Graft Survival In Kidney Transplantation Research Articles

Kidney transplantation from deceased donors with elevated serum creatinine.

Elevated donor serum creatinine has been associated with inferior graft survival in kidney transplantation (KT). The aim of this study was to evaluate the impact of elevated donor serum creatinine on short and long-term outcomes and to determine possible ways to optimize the use of these organs. All kidney transplants from 01-2000 to 12-2012 with donor creatinine ≥ 2mg/dl were considered. Risk factors for delayed graft function (DGF) were explored with uni- and multivariate regression analyses. Donor and recipient data were analyzed with uni- and multivariate cox proportional hazard analyses. Graft and patient survival were calculated using the Kaplan-Meier method. Seventy-eight patients were considered. Median recipient age and waiting time on dialysis were 53years and 5.1years, respectively. After a median follow-up of 6.2years, 63 patients are alive. 1, 3, and 5-year graft and patient survival rates were 92, 89, and 89% and 96, 93, and 89%, respectively. Serum creatinine level at procurement and recipient's dialysis time prior to KT were predictors of DGF in multivariate analysis (p = 0.0164 and p = 0.0101, respectively). Charlson comorbidity score retained statistical significance by multivariate regression analysis for graft survival (p = 0.0321). Recipient age (p = 0.0035) was predictive of patient survival by multivariate analysis. Satisfactory long-term kidney transplant outcomes in the setting of elevated donor serum creatinine ≥2mg/dl can be achieved when donor creatinine is <3.5mg/dl, and the recipient has low comorbidities, is under 56years of age, and remains in dialysis prior to KT for <6.8years.

Early renal function recovery and long-term graft survival in kidney transplantation.

Following kidney transplantation (KTx), renal function improves gradually until a baseline eGFR is achieved. Whether or not a recipient achieves the best-predicted eGFR after KTx may have important implications for immediate patient management, as well as for long-term graft survival. The aim of this cohort study was to calculate the renal function recovery (RFR) based on recipient and donor eGFR and to evaluate the association between RFR and long-term death-censored graft failure (DCGF). We studied 790 KTx recipients between January 1990 and August 2014. The last donor SCr prior to organ procurement was used to estimate donor GFR. Recipient eGFR was calculated using the average of the best three SCr values observed during the first 3months post-KTx. RFR was defined as the ratio of recipient eGFR to half the donor eGFR. 53% of recipients had an RFR ≥1. There were 127 death-censored graft failures (16%). Recipients with an RFR ≥1 had less DCGF compared with those with an RFR <1 (HR 0.56; 95% CI 0.37-0.85; P=0.006). Transplant era, acute rejection, ECD and DGF were also significant determinants of graft failure. Early recovery of predicted eGFR based on donor eGFR is associated with less DCGF after KTx.

Clinically-relevant threshold of preformed donor-specific anti-HLA antibodies in kidney transplantation

BackgroundPretransplant anti-HLA donor-specific antibodies (DSA) are recognized as a risk factor for acute antibody-mediated rejection (AMR) in kidney transplantation. The predictive value of C4d-fixing capability by DSA or of IgG DSA subclasses for acute AMR in the pretransplant setting has been recently studied. In addition DSA strength assessed by mean fluorescence intensity (MFI) may improve risk stratification. We aimed to analyze the relevance of preformed DSA and of DSA MFI values. Methods280 consecutive patients with negative complement-dependent cytotoxicity crossmatches received a kidney transplant between 01/2008 and 03/2014. Sera were screened for the presence of DSA with a solid-phase assays on a Luminex flow analyzer, and the results were correlated with biopsy-proven acute AMR in the first year and survival. ResultsPretransplant anti-HLA antibodies were present in 72 patients (25.7%) and 24 (8.6%) had DSA. There were 46 (16.4%) acute rejection episodes, 32 (11.4%) being cellular and 14 (5.0%) AMR. The incidence of acute AMR was higher in patients with pretransplant DSA (41.7%) than in those without (1.6%) (p<0.001). The median cumulative MFI (cMFI) of the group DSA+/AMR+ was 5680 vs 2208 in DSA+/AMR− (p=0.058). With univariate logistic regression a threshold value of 5280 cMFI was predictive for acute AMR. DSA cMFI’s ability to predict AMR was also explored by ROC analysis. AUC was 0.728 and the best threshold was a cMFI of 4340. Importantly pretransplant DSA>5280 cMFI had a detrimental effect on 5-year graft survival. ConclusionsPreformed DSA cMFI values were clinically-relevant for the prediction of acute AMR and graft survival in kidney transplantation. A threshold of 4300–5300 cMFI was a significant outcome predictor.

