终末期肾病患者冠状动脉钙化相关因素的研究

目的：分析终末期肾病（ESRD）患者冠状动脉钙化情况及相应临床指标的关系，慢性肾功能衰竭（CRF）患者冠状动脉钙化的相关因素。方法：对39例ESRD患者应用多层螺旋CT检测冠状动脉钙化积分情况，同时记录透析龄、吸烟史及体重指数；抽血监测血肌酐、钙、磷、镁、血胆固醇、甘油三酯、低密度脂蛋白、白蛋白、C反应蛋白（CRP）、甲状旁腺素．并计算钙磷乘积及内生肌酐清除率。结果：39例ESRD患者29例（74．34％）存在不同程度的冠状动脉钙化，透析治疗的患者冠状动脉钙化率达80．76％；随着透析时间的延长，冠状动脉钙化程度加重。钙化组血磷、钙磷乘积、CRP较无钙化组显著增高，P〈0．05．而钙化组血浆白蛋白较无钙化组显著降低，P〈0．01。结论：血磷及钙磷乘积升高是导致冠状动脉钙化的重要因素：CRP升高、低血浆白蛋白亦与冠状动脉钙化密切相关。维持性血液透析治疗的患者存在较高的冠状动脉钙化率。     

糖尿病终末期肾病血液透析患者危险因素的初步分析

目的探讨影响糖尿病终末期肾病（ESDN）血液透析患者长期生存率的几种危险因素。方法选择34例ESDN血液透析患者和同期透析的46例非糖尿病终末期肾病（Non—ESDN）血液透析患者，回顾分析死亡率、死亡原因、并发症、营养状态及血生化改变：结果ESDN组1年死亡率、3年死亡率分别为17．6％和38．2％，3年死亡率明显高于Non—ESDN组（P〈0．01），主要死因为心血管病变（47．4％）和感染性疾病（26．3％），主要并发症是心血管病变（94．1％）；两组营养状态评估（SGA）均差，但ESDN组的血浆白蛋白明显低于Non—ESDN组。结论ESDN患者并发症发生率及死亡率均比Non—ESDN高，积极治疗并发症、改善营养状态是提高患者生存率的关键：     

终末期肾病患者维持性血液透析中发生相关高血压易患因素分析

目的：分析终末期肾病患者维持性血液透析（MHD）中发生相关高血压（IDH）常见易患因素。方法肾内科血液净化中心接受MHD治疗的终末期肾病患者191例,均按MHD中是否发生IDH进行分组,并接受了“MHD中发生IDH常见易患因素调查表”评估,比较各种观察指标。结果191例接受MHD治疗的终末期肾病患者中,维持性血液透析中发生IDH患者57例（29.84%）, IDH组中透析总时间、透析频率、血红蛋白（Hb）及透析充分性标准值（Kt/V）均明显低于对照组,而IDH组中平均年龄、超滤率、血尿素氮（ BUN）、血清磷（P）、血甲状旁腺素（PTH）及透析期间体质量增加量（IDWG）均明显高于对照组（P〈0.01或P〈0.05）。结论大龄、透析时间短、频度少及质量差、电解质紊乱和营养现况不佳均可能是终末期肾病患者MHD中发生IDH的易患因素。     

早期糖尿病肾病发展至终末期的相关危险因素分析

目的 探究早期糖尿病肾病发展至终末期的相关危险因素分析.方法 将2018年1月-2021年1月定期到我院接受检查或治疗的首次诊断为Ⅰ-Ⅱ期DKD 200例患者的临床资料进行回顾性分析,根据患者3年内是否进展为ESRD分为进展组(GFR下降大于60ml/min)和未进展组,采用多因素logistic回归方法对患者相关危险变量因素进行分析.结果 经过文献查找发现患者的血压、糖尿病水平、血尿酸水平、凝血功能eGFR下降率、糖化血红蛋白为影响DKD进展的因素,且组间患者指标差异显著(P<0.05)经过logistic回归方法分析后,发现eGFR下降率、糖化血红蛋白、血尿酸水平,联合使用3种以上降压药是影响患者早期DKD进展为ESRD的主要危险因素.结论 控制糖尿病患者的糖化血红蛋白,血尿酸水平以及eGFR下降率等指标有助于防止患者发生ESRD,临床中需要密切监测患者上述指标水平,通过指标监测,掌握患者疾病水平,有针对性的对患者疾病进行治疗.还会在一定程度上推动临床医学的发展,为疾病诊治,预防奠定基础.     

