Cyclosporine withdrawal from a mycophenolate mofetil-containing immunosuppressive regimen in stable kidney transplant recipients: a randomized,controlled study

BACKGROUND: Long-term maintenance immunosuppression with cyclosporine (CsA) is associated with chronic transplant nephropathy and adverse effects on blood pressure and lipid profile. Several nonrandomized studies suggest that CsA might safely be withdrawn from immunosuppressive regimens containing mycophenolate mofetil (MMF; CellCept). METHODS: A randomized, controlled study with 187 patients enrolled from 21 centers was conducted to compare CsA withdrawal with ongoing CsA therapy in stable renal transplant recipients receiving a triple-drug immunosuppressive regimen of MMF (2 g/day), CsA (Neoral), and corticosteroids. The primary endpoint was creatinine clearance at 6 months after complete withdrawal. RESULTS: In the intent-to-treat population, CsA withdrawal was associated with lower total cholesterol and low-density lipoprotein cholesterol (-0.3 mmol/L, P=0.02; -0.4 mmol/L, P=0.015). There was a trend toward improved creatinine clearance (4.5 mL/min, P=0.16) and serum creatinine (-1 vs. +4 micromol/L, P=0.34). In the per-protocol population, which excluded patients with acute rejections, the improvements in creatinine clearance and serum creatinine were statistically significant (7.5 mL/min, P=0.02; -11 vs. +4 micromol/L, P=0.0003). Reversible acute rejections, the majority of which were mild, occurred in nine CsA withdrawal versus two CsA continuation patients (10.6% vs. 2.4% of each group, P=0.03), with no graft loss. CONCLUSION: Withdrawal of CsA from an MMF-containing triple-drug immunosuppressive regimen improves renal function and lipid profile at the cost of a modest increase in acute rejections, without graft loss.     

Blood pressure reduction with HMG-CoA reductase inhibitors in renal transplant recipients

BACKGROUND: Besides lowering lipid levels, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) modulate endothelial function and decrease vascular tone. The effect of statin therapy on blood pressure has not been previously examined in renal transplant recipients. METHODS: We identified 113 stable recipients with graft survival>1 year and started on a statin >or=1 year post-transplant with no subsequent alteration in type or dose, as well as >or=6 months' follow-up post-statin introduction along with no changes in antihypertensive medication type or dosage. This "statin" group was compared to a control group matched 1:1 by age, gender, donor source, year of transplant, and time since transplant who met identical criteria but were not begun on a statin. Baseline, 6 months, and 12 months outpatient blood pressure were reviewed and compared along with other possible blood pressure predictors. A multivariate analysis was performed controlling for other influences on blood pressure change. RESULTS: Blood pressure and baseline characteristics other than lipid levels were similar in the two groups. The systolic, diastolic, and mean arterial blood pressure decreased by 7 mm Hg (P = 0.005), 3 mm Hg (P = 0.05), and 4 mm Hg (P = 0.007), respectively, at 12 months' post-statin introduction, while no blood pressure change was seen in the control group (P = NS). At 12 months, the systolic, diastolic, and mean arterial blood pressures were lower in the statin group compared to the control group (P = 0.05, 0.03, and 0.02, respectively). These changes in blood pressure were independent of changes in serum lipid levels. CONCLUSION: Renal transplant recipients exhibit a significant blood pressure reduction associated with statin therapy. This finding has important mechanistic and clinical implications in the management of cardiovascular disease risk factors in this population.     

Pretransplantation systolic blood pressure and the risk of delayed graft function in young living-related renal allograft recipients

Delayed graft function (DGF) is associated with decreased long-term renal allograft survival, however, the entire mechanism of action of DGF has not yet been established. The goal of this study was to determine possible risk factors for DGF in young living-related renal allograft recipients. We retrospectively analyzed the outcome of 142 renal transplant recipients (115 men and 27 women; mean age, 29.7 +/- 9.43 years; 114 living-related donors and 28 cadaveric donors). Data recorded for each patient and donor included gender, age at transplantation, duration of pretransplantation dialysis (recipients only), body mass index, number of human leucocyte antigen mismatches, panel-reactive antibodies, donor creatinine clearance, body weight, systolic and diastolic blood pressure levels, lipid profile, and biochemical parameters. Having obtained the transplant from a cadaveric donor (P<.000, odds ratio [OR]=17.556, confidence interval [CI]=5.961-51.743) and a pretransplantation systolic blood pressure level in the recipient of <120 mm Hg (P<.021, OR=3.600, CI=1.214-10.672) were possible risk factors for DGF. When only living-related recipients were considered, the systolic blood pressure level was significantly associated with DGF. We concluded that a pretransplantation systolic blood pressure level <120 mm Hg is a risk factor for DGF and that preoperative blood pressure control and intervention may help to decrease the risk of DGF.     