Impact of preformed and de novo anti-HLA DP antibodies in renal allograft survival

The influence of antibodies against HLA-DP antigens detected with solid-phase assays on graft survival after kidney transplantation (KT) is uncertain. We evaluated with Luminex® the prevalence of pre- and posttransplant DP antibodies in 440 KT patients and their impact on graft survival. For 291 patients with available pretransplant samples, DP antibodies were present in 39.7% KT with pretransplant HLA antibodies and 47.7% with DSA. Graft survival of KT with pretransplant class-II DSA was worse than with non-DSA (p=0.01). DP antibodies did not influence graft survival. Of 346 patients monitored post-KT, 17.1% had HLA class-II antibodies, 56% with DP antibodies. Class-II DSA was detected in 39%, 60.9% of them had DP antibodies. Graft survival was worse in patients with class-II DSA (p=0.022). DP antibodies did not change these results. The presence of isolated DP antibodies was a rare event both pre- and posttransplantation (1.03 and 0.86%). The presence of pretransplant and posttransplant DSA is associated with a negative impact on graft survival. However, the presence of DP antibodies does not modify this impact significantly.

Immunosuppressive Medications.

Immunosuppressive agents are commonly used in the nephrologist's practice in the treatment of autoimmune and immune-mediated diseases and transplantation, and they are investigational in the treatment of AKI and ESRD. Drug development has been rapid over the past decades as mechanisms of the immune response have been better defined both by serendipity (the discovery of agents with immunosuppressive activity that led to greater understanding of the immune response) and through mechanistic study (the study of immune deficiencies and autoimmune diseases and the critical pathways or mutations that contribute to disease). Toxicities of early immunosuppressive agents, such as corticosteroids, azathioprine, and cyclophosphamide, stimulated intense investigation for agents with more specificity and less harmful effects. Because the mechanisms of the immune response were better delineated over the past 30 years, this specialty is now bestowed with a multitude of therapeutic options that have reduced rejection rates and improved graft survival in kidney transplantation, provided alternatives to cytotoxic therapy in immune-mediated diseases, and opened new opportunities for intervention in diseases both common (AKI) and rare (atypical hemolytic syndrome). Rather than summarizing clinical indications and clinical trials for all currently available immunosuppressive medications, the purpose of this review is to place these agents into mechanistic context together with a brief discussion of unique features of development and use that are of interest to the nephrologist.

Impact of Lymphocyte Depleting Antibody(LDA) On Rate of Acute Rejection (AR) in Patients With Delayed Graft Function (DGF).

Introduction: DGF impacts AR & graft survival in kidney transplantation (KTx). The KDIGO guideline suggest use of LDI when DGF is likely; but there is no robust data. The impact of LDI on risk of AR in patients with&without DGF was evaluated using OPTN registry. Methods: Adults receiving cadaver kidneys between 2002-11 were studied. Treated AR at 12 months post-KTx was analyzed per known risk factors (RFs) including recipient race, HLA 5/6 antigen mismatch, repeat transplant, ABOi, PRA >0%, ECD organ, cold time > 24 hours and DGF. Multivariable logistic regression model was fit to the data to evaluate whether the incidence of AR in patients with and without DGF is differentially impacted by the use of different induction strategies: No induction, Thymoglobulin(THY), alemtuzumab(C1H) and IL-2 receptor antagonists(IL2-Ra). Results: 73,984 patients were included. RFs by antibody induction are presented in Table 1. Odds of AR was significantly higher in patients who had DGF vs no DGF (Adjusted OR [aOR] =1.95; 95% CI=1.85-2.05), independent of known RFs for AR.Table: No Caption available.However, the impact of DGF was differentially affected by AI strategy (two-way interaction: p<0.001), represented graphically in Figure 1. Adjusted incidence of AR was similar in all groups of patients who had no DGF. In DGF group, AR was significantly lower in THY or C1H vs no induction (aOR=0.65; 95% CI=0.59-0.73 and aOR=0.72; 95% CI=0.60-0.85, respectively) while the incidence of AR remained similar in IL2-Ra vs no induction (aOR=1.12; 95%CI 0.99-1.26).Figure: No Caption available.Conclusion: DGF is an important risk factor for AR. The use of LDI significantly reduces the risk of AR in adult deceased donor renal transplant recipients who develop DGF. We recommend the routine use of LDI when the anticipated risk of DGF is high.

