不同保温方式对全髋关节置换术老年患者体温的影响

目的探讨不同保温方式对老年全髋关节置换术患者体温和热舒适度的影响。 方法研究的纳入标准：经影像学检查确诊为股骨颈骨折;年龄≥65岁;根据美国麻醉医师协会制定的分级标准进行分级为Ⅰ～Ⅱ级;无语言交流障碍;术后入麻醉恢复室(PACU)进行麻醉复苏。排除标准：凝血功能异常者;患有耳道疾病者;甲状腺功能亢进或甲状腺功能低下者;免疫功能异常者;病态性肥胖症;术前4周有发热或感染患者。选择于青岛市市立医院麻醉手术科在腰硬联合麻醉下行单侧全髋关节置换术的老年患者120例,采用随机数字表法将患者分为4组,每组30例,分别为：充气式升温毯组(A组)、液体加温组(B组)、充气式升温毯联合液体加温组(M组)和对照组(C组),记录并比较4组患者入室时(T₁)、切皮时(T₂)、手术结束时(T₃)和出室时(T₄)的鼓膜温度,及围术期计划外低体温发生率、麻醉恢复室停留时间、寒战发生情况和热舒适度。计量资料采用Kolmogorov-Smirnov法进行正态检验,对于符合正态分布且方差齐性的计量资料比较,采用方差分析或t检验;对于不符合正态分布和/或方差不齐的计量资料比较,采用秩和检验。计数资料比较应用卡方检验或Fisher确切概率法。 结果4组患者T₁时鼓膜温度差异无统计学意义(F＝0.461,P>0.05);在T₂～T₄时,与C组比较,A组(T₂～T₄：t＝11.504、10.056、14.205)和M组(T₂～T₄：t ＝13.710、12.086、19.101)患者鼓膜温度明显升高(P<0.05),而B组患者比较差异无统计学意义(T₂～T₄：t ＝1.840、－1.386、1.371,P>0.05);与A组比较,B组(T₂～T₄：t＝9.628、10.409、11.315)和C组(T₂～T₄：t＝11.504、10.056、14.205)患者鼓膜温度明显降低(P<0.05),M组(T₂～T₄：t＝－1.493、－1.072、－1.179)鼓膜温度差异无统计学意义(P>0.05)。与C组比较,B组患者低体温事件发生率(χ²＝0.073)、寒战发生次数与程度(χ²＝0.077)、PACU停留时间(t＝－0.250)、热舒适度评分(U＝438.000)差异无统计学意义(P>0.05);A组和M组低体温事件发生率(C组vs A组：χ²＝5.963,C组vs M组：χ²＝4.356)、寒战发生次数与程度(C组vs A组：χ²＝6.667,C组vs M组：χ²＝6.667)、PACU停留时间明显降低(C组vs A组：t＝－3.701,C组vs M组：t＝－4.023),热舒适度评分明显升高(C组vs A组：U＝206.500,C组vs M组：U＝211.500)(P<0.05)。 结论单纯采取充气式升温毯可维持全髋关节置换术老年患者术中体温平稳,降低低体温和寒战发生次数,减少PACU停留时间,提高热舒适度,为患者提供有效的围术期体温保护。     

不同剂量非布司他对慢性肾脏病4期合并无症状高尿酸血症患者的疗效及安全性观察

目的:探讨不同剂量非布司他对慢性肾脏病4期合并无症状高尿酸血症患者的疗效及安全性。方法:选取我院慢性肾脏病4期合并无症状高尿酸血症患者60例,按照随机数字表法分为非布司他20 mg/d(A1组)、非布司他40 mg/d(A2组)和对照组各20例。三组均给予降压、碱化尿液、控制饮食等常规治疗。比较三组患者治疗前、治疗6周和治疗12周后的估算肾小球滤过率(eGFR)、血尿酸改变及药物不良反应发生情况。结果:治疗12周后A1组的平均eGFR较治疗前上升(从23.40±4.41到28.85±6.15 ml·min~(-1)·1.73 m~(-2))差异有统计学意义(P0.05);A2组的平均eGFR较治疗前上升(从23.40±4.78到23.55±8.83 ml·min~(-1)·1.73 m~(-2))差异无统计学意义(P0.05)。对照组平均eGFR较治疗前下降(从23.60±4.26到23.05±8.18 ml·min~(-1)·1.73 m~(-2))差异有统计学意义(P0.01)。治疗6周后A2组的血尿酸水平较治疗前明显下降(从9.00±1.07到5.75±0.64 mg/L),差异有统计学意义(P0.01)。治疗12周后A1组的血尿酸水平较治疗前明显下降(从9.07±1.70到5.70±1.35 mg/L),差异有统计学意义(P0.01)。治疗组患者治疗期间未发现明显不良反应。结论:非布司他能有效降低CKD4期患者血尿酸,低剂量非布司他降低血尿酸水平速度较慢但能有效延缓eGFR下降。     