Systolic Blood Pressure Diurnal Variation is Not a Predictor of Renal Target Organ Damage in Kidney Transplant Recipients

Elevated blood pressure and diurnal blood pressure variation detected by ambulatory blood pressure monitoring has been shown to be predictive of worse outcome in end-stage renal disease patients in small studies. What has been lacking is a large study to determine whether these ambulatory blood pressure monitoring (ABPM)-derived variables are predictors of worse outcome in renal transplant recipients. All the patients that underwent renal transplantation and follow up at this institution from January 1998 till October 2002 were involved in this study (n=177). All patients were followed up for at least 48 weeks. Last creatinine correlated positively with duration of dialysis (p=0.035, r=0.158), kidney-donor age (p<0.0001, r=0.377), early kidney function (p<0.0001, r=0.610, r=0.683), 24-h systolic blood pressure (SBP) load (p=0.002, r=0.228), and ABPM-derived pulse pressure (p<0.0001, r=0.269). However neither office blood pressure nor SBP diurnal variation were predictors of kidney outcome. Regression analysis showed that early kidney function was the only independent predictor of transplant outcome (p<0.0001). Systolic blood pressure diurnal variation, though an important predictor of target organ damage in chronic kidney disease patients, was not a predictor of renal transplant function in renal transplant recipients. Only early kidney function was an independent predictor of later serum creatinine.     

Elevated urinary angiotensinogen a marker of intrarenal renin angiotensin system in hypertensive renal transplant recipients: does it play a role in development of proteinuria in hypertensive renal transplant patients?

The aim of this study was to evaluate the relationship of local intrarenal renin angiotensin system (RAS) with hypertension and proteinuria in renal transplant recipients. Sixty-nine nondiabetic renal transplant recipients (39 male, mean age: 36.3 ± 11.5 years) were included in this study. All patients were in stable condition with GFR greater than 30 ml/min/1.73 m(2); (MDRD). Hypertension was defined to be present if there was a recorded diagnosis of hypertension, systolic blood pressure >130 mmHg and/or diastolic blood pressure >80 mmHg according to ambulatory blood pressure monitoring. None of the hypertensive patients were receiving RAS blockers. Spot urine samples were obtained to measure urinary angiotensinogen (AGT) using human AGT-ELISA, urinary creatinine and protein levels. The demographic properties and laboratory findings were similar between hypertensive and normotensive transplant recipients. Urinary AGT-creatinine ratio (UAGT/UCre) was significantly higher in hypertensive patients compared with the normotensives (8.98 ± 6.89 μg/g vs. 5.48 ± 3.33 μg/g; P = 0.037). Importantly, a significantly positive correlation was found between UAGT/Ucre levels and proteinuria in hypertensive patients (P = 0.01, r = 0.405). Local intrarenal RAS probably plays an important role in the development of hypertension and proteinuria in renal transplant recipients.     

Factors affecting the therapeutic response of enalapril in treatment of post transplant erythrocytosis

Summary: Enalapril was used for post transplant erythrocytosis (PTE) in 19 stable male hypertensive renal allograft recipients. Post transplant erythrocytosis was defined as haematocrit (Hct) >0.45 for 3 consecutive months. Dosage of enalapril was adjusted according to the blood pressure of individual patients and varied from 2.5 mg to 20 mg per day in divided doses. Patients'serum creatinine level, blood pressure and haematocrit were monitored. Therapeutic response was expressed as percentage drop in Hct (Δ%Hct). Factors affecting Δ%Hct was then determined. After 32 weeks of treatment, haematocrit fell from 0.495 ± 0.021 to 0.396 ± 0.053, which represented a 19.9% drop (paired Student's t-test, P > 0.001). With multiple regression analysis, reciprocal of plasma creatinine (RCr) prior to enalapril therapy (B = 3.40 ± 0.72, P > 0.0005), dose of enalapril adjusted with bodyweight (B = - 0.058 ± 0.020, P > 0.02, and pre-treatment haematocrit level (B = - 1.90 ± 0.71, P > 0.02) were found to be independent factors affecting Δ%Hct. We concluded that the dosage of enalapril, renal allograft function and severity of erythrocytosis were the major factors affecting the therapeutic response of PTE by enalapril treatment.     

