Early Acute Rejection Episodes Research Articles

Study of the effect of early and late acute rejection episodes on renal graft survival

Background It has been demonstrated that acute rejection (AR) episodes are major risk factors of renal allograft loss. Still the impact of early acute rejection (EAR) on long-term graft survival is debated. The aim of this study was to study the impact of early acute rejection (EAR) and late acute rejection (LAR) on renal allograft survival. Patients and methods In this retrospective study we investigated the timing and frequency of AR episodes in 120 kidney transplant recipients for a 3-years period. Patients were divided into three groups; Group I: No acute rejection (No-AR), Group II: Early acute rejection (EAR), and Group III: Late acute rejection (LAR). The graft survivals in the three groups and the associated risk factors were analyzed. Results Of the 120 recipients one patient died (0.08%) and 14 grafts were lost (11.6%). The graft survival durations were 35.2, 23.6 and 27.2 months and the 3-years survival rates were 93%, 63.3% and 66.7% in the three groups respectively. The graft survival durations and rates were significantly higher in group I compared to groups II and III with no significant differences between the last two groups. Conclusion Both EAR and LAR have deleterious effects on graft survival following kidney transplantation.

Extracellular Vesicles as a Novel Therapeutic Option in Liver Transplantation.

Longterm liver graft dysfunction and immunological rejection remain common adverse events, in part due to early acute rejection episodes initiated by ischemia/reperfusion injury (IRI) immediately following transplantation. Novel treatment methods are therefore required to ameliorate liver IRI and to promote longterm allograft acceptance. Extracellular vesicles (EVs) derived from tolerogenic phenotype cells may serve as a novel therapeutic option in liver transplantation due to their immunomodulatory and proregenerative effects. Studies of hepatic IRI along with animal liver allograft models have demonstrated that EVs isolated from mesenchymal stem/stromal cells, immature dendritic cells, and hepatocytes can reduce graft injury through mechanisms including enhancement of mitochondrial autophagy, inhibition of immune response, and promotion of tissue regeneration. These preclinical models may soon move translationally into clinical practice, necessitating the generation of robust methods to generate clinical-grade EVs. These methods must address issues of reproducibility and ability to scale up the tolerogenic cell cultivation, EV isolation, and EV characterization. Once generated, the efficient delivery of EVs to the donor organ prior to transplantation remains an issue that could be resolved through the novel organ storage method ex vivo machine perfusion (EVMP). In this review, we summarize studies that have used tolerogenic cell-derived EVs to ameliorate hepatic IRI and promote liver allograft acceptance, discuss the steps toward generation of clinical-grade EVs, and introduce EVMP as a novel method to efficiently deliver EVs.

The Pre-Transplant Drop in Panel-Reactive Antibodies Titer Evaluated Using Complement-Dependent Cytotoxicity (PRA-CDC) and the Risk of Early Acute Rejection in Sensitized Kidney Transplant Recipients.

Background: The panel-reactive antibodies that use the complement-dependent cytotoxicity test (PRA-CDC) are still a standard method for monitoring the degree of immunization in kidney transplant candidates on active waiting lists in some countries, including Poland. The aim of this study was to analyze the relationship between the maximum and the last pre-transplant PRA titer on the percentage of positive cross-matches and rate of early acute rejection episodes. Material and methods: The retrospective analysis included 528 patients from two transplant centers. All patients were divided into three groups, depending on their peak and last pre-transplant PRA titers. There were 437 (82.8%) patients with peak PRA <20% (non-sensitized group, non-ST) and 91 (17.2%) patients with peak PRA >20%. Among the latter group, 38 had maintained PRA level >20% at the time of transplantation (sensitized patients, ST), whereas 53 had pre-transplant PRA ≤20% (previously sensitized patients, prev-ST). Results: The percentages of positive crossmatches were 76.9% in ST and 53.7% in prev-ST groups versus 18.4 in non-ST group (both p < 0.001). The acute rejection rates were 18.9, 17.6 and 6.8%, respectively (p < 0.001 for ST or prev-ST versus non-ST). The pre-transplant PRA titer drop did not decrease the risk of early acute rejection [OR = 1.09 (95% CI: 0.31–3.85)] in a multiple logistic regression analysis. The occurrences of primary graft non-function and delayed graft function were similar in all study groups. Conclusions: Previously immunized kidney transplant candidates even with substantial decrease in pre-transplant PRA-CDC levels are still at high immunological risk when compared with non-immunized patients, and they should receive lymphocyte-depleting induction therapy.

