Cadaveric Kidney Transplant Recipients Research Articles

Metabolic Risk Profile and Graft Function Deterioration 2 Years After Kidney Transplant

Studies exploring the association of body weight and metabolic status with graft function deterioration (GFD) after kidney transplantation have produced inconsistent findings. Few studies have examined whether metabolically healthy overweight or obesity (MHO) may contribute to GFD. To evaluate associations of overweight or obesity and metabolic disorders with GFD in recipients of kidney transplant. This multicenter retrospective cohort study was conducted from January 1, 2020, through June 30, 2021, with a follow-up period of 2 years after kidney transplantation. Participants included adult recipients of cadaveric kidney transplant in 4 transplantation centers in China. Participants were classified as 4 metabolic phenotypes according to their BMI and metabolic status. Data were analyzed from July to August 2023. Overweight and obesity were characterized by body mass index (BMI; calculated as weight in kilograms divided by height in meters squared) of 24 or greater. Metabolic disorder was identified by existence of a minimum of 2 of 4 conditions: hypertension, hyperglycemia, increased triglyceride, and decreased high-density lipoprotein cholesterol. The main outcome was GFD, defined as a decrease in estimated glomerular filtration rate of at least 25% within 6 months to 2 years after transplant. A total of 1260 adult recipients of cadaveric kidney transplant (mean [SD] age, 43.97 [11.51] years; 755 [59.92%] male) were included in the study, and 127 (10.08%) participants experienced the primary outcome of GFD during follow-up. After accounting for confounding factors in multivariable analyses, overweight or obesity (odds ratio [OR], 1.64; 95% CI, 1.10-2.44; P = .02) and metabolic disorder (OR, 1.71; 95% CI, 1.12-2.63; P = .01) were associated with increased risk of GFD. The MHO subgroup exhibited a greater risk for GFD (OR, 2.37; 95% CI, 1.01-5.57; P = .048) compared with participants who did not have overweight or obesity or metabolic disorder. All components of metabolic disorder, with the exception of elevated triglyceride, were associated with GFD. There was a dose-response association of number of metabolic disorder components (OR per 1 additional condition, 1.40; 95% CI, 1.20-1.63; P < .001) and BMI (OR per 1-unit increase, 1.90; 95% CI, 1.03-1.15; P = .002) with increased risk for GFD. A nonlinear association was observed between BMI and risk of GFD. In this cohort study of recipients of cadaveric kidney transplant, individuals with overweight or obesity or metabolic disorder had a significantly higher risk of experiencing GFD. Individuals with MHO had an elevated risk for graft function deterioration. Additional studies with larger sample size and longer follow-up are necessary to validate our findings.

Non-meningeal, non-pulmonary cryptococcosis with limited posterior uveitis in a kidney organ transplant recipient with antibody-mediated rejection: a case report

BackgroundCryptococcosis is one of the most frequent fungal eye infections in patients with immunosuppression. Currently, treatment approaches for non-meningeal, non-pulmonary cryptococcosis are based on those used for cryptococcal meningitis or pneumonia.Case presentationWe present a rare case of non-meningeal, non-pulmonary cryptococcosis with clinical manifestations limited to one eye of a cadaveric kidney transplant recipient with chronic-active antibody-mediated rejection. Typical manifestations, diagnosis, and treatments, including antifungal therapies, adjunctive therapies, and immunosuppression reduction, are discussed. After timely diagnosis and treatment, her visual acuity recovered to baseline without recurrence or sequelae of cryptococcosis.ConclusionsClinicians should be aware of rare presentations of fungal infections, especially when a kidney transplant recipient with rejection has been treated with intensive immunosuppressants. Early diagnosis with individualized therapies may have a favorable prognosis.

Effects of recipient education disparity on living donor kidney transplant outcomes across different ethnic groups: a retrospective study in the United States.

