Citations

AbstractBackgroundThe objective of this meta‐analysis of randomised controlled clinical trials (RCT) was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia.AimsFebuxostat is a xanthine oxidase inhibitor that decreases uric acid production. Recent studies suggested the renoprotective effect of febuxostat among hyperuricaemia patients. The aim of this study was to evaluate the effects of febuxostat on kidney function in patients with hyperuricaemia.MethodsWe conducted electronic searches in PubMed, Embase and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify RCT that examined the effects of febuxostat in adult patients with hyperuricaemia on serum creatinine, estimated glomerular filtration rate (eGFR), albuminuria, blood pressure parameters, major cardiovascular events, diarrhoea, joint pain, stroke and arrhythmia.ResultsNine RCT with 2141 participants were included in this meta‐analysis. Compared to placebo, the febuxostat group showed a higher eGFR at 6 months with a weighted mean difference (WMD) of 2.86 mL/min/1.73 m2 (P < 0.001), as well as the end of studies (eGFR WMD 2.69 mL/min/1.73 m2, P < 0.001). There was also lower serum creatinine (SrCr WMD = −0.04 mg/dL, P < 0.001), reduction in systolic blood pressure (SBP WMD = −1.18 mmHg, P < 0.001) and diastolic blood pressure (DBP WMD = −1.14 mmHg, P = 0.04). There was no statistical difference between febuxostat and placebo in major cardiovascular events, diarrhoea, joint symptoms, stroke events and arrhythmia. Subgroup analysis among chronic kidney disease showed the febuxostat group had higher eGFR than the placebo group (eGFR WMD = 2.69 mL/min/1.73 m2, P < 0.001).ConclusionTreating hyperuricaemia with febuxostat may slow the progression of chronic kidney disease irrespective of baseline renal function without significantly associated increased risks of major cardiovascular events, diarrhoea, joint symptoms, arrhythmia and stroke, compared to placebo.

Background and objectives: Calcium concentration is strictly regulated at both the cellular and systemic level, and changes in serum calcium levels can alter various physiological functions in various organs. This study aimed to assess the association between changes in calcium levels during hospitalization and mortality. Materials and Methods: We searched our patient database to identify all adult patients admitted to our hospital from January 1st, 2009 to December 31st, 2013. Patients with ≥2 serum calcium measurements during the hospitalization were included. The serum calcium changes during the hospitalization, defined as the absolute difference between the maximum and the minimum calcium levels, were categorized into five groups: 0–0.4, 0.5–0.9, 1.0–1.4, 1.5–1.9, and ≥2.0 mg/dL. Multivariable logistic regression was performed to assess the independent association between calcium changes and in-hospital mortality, using the change in calcium category of 0–0.4 mg/dL as the reference group. Results: Of 9868 patients included in analysis, 540 (5.4%) died during hospitalization. The in-hospital mortality progressively increased with higher calcium changes, from 3.4% in the group of 0–0.4 mg/dL to 14.5% in the group of ≥2.0 mg/dL (p < 0.001). When adjusted for age, sex, race, principal diagnosis, comorbidity, kidney function, acute kidney injury, number of measurements of serum calcium, and hospital length of stay, the serum calcium changes of 1.0–1.4, 1.5–1.9, and ≥2.0 mg/dL were significantly associated with increased in-hospital mortality with odds ratio (OR) of 1.55 (95% confidence interval (CI) 1.15–2.10), 1.90 (95% CI 1.32–2.74), and 3.23 (95% CI 2.39–4.38), respectively. The association remained statistically significant when further adjusted for either the lowest or highest serum calcium. Conclusion: Larger serum calcium changes in hospitalized patients were progressively associated with increased in-hospital mortality.

Abstract Serum albumin is a marker of nutritional and frailty status. This study aimed to assess the association between serum albumin at the time of admission and the risk of acute respiratory failure (ARF) in hospitalized patients This cohort study, performed at a tertiary referral hospital, included all hospitalized adult patients from January 2009 to December 2013 who had serum albumin measurement and were not on mechanical ventilation within 24 hours of hospital admission. Serum albumin was stratified into 2.4, 2.5 to 2.9, 3.0 to 3.4, 3.5 to 3.9, 4.0 to 4.4, and ≥4.5 g/dL. Multivariate logistic regression analysis was performed to obtain adjusted odds ratio (OR) of risk of ARF requiring mechanical ventilation based on various admission serum albumin levels. Of 12,719 patients, ARF requiring mechanical ventilation occurred in 1128 (8.9%) during hospitalization. Hypoalbuminemia was associated with increased risk of ARF, in particular when serum albumin was ≤2.4 g/dL. Compared with serum albumin of 4.0–4.4 g/dL, serum albumin ≤2.4 g/dL at admission was associated with 2.38-time higher odds of ARF during hospitalization (OR 2.38, 95% confidence interval [CI] 1.84–3.07). In contrast, elevated serum albumin ≥4.5 g/dL was associated with lower odds of ARF (OR 0.68, 95% CI 0.48–0.97). Admission serum albumin level lower than 3.5 g/dL was associated with a higher risk of ARF requiring mechanical ventilation, whereas elevated serum albumin level at least 4.5 g/dL was associated with a lower risk of ARF. Therefore, admission albumin level at admission might be useful in the prediction of ARF during hospitalization.