ⅠB期非小细胞肺癌不同亚组的预后研究

目的探讨ⅠB期非小细胞肺癌(NSCLC)不同亚组的预后因素。 方法回顾性分析2008年3月至2013年12月间在福建医科大学附属协和医院胸外科接受手术切除的138例ⅠB期NSCLC患者的临床和随访资料。基于国际抗癌联盟(UICC)第七版肺癌分期,再根据肿瘤大小和脏层胸膜受侵情况,将患者细分为3组。ⅠB-a组：肿瘤直径≤3cm且脏层胸膜受侵;ⅠB-b组：3cm<肿瘤直径≤5cm且无脏层胸膜受侵;ⅠB-c组：3cm<肿瘤最大径≤5cm且脏层胸膜受侵。运用Kaplan-Meier生存分析和Cox比例风险模型,对影响NSCLC预后的因素进行分析。 结果ⅠB期NSCLC患者3年总体生存率为88.1%,其中ⅠB-a组75例,ⅠB-b组32例,ⅠB-c组31例,3年生存率分别为92.0%、90.6%和74.1%,3组生存率比较差异有统计学意义(χ²＝6.784,P＝0.034)。单因素分析显示,无论患者的性别(χ²＝0.103,P＝0.567)、年龄(χ²＝2.463,P＝0.117)、手术切除方式(χ²＝0.809,P＝0.368)、是否接受术后辅助化疗(χ²＝0.077,P＝0.791),还是肿瘤的位置(χ²＝0.091,P＝0.674)、脏层胸膜是否受侵犯(χ²＝0.085,P＝0.771)均无统计学意义,而肿瘤大小(χ²＝13.937,P＝0.007)和分化程度(χ²＝21.198,P＝0.000)均有统计学意义。进一步多因素分析显示,只有肿瘤低分化(RR＝0.027,95%CI为0.065～0.666,P＝0.003)和中分化(RR＝1.627,95%CI为1.020～2.597,P＝0.008)有统计学意义。 结论ⅠB期NSCLC不同亚组的3年生存率存在统计学差异,TNM分期对ⅠB期的定义可能仍有待改进。肿瘤大小及分化程度是影响患者3年生存率的重要因素,肿瘤中低分化是影响患者3年生存率的独立因素,而术后辅助化疗无影响,该结论有待进一步证实。     

非布司他与别嘌醇治疗慢性肾脏病合并高尿酸血症的疗效比较

目的探讨非布司他与别嘌醇在治疗慢性肾脏患者合并高尿酸血症的临床疗效分析比较。方法回顾性分析2013年1月至2015年2月中国人民解放军第174医院收治的78例慢性肾脏病合并高尿酸血症患者,并根据治疗方法将其分为对照组和治疗组。2组患者均采用优质低蛋白饮食、降压[钙通道阻滞剂和(或)β受体阻滞剂]、纠正贫血(促红细胞生长素)、补充α酮酸(开同)及纠正水、电解质酸碱平衡(碳酸氢钠)等综合治疗;观察组加用非布司他20 mg/d,对照组加用别嘌醇100 mg/d;2组均治疗观察24周。分析治疗前后2组患者血肌酐、血尿酸及临床疗效,并进行统计学分析。结果 2组治疗前后实验室相关指标比较结果表明2组治疗后血尿酸与治疗前比较,均有显著改善(均P0.05),且治疗组患者治疗后尿酸与对照组行组间比较有统计学差异(P0.05)。治疗组治疗后血肌酐与治疗前比较明显降低,有统计学差异(P0.05);而对照组治疗前后血肌酐无明显变化(P0.05)。治疗组临床总有效率高于对照组(P0.05)。2组均未发现明显的不良反应。结论非布司他相对于别嘌醇降低血尿酸水平的作用更强,且可改善肾功能,药物不良反应较小,因此在治疗慢性肾脏合并高尿酸血症患者上具有良好的应用前景。     