西罗莫司替代钙调磷酸酶抑制剂方案治疗肾移植后“爬行肌酐”患者的疗效观察（附28例报告）

目的探讨采用西罗莫司替代钙调磷酸酶抑制剂（CNI）方案治疗肾移植后＂爬行肌酐＂患者的临床疗效。方法具有＂爬行肌酐＂表现的28例患者中,术后采用以环孢素（CsA）为主的三联免疫抑制方案20例,采用以他克莫司（FK506）为主的三联免疫抑制方案8例。患者确诊后即停用CsA或FK506,24h后给予西罗莫司,初始剂量6mg,维持剂量为2mg/d,以后根据西罗莫司的血药浓度来调整剂量,使其血药谷浓度维持在5～9μg/L,药物替代前后麦考酚吗乙酯（MMF）及肾上腺皮质激素（激素）的用量不变。随访6个月,定期观察移植物肾功能,记录排斥反应的发生情况,并监测血常规、血糖、血脂、肝功能等指标。结果移植物肾功能明显改善16例,患者的血清肌酐（Scr）由替代前（205±20）μmo1/L降为替代后的（153±18）μmo1/L,内生肌酐清除率（Ccr）由（51±3）ml/min升高为（56±3）ml/min（均为P〈0.05）;移植物肾功能维持稳定8例,移植物肾功能继续恶化2例。治疗中,1例发生急性排斥反应,移植肾失功并恢复血液透析,1例西罗莫司替代后出现明显骨髓抑制而放弃替代治疗,恢复替代前的免疫抑制方案。结论西罗莫司替代CNI治疗肾移植后＂爬行肌酐＂患者是一种比较安全并有效的方法,可明显改善移植物肾功能,但会使患者血脂升高。     

Renal effects of amlodipine in normotensive renal transplant recipients.

Renal effects of amlodipine in normotensive renal transplant recipients. The use of cyclosporin A (CsA) has improved the success of renal transplantation, but is associated with hypertension and significant renal toxicity. Previous reports suggest that calcium channel blockers may be useful in opposing the adverse effects of CsA. We have evaluated the effects of amlodipine (5 mg, once daily for 8 weeks) on renal function in 27 normotensive renal transplant recipients with stable renal function, in a double-blind, placebo-controlled, multicentre, cross over study. Amlodipine significantly reduced serum creatinine concentration relative to placebo (mean+/-SD: 168+/-65 vs 177+/-66 micromol/l; P=0.002) and there was a strong trend towards an increase in effective renal plasma flow on amlodipine relative to placebo (238+/-92 vs 217+/-87 ml/min; P=0.055). Glomerular filtration rate and lithium clearance were unaffected. Trough CsA blood concentration was unaffected. Amlodipine was well tolerated, with a low incidence of adverse events, and did not affect blood pressure or heart rate. In conclusion, amlodipine reduced serum creatinine in normotensive renal transplant recipients after only 8 weeks treatment, and was well tolerated in concomitant administration with CsA.     

Fish oil treatment for kidney transplant recipients: a meta-analysis of randomized controlled trials