Relationship Between Individual Components of the Extended-Criteria Donor Definition and the First Post-transplant Kidney Graft Resistance Index, Measured by Doppler Sonography

BackgroundDespite an increasing utilization of kidneys procured from expanded-criteria donors, little is known about the effects of particular expanded-criteria donors definition components, that is, hypertension, increased creatinine prior to procurement, and cerebrovascular cause of death on the kidney graft Doppler parameters measured shortly after transplantation, whose increased values are associated with unfavorable outcomes. Hence, we analyzed the relationship between expanded-criteria donors components and resistance index values measured within 2 to 3 days post-transplant. Material and MethodsThe initial post-transplant resistance index value was measured in 676 consecutive successful first cadaveric kidney graft recipients without delayed graft function or early acute rejection episode. We analyzed resistance index values in 460 patients transplanted with organs from donors <50 years and in 216 recipients with organs from donors >50 years old. ResultsIn general, expanded-criteria donors status did not influence the initial resistance index values in the whole study group. Unexpectedly, in older donor groups, both the occurrence of donor hypertension and cerebrovascular cause of death resulted in significantly lower resistance index values in kidney graft recipients (0.73 ± 0.10 vs 0.76 ± 0.11 in the non-hypertension group, P = .013 and 0.74 ± 0.11 vs 0.78 ± 0.10 in the non-cerebrovascular cause of death group, P = .015, respectively). In the Cox proportional regression model for graft survival, cerebrovascular cause of death was increasing the risk of graft loss by 55%, while recipient's age had the opposite effect, decreasing the risk of graft loss by 2% per year. ConclusionsRegardless of the limited influence of expanded-criteria donor status on first post-transplant resistance index value, the long-term observation shows moderate but significantly worse kidney graft survival, mostly as a result of the cerebrovascular cause of donor's death.

Total Recall: Can We Reshape T Cell Memory by Lymphoablation?

Despite recent advances in immunosuppression, donor-reactive memory T cells remain a serious threat to successful organ transplantation. To alleviate damaging effects of preexisting immunologic memory, lymphoablative induction therapies are used as part of standard care in sensitized recipients. However, accumulating evidence suggests that memory T cells have advantages over their naive counterparts in surviving depletion and expanding under lymphopenic conditions. This may at least partially explain the inability of existing lymphoablative strategies to improve long-term allograft outcome in sensitized recipients, despite the well-documented decrease in the frequency of early acute rejection episodes. This minireview summarizes the insights gained from both experimental and clinical transplantation as to the effects of existing lymphoablative strategies on memory T cells and discusses the latest research developments aimed at improving the efficacy and safety of lymphoablation.

Patterns of Early Rejection in Renal Retransplantation: A Single-Center Experience.

It has been reported that kidney retransplant patients had high rates of early acute rejection due to previous sensitization. In addition to the acute antibody-mediated rejection (ABMR) that has received widespread attention, the early acute T-cell-mediated rejection (TCMR) may be another important issue in renal retransplantation. In the current single-center retrospective study, we included 33 retransplant patients and 90 first transplant patients with similar protocols of induction and maintenance therapy. Analysis focused particularly on the incidence and patterns of early acute rejection episodes, as well as one-year graft and patient survival. Excellent short-term clinical outcomes were obtained in both groups, with one-year graft and patient survival rates of 93.9%/100% in the retransplant group and 92.2%/95.6% in the first transplant group. Impressively, with our strict immunological selection and desensitization criteria, the retransplant patients had a very low incidence of early acute ABMR (6.1%), which was similar to that in the first transplant patients (4.4%). However, a much higher rate of early acute TCMR was observed in the retransplant group than in the first transplant group (30.3% versus 5.6%, P < 0.001). Acute TCMR that develops early after retransplantation should be monitored in order to obtain better transplant outcomes.