Previous studies have shown that education level is associated with the prognosis of cadaveric kidney transplant recipients. However, it is unclear whether education affects the prognosis of living kidney transplant (LDKT) recipients. In addition, it remains to be determined whether the uneven distribution of educational levels consistently affects the prognosis of LDKT recipients across ethnic groups (White, Black, Hispanic and Asian). After establishing inclusion and exclusion criteria, we conducted a retrospective study of LDKT recipients who received their first single LDKT between 2005 and 2020. The LDKT recipients were divided into lower- and higher-education groups according to categorize the educational level of recipients, and transplant outcomes, including graft survival, patient survival, and death-censored graft survival (DCGS), were analyzed and compared. Graft survival, DCGS and patient mortality were significantly better in the higher-education group compared with those in the lower-education group (P<0.001), with the risk of graft failure, death censored graft failure (DCGF) and patient mortality increasing by 11%, 15% and 7% in the lower-education group, respectively. Furthermore, compared with the higher-education group, the risk of graft failure in Black recipients increased by 18% [adjusted hazard ratio (aHR), 1.18; 95% confidence interval (CI): 1.07 to 1.30], and the risk of patient mortality among White recipients decreased by 7% (aHR, 0.93; 95% CI: 0.87 to 0.99). However, there were no significant differences in graft failure and patient mortality among Hispanic and Asian recipients, respectively. This study revealed that LDKT recipients with a higher education level had better transplant outcomes. However, these transplant outcome differences were mainly found in White and Black recipients. These data confirm the significant effect of different levels of education on the prognosis of LDKT recipients.

P8.123: A Retrospective Comparison of ABO Incompatible With ABO Compatible and Cadaveric Renal Transplant: Single Centre Experience

Introduction: ABO incompatibility was a major barrier in kidney transplantation. Advances in immunosuppressive therapy and desensitization protocol have made ABO incompatible transplants safe and effective. The present study is a retrospective comparison of ABO incompatible with ABO compatible and Cadaveric renal transplant in single centre. Method: The study includes 7 ABO incompatible, 14 similar age and HLA matched ABO compatible and 7 cadaveric kidney transplant recipients. All ABO incompatible recipients underwent desensitization with Rituximab and plasmapheresis with IVIg. Their outcomes at 6 months in terms of eGFR calculated by MDRD formula, incidence of rejection and infection as well as graft survival and patient survival were compared. Result: The outcome in terms of eGFR at 6 months was equivalent in ABO compatible (66.90ml/min/1.73m2) and ABO incompatible (60.42ml/min/m2) group and was significantly lower in the cadaveric group (45.32ml/min/m2). The incidence of infection at 6 months was equal in ABO incompatible (28.5%) and ABO compatible group (28.5%) and it was significantly higher in cadaveric transplant groups (42.85%). There was one incidence of acute rejection and one graft loss in cadaveric transplant group whereas no rejection and graft loss in ABO compatible and ABO incompatible transplant group. All three groups had 100% patient survival. Conclusion: The graft function, risk of infection and graft survival at 6 months in ABO incompatible transplant is non inferior to ABO compatible transplant and is superior to Cadaver transplant. ABO incompatible transplant also circumvents the waiting period on dialysis and mortality and morbidity associated with it.

Right renal vein lengthening with cava patch in cadaveric donor kidney transplantation: cohort study

Background: Right kidney transplant can become a surgical challenge, due to anatomical length disparity between the right and left veins. From 2011, lengthening of the right renal vein has been used in our program. The objective was to evaluate the outcome among kidney transplant recipients with or without the use of a cava patch, comparing safety, complications and patient / graft survival in both groups.Methods: Retrospective single center cohort study between 2011-2020 in a Kidney transplant program at Mexico.Results: 27 right cadaveric kidney transplant recipients were identified, 13 (48%) with and 14 (52%) without right renal vein lengthening (RRVL). Median overall operative time was 135 (120-157) minutes, with no significant difference between groups (p=0.181), even in overweight or obese recipients. Perioperative bleeding and postoperative drainage output was similar in both groups. There were two graft failures among recipients without RRVL one due to arterial bleeding and the other secondary to venous thrombosis. After one year of follow up, renal graft function and graft survival was similar in both groups.Conclusions: RRVL technique is safe and facilitates anastomoses in complex cases. Although no statistically significant difference in operative time was found between the groups, the RRVL technique in overweight / obese patients was thirty minutes faster. Routine use of this technique is suggested in cadaveric donor right kidney transplants.