BACKGROUND: Calcineurin inhibitors have adverse effects that contribute to nephrotoxicity and cardiovascular risk profile, and these may be reduced by administration of fish oil. The aim of this review was to assess the benefits and harms of fish oil supplementation in kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen. METHODS: The Cochrane Controlled Trials Registry, MEDLINE, and EMBASE were searched for randomized controlled trials of fish oil treatment in kidney transplant recipients on a calcineurin inhibitor-based immunosuppressive regimen. Trials comparing fish oil to both placebo and statins were included. Data were extracted for patient and graft survival, acute rejection, calcineurin inhibitor toxicity, cardiovascular events, adverse effects, compliance, renal function, blood pressure, and lipid profile. Dichotomous outcomes were reported as relative risk and continuous outcome measures as weighted mean differences (WMD), with 95% confidence intervals. RESULTS: Sixteen suitable trials were analyzed. Fish oil treatment was associated with a lower diastolic blood pressure (WMD 4.5 mmHg, P=0.004) and higher high-density lipoprotein (HDL) cholesterol (WMD 0.12 mmol/L, P=0.01) but did not affect the other outcomes. Fishy aftertaste and gastrointestinal upset were common but did not result in significant dropout. Fish oil effects on lipids were not significantly different than low-dose statins. CONCLUSION: There is insufficient evidence from currently available randomized controlled trials to recommend fish oil therapy to improve renal function, rejection rates, and patient or graft survival. Improvements in HDL cholesterol and diastolic blood pressure were too modest to recommend routine use.     

肾移植术后将CCB替换为ARB控制高血压和蛋白尿的效果

目的 研究肾移植术后将钙通道阻滞剂(CCB)替换为血管紧张素受体阻滞剂(ARB)控制肾移植远期高血压和蛋白尿的有效性和安全性.方法 将肾移植术后5～20年,并服用CCB药物治疗高血压的127例受者纳入研究,所有受者均无糖尿病,移植肾功能保持稳定.采用随机数字表法将受者分为2组,实验组65例,纳入研究前受者均单用CCB,纳入研究后停用CCB,改用氯沙坦50～100 mg/d;对照组62例,维持CCB用药不变.对两组受者进行随访,随访时间为2年,观察血、尿常规,肝、肾功能,血脂,电解质,24 h尿蛋白定量,以及CNI血药浓度等指标的变化.结果 随访期间,两组受者的血压均能保持在正常水平.实验组受者24h尿蛋白定量由随访前的(176.32±54.54)mg下降至随访2年时的(155.69±62.25)mg,差异有统计学意义(P＜0.05);随访2年时,对照组受者的尿蛋白水平略有上升,但差异无统计学意义(P＞0.05);实验组受者的血脂水平与随访前相比,差异无统计学意义(P＞0.05),但高密度脂蛋白水平由随访前的(2.25±0.26)mmol/L升高到随访2年时的(2.46±0.31)mmol/L,差异有统计学意义(P＜0.05).两组受者随访前与随访2年后的血常规、肝肾功能、血钾及CNI血药浓度等检查指标的差异均无统计学意义.结论 肾移植术后远期使用CCB和ARB治疗高血压都是安全、有效的,而应用ARB对于减少蛋白尿和降低心血管事件的风险可能会更好.     

Electrolyte Free Water Clearance Could Be an Early Sign of Renal Dysfunction in Renal Transplant Patients

Data on free water excretion capacity of renal transplant recipients are scant. The aim of this study was to evaluate the ability of electrolyte free water clearance (E-CH₂O) by the allograft in renal transplant patients and the effects of various immunosuppressive drugs. Renal transplant recipients with good graft function (creatinine < 1.5 mg/dL) as well as controls were divided into five groups according to their immunosuppressive regimen: group I, azathioprine (n = 15); group II, cyclosporine (n = 28); group III, tacrolimus (n = 28); group IV healthy controls (n = 20); and group V renal transplant donors (n = 16). Following a 12-hour fast, we administered oral water loading (20 mL/kg) with urine collection for 3 hours. We calculated creatinine clearance for 3 hours and E-CH₂O. No matter which immunosuppressive drug, the E-CH₂O of recipients (groups I, II, and III) was lower than that of donors or healthy controls. The creatinine clearance of the cyclosporine arm was significantly lower than all of the other groups. Decreased E-CH₂O in renal transplant patients might be due to diminished water input to the loop of Henle related to subclinical allograft insufficiency as a result of posttransplantation pathology and/or immunosuppressive drug therapy or the transport of water into the extrarenal interstitium as a result of vascular endothelial dysfunction due to the pretransplant uremic milleu.     