糖尿病终末期肾病维持性血液透析患者死亡原因分析

目的：探讨导致糖尿病终末期肾病（ESDN）血液透析患者死亡的原因,以提高此类患者的生存率。方法：回顾性分析20例ESDN血透患者和22例非ESDN血透患者的死亡率、死亡原因、营养状态、血生化指标。结果：ESDN组1、3年死亡率分别为21．6％和40．3％,均高于非ESDN组。死亡原因主要为心血管疾病（45．5％）和感染性疾病（28．3％）。ESDN患者的营养状态明显差于非ESDN患者。结论：ESDN死亡率高于非ESDN患者,与基础病的合并症多、营养状态差有关,故积极治疗并发症,改善营养状态是减少死亡的有效手段。     

糖尿病终末期肾病患者肾移植研究

目的：分析糖尿病终末期肾病肾移植的特点，探讨其并发症的防治措施。方法：对41例糖尿病终末期肾病患者进行肾脏移植，术后严格监测血糖、血肌酐水平变化，及时调整胰岛素和免疫抑制剂用量，结合随访资料进行临床分析。结果：肾移植术后急性排斥反应发生率16．8％，感染发生率48．2％，心脑血管疾病死亡率4．9％；1年、3年人／肾存活率分别为92．2％／89％和85％／81％。结论：肾移植是糖尿病终末期肾病的有效治疗措施．防治心脑血管并发症。有效控制血糖和感染是成功的关键。     

女性终末期肾病患者并发甲状腺结节的影响因素

目的 探讨女性终末期肾病(ESRD)患者并发甲状腺结节(TN)的影响因素.方法 女性ESRD患者112例,依据甲状腺超声检查结果分为TN组(78例)和非TN组(34例),分析两组患者临床资料,采用多因素logistic回归分析女性ESRD患者并发TN的影响因素.结果 年龄、职业、TN家族史、吸烟史、进食海产品、乳腺结节...     

终末期肾病患者维持性血液透析前后认知功能状况及危险因素研究

目的 观察终末期肾病患者维持性血液透析前后的认知功能状况和高危因素.方法 80例在本院接受诊治的终末期肾病患者,中文版蒙特利尔认知评估量表评估终末期肾病血液透析前、血液透析4周、透析8周的认知功能状况;评估终末期肾病患者血液透析后认知功能状态的高危影响因素.结果 终末期肾病患者血液透析8周MoCA评分显著低于血液透析4...     

终末期肾病患者高血压的发生与血尿酸相关性的研究

目的:探讨末期肾病进行血液透析患者高血压的发生与血尿酸的关系,从而了解血尿酸对高血压的影响机制。方法:针对我院血液透析中心现有维持性血液透析患者80例,统计高血压的患病率、高尿酸血症发生率和控制情况。结果:在80例常规透析的患者中高血压的患病人数57例,占71%,这57例患者中血尿酸增高者23例,占40%,与血压正常组有明显差异(P<0.05),在尿酸降低的同时,血压有所降低(P<0.05),结论:通过本研究内容初步了解透析患者高血压的发生与血尿酸的关系,为透析高血压患者治疗提供新思路。     

