肾移植后急性排斥反应发生相关术前因素分析

目的探讨影响肾移植术后发生急性排斥反应的相关术前因素,为预防移植肾急性排斥反应的发生提供临床依据。方法回顾性分析2002年1月～2008年12月在浙江大学医学院附属第一医院肾脏病中心首次接受同种异体尸体肾移植受者1316例资料,记录基线资料及术后急性排斥反应发生情况;按群体反应性抗体(PRA)水平10%和≥10%将受者分为PRA阴性组和致敏组;以2005年10月1日为界分为回顾性HLA配型组和前瞻性HLA配型组。统计分析各基线资料对术后急性排斥反应发生的影响以及不同组间急性排斥反应发生率的差异。结果手术时受者年龄、术前PRA水平、热缺血时间、HLA错配数对术后急性排斥反应的发生有显著影响。致敏组术后6个月内急性排斥反应发生率(58.8%比17.9%,P0.001)以及6个月内组织病理学检查证实急性排斥反应发生率(29.4%比11.9%,P=0.028)均显著高于PRA阴性组。采用前瞻性HLA配型后受者HLA错配数减少,且术后6个月内急性排斥反应发生率也降低(20.9%比15.5%,P=0.012)。结论术前检测受者的PRA水平从而准确评估其致敏状态,尽可能选择良好的HLA配型谱可减少移植肾术后急性排斥反应的发生。     

Time-dependent changes in cardiac growth after kidney transplantation: the impact of pre-dialysis ventricular mass.

BACKGROUND: Left ventricular hypertrophy (LVH) is common in chronic kidney disease (CKD), including kidney transplant recipients. However, time-related left ventricular mass changes (DeltaLVM) from pre-dialysis stage to beyond the first post-transplant year have not been clearly identified. METHODS: We studied a cohort of 60 stages 4-5 CKD patients without overt cardiac disease, who underwent three echocardiograms during follow-up: at pre-dialysis stage, on dialysis and after kidney transplantation (KT). Multiple linear regression was used to model DeltaLVM from baseline study. Cox proportional analysis was used to determine risk factors associated with either de novo LVH or>20% DeltaLVMI over time. RESULTS: Patients with baseline LVH (n=37; 61%) had a higher body mass index (BMI) than those without LVH (n=23; 39%) (P=0.013). BMI, haemoglobin levels (P=0.047) and non-use of angiotensin-converting enzyme inhibitors (ACEI) (P=0.057) were associated with baseline left ventricular mass index (LVMI). Twelve out of 23 patients (52%) with normal LVM at baseline, developed either de novo LVH or>20% DeltaLVMI at follow-up. On the other hand, 29 (78%) of those with initial LVH maintained this abnormality, and 8 (22%) normalized LVM post-transplantation. Factors associated with DeltaLVMI were age (P=0.01), pre-dialysis LVMI (P<0.0001), serum creatinine (P=0.012) and the use of ACEI post-transplantation (P=0.009). In Cox analysis, pre-dialysis LVMI was associated with de novo LVH or>20% DeltaLVMI over time (hazard ratio 1.009; 95% confidence interval 1.004 to 1.015; P=0.001). CONCLUSIONS: Successful KT may not completely normalize LVM post-transplantation. Pre-dialysis LVMI, traditional risk factors and no use of ACEI may perpetuate cardiac growth following KT.     

Vesicoureteral reflux after kidney transplantation in children.

BACKGROUND: The prevalence and significance of vesicoureteral reflux (VUR) after kidney transplantation in adults varies between authors and there have been few reports in children. METHODS: We conducted a retrospective study in a single-centre paediatric cohort. Fifty-five of the 84 children who underwent kidney transplantation over a 5-year period were checked with routine cystography after a median of 8 months post-transplantation. Graft function and urinary-tract infections were assessed during the first 6 years after transplantation. RESULTS: VUR into the graft was present in 58% of the patients. Graft function and incidence of urinary-tract infections were similar in the two groups, independent of VUR. After having excluded infections attributed to the presence of a catheter, actuarial survival rates without pyelonephritis and without pyelonephritis following a first lower urinary-tract infection were worse in patients with VUR (P:=0.017 and P:=0.0039 respectively). None of the eight patients with VUR treated with antibiotic prophylaxis after a first acute pyelonephritis (APN) episode presented subsequent APN after 4.4+/-3.3 years on therapy. CONCLUSIONS: VUR to the graft occurred in more than half paediatric renal transplant recipients. This condition was associated with an increased risk of APN. Long-term antibiotic prophylaxis seems to be able to prevent APN in transplanted children with VUR.     