3种免疫抑制剂替换方案治疗肾移植术后“爬行肌酐”的疗效观察

目的：观察3种免疫抑制剂替换方案治疗肾移植术后“爬行肌酐”患者的疗效。方法：回顾性分析1992年12月～2005年11月间53例术后出现“爬行肌酐”肾移植受者的临床资料,按出现“爬行肌酐”后采用的替换治疗方案分为FK506组（n=24）、MMF组（n=18）和SRL组（n=11）,观察治疗前后的移植肾功能及血压、血糖、血脂等的变化,并比较随访12个月的情况。结果：FK506组治疗后移植肾功能较前明显好转,血肌酐下降明显（P〈0.05）,同时降低了血脂水平,减少降脂药物及抗高血压药物的使用,替换后的血糖升高不明显;MMF组治疗后可以延缓大部分病例的移植肾功能减退,降低血脂水平,减少抗高血压药物的使用以及肝脏、骨髓毒性;SRL组治疗后亦可以延缓部分病例的移植肾功能恶化,但可引起或加重高脂血症及贫血。结论：对肾移植术后“爬行肌酐”患者采用的3种免疫抑制剂替换方案都可以有效地改善或稳定移植肾功能。     

The influence of calcineurin inhibitors on pulse wave velocity in renal transplant recipients

BACKGROUND: Pulse wave velocity (PWV) is a marker of the arterial wall stiffness and independent cardiovascular risk factor in hemodialysis patients. Cyclosporine A (CyA) and tacrolimus (TAC) are known to differ in the influence on cardiovascular risk factors in renal transplant recipients. Recent studies suggest that CyA may decrease arterial compliance. The aim of the study was to assess the influence of CyA and TAC on the PWV and arterial wall stiffness in renal transplant recipients. METHODS: The study population consisted of two groups of cadaveric renal transplant recipients, 76 patients each, matched for age, sex, blood pressure, body mass index, and length of the post-transplant follow-up. PWV between carotid and femoral artery was measured using a Complior device. Fasting blood was sampled for serum creatinine, lipid profile, uric acid, glucose, and C-reactive protein. RESULTS: Aortic pulse wave velocity -- a marker of increased arterial stiffness -- was significantly higher in CyA group compared with TAC group (9.33 +/- 2.10 vs. 8.54 +/- 1.35, respectively; p < 0.01). Uric acid, total cholesterol, triglycerides, and LDL-cholesterol concentrations were significantly higher in CyA group. Significant correlations were found between PWV and age, systolic and diastolic blood pressure, and fasting glucose in the CyA group, but only between PWV and age in TAC group. CONCLUSION: CyA-based immunosuppressive therapy is associated with an unfavorable profile of cardiovascular risk factors and increased arterial stiffness in renal transplant recipients.     

颅脑损伤尿崩症供者维护策略及其供肾移植疗效分析

目的总结颅脑损伤尿崩症供者维护策略并评价其供肾移植后临床疗效。 方法回顾性分析2016年1月至2018年9月武汉大学人民医院器官移植科完成的颅脑损伤尿崩症供者供肾移植供、受者临床资料，总结此类供者临床维护策略、吻合方式及供肾移植术后受者情况。采用配对t检验比较尿崩症供者治疗前后血压、每小时尿量、心率、血钠水平、尿比重、体温、血浆渗透压及血清肌酐等指标。P<0.05为差异有统计学意义。 结果经系统性抗尿崩治疗后，12例尿崩症供者血压、每小时尿量、心率、血钠水平、尿比重、体温、血浆渗透压及血清肌酐均明显改善，差异均有统计学意义(P均<0.05)。供肾获取时均灌注良好，颜色和质地佳，无血栓和瘀斑等情况。修整后复灌均采用输血器灌注，灌注良好。24例受者中，19例移植后移植肾立即发挥功能，血清肌酐恢复至133 μmol/L以下，平均时间为术后(10±3)d；5例发生移植肾功能延迟恢复(DGF)，术后维持血液透析时间为(9±3) d，DGF恢复[eGFR≥30 mL·min^－1·(1.73 m²)^－1]平均时间为术后(23±4) d。1例发生DGF受者于术后第2天因移植肾出血，二次手术止血后于术后第19天恢复。术后3个月，24例受者平均血清肌酐为(105±43) μmol/L。2例受者于围手术期发生急性排斥反应，应用兔抗人胸腺细胞球蛋白(rATG)后逆转。截至2018年12月，7例受者出现移植后并发症：4例发生急性排斥反应，其中2例经甲泼尼龙冲击治疗后恢复，2例经甲泼尼龙＋rATG治疗后恢复；2例出现肺部感染，经积极抗感染治疗后恢复；1例术后3个月出现移植肾动脉狭窄，行移植肾动脉支架植入术后恢复。 结论尿崩症是颅脑损伤供者常见临床综合征，其发生可能会影响供肾质量，对尿崩症进行全面监测和积极治疗后，有助于供肾功能的维护，促进移植肾功能早期恢复。     

