Safety and Efficacy of Benzbromarone and Febuxostat in Hyperuricemia Patients with Chronic Kidney Disease: A Prospective Pilot Study

Background

To compare the safety and efficacy of benzbromarone and febuxostat in hyperuricemia patients with estimated glomerular filtration rate (eGFR) 20–60 mL/min/1.73 m².

Methods

This study was a single-centered, parallel-grouped, randomized clinical trial (RCT). We randomly assigned hyperuricemia participants with eGFR 20–60 mL/min/1.73 m² into benzbromarone and febuxostat treatment group. Drugs were adjusted by titration from small doses.

Results

Seventy-three eligible participants enrolled, 66 subjects (33 in each group) were included finally for analysis. When compared to baseline, serum uric acid (SUA) decreased significantly after treatment in both groups, but no differences were detected among all the follow-up points. After 12-month treatment, eGFR did not have significant change in both groups. In the benzbromarone group, kidney stones in one case increased in quantity. In the febuxostat group, kidney stones in one case became smaller in size and in two cases vanished completely. Both drugs did not increase myocardial enzymes significantly after the treatment. In addition, hemoglobin increased significantly in the two groups (p?<?0.05).

Conclusions

Benzbromarone and febuxostat could reduce SUA and maintain renal function in chronic kidney disease (CKD) patients with eGFR 20–60 mL/min/1.73 m². Urate-lowering therapy with benzbromarone or febuxostat could increase serum hemoglobin level and potentially improve anemia.

     

Adiponectin in Patients with Chronic Kidney Disease

Adiponectin is one of many so called "adipokines"—cytokines, chemokines, growth factors, and complement proteins secreted by adipose tissue—that can affect the function of other organs. This antiatherogenic and insulin-sensitizing polypeptide is eliminated from the circulation mostly by the kidneys. Thus, in patients with chronic kidney disease, adiponectin accumulates in the circulation; its plasma concentration is approximately three times higher in end stage kidney disease than in healthy subjects. As no biological consequences of these unusually high adiponectin concentrations have been demonstrated, this polypeptide cannot be considered as a uremic toxin. On the contrary, inadequately low instead of high plasma adiponectin concentration is recognized as a new nontraditional risk factor of cardiovascular morbidity and mortality in these patients. This review summarizes the causes and clinical consequences of adiponectin accumulation in the circulation of patients with chronic kidney disease.     

Association Between Nonadherence and Transient Hyperuricemia in Pediatric Kidney Transplantation

BackgroundNonadherence among pediatric transplant recipients is a significant problem that reduces graft survival and leads to poor kidney graft outcomes. It is, however, extremely difficult to detect during a regular follow-up. This study, therefore, aimed to investigate the risk factors involved in nonadherence, focusing on unexplained transient hyperuricemia in pediatric kidney transplant (KTx) recipients at a single pediatric center.MethodsThis retrospective study included 167 patients who underwent KTx at our pediatric center. A Cox proportional hazards analysis was performed to evaluate the risk of nonadherence using the following factors: age, sex, body mass index SD score, transient hyperuricemia, hypertension, and follow-up period.ResultsNonadherence was identified in 19 patients (11%), with the average (SD) age and post-KTx duration at diagnosis being 17.21 (4.73) years and 79.21 (38.77) months, respectively. Thirty-four patients (20%) were diagnosed with transient hyperuricemia at a median of 14 months after KTx. On multivariate Cox regression analysis, transient hyperuricemia was the only independent risk factor for nonadherence after KTx.ConclusionsTransient hyperuricemia was identified as one of the risk factors for nonadherence after KTx; therefore, careful monitoring for transient hyperuricemia may allow early detection of nonadherence.     

Hyperuricemia Predicts Kidney Disease Progression After Acute Allograft Dysfunction

Background

Hyperuricemia is associated with the development of new cardiovascular events and chronic allograft nephropathy in patients with decreased allograft function. This study investigates whether hyperuricemia in kidney transplant recipients should be considered as an independent predictor of kidney disease progression after acute allograft dysfunction.

Methods

Between September 1, 2010, and December 31, 2012, 124 patients who underwent kidney graft biopsy for acute allograft dysfunction were enrolled. Participants were divided into 2 groups: A hyperuricemic group (n = 57) and a normouricemic group (n = 67). The mean serum uric acid (UA) level was obtained by averaging all measurements, once per month for 3 months, before the study began. Clinical and laboratory data were collected. We investigated the role of hyperuricemia on the composite end point (CEP) of doubling of serum creatinine and graft failure by using Cox regression and Kaplan-Meier plots.