关节镜下两种手术方式治疗盘状半月板损伤的临床疗效对比

目的对比关节镜下半月板成形术及半月板全切除术治疗盘状半月板损伤的临床效果。 方法选取2014年8月至2016年8月广东医科大学附属医院收治半月板损伤患者68例为研究对象,患者确诊为盘状半月板损伤不伴韧带松弛或损伤,单侧膝关节发病,无关节畸形及严重骨质疏松。依据术式的不同将其分为A组(25例)和B组(43例),A组施行关节镜下全切除术,B组施行关节镜下半月板成形术。采用配对t检验和χ²检验比较两组患者Lysholm评分情况、术后3个月美国特种外科医院(HSS)评分、MRI复查情况和并发症发生情况。 结果两组患者术后切口均Ⅰ级愈合。A组半月板的优良率(64.00%)显著低于B组(79.06%),差异有统计学意义(χ²＝12.84,P<0.05)。术前两组患者Lysholm评分比较,差异无统计学意义(P>0.05);术后3个月,A组和B组患者的Lysholm评分[(77±16)分、(93±19)分]均较术前[(56±12)分、(66±14)分]显著提高(t＝4.541、5.231,P<0.05),且B组的Lysholm评分显著高于A组,差异有统计学意义(t＝5.132,P<0.01)。B组的术后3个月膝关节评分(HSS)总分(88.0±2.3)分均明显高于对照组的(71.2±2.0)分,差异有统计学意义(t＝3.707,P<0.05),但两组患者疼痛、肌力评分比较,差异无统计学意义(P>0.05)。MRI评估显示B组的完全愈合率高于A组,且A组发现2例有关节退行性病变。 结论半月板成形术及全切除术术式均具有良好的近期疗效。但半月板成形术能最大程度地恢复膝关节功能,减少膝关节退行性病变等并发症的发生,疗效优于全切除术。     

帕洛诺司琼在加速康复外科中的作用

目的探讨帕洛诺司琼在加速康复外科中的作用,为临床患者的围手术期康复提供更优质的服务。 方法采用前瞻性、随机的研究方法,选择2015年9月至2016年2月拟行结直肠腹腔镜手术者120例,随机分为3组,各40例,各组术后行同配方的静脉镇痛。A组手术结束前1 h静推托烷司琼6 mg;B组手术结束前1 h静推帕洛诺司琼0.25 mg;C组手术结束前1 h静推帕洛诺司琼0.25 mg,静脉镇痛泵中静脉泵注帕洛诺司琼0.25 mg/72 h。记录并比较各组患者术后恶心、呕吐（PONV）等并发症发生率以及下床天数、出院时间。 结果B组和A组术后恶心、呕吐发生率差异无统计学意义,C组较之A组、B组在术后24 h后PONV发生率差异有统计学意义（χ²=5.165、5.165,P=0.023、0.023）;C组、B组较之A组术后镇痛24 h内除PONV外其余并发症发生率差异无统计学意义,24 h后除PONV外其余并发症发生率差异有统计学意义（χ²=4.500、6.275,P=0.033、0.012）;C组较之A组、B组术后下床天数（t=3.718、2.975,P<0.001、0.004）、出院时间（t=6.650、5.440,均P<0.001）差异有统计学意义。 结论帕洛诺司琼持续用药效果更稳定,可降低术后恶心、呕吐发生率,加速患者术后康复。     

三种术式治疗再发性胆总管结石的疗效及安全性比较

目的比较腹腔镜结合内镜、腹腔镜结合十二指肠镜和开腹术治疗再发性胆总管结石的疗效及安全性。 方法回顾性分析2014年4月至2018年3月161例再发性胆总管结石患者的临床资料,分为A组(腹腔镜联合内镜治疗,n＝67例)、B组(腹腔镜联合十二指肠镜镜治疗,n＝63例)、C组(传统开腹术,n＝31例),数据处理应用统计学软件SPSS18.0完成,手术相关指标的比较采用单因素方差分析,两两比较采用LSD－t检验;术后并发症发生率、中转开腹率等采用χ²检验;P<0.05为差异有统计学意义。 结果A组手术时间长于B组和C组(P<0.05),A组和B组的术中出血量和排气时间均低于C组(P<0.05),B组的住院时间低于A组和C组(P<0.05)。A组并发症发生率最低,C组最高,差异具有统计学意义(P<0.05)。A组患者结石直径和结石数目均高于B组患者(P<0.05),A组和B组中转开腹率的差异不明显(P>0.05)。 结论腹腔镜结合内镜与腹腔镜结合十二指肠镜治疗再发性胆总管结石的疗效及安全性均优于开腹治疗,值得推广应用。     