肾移植术后早期移植肾动脉狭窄的诊断与治疗

目的总结肾移植术后早期发生移植肾动脉狭窄(TRAS)受者诊疗经验。 方法回顾性分析2014年1月1日至2018年8月31日复旦大学附属中山医院肾移植术后并发TRAS的16例受者(TRAS组)临床资料,并选取同期16例未发生TRAS的肾移植受者作为对照组。采用配对t检验比较两组受者介入治疗前年龄、等待移植时间、血清肌酐、估算肾小球滤过率(eGFR)、收缩压/舒张压、移植肾动脉峰值流速(PSV)和段间动脉阻力指数(RI),以及TRAS组治疗后与TRAS组治疗前、对照组治疗后血清肌酐、eGFR、收缩压/舒张压、移植肾动脉PSV、段间动脉RI的差异。采用χ²检验比较两组受者性别、供肾来源、透析方式、供肾侧别、供肾动脉吻合方式及移植肾功能延迟恢复发生情况;采用Fisher确切概率法比较两组受者移植前糖尿病、高血压和急性排斥反应发生情况。P<0.05为差异有统计学意义。 结果TRAS组受者中13例行球囊扩张,2例置入球扩支架。随访至2018年8月31日,期间除1例受者因慢性排斥反应行移植肾切除术外,余15例受者移植肾功能均稳定。两组受者年龄、性别、移植前糖尿病、移植前高血压、等待移植时间、供肾来源、透析方式、供肾侧别、供肾动脉吻合方式、移植前血清肌酐、移植肾功能延迟恢复及急性排斥反应发生情况差异均无统计学意义(P均>0.05)。介入治疗前,TRAS组受者平均血清肌酐、收缩压及移植肾动脉PSV分别为(5.6±3.5)mg/dL、(144±9)mmHg(1 mmHg＝0.133 kPa,下同)和(3.4±1.6)m/s,均高于对照组[(1.9±0.8)mg/dL、(130±19)mmHg和(1.3±0.5)m/s],差异均有统计学意义(t＝3.94、2.35和4.73,P均<0.05);TRAS组受者平均eGFR和段间动脉RI分别为(18±15)mL/min和0.5±0.1,均低于对照组[(49±20)mL/min和0.6±0.1],差异均有统计学意义(t＝－4.84和－3.88,P均<0.05)。介入治疗后,TRAS组受者平均血清肌酐、收缩压、舒张压和移植肾动脉PSV分别为(3.2±1.5)mg/dL、(128±16)mmHg、(76±8)mmHg和(2.0±1.0)m/s,较治疗前均有所下降,差异均有统计学意义(t＝3.63、4.40、3.72和3.03,P均<0.05),但平均血清肌酐高于仍高于对照组[(1.5±0.5)mg/dL],差异有统计学意义(t＝3.93,P<0.05)。TRAS组受者平均eGFR和段间动脉RI分别为(26±13)mL/min和0.6±0.1,均高于治疗前,差异均有统计学意义(t＝－4.65和－3.25,P均<0.05);但平均eGFR仍低于对照组[(58±17)mL/min],差异有统计学意义(t＝－5.75,P<0.05)。 结论对于肾移植术后怀疑发生TRAS的受者应先进行彩色多普勒血流显像检查,然后再根据血管动脉造影进行确诊。介入治疗可有效改善TRAS受者移植肾功能。     