Renal transplant: Tacrolimus use and two weeks post-transplant serum creatinine levels predict early acute rejections

AimImproved results have made renal transplantation the favored option for treating patients with end stage renal disease. Although the risk of allograft rejection still remains a major concern for short- and long-term grafts survival, serum creatinine is the most successful biomarker to predict acute renal rejection. MethodsPresent analysis was carried out to assess the extent of additional risk of acute renal rejection with elevated baseline serum creatinine. Data were observed from December 2009 to April 2013 on various factors on 307 patients, who underwent renal transplant at Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPGIMS, Lucknow). Follow-up data of 90 days post-transplant were analyzed. Cox Proportional Hazards model was applied to identify the determinants of graft rejection. Survival curves for various contributing factors were obtained. ResultsPatients treated with cyclosporine were 3.83 times more prone to have acute rejection at 3 months than those treated with tacrolimus. Compared to those with creatinine <1.10mg/dl, hazards of acute rejection at 3 months were similar in those with creatinine between 1.10 and 1.50mg/dl (HR=1.73), while 16.01 times higher in those with creatinine ≥1.50mg/dl. ConclusionsRenal transplant cases with elevated creatinine at two weeks post-transplant and those on cyclosporine-based immunosuppression are at higher risk of acute rejection and would require more frequent follow-ups and monitoring to diagnose early acute rejection episodes.

IL-17 Producing CD4+ Cells Infiltrate the Graft During Early Rejection Episodes.

IL-17 is regarded as a major effector cytokine with pro-inflammatory actions in autoimmune diseases. IL-17 has pleiotropic and environmental specific functions by promoting adaptive cytotoxic T-lymphocyte responses during inflammation. Therefore, it is tempting to speculate that IL-17 is important in inflammatory responses seen after organ transplantation. We determined IL-17 mRNA expression in the transplanted heart during early and late acute rejection episodes, and during immunological quiescence. Additionally, we analysed whether IL-17 is derived from graft-infiltrating lymphocytes. Endomyocardial biopsies (EMBs: n=41) from heart transplant recipients (n=29) who experienced an early (≤3 months) or late (>3 months) acute rejection episode or during an immunological quiescence period, were analysed for the presence of IL-17 mRNA. IL-17 production determined by flowcytometry was analysed in cultures of graft-infiltrating lymphocytes (GILs) derived from acute rejection (n=5) and non-rejection (n=5) EMBs stimulated with PMA and ionomycine. Twenty-two percent (9/41) of EMBs were positive for IL-17 mRNA. All (9/26) were observed in the early period after transplantation, while none (0/15) of the late biopsies expressed IL-17 mRNA (p=0.02). During early acute rejection, 56% (5/9) of the EMBs did express IL-17 mRNA, while EMBs from late acute rejections (0/5) did not express IL-17 mRNA (p=0.09). Only CD4+ cells from GIL cultures produced IL-17. In 60% of GIL cultures from acute rejection EMBs a significant proportion of CD4+ cells produced IL-17, while only one GIL culture from non-rejection EMBs contained CD4+IL-17+ cells. All CD4+IL-17+ cells expressed CD161, a cell surface expression marker of Th17 cells. CD8+ cells did not produce IL-17 neither expressed CD161. In conclusion, particularly early after heart transplantation IL-17 producing CD4+ T-cells home to the graft contributing to the acute rejection process.

Unexpected Colonic Perforation in a Renal Recipient. A Case Report

Gastrointestinal complications such as gastrointestinal bleeding and perforation due to immunosuppressant use are seen more frequently after solid organ transplantation. A 52-year-old male was admitted on the 7th day of a living donor renal transplantation with serous drainage at the incision site. He had no abdominal complaints. He was on triple immunosuppressant therapy. Abdominal plain X-ray and ultrasonography were normal, but diffuse extraluminal air was detected on the computed tomography scan. There were no pathological laboratory findings regarding the function of the renal allograft. We began the operation laparoscopically and then converted to laparotomy. Sigmoid colonic perforation was detected on the antimesenteric side. Neither diverticulitis nor ischemia was observed, and no evidence of iatrogenic injury was seen. There was no transrectal instrumentation history. Omentoplasty and sigmoid loop colostomy were performed. He was discharged on the 9th day following the operation. His colostomy was closed one year after the operation. Gastrointestinal complications can be fatal, but do not seem to influence the long-term survival or renal allograft function. Most of them are seen after using high doses of immunosuppressants to manage the early postoperative period or episodes of acute rejection. Early diagnosis and aggressive treatment play an important role in survival.