Review of the waiting list for cadaveric kidney transplant Recipients: A Single institution study

Aim: The gold standard treatment of end-stage renal failure is kidney transplantation. In western countries, more than 80% of kidney transplants are cadaveric transplants, in Turkey, this ratio is below 25% due to insufficient cadaveric organ supply. In this study, we aimed to give a general assessment of cadaveric kidney transplant of patients on the waiting list of Istanbul University Medical Faculty General Surgery Organ Transplantation Unit.Material and Methods: Patients waiting for transplantation for a cadaveric kidney on National Organ Waiting List have been evaluated for demographic data, mean duration of dialysis, concomitant diseases, dialysis type, blood groups, end-stage renal failure etiologies, additional diseases that developed during kidney transplant waiting period, and their final status.Results: Two hundred and forty-four patients were included in the study. There were 122 female and 122 male. The median age was 52 (2-77) years. The most common etiology of renal failure was hypertensive nephrosclerosis. The median waiting time was 89 months (13-390). Though there was no difference between female and male patients according to median age, height and BMI, there was a significant difference according to waiting duration (F/M 113/75 months, p 0,017). In the last 1 year, 13 patients died while they were waiting for a kidney transplant and 17 patients lost their chance of kidney transplant due to developing diseases.Conclusion: To increase Turkey’s organ transplantation and cadaveric transplant donation on the waiting list we need to develop donation policy for a shorter period of dialysis and to ensure that patients receive transplantation earlier.Keywords: Dialysis period; kidney transplantation; cadaveric waiting list.

Successful Treatment of Strongyloides stercoralis Hyperinfection in a Kidney Transplant Recipient: Case Report

Strongyloides stercoralis (SS) can cause hyperinfection and disseminated infection in immunosuppressed individuals, with risk of mortality. We report the case of a cadaveric kidney transplant recipient who developed gastrointestinal symptoms and eosinophilia, approximately 3 months after transplantation. Stool examination and esophagogastroduodenoscopy with biopsies were positive for SS larvae. The patient was started on oral ivermectin and immunosuppression was reduced, but still the clinical picture got worse with metabolic ileus and respiratory symptoms, with the need for administration of subcutaneous ivermectin and combined therapy with albendazol. The patient survived and graft function was preserved. The patient was unlikely to be the source of infection. We also present a review of cases of SS infection in kidney transplant recipients.

Study of The Effects of N-Acetylcysteine on Oxidative Stress Status of Patients on Maintenance-Hemodialysis Undergoing Cadaveric Kidney Transplantation.

N-acetylcysteine (NAC) is a potent antioxidant that acts through regenerating glutathione stores and scavenging oxygen-free radicals. This study assesses the short-term effects of NAC in cadaveric kidney transplant (KT) recipients. A double blind, randomized, placebo controlled trial was designed and patients were randomly assigned to receive either NAC or placebo. Glutathione peroxidase (GPX) activity in erythrocytes and serum malondialdehyde (MDA) levels were measured and serum creatinine levels and estimated glomerular filtration rate (eGFR) determined in the early phase after transplantation, were also compared between two study groups. Thirty-seven males and 20 females, with mean ± SD age of 44.6 ± 12.4 years completed the study. Significant difference (P = 0.02) was seen between GPX activity reduction in the placebo group, and that of the NAC group and on the levels of MDA there was no significant difference between two study groups (P = 0.53). Significant improvement in immediate graft function (IGF), (68% versus 40%, P = 0.05) and the first week eGFR were observed in the NAC group compared to the placebo group (52.46 ± 2.77 versus 38.75 ± 19.67 mL/min/1.73 m2, P = 0.02). It seems that the protective mechanisms of NAC, other than its antioxidant properties, can be favorable in KT patients.