经皮腔内血管成形术联合支架置入治疗移植肾动脉狭窄的临床分析

目的  探讨经皮腔内血管成形术（PTA）联合支架置入治疗肾移植术后移植肾动脉狭窄（TRAS）的临床疗效。方法  回顾性分析21例肾移植术后TRAS行PTA联合支架置入治疗患者的临床资料。总结肾移植受者中TRAS的发生情况,比较TRAS患者介入治疗前后相关指标变化情况,分析TRAS患者的预后情况。结果  507例肾移植受者中有21例发生TRAS,发生率为4.1%（21/507）。TRAS诊断时间为术后5（4,7）个月,67%（14/21）在术后6个月内出现TRAS。与介入治疗前比较,介入治疗后1周和1个月TRAS患者血清肌酐、收缩压、舒张压以及移植肾动脉峰值血流流速均降低,估算肾小球滤过率（eGFR）、叶间动脉阻力指数均升高,差异均有统计学意义（均为P < 0.05）。PTA联合支架置入术后随访期间,共有1例出现移植肾动脉再发狭窄,经单纯球囊扩张后好转,1例右股动脉穿刺点假性动脉瘤形成,1例移植肾动脉闭锁导致肾脏萎缩失功,其余18例术后均恢复良好。结论  PTA联合支架置入是肾移植术后TRAS首选治疗方式,可明显改善移植肾功能,显著延长移植肾的生存时间。     

An investigation of the effect of advancing uraemia, renal replacement therapy and renal transplantation on blood pressure diurnal variability

Background: Ambulatory blood pressure recordings have been shown to correlate better with target organ damage than have isolated clinic blood pressure readings. There have been some small studies demonstrating that abnormal blood pressure diurnal rhythm is common in uraemia and in patients on renal replacement therapy. Abnormal blood pressure diurnal rhythm itself may be at risk factor for accelerated target organ damage. Methods: We retrospectively studied 480 ambulatory blood pressure recordings in 380 patients with essential hypertension, secondary hypertension, and on renal replacement therapy. We examined diurnal blood pressure rhythm in each group. Results: Abnormal blood pressure diurnal rhythm (non-dipping) is significantly more prevalent in patients with underlying renal disease, even with normal excretory renal function (53%) than in age-, sex-, and race-matched controls with essential hypertension ((30%), P <0.01). In patients with renal disease the prevalence of non-dipping rose with worsening renal function, reaching statistical significance once plasma creatinine was greater than 400 &mgr;mol/l. There was a direct correlation between plasma creatinine and percent decline in blood pressure at night for both systolic (r=0.23) and diastolic (r=0.24) blood pressure in patients with underlying renal disease and impaired excretory renal function. High prevalences of abnormal diurnal BP rhythm are seen in patients on haemodialysis (82%), peritoneal dialysis (78%), patients with plasma creatinine >600 &mgr;mol/l (75%), and in renal transplant recipients (74%). Conclusion: Abnormal blood pressure diurnal rhythm ('non-dipping') is significantly more common in secondary than in primary hypertension, even with normal renal function. Abnormal blood pressure diurnal rhythm becomes increasingly common with advancing uraemia. Once the plasma creatinine is greater than 600 &mgr;mol/l the prevalence of non-dipping is the same as that seen with renal replacement therapy. This phenomenon is not modulated by successful renal transplantation.     

Findings of Doppler sonography do not correlate with serum lipoprotein and total homocysteine concentrations in renal transplant recipients

Atherosclerosis may be evaluated by structural or functional changes of the main arteries. We sought to investigate the probable associations of static and dynamic arterial changes with lipoprotein (a) and homocysteine levels, the two risk factors for atherosclerosis. Intima-media thickening and vasodilatory responses to nitroglycerine of the common carotid artery and the renal transplant artery were studied by color Doppler sonography in 75 renal transplant recipients and 30 controls. At 3, 5, and 10 minutes after 0.4 mg of sublingual nitroglycerine are measured resistive index and peak systolic velocity of the common carotid artery and renal transplant artery. Intima-media thickening in renal transplant recipients and controls were 0.86 +/- 0.34 mm and 0.74 +/- 0.14 mm (P = .05), respectively. Although intima-media thickness did not correlate with the duration of renal transplantation, it was significantly higher in older renal transplant recipients. Peak systolic velocity of common carotid artery was significantly decreased by nitroglycerine in the controls (81.8 +/- 16.7 m/s to 73.2 +/- 12.8 m/s, P = .03). This decrement was more obvious in renal transplant recipients, especially at 10 minutes (69.6 +/- 18.5 m/s vs 59.3 +/- 2 m/s, P = .01). These reductions did not correlate with intima-media thickening, latter of which also did not correlate with homocysteine concentrations, which were higher among renal transplant patients with creatinine more than 1.8 mg/dL. Basal resistive indices of the common carotid artery and renal transplant artery were higher among graft recipients with dysfunction than recipients with good function, (0.7 vs 0.59, P = .003). In conclusion, neither homocysteine nor lipoprotein(a) concentrations predict static and dynamic vascular properties.     