Use of Expanded Criteria Donors Gives Significantly Poorer Long-Term Graft Survival

Introduction: The use of expanded criteria donor (ECD) kidneys remains controversial as various groups have reported conflicting outcomes in terms of long-term graft outcomes. It is however well-known that ECD kidneys afford shorter graft survival as compared to kidneys from a standard criteria donor (SCD). In Singapore, patients with end stage renal failure (ESRF) must meet strict medical criteria before they are allowed to be placed on the National Transplant Registry to await a deceased donor kidney, including the absence of clinically overt cardiovascular and cerebrovascular disease. The aim of this study was to determine if there is a difference in long-term graft survival between recipients of SCD and ECD kidneys. Methods: A retrospective review was conducted on all deceased donor renal transplants (DDRT) performed at the Singapore General Hospital from 1st January 2000 to 31 December 2010. Results: During this period, 272 adults underwent a DDRT, with 226 (58.7%) receiving an SCD kidney (Group 1), and 46 (12.0%) receiving an ECD kidney (Group 2). The etiology of ESRF was predominantly chronic glomerulonephritis in both groups (83.1% Group 1 vs 73.9% Group 2, p = 0.75). The mean dialysis duration pretransplant was similar in both groups (45.3+8.7 vs. 46.7+9.0 months in Groups 1 and 2 respectively, p=0.28). While an increased incidence of early acute rejection (a rejection episode within 3 months post-transplant), and delayed graft function (a need for dialysis within a week post-transplant), are risk factors for decreased long-term graft function, the incidence of both events was similar in both groups (10.2% vs. 19.6%, p=0.07, and 42.5% vs. 54.4%, p=0.14, in Groups 1 and 2 respectively). Graft survival at 1 year was similar in both groups (96.0% Group 1 and 91.3% Group 2), but at 5 years there was a clear difference in graft survival (97.1% Group 1 and 68.4% Group 2). The 10-year graft survival was significantly reduced in recipients of ECD kidneys (p< 0.001) (Figure 1). Long term graft survival as described by half-lives was less than 6 years for ECD grafts and more than 10years for SCD grafts.[Figure 1]Conclusion: Patients receiving ECD kidneys, regardless of whether they have experienced an early acute rejection episode or delayed graft function, have a significantly reduced long-term graft survival. This is despite being in similar health as SCD recipients, with the absence of clinically overt cardiovascular and cerebrovascular disease pre-transplant. The use of ECD kidneys should be considered only in selected recipients.

The Impact of Early Corticosteroid Withdrawal on Graft Survival in Liver Transplant Recipients

BackgroundThere has been increased interest in recent years in reducing or eliminating steroids from the immunosuppression regimen of transplant recipients to reduce adverse effects associated with their use. The purpose of this study was to compare clinical outcomes between early versus late steroid withdrawal after liver transplant to determine the optimal duration of steroid use in this population. MethodsThis large-scale, retrospective analysis of liver transplants occurred at our institution between 2000 and 2009. Patients were excluded if they were <18 years old, received a multiorgan transplant, or remained on steroids for >1 year. The early steroid withdrawal group had steroids eliminated by 3 months posttransplant; late steroid withdrawal patients had steroids withdrawn between 3 and 12 months posttransplant. ResultsA total of 586 liver transplants occurred during the study period; 330 patients were included in the analysis. Graft survival was significantly lower in the early steroid withdrawal group. There was no difference in patient survival or overall acute rejection. However, the late steroid withdrawal group had a significantly higher rate of early acute rejection episodes. There was no difference with regard to new-onset diabetes after transplant, hyperlipidemia, or cardiovascular events between groups. ConclusionThe results of this study suggest that late corticosteroid withdrawal is associated with better long-term graft survival without increasing the rates of diabetes, hyperlipidemia, or cardiovascular events in liver transplant recipients. A prospective study is warranted to confirm these findings.