Improvement of left ventricular function after renal transplantation in a patient with uremic cardiomyopathy: Report of a case

The improvement of heart function in a patient on hemodialysis with dilated cardiomyopathy by renal transplantation is herein reported. The patient was a 35-year-old woman. Hemodialysis had been initiated 3 months before, but she experienced difficulty with hemodialysis maintenance and exhibited congestive heart failure. The ejection fraction (EF) was decreased to 36.6% in the echocardiogram, and an intracardiac biopsy of the right ventricle showed myofiber degeneration and interstitial edema upon examination by light microscopy. She then underwent renal transplantation, and the postoperative recovery was almost uneventful. The cardiothoracic ratio decreased rapidly to around 40% after 1 month, although her body weight increased. The ejection fraction increased to 50% in the echocardiogram. An intracardiac biopsy of the right ventricle revealed disoriented myofibers, but myofiber degeneration improved, and no interstitial edema was present upon examination by light microscope. The electron microscopy showed that the intracellular edema had disappeared and other degenerative changes had also improved. The patient was discharged on the 44th postoperative day, with a serum creatinine of 1.3 mg/dl.     

Membranous nephropathy: recurrence after kidney transplantation

BACKGROUND.: It is supposed that about 5% of dialysis patients had membranousnephropathy as a cause for their renal failure. Despite of thisprevalence, only 33 cases of recurrent membranous nephropathyafter kidney transplantation have been reported in the Englishliterature. METHODS.: Among 509 recipients of renal allografts, membranous glomerulonephritiswas the cause of renal failure in five patients, who receivedsix transplants. RESULTS.: Recurrence of the disease was observed in three allografts (50%)in three patients, all of them were on treatment with cyclosporinand low-dose prednisone. Proteinuria appeared at 2, 5 and 19months after grafting. One patient experienced a spontaneousremission after 12 months and he is free from proteinuria andwith good renal function after 5 years. The remaining two patientspresented progressive renal function deterioration and returnedto haemodialysis 24 and 17 months after the appearance of proteinuria.In these patients increasing the immunosuppression did not produceany beneficial effect. One of those patients underwent a secondtransplant; recurrence of the membranous nephropathy has notbeen observed after 3 years of follow-up. CONCLUSIONS.: In this study three new cases of recurrence of membranous nephropathyare reported. One patient experienced a spontaneous remissionof proteinuria. Recurrence of membranous nephropathy in renalallograft was very high in our series. Its appearance was associatedwith poor prognosis of the graft in most patients, althoughspontaneous remission of proteinuria is possible.     

Bone disease after kidney transplantation.

Post-transplant renal osteopathy (ROP) remains a serious problem, which contributes to substantial long-term morbidity of the graft recipients. Bone loss is most pronounced during the first months after engraftment; concerning bone density development in long-term transplant recipients, controversial data exist. The clinical impact of ROP is a marked increase in fracture rate following kidney transplantation compared with both general population and patients on dialysis treatment. The following review will focus on post-transplant ROP and discuss its epidemiology, the clinical features, factors contributing to the pathogenesis of this complication, as well as the evaluation, prevention and treatment options available for kidney allograft recipients.     