Results

Over a mean follow-up of 14.27 months, the hyperuricemic group had a poor cumulative survival and easily reached the CEP of doubling of serum creatinine and graft failure (P = .025) with a first-year cumulative incidence of 29.84% and a second-year cumulative incidence of 35.09%. Cox regression models revealed that age at biopsy (unadjusted hazard ratio [HR], 1.03; 95% CI, 1.00–1.06), hyperuricemia (HR, 2.24; 95% CI, 1.13–4.46), and interstitial fibrosis and tubular atrophy (IF/TA), including <25% of parenchyma affected (HR, 3.71; 95% CI, 1.34–10.31) and ≥25% of parenchyma affected (HR, 5.10; 95% CI, 1.83–14.19), were highly associated with poor outcome. After adjusting different variables, hyperuricemia and IF/TA were still significant.

Conclusion

Persistently high serum UA and IF/TA both contribute to the risk of kidney disease progression after acute allograft dysfunction.     

合并慢性前列腺炎的慢性肾脏病患者临床病理特点

目的：探讨合并慢性前列腺炎（CP）的男性慢性肾脏病（CKD）患者临床病理特点。方法：比较伴CP与不伴CP的CKD患者的年龄、婚姻情况、蛋白尿、血尿、肾功能水平及病理类型等临床病理指标。结果：（1）合并CP组平均年龄较不伴CP组大[（232.6±12.7）岁vs（9.5±11.4）岁],CP组已婚率高（63.7%vs47.3%）（P均〈0.05）;大量蛋白尿（〉3.5g/24h）52例（57.1%）,CP组中最常见的3种肾脏病为IgA肾病31例（34.1%）,非IgAN系膜增生性肾小球肾炎24例（26.4%）,膜性肾病12例（13.2%）,其中膜性肾病的发生率较不伴CP组（4.4%）高（P〈0.05）;伴CP的IgAN患者血管襻IgA沉积率较不伴CP患者高（P〈0.05）。（3）CP组与不伴CP组在蛋白尿、血尿、肾功能方面比较差异无统计学意义。结论：伴CP的CKD者年龄较大,多为已婚,半数伴大量蛋白尿,具有一定的临床病理特点,CP可能造成某些CKD患者慢性化改变。     

Pharmacology of Bisphosphonates in Patients with Chronic Kidney Disease

Bisphosphonates are medications which bind strongly to mineral. They are ingested by osteoclasts and inhibit an enzyme necessary for bone resorption. The gastrointestinal absorption is poor and the only method of excretion is renal. Therefore, in patients with CKD the body accumulates a higher percentage of a dose of bisphosphonate. These medications remain attached to bone mineral for many years. Although the primary action is to inhibit bone resorption, secondarily bone formation is also inhibited, and in patients with CKD bisphosphonate use often leads to adynamic bone. In some experimental models in animals, the bisphosphonates can inhibit vascular calcification but this effect has not been seen in humans. Intravenous bisphosphonates may cause renal damage but oral doses do not reduce creatinine clearance. In stage 3 CKD, in patients who still have normal PTH, calcium, and alkaline phosphatase, randomized trials show similar benefits as in patients without CKD. Data from stage 4 and 5 CKD are very limited and no clear benefit has been shown.     

Prevalence of Chronic Kidney Disease in the Black Sea Region,Turkey, and Investigation of the Related Factors with Chronic Kidney Disease

We aimed to assess the prevalence of CKD in the Black Sea Region, Turkey, and to evaluate any relationship between age, gender, diabetes, obesity, hypertension, and CKD. This study was conducted in 70 different areas in Tokat Province in the Black Sea Region, in the northern part of Turkey. The estimated glomerular filtration rate (eGFR) was calculated from the serum creatinine using MDRD formulas. CKD-defined estimated GFR was lower than 60 mL/min/1.73m². A total of 1,079 persons were included in this study (mean age 41.4±17 years [range: 18–95 years], 49.4% males, 50.6% living in an urban area). Of the 1,079 individuals, 5.28% were diabetic, 22.9% were obese, and 37.8% were hypertensive. CKD was found in 62 of them (5.75%). The prevalence of CKD was 5.58% in non-diabetics and 8.77% in diabetics. No significant differences were found between two groups. The prevalence of CKD was 3.77% in non-hypertensive individuals and 8.82% in hypertensive patients, and 4.46% in non-obese and 9.31% in obese. The evident significant differences were found between groups (p < 0.0001 and p = 0.004, respectively). The prevalence of CKD increased with age within our population. A salient observation was the markedly higher prevalence of CKD in females than males (p = 0.046). There was an inverse correlation between eGFR and age (r = 0.529, p < 0.0001). The overall prevalence of CKD was 5.75% in general population. The prevalence of CKD increased with age within our population. Age, gender, obesity and hypertension were found to be significant risk factors for development of CKD in our population.     