Potential renal protective benefits of intra-operative BNP infusion during cardiac transplantation

BACKGROUND: Recombinant BNP (nesiritide) is known to reduce endothelin levels, cause afferent arteriole vasodilation, and increase natriuresis and diuresis. We hypothesized that intraoperative infusion of BNP may benefit renal function in cardiac transplant patients. METHODS: From June 2003 to September 2005, 22 consecutive heart transplant patients received BNP at a dose of 0.01 microg/kg/min before initiation of cardiopulmonary bypass (group A). BNP infusion was continued for a mean of 3.3 +/- 1.9 days. Hemodynamics, urine output, and serum creatinine levels were prospectively collected and compared with 22 consecutive patients who underwent heart transplantation between May 2002 and June 2003 following the identical transplant protocol, but without BNP infusion (group B). RESULTS: At 24 hours postoperatively, mean blood pressure was comparable between groups (87 +/- 11 mm Hg vs 89 +/- 17 mm Hg, P = .7), but pulmonary artery pressure (18 +/- 5 mm Hg vs 24 +/- 5 mm Hg, P = .001) and central venous pressure (12 +/- 5 mm Hg vs 16 +/- 4 mm Hg, P = .01) were lower with BNP infusion, whereas cardiac index was augmented (2.8 +/- 0.5 vs 2.4 +/- 0.6, P = .03). Requirement of low-dose inotropic and vasopressor support was equally distributed between groups (P > or = .72). Postoperative urine output for the initial 24 hours was higher in group A (84 +/- 15 vs 55 +/- 36 mL/h, P = .01). None of the patients with BNP infusion required additional diuretics or renal replacement therapy during the first week after transplantation. Mean postoperative serum creatinine levels as compared with preoperative values remained unchanged within group A (P = .12), but increased significantly in group B (P < .001). CONCLUSIONS: Intraoperative BNP infusion in heart transplant recipients was associated with favorable postoperative hemodynamics, significantly improved urine output, and stable serum creatinine levels. A prospective, randomized, multicenter trial is warranted to evaluate the potential renal protective benefits of intraoperative BNP infusion in this patient population.     

Studies on structural changes of the carotid arteries and the heart in asymptomatic renal transplant recipients.

BACKGROUND: The present study was designed to characterize early structural changes of large arteries in renal transplant recipients with no clinical evidence of cardiovascular disease and normal blood pressure values, and to analyse the relationship between arterial alterations and those of the heart. METHODS: Intima media thickness and atherosclerotic plaques of the carotid arteries as well as left ventricular geometry and function were examined in 35 asymtomatic renal transplant recipients and 29 age- and sex-matched healthy controls by high resolution B-mode ultrasound and by echocardiography. RESULTS: Intima-media thickness of the carotid arteries was significantly higher in renal transplant recipients (1.21+/-0.08 mm) than in healthy controls (0.74+/-0.04 mm) (P<0.001). Atherosclerotic plaques were found in the majority of renal transplant recipients (71% vs 14% in healthy controls, P<0.001). Left ventricular mass index was significantly increased in the group of renal transplant recipients (264+/-13 g, 146+/-7 g/m2) when compared with healthy controls (155+/-8 g, 83+/-4 g/m2) (P<0.001). Multiple regression analysis in renal transplant recipients showed that intima media thickness of the carotid arteries was significantly related to left ventricular mass index (P<0.02), but not to age, blood pressure, body mass index, serum creatinine, cholesterol and lipoprotein (a) levels. In the group of healthy controls, intima-media thickness of the carotid artery was related to age (P<0.002), but not to left ventricular mass index or the other independent variables. CONCLUSIONS: The present study documents pronounced intima-media thickening in asymptomatic renal transplant recipients. Atherosclerotic lesions are present in most renal transplant recipients with no clinical evidence of cardiovascular disease. We observed a parallelism between arterial wall thickening and left ventricular hypertrophy, although blood pressure levels were normal during haemodialysis therapy and after renal transplantation.