微创锁定加压钢板术治疗胫腓骨远端骨折

目的探讨微创锁定加压钢板术对胫腓骨远端骨折(DTF)患者关节功能及并发症的影响。 方法选取2017年1月至2018年12月阳山县人民医院DTF患者75例，纳入A3型DTF诊断、年龄>18岁、知情同意者，排除有本次手术治疗禁忌证或有骨关节炎、骨肿瘤等其他骨病或其他部位骨折者。依据随机数字表法分为微创组(n＝38)和开放手术组(n＝37)，微创组给予微创锁定加压钢板术治疗，开放手术组给予开放性复位锁定加压钢板术治疗，计数资料采用卡方检验，等级资料采用秩和检验，计量资料采用t检验，比较两组手术情况、骨折愈合、关节功能、并发症。 结果微创组切口长度、术中出血量、住院时间、骨折愈合时间明显低于开放手术组，差异有统计学意义(t＝13.771、5.697、12.431、15.644，均为P<0.05)，微创组手术时间高于开放手术组，但差异无统计学意义(P>0.05)；微创组骨折愈合、关节功能优良率明显高于开放手术组，差异有统计学意义(χ²＝4.789、3.973，均为P<0.05)；微创组并发症发生率明显低于开放手术组，差异有统计学意义(χ²＝4.341，P<0.05)。 结论微创锁定加压钢板术治疗DTF的疗效良好，有利于促进患者骨折愈合、关节功能恢复，且可减少并发症，值得临床推广。     

踝关节镜检在治疗急性踝关节骨折中的作用

目的探讨应用关节镜探查急性踝关节骨折时关节内合并病变,并辅助进行踝关节骨折的复位及固定的可能性及优缺点。 方法回顾性分析中山大学孙逸仙纪念医院骨科2016年3月至2017年11月诊断为"急性踝关节骨折"的患者,共78例。所有患者在行踝关节镜检＋切开复位内固定,记录关节镜下软骨损伤、三角韧带损伤、下胫腓联合损伤及游离碎片,采用卡方检验分析关节内病变与骨折类型的相关性。 结果在所有患者中,Weber A型骨折6例,Weber B型骨折45例,Weber C型骨折27例。骨软骨损伤共51例,其中Weber A/B/C分别0/33/18例;胫腓联合损伤39例,其中Weber A/B/C分别0/18/21例;三角韧带损伤27例,其中Weber A/B/C分别0/21/6例;关节腔游离碎片7例,其中Weber A/B/C分别0/4/3例。Weber B型骨折与Weber C骨折距骨软骨损伤发生无统计学差异(χ²＝0.363,P >0.05),但软骨损伤程度,Weber B型骨折更重(Fisher确切检验,P ＝0.007)。胫腓联合损伤,Weber B型骨折与Weber C骨折两组之间相比无统计学差异(χ²＝ 2.4 ,P >0.05);在Weber C骨折中,后踝骨折与胫腓联合不稳明显相关(Fisher确切检验,P ＝0.02)。三角韧带损伤,Weber B型骨折与Weber C骨折两组之间相比有统计学差异(χ²＝4.302, P<0.05);但当将内踝骨折与三角韧带损伤定义为内侧不稳时,两组之间无统计学差异(Fisher确切检验,P ＝0.07)。 结论在急性踝关节骨折时,关节镜探查可同时发现并处理合并的踝关节内病变,并辅助进行踝关节骨折的复位及固定,是提高切开内固定手术疗效的有益辅助工具。     