Infrared Fluorescence Imaging of Lymphatic Regeneration in Nonhuman Primate Facial Vascularized Composite Allografts

Clinical vascularized composite allografts (VCA), although performed with good success, have been characterized by rejection episodes and postoperative graft edema. We investigated lymphatic donor-recipient reconstitution and lymphatic regeneration in a nonhuman primate facial VCA model. Heterotopic partial face (n = 9) VCAs were performed in cynomolgus macaques. Grafts were monitored for rejection episodes and response to immunosuppressive therapies as previously described. Donor and recipient lymphatic channels were evaluated using a near-infrared handheld dual-channel light-emitting diode camera system capable of detecting fluorescence from indocyanine green injections. Graft lymphatic channels were serially evaluated from postoperative day 0 to 364. Preoperative imaging demonstrated superficial lymphatic anatomy similar to human anatomy. Initial resolution of facial allograft swelling coincided with superficial donor-recipient lymphatic channel reconstitution. Reconstitution occurred despite early acute rejection episodes in 2 animals. However, lymphatic channels demonstrated persistent functional and anatomic pathology, and graft edema never fully resolved. No differences in lymphatic channels were noted between grafts that developed transplant vasculopathy (n = 3) and those that did not (n = 6). Dynamic changes in patterns of lymphatic drainage were noted in 4 animals following withdrawal of immunosuppression. Donor-recipient lymphatic channel regeneration following VCA did not result in resolution of edema. Technical causes of graft edema may be overcome with alternative surgical techniques, allowing for direct investigation of the immunologic relationship between VCA graft edema and rejection responses. Mechanisms and timing of dynamic donor-recipient lymphatic channel relationships can be evaluated using fluorescent imaging systems to better define the immunologic role of lymphatic channels in VCA engraftment and rejection responses, which may have direct clinical implications.

Delayed graft function, allograft and patient srvival in kidney transplantation.

Delayed Graft Function (DGF) is a common complication of renal transplants and the long-term relation between DGF and survival of patients and grafts is not well established. This is a historical cohort study of transplanted patients in Taleghani Hospital of Shahid Beheshti University in Iran between 1994 and 2010. Patients who required dialysis during the first week after transplantation were considered to have DGF. The patients' conditions were updated to determine existing graft function, graft loss or patients' death at one year and five years post transplantation in relation to the presence or absence of DGF. DGF complicated 67/385 transplants (17.4%). Causes included acute tubular necrosis (58.2%), accelerated rejection (29.9%), transplant renal artery thrombosis (9%) and renal vein thrombosis (3%). More kidneys in the DGF group were procured from cadaveric donors (6% versus 0.9%, P = 0.02). At hospital discharge, patients with DGF had significantly higher mean creatinine level (4.4 ± 2.8 versus 2.0 ± 1.7; P = 0.001) compared to other patients. They also had more early acute rejection episodes and more late acute rejection episodes (34.3% versus 2% and 16.4% versus 3%, respectively; P = 0.0001) compared to other patients. The proportion of functioning grafts was significantly lower in the DGF group at 1-year (53.7% versus 95.3%, P = 0.0001) and 5-years (22.4% versus 61.6%, P = 0.001) compared to patients without DGF. The DGF group had a significantly higher acute rejection rate and an increased risk of graft loss at one and five years.

Soluble Human Leukocyte Antigen-G in Pediatric Renal Transplantation

Soluble Human Leukocyte Antigen-G in Pediatric Renal Transplantation

Role of combination of l‐arginine and α‐tocopherol in renal transplantation ischaemia/reperfusion injury: a randomized controlled experimental study in a rat model

What's known on the subject? and What does the study add? Renal ischaemia/reperfusion (I/R) injury is an inevitable consequence of kidney transplantation. It contributes to delayed graft function (DGF), acute renal failure and graft rejection. The present study investigates for the first time the impact of a combination of L-arginine and alpha tocopherol on the renal ischemia/reperfusion injury in a rodent model of kidney transplantation. We found that concomitant administration of L-arginine and α-tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys. To investigate the role of L-arginine and α-tocopherol in ischaemia/reperfusion injury in a kidney transplanted rat model. In total, 40 male Sprague-Dawley rats subjected to renal transplantation received FK506 (tacrolimus) to overcome early acute rejection episodes. Animals were divided randomly into four groups (ten rats each). Group I were treated with FK506 (2 mg/kg/bw/day) and served as the control group. Group II were treated with L-arginine 300 mg/kg/bw. Group III were treated with α-tocopherol 30 mg/kg/bw. Group IV were treated with L-arginine and α-tocopherol. Urine and blood samples were taken at 0 (before operation), 2, 7 and 14 days post-transplantation for estimation of urine sodium, creatinine, fractional excretion of sodium, serum creatinine, sodium and blood urea nitrogen. Histological examination and measurement of malondialdehyde in kidney tissues were also performed. Serum creatinine and blood urea nitrogen significantly decreased in L-arginine and α-tocopherol, as well as combination groups, compared to the control group. Malondialdehyde was significantly decreased in the combination group compared to L-arginine and α-tocopherol alone. Histological examination of the control group showed that acute tubular necrosis was markedly decreased in transplanted kidneys treated with a combination of both L-arginine and α-tocopherol. Concomitant administration of l-arginine and α-tocopherol has a more protective effect and synergistic antioxidant effect on ischaemia/reperfusion injury in transplanted rat kidneys.

