration ( p = 0.62).ConclusionsTiming of the embedment procedure should include appraisal of both eGFR and serum albumin. Appropriate consideration of these values together may help minimize excessive embedment periods and decrease futile placements while preserving procedure benefits.

scholarly journals Bidirectional Interaction of Thyroid-Kidney Organs in Disease States

2020 ◽  
Vol 2020 ◽  
pp. 1-16
Author(s):  
Fateme Shamekhi Amiri
Keyword(s):  
Glomerular Filtration Rate ◽  
Thyroid Hormones ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Hormone Replacement ◽  
Laboratory Data ◽  
Overt Hypothyroidism ◽  
Kidney Dysfunction ◽  
Disease States

Purpose. Thyroid hormones play an important role in growth, development, and physiology of the kidney. The kidney plays a key role in the metabolism, degradation, and excretion of thyroid hormones and its metabolites. The aim of this study is to investigate the prevalence of disease states of thyroid-kidney organs and detecting the correlation between thyroid and kidney function abnormalities. Materials and Methods. In this retrospective study, a total of forty-five patients with thyroid and kidney dysfunction were investigated. Clinical features, laboratory data at initial presentation, management, and outcomes were collected. The paper has been written based on searching PubMed and Google Scholar to identify potentially relevant articles or abstracts. Median, percentage, mean ± standard deviation (SD), and the two-tailed t-test were used for statistical analyses. The correlation between variables was assessed by Pearson’s, Spearman’s correlation tests and regression analyses. Results. The mean ± SD of age of study patients was 48.2 ± 22.93 years (ranging from 1 to 90 years). There was no correlation between serum thyroid-stimulating hormone, free thyroxine levels with estimated glomerular filtration rate, and proteinuria. No association between antimicrosomal antibodies with estimated glomerular filtration rate was seen. Cardiovascular disease was the most common complication of overt hypothyroidism in kidney dysfunction patients. Conclusion. The present study showed more prevalence of primary hypothyroidism in comparison with other thyroid dysfunctions in patients with kidney dysfunction. Reduced mean values of thyroid function profiles after treatment suggest that this thyroid disease should be considered and ameliorated with thyroid hormone replacement therapy in patients with kidney disease.

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