终末期肾病透析患者氧化应激水平的变化

目的探讨终末期肾病(ESRD)透析患者血浆总丙二醛(tMDA)和游离丙二醛(fMDA)的浓度变化。方法 ESRD患者79例分为ESRD保守治疗(ESRD组,26例)、血液透析(HD组,30例)和腹膜透析(PD组,23例)三组;另设正常对照组30例。采用同位素稀释GC-MS法检测患者fMDA和tMDA浓度,计算结合丙二醛(bMDA)值(bMDA=tMDA-fMDA)。结果 ESRD组、HD组和PD组血浆tMDA和bMDA浓度均高于对照组[(6.94±1.50)μmol/L,(5.70±1.20)μmol/L和(4.40±1.00)μmol/L vs.(1.70±0.50)μmol/L和(6.49±1.70)μmol/L,(4.43±1.20)μmol/L和(3.21±1.00)μmol/L vs.(1.26±0.30)μmol/L](P<0.01)。PD组和HD组fMDA水平均高于ESRD组[(1.22±0.60)μmol/L和(1.31±0.60)μmol/L vs.(0.48±0.30)μmol/L](P<0.01)。多元统计分析结果显示,tMDA和bMDA水平与残余肾功能(γ=-2.160,P<0.05)和白蛋白水平(γ=-2.049,P<0.05)呈负相关。促红细胞生成素(EPO)剂量与fMDA水平呈负相关(γ=-2.178,P<0.05)。结论 fMDA浓度的变化可提示近期的肾脏损伤,而bMDA则可提示肾脏的陈旧损伤。ESRD未透析患者不能将bMDA从肾脏中清除;透析尤其是血液透析,加剧了患者肾脏的氧化损伤。     

Influenza vaccination in patients with end-stage renal disease

Introduction: Patients with end-stage renal disease (ESRD) are considered at higher risk of influenza-related complications and are listed worldwide among the subjects for whom yearly influenza vaccination is strongly recommended. However, influenza vaccination coverage of patients with ESRD is significantly lower than desired.

Areas covered: This paper explores why compliance with official recommendations for influenza vaccination is poor in patients with ESRD and analyzes the true risk of infection as well as the immunogenicity, the effectiveness and the safety of influenza vaccination in these patients.

Expert opinion: Epidemiological and clinical data support the importance of influenza in conditioning clinical deterioration of patients with ESRD, particularly in relation to their level of immunosuppression. However, the variable levels of immunodeficiency detected in patients with ESRD may reduce the immune response to influenza vaccination, which appears to be lower than that usually found in healthy subjects. However, few studies are available, and they are difficult to compare for several reasons. Additionally, limited data have been collected on influenza vaccine effectiveness, although the available studies support positive results of vaccination on outcomes of severe disease. Despite such limitations, it is important to highlight that all the available studies have confirmed the good safety and tolerability of inactivated influenza vaccines. These findings, together with the risks associated with influenza in these patients, support annual influenza vaccination in patients with ESRD as well as vaccination of their close contacts and should be presented in educational programs organized for nephrologists and patient associations.     

Vimentin cleavage in end-stage renal disease is not related to apoptosis

Anti-vimentin auto-antibodies contribute to chronic allograft nephropathy. They exist in sera of end-stage renal disease patients on hemodialysis (ESRD) already before renal transplantation. We found recently that a 49 kDa vimentin fragment is increased in lymphocytes of ESRD patients which is presented on the cell surface. In vitro studies showed that such a fragment is formed during apoptosis by active caspase-3. We hypothesized that vimentin degradation in leukocytes of ESRD patients correlates to caspase-3 activation in vivo. Lymphocytes and monocytes were isolated from ESRD patients and from healthy volunteers and analyzed for vimentin expression and caspase-3 activation. In addition, apoptosis was induced in vitro and quantified by flow cytometry. ESRD monocytes have shown only the full length 60 kDa vimentin isoform. ESRD lymphocytes, however, showed in addition a strongly increased expression of the 49 kDa vimentin in all samples. Caspase-3 activation was found in 60% of ESRD lymphocytes and 66% of ESRD monocytes but not in healthy volunteers. UV-mediated induction of apoptosis was not associated with vimentin degradation. These experiments could confirm increased vimentin degradation in ESRD lymphocytes. However, we could not validate any correlation to apoptosis.     

Bioavailability of labetalol in patients with end-stage renal disease.