Early and Long-Term Outcomes of Kidney Grafts Procured From Multiple-Organ Donors and Kidney-Only Donors

BackgroundThe deceased-donor kidney pool consists of 2 different populations: multiple-organ donors (MOD) and kidney donors alone (KDA). In MOD, more complicated procedure and lowest priority for kidney procurement may affect graft survival. On the other hand, poor donor status and higher comorbidity are more frequent in KDA transplants. The aim of this study was to provide detailed characteristics of the 2 groups of kidney donors (KDA vs MOD) in our center and to analyze the potential influence of the donor type on the early and long-term kidney graft function and recipient outcome. MethodsWe performed a retrospective analysis of 729 first cadaveric kidney transplant recipients: 499 of them received the organ from MOD, 230 from KDA. ResultsThe frequency of delayed graft function (DGF) was higher in KDA than in MOD transplants (38.7 vs 25.1%; P < .001). Multivariate logistic regression analysis revealed that donor age, KDA, and early acute rejection independently increased the risk of DGF occurrence, whereas recipient age and cold ischemia time increased the risk of primary graft nonfunction. Kidney excretory function was significantly worse in KDA up to 10 years after transplantation. There were no differences in kidney graft and patient survivals, frequency of proteinuria, acute rejection, and cytomegalovirus episodes, and post-transplantation diabetes. Conclusions(1) The use of a kidney from KDA negatively affects early and late kidney graft function compared with MOD. (2) The long-term kidney graft and patient survivals are not affected by the type of organ procurement.

Urinary monocyte chemoattractant protein-1 levels and interstitial changes in the renal cortex and their relationship with loss of renal function in renal transplant patients with delayed graft function.

BackgroundInflammatory cell infiltration and residual areas of fibrosis in kidneys after renal transplantation can lead to functional abnormalities with long-term implications.ObjectivesThe aim of this study was to determine urinary monocyte chemoattractant protein-1 (uMCP-1) levels, relative cortical interstitial area (RCIA), and cortical tubulointerstitial macrophage infiltration in renal transplant patients with delayed graft function (DGF) and their possible correlation with graft outcome.DesignPatients were followed after biopsies for one year, and their renal function and structure were evaluated, as well as parameters of inflammatory process.SettingClinical Hospital of the School of Medicine of Ribeirão Preto.PatientsTwenty-two cadaveric kidney transplant recipients with DGF were followed for one year.MeasurementsRenal function, RCIA, macrophages infiltration and uMCP-1 levels were evaluated.MethodsRenal function was evaluated by plasma creatinine levels. RCIA was determined by morphometry. Immunohistochemical staining of macrophages was performed using an anti-CD68 monoclonal antibody. uMCP-1 levels were determined using a human MCP-1/CCL2 immunoassay kit.ResultsThere was a significant increase in uMCP-1 levels in transplant patients compared with controls (p < 0.001). RCIA was 7.1% (6.4 to 9.2; median and 25th to 75th percentiles) in controls and 37.1% (28.1 to 43.7) in patients with kidney transplants (p < 0.001). The patients who presented with a higher RCIA in the first biopsy showed higher levels of plasma creatinine one year after transplantation (r = 0.44; p < 0.05). The number of tubulointerstitial macrophages per 0.10 mm2 grid field was higher in the renal cortex of transplant patients compared with the controls (19.4 (9.0 to 47.1) vs. 2.5 (1.8 to 3.4), p < 0.001). There was also a positive correlation between the RCIA and the number of tubulointerstitial macrophages in the renal cortex of these patients (r = 0.49; p < 0.001).LimitationsThe number of patients studied was relatively small and may not be reflecting outcomes over a larger spectrum of kidney cadaveric transplants.ConclusionsOur results demonstrate increased levels of uMCP-1 in transplant patients with DGF, in addition to increased tubulointerstitial macrophage infiltration and RCIA, which could predict the outcome of renal function in these patients.