慢性肾脏病非透析患者血尿酸与Ca~(2+)、P~(3-)、iPTH的相关性分析

目的:探讨慢性肾脏病(chronic kidney disease,CKD)非透析患者血尿酸(serum uric acid,SUA)与Ca~(2+)、P~(3-)、i PTH的相关性。方法:选择CKD3～5期非透析患者166例,根据SUA水平分为高尿酸组(UA≥420μmol/L)和正常尿酸组(UA 420μmol/L)。分别比较两组患者一般资料及生化指标的差异,分析影响SUA的因素以及其与Ca~(2+)、P~(3-)、i PTH的相关性。结果:CKD患者中高尿酸血症的发生率高达40. 96%; HUA组Scr、BUN、P~(3-)、i PTH、ALP、FBG明显高于正常尿酸组,e GFR明显低于正常尿酸组,差异有统计学意义(P 0. 05); SUA与Scr、BUN、P、i PTH、ALP呈正相关,与e GFR呈负相关,差异有统计学意义(P 0. 05); Logistic回归分析提示BUN、ALP、e GFR为SUA升高的危险因素。结论:CKD非透析患者SUA与Ca~(2+)、P~(3-)、i PTH存在相关性。SUA可能参与了CKD非透析患者钙磷代谢紊乱的发生发展。     

Effect of urate-lowering therapy with febuxostat on oxidative stress in hyperuricemic patients with chronic kidney disease stages 3-5

Objective To estimate the effect of urate-lowering therapy with febuxostat on oxidative stress in chronic kidney disease (CKD) stages 3-5 patients with hyperuricemia (HUA). Methods The study was a prospective cohort study. The patients of CKD stages 3-5 with HUA between June 2015 and June 2018 in the Affiliated Hospital of Qingdao University were prospectively analyzed. The patients were assigned to febuxostat (A) group, allopurinol (B) group and non-hyperuricemia (C) group according to the level of serum uric acid and the choice of urate-lowering drugs. Serum uric acid, hypersensitive C-reactive protein (hs-CRP), plasma malondialdehyde (MDA), superoxide dismutase (SOD) and endothelin-1 (ET-1) were measured at baseline, 1 month and 3 months after treatment and the changes of the values of inflammation and oxidative stress before or after treatment were compared. According to the level of serum uric acid, patients were divided into attainment group and nonattainment group, and the correlation between uric acid and oxidative stress was analyzed at baseline and 3 months after treatment respectively. Results There was no significant difference in baseline levels of serum uric acid, inflammation and oxidative stress between group A and group B (P＞0.05). The levels of serum uric acid, hs-CRP, MDA and ET-1 of group A and group B were significantly higher than those of group C, but the level of SOD of group A and group B was significantly lower than that of group C at baseline (P＜0.001). After treatment for 1 month and 3 months, the values of serum uric acid, hs-CRP, MDA and ET-1 in group A were significantly lower than those in group B, while the level of SOD in group A was significantly higher than that in group B (P＜0.001). Compared with pre-treatment period, both the serum uric acid, hs-CRP, MDA and ET-1 levels of group A and group B were declined significantly while SOD had a significant rise after 3 months treatment (P＜0.001). The changes of group A were significantly higher than those of group B (P＜0.001). At baseline and 3 months after treatment, serum uric acid was positively related to hs-CRP, MDA and ET-1, but negatively related to SOD in nonattainment group (| r |＞0.50, P＜0.001); serum uric acid was positively related to hs-CRP, MDA and SOD (| r |＞0.70, P＜0.001), and there was no correlation between serum uric acid and ET-1 in attainment group (P＞0.05). Conclusions Febuxostat performed better than allopurinol in lowering urate and inhibiting oxidative stress in CKD stages 3-5 patients with HUA, thus reducing vascular endothelial injury. Elevated serum uric acid may be one of the important factors that promote oxidative stress and increase endothelial damage in CKD patients.     