Cardiac impact of the arteriovenous fistula after kidney transplantation: a case‐controlled,match‐paired study

In kidney transplant (KT) recipients, cardiac impact of the persistence of an asymptomatic arteriovenous fistula (AVF) for hemodialysis has not been fully elucidated. Seventy‐six patients (mean age: 49 years) without history of diabetes or cardiovascular disease underwent an echocardiography. Thirty‐eight had a functioning AVF and were match‐paired for age, gender and KT duration. Left ventricular mass index (LVMI) was significantly higher in patients with functioning AVF: 135.1 ± 30.3 vs. 112.4 ± 28 g/m² (P = 0.001). Exposure to AVF increased the risk of developing high LVH fourfold. Search for a dose‐effect of AVF flow revealed a trend towards increasing LVMI with higher flow: 142.6 ± 30 vs. 126.9 ± 23.9 g/m² (P = 0.084) (median flow of the population as cut‐off). Other significant changes were observed in left ventricular dimensions: greater end diastole‐ and systole diameters, both larger left and right atria, and left atrium diameter. Our study suggests that, in stable asymptomatic KT patients, functioning AVF has significant impact on cardiac mass, cardiac index and left ventricular dimensions. The effects on morbidity and mortality were to be investigated.     

Changes in left ventricular volume and predictors of cardiac events after endoventricular circular patch plasty

Objective: The aim of this study was to identify predictors of cardiac events after endoventricular circular patch plasty (Dor operation) by analyzing our experience with Dor operation. Methods: Thirty patients with left ventricular aneurysm and/or ischemic cardiomyopathy who underwent Dor operation were included in this study. Hemodynamic and clinical results were analyzed, and the predictors of cardiac events were examined. Results: Hospital mortality was 3.3%. Postoperative clinical status and left ventricular (LV) function in all survivors significantly improved. The survival rates at 1, 3, and 5 years after operation were 93%, 89% and 89%. The corresponding cardiac event-free rates were 75%, 67% and 49%. Pre- and postoperative LV function and volume did not differ significantly between patients with or without cardiac events. However, the proportion of reduced end-diastolic volume index (EDVI) (preoperative EDVI-postoperative EDVI) to preoperative EDVI was significantly higher in patients with cardiac events than in cardiac event-free patients. Postoperative LV volume re-increased in the cases with cardiac events during follow-up. Cox regression analysis confirmed that preoperative clinical premature ventricular contraction and end-systolic volume index (ESVI), postoperative EDVI, ESVL and ejection fraction were independent predictors of late cardiac events. There was a significant positive correlation between preoperative ESVI and postoperative EDVI. Conclusion: Though LV function significantly improved after Dor operation, LV reconstruction with excessive reduction can cause restarting LV remodeling and increasing mortality and morbidity. Therefore, LV reconstruction of appropriate sizes and shapes, considering the function of residual myocardium, has a significant effect on prognosis. It is highly reasonable to expect that preoperative ESVI can predict the optimal size of reconstructed left ventricle. Read at the Fifty-sixth Annual Meeting of the Japanese Association for Thoracic Surgery, Panel Discussion, Tokyo, November 19–21,2003.     

Surgical complications and renal function after kidney alone or simultaneous pancreas-kidney transplantation: a matched comparative study.

BACKGROUND: In selected type 1 diabetic (T1DM) patients with end-stage renal disease (ESRD), simultaneous pancreas-kidney transplantation (SPKT) offers higher long-term graft and patient survival, but also higher initial morbidity and mortality than cadaveric kidney transplantation alone (CKTA). The development of new immunosuppressive regimens and surgical approach has improved this initial outcome, but little is known about their effect on short-term renal function and surgical complications related to the renal graft. METHODS: We analysed retrospectively the short-term follow-up of 45 T1DM patients consecutively transplanted during 42 months (20 SPKT and 25 CKTA) in order to compare short-term (6 months) renal allograft function and surgical complications related to the renal allograft in both groups. RESULTS: There were no differences in donor characteristics. SPKT recipients had a significantly shorter time on dialysis and cold ischaemia time, with a higher number of HLA mismatches. There was no difference in acute rejection incidence, but delayed kidney graft function was less frequent in SPKT (5% vs 32%; P<0.05). Plasma creatinine level at discharge and 6 months was significantly lower in SPKT (1.1+/-0.3 vs 1.6+/-0.7; P<0.005 and 1.1+/-0.3 vs 1.5+/-0.6; P<0.05, respectively). There were no differences in surgical renal complications (haemorrhage, thrombosis or arterial stenosis, ureter leaks or stricture, lymphoceles or dehiscences). Two SPKT patients needed reintervention on the renal allograft and only one CKTA patient. CONCLUSIONS: In the modern transplant era, SPKT in ESRD diabetic patients, offers a slightly better short-term kidney allograft function without significant increase in surgical morbidity, compared with CKTA.     