Ambulatory Blood Pressure Monitoring in Kidney Transplant Patients: RETENAL Study

Hypertension is common following renal transplantation, affecting up to 80% of transplant recipients. It is generally accepted that hypertension is associated with poor graft survival and reduced life expectancy, contributing to increased cardiovascular risk factors and mortality rates. The aim of the study was to compare the blood pressure (BP) control in kidney transplant patients through the use of ambulatory BP monitoring (ABMP) versus office BP measurements (oBP). A multicenter, cross-sectional, observational study was conducted in 30 nephrology/kidney transplant units. Eligible patients included hypertensive cadaveric kidney transplant recipients aged <70 years, with a functioning kidney for at least 1 year and with an estimated glomerular filtration ≥30 mL/min/1.73 m2 and a serum creatinine < 2.5 mg/dL. Recorded data included demographic characteristics, oBP, and ABPM and labroatory investigations. The 868 patients showed a mean recipient age of was 53.2 ± 11.6 years and mean follow-up after transplantation, 5.5 ± 2.8 years. Mean systolic and diastolic oBP were 140.2 ± 18 and 80.4 ± 10 mm Hg, respectively. Seventy-six percent of patients had oBP higher than or equal to 130/80 mm Hg. Mean 24 hour ABPM were 131.5 ± 14 and 77.4 ± 8.7 mm Hg for systolic and diastolic BP, respectively. Using the ABPM, we observed that 36.5% of subjects were controlled (mean 24-hour BP < 130/85 mm Hg). The two methods (oBP and ABPM) showed significant agreement. After ABPM, 65% of patients diagnosed as true controlled hypertension were considered to have white-coat RH. In clinical practice ABPM may help for better adjustment of drugs for adequate BP control.

Clinical study of single-dose of recombinant humanized anti-CD3 monoclonal antibody injection in kidney transplant recipients

To evaluate short-term and long-term safety of using single-dose escalation of recombinant humanized anti-CD3 monoclonal antibody (OKT3) in kidney transplantation recipients. A total of 29 recipients of cadaveric kidney transplant from June 2008 to December 2008 were sequently assigned to receive single-dose intravenous injection of OKT3 with different doses of 2.5 mg (n = 9), 5.0 mg (n = 10) and 10.0 mg (n = 10) at Days 7 - 14 post-operation. Meanwhile, a control group was established by selecting kidney transplant recipients, who did not participate in the trial in the same period. All patients were followed up for at least 2 years. During this period, liver function, kidney function, hemoglobin and other biochemical indicators were monitored and adverse events recorded over time. No obvious first dose effect was observed, except low heat (7/29), chills (4/29), mild liver damage (2/29), upper respiratory tract infection and headache (1/29) across all doses. Other adverse reactions were mild, unrelated with doses. The 2-year patients/grafts survival rates of treatment group and control group were 100%/100%, and 100%/97%, respectively. The incidence of acute rejection confirmed by renal biopsy was 6.9% (2/29) and 10.0% (3/30) in treatment group and control group, respectively. The incidence of lung infection was 10.3% (3/29) and 13.3% (4/30), respectively. The values of serum creatinine at 1 week and 3, 6, 12, 24 months showed no statistically significance in two groups (all P > 0.05). It is safe to use single-shot OKT3 intravenously in kidney transplant recipients. The recombinant humanized OKT3 may be an effective immunosuppressive agent with milder toxicity for solid organ transplantation.