Effect of urate-lowering therapy on renal function in chronic kidney disease stages 2-5

Objective To investigate the effect of urate-lowering therapy on renal function in chronic kidney disease (CKD) stages 2-5 patients with hyperuricemia (HUA). Methods A total of 132 patients of CKD stages 2-5 with HUA between July 2016 and December 2017 in Department of Nephrology of the Second Affiliated Hospital of Anhui Medical University were prospectively and self-controlled analyzed. Serum uric acid (SUA), estimated glomerular filtration rate (eGFR) and other clinical parameters were measured at baseline and after 1-6 months treatment. The patients were divided into group A (CKD stages 2-3a) and group B (CKD stages 3b-5) on the baseline value of eGFR. The changes of SUA and eGFR before and after treatment were compared. According to the level of SUA after 6 months treatment, patients were divided into attainment group (SUA＜360 μmol/L) and nonattainment group (SUA≥360 μmol/L). The difference of renal function in pre-treatment and post-treatment was compared. Multiple stepwise linear regression was used to analyze the relationship among the change of eGFR after receiving 6 months' treatment (deGFR) and SUA level, baseline eGFR and other indexes. Results After 1, 3, 6 months treatment, the average levels of SUA, Scr and urea nitrogen of all patients were decreased significantly while eGFR value was increased significantly (all P＜0.050) than those in pre-treatment period. After six-month-therapy, proteinuria and hematuria were improved significantly in all patients (P＜0.001, P=0.001). Compared with pre-treatment period, both the SUA levels of group A and group B were declined significantly while eGFR had a significant rise after treatment (P＜0.001). The change of eGFR post-treatment in group A was significantly higher than that of group B [(13.64±15.35) vs (8.97±9.79) ml?min-1?(1.73 m2)-1, P=0.044]. At 6 months after treatment, the eGFR value increased markedly in both attainment group and nonattainment group compared with pre-treatment period (P＜0.001). After six-month-therapy, the eGFR value in attainment group was increased more obviously than that of nonattainment group [(13.96±14.64) vs (8.03±9.69) ml?min-1?(1.73 m2)-1, P=0.021]. Multiple stepwise linear regression analysis showed that the baseline eGFR value was an influencing factor of deGFR (b=0.161, P=0.020). Conclusions The renal function of CKD stages 2-5 patients with HUA can be significantly improved by urate-lowering therapy, which can effectively reduce proteinuria and hematuria.     

The urate-lowering efficacy of febuxostat and its effect on renal function in hyperuricemic patients with chronic kidney disease stages 3-5

Objective To investigate the urate-lowering efficacy and renal effect of febuxostat in hyperuricemic patients with chronic kidney disease (CKD) stages 3-5. Methods A prospective, randomized, controlled trial of CKD stages 3-5 patients with hyperuricemia was conducted from June 2015 to June 2016. Patients were randomly assigned to either febuxostat group (treatment group) or allopurinol group (control group). Patients in treatment group received febuxostat 40 mg/d after study initiation, and the dosage was changed to 20 mg/d if serum uric acid (sUA)＜360 μmol/L. Patients in control group were administered a dose of 100 mg/d of allopurinol. Serum uric acid, serum creatinine and other clinical parameters were measured at baseline and 1-6 months after treatment. The rate of achieving target sUA level and the change of eGFR in two groups were performed using SPSS 21.0. Results A total of 98 patients met the inclusion criteria and completed the trial. The treatment group and the control group had 51 cases and 47 cases, respectively. There was no significant difference between the two groups in age, sex, body mass index (BMI), blood pressure, serum creatinine, eGFR, sUA and renal diseases (P＞0.05). At month 1-6, there were significant differences between treatment group and control group in the rate of achieving target sUA level (P＜0.01). At month 1 and month 3, no statistical difference was observed in the change of eGFR between the two groups (P=0.624, P=0.319). At month 6, the changes in eGFR were +2.23 ml?min-1?(1.73 m2)-1 and -4.36 ml?min-1?(1.73 m2)-1 in the treatment and control group, respectively, and the difference between the two groups was significant (P=0.037). In patients with CKD stages 3-5, generalized estimating equation showed that after adjusting for confounding variables, the eGFR increased 1.149 ml?min-1?(1.73 m2)-1 (P=0.003) and 24-hour urinary protein decreased 0.019 g/d (P=0.037) when per 60 μmol/L decreased in sUA. Febuxostat 20 mg/d was able to keep target sUA levels in 90.2% patients with CKD stages 3-5 within half a year and no serious adverse effects appeared. Conclusions Febuxostat performs better than allopurinol in lowering urate and delaying progression of renal function in patients with CKD stages 3-5 and HUA. Febuxostat 20 mg/d may be the effective and safe maintenance dose to maintain target sUA level in patients with CKD stages 3-5, but whether it can be used as the best long-term maintenance dose needs to be further studied.     