Dietary Assessment of Individuals with Chronic Kidney Disease

Examining the quality and quantity of food intake by appropriate methods is critical in the management of patients with chronic kidney disease (CKD). The four commonly used dietary assessment methods in CKD patients include short‐term dietary recalls, several days of food records with or without dietary interviews, urea kinetic based estimates such as protein nitrogen appearance calculation, and food histories including food screeners and food frequency questionnaires (FFQ). There are a number of strengths and limitations of these dietary assessment methods. Accordingly, none of the four methods is suitable in and of itself to give sufficiently accurate dietary information for all purposes. Food frequency questionnaires, which is the preferred method for epidemiological studies, should be used for dietary comparisons of patients within a given population rather than individual assessment. Food histories including FFQ and dietary recalls may underestimate important nutrients, especially in CKD patients. Given the large and increasing number of dialysis patients and work responsibilities of renal dietitians, routine analysis of dietary records and recalls is becoming less feasible. Ongoing and future studies will ascertain additional strengths and limitations of dietary assessment methods in CKD populations including the assessment of food intake during an actual hemodialysis treatment.     

Chronic Kidney Disease in Cancer Survivors

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Bisphenol A in Chronic Kidney Disease

The estrogenic endocrine‐disrupting substance bisphenol A (BPA) is extensively used as a starting material for a variety of consumer plastic products including dialyzer materials. The present study was performed to explore plasma BPA levels in patients with impaired renal function and to investigate if dialyzers differing in elutable BPA influence plasma levels in patients on maintenance hemodialysis. In vitro BPA was eluted from high‐flux polyethersulfone (PUREMA H, referred as PUR‐H), high‐flux polysulfone (referred as HF‐PSu), and low‐flux polysulfone (referred as LF‐PSu) dialyzers by recirculation with water for 180 min. In a cross‐sectional clinical study, plasma BPA levels of outpatients with different stages of chronic kidney disease (CKD) from four different centers were determined. Furthermore, in a prospective, randomized, and crossover setting, 18 maintenance dialysis patients were subjected successively to 4 weeks of thrice‐weekly hemodialysis with each LF‐PSu, HF‐PSu, and PUR‐H. In addition, the fractions of protein‐bound and free BPA were determined in a subset of dialysis patients. The mass of BPA eluted from the blood compartments in vitro under aqueous conditions varied for the three dialyzers being very low for PUR‐H (6.2 ± 2.5 ng; P < 0.001), intermediate for HF‐PSu (48.1 ± 7.7 ng), and highest for LF‐PSu (140.8 ± 38.7 ng; P < 0.01). In 152 prevalent patients with CKD enrolled in the cross‐sectional trial, plasma BPA started to rise after stage 3. Maintenance hemodialysis patients had more than six times higher BPA concentrations than patients with CKD stage 5 not yet on dialysis (10.0 ± 6.6 vs. 1.6 ± 1.8 ng/mL; P < 0.001). The BPA concentrations highly and inversely correlated with renal function. In the randomized controlled study, the plasma BPA concentrations were highly elevated compared with healthy controls (range 9.1 ± 4.5–12.0 ± 6.0 ng/mL vs. ≤0.2 ± 0.1 ng/mL; P < 0.001), but no change of the plasma levels was observed during hemodialysis with any of the three dialyzers in the course of a single treatment and over a period of 4 weeks. The protein‐bound fraction of plasma BPA in the dialysis patients was 74 ± 5%. Renal function and, most likely, the total quantity of ingested BPA are essential parameters affecting plasma BPA concentrations. Dialyzers are one additional source of BPA, but differences in the elutable BPA content are not associated with a significant effect on BPA plasma levels in Western European maintenance dialysis patients. Due to high protein binding, the removal of BPA by hemodialysis is limited.