Effect of long-term steroid withdrawal in renal transplant recipients: a retrospective cohort study

Background. Steroids are largely effective for the immunosuppressive treatment in renal transplant patients, but cause severe side effects. Whether steroid withdrawal confers long-term beneficial effects remains unclear.Methods. Data on 4481 cadaveric kidney transplant recipients were collected to estimate the impact of steroid withdrawal on kidney function and graft and patient survival using multivariate Cox regression models.Results. A total of 923 patients (20.6%) had steroid treatment withdrawn. This was more common in recipients from younger donors and in older recipients, and in recipients with a first transplant, those who had pre-transplant or de novo diabetes mellitus and those with fewer episodes of acute rejection (AR) (22.4% vs. 29.2%, P < 0.001). Cox multivariate analysis stratifying by propensity scores showed that long-term steroid therapy was associated with a 70% increase in the risk of patient death. The repeated measures linear model showed that, although the abbreviated Modification of Diet in Renal Disease (aMDRD) values changed over time (P = 0.002), this was independent of steroid withdrawal (P = 0.08). In addition, of the 772 (17.2%) recipients who developed de novo diabetes mellitus, 204 (26.4%) ceased antidiabetic therapy, with more of these among those who ceased steroids (23% vs. 33.3%, P = 0.003). Blood pressure, cholesterol and triglyceride values were all significantly lower in the patients who ceased steroids.Conclusions. Steroid withdrawal in selected patients had no negative effect over time on renal function and graft survival, and it was associated with reduced mortality.

Corticosteroid avoidance in adult kidney transplant recipients under rabbit anti-T-lymphocyte globulin, mycophenolate mofetil and delayed cyclosporine microemulsion introduction

We conducted the first prospective, randomized, open-label multicenter study in low-immunologic risk adult recipients of primary cadaver kidney transplants receiving rabbit anti-T-lymphocyte globulin, mycophenolate mofetil, cyclosporine microemulsion introduced on day 5, with and without corticosteroids. Patients were randomly assigned according to age and cold ischemia time to receive corticosteroids for at least 6 months or no corticosteroids at all. The main efficacy evaluation criterion was acute rejection (including all treated episodes and those biopsy-confirmed) during the first year following transplantation. For this purpose, this report includes the actual results of the whole 12-month follow-up of all randomized patients. For efficacy analysis, 98 patients were evaluated in the Steroid avoidance group and 99 in the Steroid maintenance group. Taken as a whole, 81% of the patients (n = 159) never received anti-rejection treatment. From the 38 patients who received anti-rejection treatment, 25 (25.5%) were in the Steroid avoidance group and 13 (13.1%) in the Steroid maintenance group (P < 0.031), experiencing respectively 17 (17.3%) and 7 (7.1%) biopsy-proven first episodes of acute rejection (P < 0.031). Borderline changes (6 vs. 3) were not considered as biopsy-proven acute rejections. Onset of first rejection was significantly shorter in the Steroid avoidance group (P < 0.027). First-line anti-rejection treatment response, need for any rescue therapy, as well as histologic severity of rejection episodes did not statistically differ between the groups. One-year post-transplantation analysis showed no differences in delayed graft function, serum creatinine, creatinine clearance, 24-h proteinuria, as well as serious adverse events between the groups. De novo diabetes (P < 0.07) or dyslipidemia (P < 0.01) as well as newly diagnosed malignancies (P < 0.059) were however more frequently observed in the Steroid maintenance group. At the end of the first post-transplant year, 99% of patients in the Steroid avoidance group and 97% of patients in the Steroid maintenance group were respectively alive (P = 0.34), with respectively 95% and 93.2% of functioning kidney grafts (P = 0.62). Our results showed that total avoidance of corticosteroids from the day of transplantation was associated with a significantly increased number of clinically diagnosed and treated, and biopsy-proven acute rejections during the first year of transplantation. Nevertheless, overall outcome, 1-year patient and graft survival as well as renal function were similar, and the patients in the Steroid avoidance group exhibited a lower incidence of de novo dyslipidemia, diabetes mellitus and malignancies often associated with steroid treatment.