Serum cholestasis markers as predictors of early outcome after liver transplantation

BACKGROUND: Early cholestasis is not uncommon after liver transplantation and usually signifies graft dysfunction. The aim of this study was to determine if serum synthetic and cholestatic parameters measured at various time points after transplantation can predict early patient outcome, and graft function. METHODS: The charts of 92 patients who underwent 95 liver transplantations at Rabin Medical Center between 1991 and 2000 were reviewed. Findings on liver function tests and levels of serum bilirubin, alkaline phosphatase (ALP), and gamma glutamyl transpeptidase (GGT) on days 2, 10, 30, and 90 after transplantation were measured in order to predict early (6 months) patient outcome (mortality and sepsis) and initial poor functioning graft. Pearson correlation, chi(2) test, and Student's t-test were performed for univariate analysis, and logistic regression for multivariate analysis. RESULTS: Univariate analysis. Serum bilirubin >/=10 mg/dL and international normalized ratio (INR) >1.6 on days 10, 30, and 90, and high serum ALP and low albumin levels on days 30 and 90 were risk factors for 6-month mortality; serum bilirubin >/=10 mg/dL on days 10, 30, and 90, high serum ALP, high GGT, and low serum albumin, on days 30 and 90, and INR >/=1.6 on day 10 were risk factors for sepsis; high serum alanine aminotransferase, INR >1.6, and bilirubin >/=10 mg/dL on days 2 and 10 were risk factors for poor graft function. The 6-month mortality rate was significantly higher in patients with serum bilirubin >/=10 mg/dL on day 10 than in patients with values of <10 mg/dL (29.4% vs. 4.0%, p = 0.004). Patients who had sepsis had high mean serum ALP levels on day 30 than patients who did not (364.5 +/- 229.9 U/L vs. 70.8 +/- 125.6 U/L, p = 0.005). Multivariate analysis. Significant predictors of 6-month mortality were serum bilirubin >/=10 mg/dL [odds ratio (OR) 9.05, 95% confidence intervals (CI) 1.6-49.6] and INR >1.6 (OR 9.11, CI 1.5-54.8) on day 10; significant predictors were high serum ALP level on day 30 (OR 1.005, 1.001-1.01) and high GGT level on day 90 (OR 1.005, CI 1.001-1.01). None of the variables were able to predict initial poor graft functioning. CONCLUSIONS: Several serum cholestasis markers may serve as predictors of early outcome of liver transplantation. The strongest correlation was found between serum bilirubin >/=10 mg/dL on day 10 and early death, sepsis, and poor graft function. Early intervention in patients found to be at high risk may ameliorate the high morbidity and mortality associated with early cholestasis.     

Diagnostic potential of circulating natriuretic peptides in chronic kidney disease.