The pharmacokinetics and pharmacodynamics of labetalol were assessed after a single oral and intravenous dose in eight patients with end-stage renal disease (ESRD) maintained on chronic hemodialysis, and in eight age-and sex-matched normal volunteers. The mean area under the serum concentration-time curve, volume of distribution, clearance, and terminal elimination half-life values after a single intravenous dose of 0.5 mg/kg of labetalol were not significantly different between ESRD patients and normal volunteers. Similarly, the absolute bioavailability of an oral dose of 200 mg of labetalol was 0.33 in ESRD patients and was not significantly different from that of normal volunteers (0.26). However, a significant decrease in the area under the mean blood pressure-time curve was found after a single oral dose in ESRD patients, which was not observed in normal volunteers. The pharmacokinetics of labetalol were not associated with changes in blood pressure. Thus, when given orally to the ESRD patient, labetalol should be slowly titrated and the blood pressure closely monitored.     

The pharmacokinetics of etanercept in patients with end-stage renal disease on haemodialysis

Inflammation is strongly associated with malnutrition and cardiovascular risk in patients with chronic renal failure on haemodialysis (HD). The acute-phase inflammatory response, defined by the increased synthesis of positive acute-phase proteins, is stimulated by the production of such cytokines as interleukin 6 (IL-6), interleukin 1 (IL-1) and tumour necrosis factor-alpha TNF-alpha The availability of cytokine antagonists allows testing of the hypothesis that suppression of inflammation reverses the malnutrition-inflammation syndrome in HD patients. Etanercept is a soluble TNF-alpha receptor fusion protein used to suppress inflammation in rheumatoid and psoriatic arthritis. Its metabolism in HD patients is unknown. In a study designed to test the safety and pharmacokinetics of etanercept in HD patients, etanercept was administered to six HD patients with albumin levels above 4.2 g dL(-1) and C-reactive protein levels <5 mg L(-1) (five men, one woman, age range 34-59 years). Etanercept (25 mg) was administered subcutaneously twice weekly immediately after dialysis for 13-16 weeks. Etanercept concentrations were measured pre- and post-dialysis by ELISA. Concentrations were compared graphically to assess whether, firstly, dialysis affects etanercept apparent clearance and, secondly, etanercept kinetics were similar between HD patients and the more extensively studied psoriasis population with normal renal function (PS). The second stage examined model-based parameter predictions of the terminal elimination rate constant (k) for HD patients. Steady-state etanercept levels were comparable between HD and PS patients. Treatment with HD had no effect on etanercept levels. When etanercept was discontinued, the terminal rate constant for HD patients was not significantly different from that observed in PS patients. No adverse effects were noted during the 3-month treatment phase and subsequent 6-month follow-up. Albumin and C-reactive protein levels did not change in these non-inflamed patients during the study period. The pharmacokinetics of etanercept in patients with chronic renal failure on HD are similar to patients with normal renal function. It is, therefore, feasible to administer etanercept to HD patients without adjusting the dose.     

Dosing of gentamicin in patients with end-stage renal disease receiving hemodialysis

The aim of this study was to evaluate dosing schedules of gentamicin in patients with end-stage renal disease and receiving hemodialysis. Forty-six patients were recruited who received gentamicin while on hemodialysis. Each patient provided approximately 4 blood samples at various times before and after dialysis for analysis of plasma gentamicin concentrations. A population pharmacokinetic model was constructed using NONMEM (version 5). The clearance of gentamicin during dialysis was 4.69 L/h and between dialysis was 0.453 L/h. The clearance between dialysis was best described by residual creatinine clearance (as calculated using the Cockcroft and Gault equation), which probably reflects both lean mass and residual clearance mechanisms. Simulation from the final population model showed that predialysis dosing has a higher probability of achieving target maximum concentration (Cmax) concentrations (> 8 mg/L) within acceptable exposure limits (area under the concentration-time curve [AUC] values > 70 and < 120 mg x h/L per 24 hours) than postdialysis dosing.     