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.

     

The impact of serum uric acid reduction on renal function and blood pressure in chronic kidney disease patients with hyperuricemia

Background

Febuxostat is tolerable in chronic kidney disease (CKD) patients with hyperuricemia. However, the long-term effect of lowering uric acid with febuxostat on renal function and blood pressure has not been elucidated.

Methods

This was a 2 years retrospective observational study. 86 CKD patients with hyperuricemia who continued with allopurinol (allopurinol group, n?=?30), switched from allopurinol to febuxostat (switched group, n?=?25), or were newly prescribed febuxostat (febuxostat group, n?=?31) were included in this study. Serum uric acid, estimated glomerular filtration rate (eGFR), blood pressure, and urinary protein were analyzed. Moreover, the impact of serum uric acid reduction on renal function and blood pressure was assessed.

Results

Serum uric acid in the switched and febuxostat groups was significantly reduced at 6 months (switched group; 8.49?±?1.32–7.19?±?1.14 mg/dL, p?<?0.0001, febuxostat group; 9.43?±?1.63–6.31?±?0.90 mg/dL, p?<?0.0001). In the allopurinol group, serum uric acid was increased (6.86?±?0.87–7.10?±?0.85 mg/dL, p?=?0.0213). eGFR was significantly increased (35.2?±?12.8–37.3?±?13.9 mL/min/1.73 m², p?=?0.0232), while mean arterial pressure (93.1?±?10.8–88.2?±?9.5 mmHg, p?=?0.0039) was significantly decreased at 6 months in the febuxostat group, resulting in the retention of eGFR for 2 years.

Conclusions

The impact of serum uric acid reduction might have beneficial effects on CKD progression and blood pressure. However, a large prospective study is needed to determine the long-term efficacy of febuxostat therapy in CKD patients with hyperuricemia.

     

Efficacy and Safety of Febuxostat,a Novel Nonpurine Selective Inhibitor of Xanthine Oxidase for the Treatment of Hyperuricemia in Kidney Transplant Recipients

Background

Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase, is a potential alternative to allopurinol for patients with hyperuricemia. In this study, we evaluated the efficacy and safety of febuxostat for the management of hyperuricemia in renal transplant recipients.

Patients and methods

Between June 2012 and January 2013, a total of 22 renal transplant recipients (56 ± 10 years old) with hyperuricemia were enrolled in this study. All patients underwent de novo kidney transplantation, except for 1 patient, who received a second kidney transplant. Ten patients receiving allopurinol and 3 patients receiving benzbromarone were converted to febuxostat at doses of 10–20 mg/d. In the remaining 9 patients, who did not have a history of other urate-lowering medications, febuxostat was initiated at a dose of 10 mg/d.

Results

Uric acid levels after initiation of febuxostat were significantly lower than before treatment (5.7 ± 0.7 mg/mL vs 8.0 ± 0.8 mg/mL; P < .001). At last follow-up visit, 16 of the 22 patients (73%) achieved uric acid levels of ≤6.0 mg/dL, despite the low dosage of febuxostat. All patients were maintained on febuxostat without serious adverse events, except for 1 patient, who discontinued febuxostat because of numbness in the arms.

Conclusions

Low-dose febuxostat is a promising alternative to allopurinol or benzbromarone for the treatment of hyperuricemia in kidney transplant recipients. The long-term urate-lowering efficacy and safety of febuxostat with regard to renal function in kidney transplant recipients with hyperuricemia requires further investigation.     

Study on the prevalence of hyperuricemia and its relationship with chronic kidney disease in the urban residents of Yunnan plateau area

Objective To investigate the prevalence of hyperuricemia (HUA) and its relationship with chronic kidney disease (CKD) among the population of Yunnan Plateau area. Methods Residents aged over 18 years old (n=4581) in the city of Yuxi, a community where original inhabitants were relatively concentrated, were randomly chosen for screening cross-sectional. Fasting blood and urine samples were collected to detect blood and urine parameters. Results The prevalence of HUA in the community residents was 25.91％, of which the prevalence of HUA was 34.15% in male and 15.55% in female. The prevalence of HUA in men was higher than that in women, and the difference was statistically significant (P＜0.01). In the age of 30-49 years old, the prevalence of HUA was higher than that in other age groups (P＜0.01). Multivariate logistic regression analysis showed that HUA, age, gender, hyperglycemia, low HDL levels were independently associated with CKD (P＜0.05). In addition, high blood uric acid (≥404 μmol/L) group has a higher risk of CKD than low blood uric acid (≤282 μmol/L) group, when divided into four groups according to the blood uric acid level (OR=3.447, 95%CI 2.218-5.375, P＜0.01). Conclusions HUA is independently associated with CKD. The prevalence of HUA in community residents of Yunnan Plateau (Yuxi) is different from their counterparts in eastern coastal area and the data of developed regions reported by studies in past 10 years.     