BACKGROUND: Measurement of natriuretic peptides, particularly brain natriuretic peptide (BNP) is an established method for the diagnosis of cardiovascular disorders, chiefly left ventricular (LV) dysfunction. The influence of renal function on the diagnostic utility of natriuretic peptides is unclear. METHODS: We performed a cross-sectional study of 296 patients with renal disease but no history of cardiac disease using echocardiography to assess LV mass and function. Circulating levels of atrial natriuretic peptide (ANP) and BNP were also measured. RESULTS: The incidence of LV hypertrophy increased with progressive renal dysfunction; from 39% in patients with near-normal renal function, to 80% in renal transplant patients. There was a negative correlation between both ANP and BNP, and glomerular filtration rate (GFR) (ANP: r = -0.28, P<0.001; BNP: r = -0.40, P<0.001). Serum ANP and BNP had sensitivity and specificity for LV hypertrophy of 39.9%, 87.4% (ANP) and 61.4%, 67.6% (BNP) respectively. Sensitivity and specificity for LV dysfunction was 77.2%, 32.4% (ANP) and 71.8%, 40.0% (BNP). Significant confounders in determining serum ANP were haemoglobin, beta blockade and albumin, while serum BNP levels were significantly confounded by GFR, albumin, haemoglobin, beta blockade and age. CONCLUSIONS: Across a spectrum of renal dysfunction, GFR is a more important determinant of serum BNP than ventricular function, and several factors are predictors of natriuretic peptide levels. In chronic kidney disease, the use of natriuretic peptides to diagnose LV hypertrophy must be interpreted in light of these other factors. The use of these peptides in renal dysfunction to diagnose LV dysfunction may be of limited value.     

Predictors of new onset diabetes after renal transplantation

The development of new onset diabetes after transplantation (NODAT) is associated with increased cardiovascular morbidity and mortality. This study aimed at identifying risk factors for the development of NODAT. We performed a retrospective review of 787 renal transplants performed between 1994 and 2004 at a single centre. NODAT was diagnosed in patients who had two random plasma glucose concentrations >11.1 mmol/L after the first month post-transplant or patients who required treatment for hyperglycaemia within the first month and continued treatment thereafter. The incidence of NODAT was 7.7%. The incidence of NODAT requiring either insulin or oral hypoglycaemic agents was 4.5%. Risk factors for the development of NODAT were older age (HR 1.04, 95% CI: 1.01-1.07, p < 0.01), heavier weight at time of transplantation (HR 1.04, 95% CI: 1.02-1.07, p < 0.01), higher mean pre-transplant random plasma glucose concentrations (HR 1.54, 95% CI: 1.14-2.08, p < 0.01), higher plasma glucose within the first seven d post-transplant (HR 1.27, 95% CI: 1.09-1.47, p < 0.01) and use of tacrolimus (HR 3.70, 95% CI: 1.61-8.46, p < 0.01). Ten yr actuarial patient survival was 67.1% in patients with NODAT compared with 81.9% for those without diabetes and 65.3% in patients known to have diabetes pre-transplant. There was no difference in graft survival. We have identified a high-risk group in which attempts should be made to reduce the incidence of NODAT by tailoring immunosuppression, lifestyle modification and selecting non-diabetogenic medications. Improvements in management of patients at higher risk of NODAT may help reduce the incidence of deaths with a functioning graft.     

Improved renal function after kidney transplantation is associated with heme oxygenase-1 polymorphism

Heme oxygenase-1 (HO-1) has a microsatellite polymorphism based on the number of guanosine-thymidine nucleotide repeats (GT) repeats that regulates expression levels and could have an impact on organ survival post-injury. We correlated HO-1 polymorphism with renal graft function. The HO-1 gene was sequenced (N = 181), and the allelic repeats were divided into subclasses: short repeats (S) (<27 repeats) and long repeats (L) (>/=27 repeats). A total of 47.5% of the donors carried the S allele. The allograft function was statistically improved six months, two and three yr after transplantation in patients receiving kidneys from donors with an S allele. For the recipients carrying the S allele (50.3%), the allograft function was also better throughout the follow-up, but reached statistical significance only three yr after transplantation (p = 0.04). Considering only those patients who had chronic allograft nephropathy (CAN; 74 of 181), allograft function was also better in donors and in recipients carrying the S allele, two and three yr after transplantation (p = 0.03). Recipients of kidney transplantation from donors carrying the S allele presented better function even in the presence of CAN.     

Prolonged aPTT after kidney transplantation due to transient lupus anticoagulants.