Direct Downregulation of Toll-Like Receptors by Anti-IL-2 Alpha Chain-Receptor Antibody in Cadaver Kidney Transplant Recipients

Direct Downregulation of Toll-Like Receptors by Anti-IL-2 Alpha Chain-Receptor Antibody in Cadaver Kidney Transplant Recipients

Subclinical peritubular capillaritis in serial graft biopsies in cadaveric kidney transplant recipient with pre‐transplant anti‐HLA antibodies

National Fukuoka-Higashi Medical Center, Koga, Japan A 63-yr-old Japanese woman on 18-yr hemodialysis (HD) program underwent cadaveric kidney transplantation from non-heart beating donor. Pre-transplant lymphocytotoxicity test was negative, but flow cytometric cross-match and flow-cytometric panel reactive antibody (PRA) screening tests were positive. Flow-PRA single-antigen test revealed several anti-HLA antibodies including donor-specific antibody (DSA). She was treated with plasma exchange (PEX) and rituximab to prevent antibody-mediated rejection (AMR). Urinary output increased from post-operative day (POD) 5 and HD was discontinued from POD8. Graft biopsy performed on POD11 showed severe peritubular capillaritis (PTCitis), numerous polymorphonuclear neutrophils (PMNs), and moderate glomerulitis. Although C4d immunostaining on PTC was negative, the case was diagnosed as subclinical AMR based on the presence of pre-transplant DSA and PTCitis with predominant PMNs. The patient was treated with additional PEX and rituximab, which increased urinary output and reduced serum creatinine (sCr). Graft biopsy repeated on POD39 showed persistent severe PTCitis, moderate interstitial infiltration, and mild tubulitis. C4d on PTC was negative again. The patient was discharged from the hospital on POD40. During the seven months follow-up at the outpatient clinic, the sCr level has shown a slight increase. In this case, the patient had DSA, which can be detected only by flow-PRA. In both graft biopsies, C4d on PTC was negative despite the presence of severe PTCitis, and thus the diagnosis of AMR could not be established. However, the significance of subclinical PTCitis is reported perhaps as an early marker for chronic AMR and to emphasize the importance of close follow-up.

Calcineurin Inhibitor-Free Immunosuppressive Strategy in Elderly Recipients of Renal Allografts From Deceased Donors: 1-Year Results From a Prospective Single Center Trial

Recently published data from our center have demonstrated the feasibility of a nephrotoxicity- and atherogenicity-free, mycophenolate mofetil (MMF)-based immunosuppressive protocol for elderly recipients of kidneys from elderly cadaveric donors. We investigated a therapeutic regimen of strictly monitored MMF (target mycophenolic acid [MPA] trough levels between 2-6 microg/mL) and steroids combined with a polyclonal-monoclonal induction regimen consisting of a low-dose, single shot of rabbit ATG (ATG-Fresenius) and the interleukin-2 receptor (IL-2R)-antibody basiliximab (d0 and d4). Between 1997 and 2007, we treated 175 elderly patients with an MMF-based, calcinearin inhibitor (CNI)-free immunosuppressive protocol. For the present cohort, 30 elderly recipients (67.8 +/- 3.8 years) of renal transplants from deceased donors (69.4 +/- 13.3 years) were recruited consecutively for this 5-year prospective, open, single center, pilot trial. One-year results of this clinical trial were patient and renal allograft survivals of 87% and 83%, respectively; death-censored 1-year graft survival was 97%. Mostly steroid-sensitive rejection episodes were observed in 46% of patients, with only 3 patients requiring serum antibody therapy. Renal allograft function was satisfactory, as reflected by a mean serum creatinine of 1.78 +/- 0.45 mg/dL and a Nankivell glomerular filtration rate (GFR) of 48.8 +/- 13.9 mg/dL at 6 months. Twenty-three percent of all patients demonstrated cytomegalovirus (CMV) infections; however, only 3.3% developed CMV disease. Application of a combined polyclonal-monoclonal induction regimen using a nephrotoxicity- and atherogenicity-free, MMF-based immunosuppressive maintenance protocol in elderly cadaveric kidney transplant recipients led to acceptable short-term outcomes, albeit at the expense of an increased rejection rate, comparable to that previously published for elderly (>50 years) recipients of allografts from elderly (>50 years) cadaveric donors.