非透析慢性肾脏病患者高尿酸血症的危险因素分析

目的 探讨和分析非透析慢性肾脏病(non-dialysis chronic kidney disease,ND-CKD)患者高尿酸血症(hyperuricemia,HUA)的发生率及其相关危险因素.方法 收集2015年1月至2019年12月于山西医科大学第二医院肾内科就诊的540例ND-CKD患者的临床资料,依据HUA...     

Usefulness of combination treatment using allopurinol and benzbromarone for gout and hyperuricemia accompanying renal dysfunction: kinetic analysis of oxypurinol

A study was conducted to determine whether combination treatment using allopurinol and benzbromarone was more useful than single allopurinol treatment for the gout and hyperuricemia accompanying renal dysfunction. The subjects were 45 male patients who received urate-lowering treatment and showed a stable serum urate level. The patients were divided into four groups according to the urate-lowering treatment and creatinine clearance (Ccr) (A group: single treatment, normofunction, B group: single treatment, hypofunction, C group: combined treatment, normofunction, D group: combined treatment, hypofunction). There were no differences in serum urate levels among the four groups. Urate clearance (CUA)and daily urinary urate excretion (UUAV) showed significantly high values in the C group, but no difference was seen in the fractional excretion of urate (FEUA) among the four groups. The dosage of allopurinol in the D group was significantly lower than in the A and B groups. Serum oxypurinol concentration in the C group was lower than that in the B group. Oxypurinol clearance (C oxypurinol) in the C group was significantly high compared with the B and D groups. There was a close correlation between C oxypurinol, Ccr, and CUA, with an especially strong correlation between C oxypurinol and CUA. There were no differences in the serum concentration and clearance of xanthine and hypoxanthine among the four groups. Results of the study suggested that combination treatment using allopurinol and benzbromarone for the gout and hyperuricemia accompanying renal dysfunction is more useful, because a lower dose of allopurinol can be used and the serum oxypurinol concentration is reduced compared with single allopurinol treatment.     

Use of xanthine oxidase inhibitor febuxostat inhibits renal interstitial inflammation and fibrosis in unilateral ureteral obstructive nephropathy

Background

Renal interstitial fibrosis is the common pathway in progressive renal diseases, where oxidative stress promotes inflammation and macrophage infiltration. Febuxostat is a novel nonpurine xanthine oxidase (XO)-specific inhibitor for treating hyperuricemia. While some reports suggest a relationship between hyperuricemia and chronic kidney disease (CKD), the renoprotective mechanism of an XO inhibitor in CKD remains unknown. Recent reports have focused on XO as a source of oxidative stress.

Methods

Here, we investigate the potential of febuxostat to reduce fibrogenic and inflammatory responses in an established interstitial fibrosis model—unilateral ureteric obstruction (UUO). Male Sprague–Dawley rats were divided into three groups: sham-operated group, vehicle-treated UUO group, and febuxostat-treated UUO group.

Results

Treatment with febuxostat diminished XO activity in obstructed kidneys, and suppressed nitrotyrosine, a marker of oxidative stress. Consequently, febuxostat inhibited early proinflammatory cytokine expression, followed by a reduction of interstitial macrophage infiltration. In addition, febuxostat suppressed transforming growth factor-β messenger RNA expression, thereby ameliorating smooth muscle alpha actin and type I collagen expression.

Conclusion

Our results provide evidence for the renoprotective action of febuxostat against the formation of interstitial fibrosis. A decrease in macrophage infiltration and interstitial fibrosis, along with a decrease of the oxidative stress marker, strongly suggests the existence of a causal relationship between them. Febuxostat may have therapeutic value in slowing or preventing interstitial fibrosis in patients with CKD.