BACKGROUND: After kidney transplantation, a renal biopsy may be needed to elucidate the reasons for lack of graft function. If the activated partial thromboplastin time (aPTT) is prolonged, the biopsy will often be postponed, as increased risk of bleeding must be expected. However, aPTT prolongation is not always due to lack of coagulation factors, but can be due to the presence of lupus anticoagulants (LAs). Clinical observations in our department indicated that a large proportion of recently kidney-transplanted patients developed prolonged aPTT values without clinical complications. METHODS: A prospective study of patients receiving a kidney transplant in 2004 was conducted to investigate the frequency and cause of prolongation of the aPTT. RESULTS: Twenty-seven patients were included in the study; none had prolonged aPTT or LAs before the transplantation. In the post-transplantation period, 19 patients (70.4%) had a significantly prolonged aPTT. Further investigation showed that for all 19 patients, prolongation was due to acquired antibodies: 13 had developed LAs and six had developed unspecific antibodies. The acquired antibodies were transient and did not affect clinical outcome. CONCLUSIONS: This is the first study investigating prolonged aPTT in the post-transplantation period. All patients with prolonged aPTT had acquired transient antibodies, i.e. LA or 'LA-like'. If a renal biopsy was requested, 70.4% of the transplanted patients would presumably have their biopsy postponed due to prolonged aPTT, but as LAs do not increase the risk of bleeding, such a delay would be unnecessary. Immediate LA investigation is therefore recommended if a recently transplanted patient requiring surgical procedures has a prolonged aPTT.     

Importance of renal mass on graft function outcome after 12 months of living donor kidney transplantation.

BACKGROUND: Few studies have directly measured the kidney weight and investigated donor parameters related to it. The aim of this study was to evaluate the kidney weight and its relationship to creatinine clearance (CrCl) after 12 months post-transplantation. METHODS: A total of 123 recipients of renal transplantation from living donors were evaluated. Demographic and anthropometric data from donors and recipients were collected in the pre-operative phase. Data about kidney weight were obtained through kidney measurement using an electronic weighing machine at the moment of transplantation. Glomerular filtration rate (GFR) was estimated through CrCl (modification of diet in renal disease formula) at the 1st, 6th, 12th and 18th month post-transplantation. RESULTS: The mean value of kidney weight was 170 +/- 31 g (166.4 +/- 29.2 g in women and 177.5 +/- 32.5 g in men). The kidney weight had a correlation with the donor's BMI (r = 0.43, P < 0.001) and with the CrCl on the 12th month (r = 0.31, P = 0.001). Using multiple linear regression, the kidney weight could be predicted through the BMI and donor's gender (R(2) = 0.21; P < 0.01). The CrCl after 12 months had a significant correlation with the graft weight/recipient weight ratio and with the donor age (R(2) = 0.22; P < 0.01). CONCLUSION: The kidney weight can be estimated using the donor's gender and BMI. The kidney weight significantly influences the CrCl 12 months after transplantation.     

Changes in endothelial function before and after renal transplantation*

Endothelial dysfunction is an early key event in the development of atherosclerotic cardiovascular disease observed in chronic renal failure patients. The role of renal transplantation (RTx) on endothelial dysfunction is still unclear. The aim of this study was to evaluate the endothelial function of chronic renal failure patients before RTx (while they were on hemodialysis, HD), and after RTx (at the 6th and 12th months) by a noninvasive method, brachial arterial ultrasound. A total of 22 (17 male, mean age: 33.9 +/- 11.6 years) RTx recipients were enrolled in the study. Endothelium-dependent vasodilation (EDD) was assessed by establishing reactive hyperemia. EDD prior to transplantation was significantly lower when compared with EDD measured at the 6th and 12th months after RTx (EDD pretransplantation: 6 +/- 3.7%, EDD at the 6th month of RTx: 8.3 +/- 2.3% and EDD at the 12th month of RTx: 12.1 +/- 3.6%, P < 0.001). When the EDD values measured at the 6th and 12th months of RTx were compared, measurements of the 12th month were found significantly higher than those of the 6th month (P < 0.001). Our results also showed that RTx has provided improvement in endothelial function by eliminating the uremic environment although not in the early post-RTx period.