Interactions between clarithromycin and digoxin in patients with end-stage renal disease

OBJECTIVE: To report a significant increase in the serum levels of digoxin associated with the use of clarithromycin in six patients undergoing renal replacement therapy. CASE SUMMARY: All six patients were males with end-stage renal disease and in need of renal replacement therapy. Four patients were anuric. The mean age was 78.8 +/- 5.8 (66-83) years. All patients except one, who was treated by hemofiltration, were treated by hemodialysis. All patients except one, who had been treated with metildigoxin (0.35 mg/week), were also taking digoxin (0.375 mg/week). Clarithromycin was administered at a dose of 200-400 mg/day for the treatment of bronchitis in all patients. The concomitant administration of clarithromycin increased serum digoxin levels from 1.8-4.0-fold in all cases. In two of six cases, a high probability of digoxin intoxication and suspicion of digoxin intoxication was evident. In three of six cases, serum digoxin levels increased within 12 days after the co-administration of clarithromycin, while in the other three cases, serum digoxin levels were increased 53-190 days after the administration of clarithromycin. CONCLUSION: The simultaneous administration of clarithromycin caused an increase in digoxin levels in six patients undergoing renal replacement therapy. The increase in the serum digoxin can be attributed to the inhibition of P-glycoprotein in the intestine and/or bile capillary rather than the kidney by clarithromycin since renal function was dramatically impaired, and four of the patients were anuric. The issue of why serum digoxin levels were increased so late in three patients undergoing renal replacement is unclear. However, this interaction seemed to be clinically significant even in ESRD patients, whose renal function was highly impaired. The simultaneous use of digoxin and clarithromycin should be avoided even in patients undergoing renal replacement therapy whose renal function is impaired, since digoxin levels may increase unexpectedly.     

Vancomycin assay performance in patients with end-stage renal disease receiving hemodialysis

STUDY OBJECTIVE: To compare the performance of polyclonal fluorescence polarization immunoassay (pFPIA) with that of enzyme-multiplied immunoassay technique (EMIT) in patients receiving vancomycin and hemodialysis. SETTING: Outpatient hemodialysis center. PATIENTS: Seven subjects with end-stage renal disease treated with hemodialysis 3 times/week with a cellulose triacetate hemodialyzer. INTERVENTION: Subjects received vancomycin 1000 mg intradialytically during the first study session and 750 mg every other hemodialysis session thereafter for 4 weeks. MEASUREMENTS AND MAIN RESULTS: Blood samples were obtained throughout the study, and vancomycin serum concentrations were determined by pFPIA and EMIT. The mean +/- SD difference (estimate of bias) between assays was -1.10 +/- 1.35 mg/L. The limits of agreement (mean difference +/- 1.96 x SD) between them were -3.80-1.60 mg/L. CONCLUSION: Our data suggest that the manufacturer's changes in the vancomycin pFPIA eliminated overestimation of drug concentrations in patients undergoing high-permeability hemodialysis.     

Prediction of pharmacokinetics of antibiotics in patients with end-stage renal disease

A novel and convenient method to predict the pharmacokinetics of several kinds of antibiotic agents in patients with end-stage renal disease (ESRD) was examined based on the in vitro extraction ratios and pharmacokinetic parameters in healthy volunteers. The dializability of 17 antibiotic agents in 4% human serum albumin solution were determined using a high-performance hemodialytic membrane for clinical use. We assumed that the off-hemodialysis clearance approximated the non-renal clearance, while the on-hemodialysis clearance was considered to be sum of the off-hemodialysis clearance and the hemodialytic clearance. The estimated on- and off-hemodialysis clearances were compared with the ones observed in ESRD patients. In order to confirm the method prospectively, an in vivo pharmacokinetic study was performed in dogs with mercury chloride-induced experimental renal failure. The in vitro extraction ratios of 9 beta-lactams were broadly ranged from 10.9 to 75.6% depending on their physicochemical properties. In contrast, those of the other antibiotics were consistent with their chemical classes: 60.5-63.2% for fluoroquinolone, 48.8-51.1% for aminoglycoside and 18.7-25.6% for glycopeptide. Both the estimated on- and off-hemodialysis clearances of the 17 antibiotics coincided well with the observed values in the literature, regardless of their physicochemical and pharmacokinetic properties. The validity and applicability of this method to three cefems, cefmetazole, cefotaxime and cefoperazone, was prospectively confirmed in the animal study. In conclusion, this new method enables the prediction of the on- and off-hemodialysis clearances of several kinds of antibiotics in ESRD patients from minimal information of their pharmacokinetics in healthy subjects and their in vitro dializability.