Bimodal Distribution of Major Cardiovascular Events in Kidney Allograft Recipients

Cardiovascular disease (CVD) is the major cause of death after renal transplantation. We have retrospectively analyzed the incidence and the time of appearance of CVD among 870 consecutive cadaveric kidney transplant recipients, including 143 patients (16.5%) who experienced a fatal or nonfatal event after transplantation. Seventy-four recipients (54%) showed a fatal CVD. Studying the various manifestations, we observed a higher frequency of cardiac events (59% of ischemic heart disease), with 15% cerebrovascular disease and 22% peripheral vascular or aortic disease. In our group, CVDs were distributed in a bimodal manner, with a higher incidence in the first posttransplantation year and a late cluster of CVD at 8 years posttransplantation. The risk of death (hazard function) for CVD increased dramatically during the 8th year after transplantation. This trend of CVD after kidney transplantation may be explained by inadequate evaluation and management of CVD risk factors during waiting list time and, after transplantation, by the cumulative effects of traditional and nontraditional risk factors.

Different Effect of Cyclosporine and Tacrolimus on Renal Expression of P-Glycoprotein in Human Kidney Transplantation

Objective To investigate the differential effects of cyclosporine (CsA) and tacrolimus (TAC) on renal expression of P-glycoprotein (P-gp) in a cohort of kidney transplant recipients. Methods We enrolled 78 cadaveric kidney transplant recipients recuring basal immunosuppressive protocol with prednisone + mycophenolate mofetil + calcineurin inhibitor (CsA or TAC). Results We performed a 3-year analysis of 60 patients. There was no difference in age, gender, or cold ischemic time between two groups, Serum creatinine, urine protein, and blood fat levels of the CsA group were significantly higher than the TAC group ( P < .05), while the creatinine clearance was remarkably lower than the TAC group ( P < .05). The incidence of tubular atrophy, arteriohyalinosis, and interstitial fibrosis and nephrotoxic lesions among the CsA group were higher than the TAC group, as well as the chronic allograft nephropathy (CAN) Banff score ( P < .05). ® P-gp was predominantly present in the a tubular apical membrane, basal membrane, and cytoplasm. The intensity and extent of tubular staining score in the CsA group were lower compared with the TAC group ( P < .01 and P < .05, respectively). Conclusion Less P-gp expression in the CsA group than the TAC group may be the molecular action pathway of the high incidence of CsA nephrotoxicity and CsA-induced CAN. This study perhaps unraveled a novel interpretation that the differences of CsA and TAC on long-term allograft survival were due to increases dynamic effects of CsA at the exposures employed in this study.

Association Between Serum Soluble CD30 and Serum Creatinine Before and After Renal Transplantation

Objective There is increasing evidence that circulating levels of soluble CD30 (sCD30) may represent a biomarker for outcome in kidney transplantation. The aim of this study was to measure the pre- and posttransplantation serum levels of sCD30 in cadaveric kidney transplant recipients and correlate them with serum creatinine. Patients and Methods Serum sCD30 was measured by a commercial enzyme-linked immunosorbent assay (ELISA) from prospective samples of 38 kidney allograft recipients serially transplanted at our center. Samples were collected at day 0 pretransplantation and at months 6, 12, 18, and 24 posttransplantation. We also studied sera from 29 patients with chronic kidney disease (CKD) at different stages of the K/DOQI guidelines, as a control group. Results Serum levels of sCD30 decreased significantly in samples posttransplantation compared with pretransplantation. The significant decrease after transplantation may be related to the improvement in renal function since we observed a significant correlation between serum levels of sCD30 and creatinine (sCr) at all times of the study. In addition, the patients with chronic renal failure showed a significant association between serum sCD30 and sCr ( r = .454; P = .013). Conclusions Our results did not suggest that the measurement of sCD30 may be used as a valuable biomarker in renal transplantation. Increased levels may be related to a decrease in its renal elimination.