AbstractBackgroundThe objective of this meta‐analysis of observational studies was to evaluate the efficacy and safety profiles of febuxostat in treating hyperuricemia among kidney transplant patients.MethodsWe conducted electronic searches in PubMed, Embase, and Cochrane Central Register of Controlled Trials from January 1960 to July 2019 to identify studies that investigated the effects of febuxostat in kidney transplant patients on uric acid as well as safety profiles including estimated glomerular filtration rate (eGFR), hemoglobin level (Hb), white blood cell counts (WBC), liver enzymes, and trough level of tacrolimus.ResultsSeven observational studies with 367 participants were included in this meta‐analysis. Compared with allopurinol, the febuxostat group demonstrated a higher odds of achieving target uric acid levels lower than 6 mg/dL within 12 months (OR = 2.9, P = .004). However, there was no statistical difference in change of uric acid (WMD = −1.0 mg/dL/y, P = .32) and change in allograft eGFR within a year (WMD = 0.01 mL/min/1.73 m2/y, P = .98) between febuxostat and allopurinol. Regarding safety profiles, there were no statistical differences in eGFR, Hb, WBC, liver enzymes (AST, ALT), and trough level of tacrolimus between baseline and at the study end. Only one study reported suspected graft loss among febuxostat group.ConclusionAmong kidney transplant patients, treating hyperuricemia with febuxostat showed a higher odds of reaching the target of serum uric acid < 6 mg/dL compared with allopurinol without causing significant side effects including change in tacrolimus level, liver function, decline in renal graft function, and bone marrow function.

AbstractCurrently, the data on independent risk factors for the progression of kidney disease in type 2 diabetes mellitus (T2DM) patients with CKD are limited. This study aimed to investigate CKD progression in T2DM patients who have reduced kidney function with baseline estimated glomerular filtration rate (eGFRs) between 15 and 59 mL/min/1.73 m2. This study was composed of a nationwide retrospective cohort of adult T2DM patients from 831 public hospitals in Thailand during the year 2015. T2DM patients with CKD stages 3 and 4 were followed up, until development of CKD stage 5, requirement of chronic dialysis, loss to follow‐up, death, or 31 May 2018, whichever came first. Cox proportional hazard regression was utilized for analysis. A total of 8464 participants were included; 30.4% were male. The mean age was 69 ± 10 years. The mean eGFR was 45 ± 11 mL/min/1.73 m2. The incidence of CKD stage 5 or the need for chronic dialysis was 16.4 per 1000 person‐years. The annual rate of eGFR decline during a mean follow‐up of 29 months was −2.3 mL/min/1.73 m2; 14.4% had a rapid decline in eGFR. The risk factors associated with progression to CKD stage 5 or the need for chronic dialysis were diabetes duration, systolic blood pressure, serum uric acid, albuminuria, and baseline eGFR. Conversely, older age and the use of renin‐angiotensin aldosterone system blockade were associated with decreased risks for rapid CKD progression and incidence CKD stage 5 or dialysis. This study identifies multiple predictive risk factors that support a multifaceted approach to prevent progression of advanced CKD.

ABSTRACTCell‐based therapies, defined here as the delivery of cells in vivo to treat disease, have recently gained increasing public attention as a potentially promising approach to restore structure and function to musculoskeletal tissues. Although cell‐based therapy has the potential to improve the treatment of disorders of the musculoskeletal system, there is also the possibility of misuse and misrepresentation of the efficacy of such treatments. The medical literature contains anecdotal reports and research studies, along with web‐based marketing and patient testimonials supporting cell‐based therapy. Both the American Society for Bone and Mineral Research (ASBMR) and the Orthopaedic Research Society (ORS) are committed to ensuring that the potential of cell‐based therapies is realized through rigorous, reproducible, and clinically meaningful scientific discovery. The two organizations convened a multidisciplinary and international Task Force composed of physicians, surgeons, and scientists who are recognized experts in the development and use of cell‐based therapies. The Task Force was charged with defining the state‐of‐the art in cell‐based therapies and identifying the gaps in knowledge and methodologies that should guide the research agenda. The efforts of this Task Force are designed to provide researchers and clinicians with a better understanding of the current state of the science and research needed to advance the study and use of cell‐based therapies for skeletal tissues. The design and implementation of rigorous, thorough protocols will be critical to leveraging these innovative treatments and optimizing clinical and functional patient outcomes. In addition to providing specific recommendations and ethical considerations for preclinical and clinical investigations, this report concludes with an outline to address knowledge gaps in how to determine the cell autonomous and nonautonomous effects of a donor population used for bone regeneration. © 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:485–502, 2020