C4d Staining In Renal Allograft Biopsies with Early Acute Rejection and Subsequent Clinical Outcome

Diffuse C4d staining in peritubular capillaries (PTCs) during an acute rejection episode (ARE) is the footprint of antibody-mediated rejection. In current clinical practice, diffuse C4d+ staining during acute rejection is regarded as an inferior prognostic sign. This case-control study investigated the prognostic role of mere C4d staining for graft outcome during an ARE in a well defined cohort of similarly ARE-treated patients. All kidney transplant recipients in the authors' center from January 1, 1995 to December 31, 2005 were reviewed. From these patients, 151 had a clinical ARE. Paraffin and/or frozen material was available for 128 patients showing a histologically proven ARE within the first 6 months after transplantation. All ARE patients were treated similarly with high-dose pulse steroids and in the case of steroid unresponsiveness with anti-thymocyte globulin. Biopsies were scored according to Banff criteria. Frozen and paraffin sections were stained by immunofluorescence (IF) and immunohistochemistry (IHC) for C4d, respectively, and scored for PTC positivity. Diffuse C4d+ staining in PTCs was found in 12.5% and 4.2% sections stained by IF or by IHC, respectively. Four patients showed diffuse positive staining with both methods but showed no different risk profile from other patients. No relation between C4d staining and clinical parameters at baseline was found. C4d staining was not associated with steroid responsiveness, graft, or patient survival. This study shows that C4d staining is not related to clinical outcome in this cohort of histologically proven early AREs.

Antithymocyte treatment of steroid-resistant acute rejection in renal transplantation

To evaluate the outcome of early (ER <3 months) and late (LR >3 months) episodes of corticosteroid resistant acute allograft rejection (CRR) treated with anti-thymocyte globulin (ATG) in pediatric renal allograft recipients. Retrospective study of 15 children, mean age 13.2 y, who received ATG for the treatment of biopsy proven CRR over a 15 year period. Seven children received ATG for ER (median 26 days post transplantation) and 8 for LR (median 763 days). There was a significant improvement in the 3 month eGFR (70.3 ml/min/1.73m(2), SD 22.3, p = 0.018) when compared with the value prior to ATG treatment (23.3 ml/min/1.73m(2), SD 10.2) in the ER group. In the LR group (4 DSA positive) there was no improvement in the eGFR at 3 months (42 ml/min/1.73m(2), SD 10.5, p = 0.32) when compared with the value prior to ATG (38 ml/min/1.73 m(2), SD 9.7). At final review, eGFR in the ER group was 72.3 ml/min/1.73m(2) (SD 33) vs. 37.7 ml/min/1.73m(2) (SD 17.9) in the LR group after a mean follow up of 10.4 y and 1.2 y, respectively. ATG therapy in CRR is associated with reversal of rejection and excellent graft outcome in children with ER. The benefits remain uncertain in LR, the etiology of which is multifactorial.

Ischaemia‐reperfusion injury in renal transplantation: the role of nitric oxide in an experimental rat model

to investigate the role of nitric oxide (NO) in ischaemia-reperfusion (I/R) injury in a renal transplant rat model, as I/R injury is a common consequence of renal transplantation and NO has many protective properties that might protect the kidney after I/R injury. in all, 30 male Sprague-Dawley rats weighing 350-400 g and aged 4-6 months underwent renal transplantation and received FK506 (an immunosuppressant) to overcome early acute rejection episodes. The rats were divided randomly into three groups (10 rats each): Group I, treated with FK506 (2 mg/kg body weight [bw], once daily), served as the control group; Group II, treated with FK506 2 mg/kg bw and L-arginine 300 mg/kg bw; and Group III, treated with FK506 (2 mg/kg bw) and, n-omega-nitro-l-arginine methyl ester (L-NAME; 50 mg/kg bw). Urine and blood samples were taken at 0 (before operation), 2, 7, and 14 days after transplantation for estimation of urine sodium, creatinine, fractional excretion of sodium, serum creatinine, sodium, and blood urea nitrogen (BUN). Kidney specimens were taken for histological examination by light microscopy. serum creatinine and BUN levels significantly decreased in the L-arginine-treated group (both P < 0.001) while they were significantly increased in the L-NAME-treated group (P < 0.005 and P < 0.001, respectively) compared with the control group at all time intervals. Light microscopic examination of the renal biopsies in the control group showed acute tubular necrosis, which was minimal in kidneys transplanted and treated with L-arginine and more markedly with L-NAME. I/R injury impaired graft function during the first week after transplantation. Injection of L-arginine before ischaemia antagonized graft deterioration and improved morphological appearance.

Cytomegalovirus Infection Renal Transplant Recipients: Risk Factors and Outcome

Cytomegalovirus (CMV) is the most common viral infection after allotransplantation; it can be a major cause of morbidity and mortality. Our aim was to analyze the main risk factors that lead to development of CMV infection and disease. We retrospectively analyzed 207 patients who received a renal allograft from May 2003 to December 2007. Three patients (D-/R-) were excluded. CMV infection was defined by the detection of 2 or more positive tests for pp65 antigenemia and CMV disease by evidence of attributable symptoms in need of antiviral treatment. Thirty-two patients (15.7%) presented active CMV infections and another 35 (17.2%), CMV disease. The mean follow-up was 27.8 +/- 17 months. Prior to transplantation, 9.2% of patients were seronegative (D+/R-) and 77.9% seropositive (D+/R+). Compared with noninfected patients, those with CMV infection/disease were older and received an allograft from an older donor. Upon logistic regression analysis, recipient age older than 55 years, induction therapy with Thymoglobulin, and maintenance immunosuppression with cyclosporine were the major risk factors to develop CMV disease. An early acute rejection episode was more frequent and renal function measured by serum creatinine poorer until 18 months posttransplantation among CMV-infected versus noninfected patients. Our data showed that CMV infection is a common complication after kidney transplantation associated with older age, induction treatment with antilymphocyte globulin, worse renal function, and increased patient morbidity.

Clinical Outcomes in Elderly Kidney Transplant Recipients are Related to Acute Rejection Episodes Rather Than Pretransplant Comorbidity

Deciding whether an elderly patient with end-stage renal disease is a candidate for kidney transplantation can be difficult. We aimed to evaluate pre- and early posttransplant risk factors that could predict outcome in elderly kidney recipients. Data from all elderly (>or= 70 years, n=354), senior (60-69 years, n=577), and control (45-54 years, n=563) patients receiving their first kidney transplant at our center from 1990 to 2005 were retrieved. Patient and graft survival were analyzed in a Cox model addressing the common risk factors including Charlson comorbidity index (CCI), pretransplant dialysis time, and early acute rejection episodes. Acute rejection in the first 90 days, Hazard ratio (HR) 1.74 (1.34-2.25); time on dialysis, HR 1.02 (1.01-1.03) per month; and donor age more than 60 years, HR 1.52 (1.14-2.01) predicted mortality in the elderly. CCI score did not predict mortality in the elderly, HR 1.05 (0.98-1.12); but did so both in senior, HR 1.17 (1.08-1.27) and control recipients, HR 1.33 (1.19-1.48). Delayed graft function, HR 3.69 (2.01-6.79); donor age more than 60 years, HR 2.42 (1.30-4.49); and presence of human leukocyte antigen antibodies, HR 3.96 (1.38-11.37) were independent predictors for death-censored graft loss in the elderly. Adequate immunosuppression with low frequency of rejection episodes improves the outcome for elderly kidney recipients as does a reduction of time on dialysis. CCI score at transplantation does not seem helpful in the selection of elderly patients for kidney transplantation but plays a significant role in patients under 70 years of age.