Patient and Graft Survival in Kidney Transplantation From Deceased Donors in Argentina, 1998-2011.

To analyze both patient and graft survival in renal transplantation in adults receiving kidneys from deceased donors in Argentina. 5181 transplants were included in the analysis. The information was taken from SINTRA 1st January 1998 until 31 December 2011 with follow-up to April 9, 2012. The Kaplan-Meier method was used to estimate survival, and time was divided in two-year and three year periods, as follows:1998-2000, 2001-2002, 2003-2004, 2005-2006, 2007-2009, 2010-2011.Tocompare the curves the log-rank test was used. The Cox regression model was used to analyze the effect of variables like age and gender of both donor and recipient, donor's cause of death (stroke,TBI,anoxia,other causes of coma and others),time on dialysis (<or> 7 years ), cold ischemia time (<or> 24 hours) and etiology of recipient's renal failure. Patient survival for the period 1998-2000 at 1 year was 89.6%, at 3 years 86.4% and 81.8% at 5 years. For the period 2001-2003 at 1 year was 90.8%, at 3 years 85.1% and at 5 years 79%. 2004-2006, at 1 year was 89.2%, at 3 years 81%, and at 5 years 74.1%. 2007-2009, at 1 year was 90.1%, at 3 years 84%, and at 5 years 76.7%. 2009-2010, at 1 year was 90.2%. Log rank 0.0583. Graft survival 1998-2000 at 1 year was 88.2%, at 3 years 82.1%, and at 5 years 75%. 2001-2003, at 1 year was 87.5%, at 3 years 79.5%, and at 5 years 70.8%. 2004-2006, at 1 year was 82.9%, at 3 years 72.1%, and at 5 years 62.5%. 2007-2009, at 1 year was 86%, at 3 years 76.3%, and at 5 years 66.3%. 2009-2010, at 1 year was 86.1%. Logrank 0.0004. The variables with statistical significance for graft survival were recipient's age 45-59 years HR 1.38 (1.22-1.57)> 60 years HR 1.90 (1.65-2.19), donor's age 45-59 years HR 1.22 (1.08-1.39)> 60 years HR 1.60 (1.34-1.91), time on dialysis> 7 years HR 1.31 (1.17-1.48), CIT>24hrs HR 1.13 (1.01-1.25), diabetic nephropathy as a cause of CRF HR 1.62 (1.31-2.01) A significant difference in graft survival curves with improved survival for the first three time periods was observed. Once the variables associated with a lower probability of survival were found the comparison of proportions showed that in the last period, 2010-2011, more recipients over> 60 years of age received a transplant, with more donors> 60 years and with more recipients with more than 7 years on dialysis. The CIT <24 h was more common the period 2010-2011, but was not enough to change the differences in survival.

An Unanticipated Role for Survivin in Organ Transplant Damage

Ischemia/reperfusion (I/R) injury is a major determinant of graft survival in kidney transplantation. Survivin, an inhibitor of apoptosis that participates in the control of mitosis and cell cycle progression, has been implicated in renal protection and repair after I/R injury; however, no study has been performed in the transplant setting. We investigated the role of survivin in modulating posttransplant I/R injury in syngeneic and allogeneic kidney grafts, and studied whether protection from I/R injury impacted on the recipient immune system, on chronic allograft nephropathy and rejection. We used genetically engineered mice with survivin haploinsufficiency and WT mice in which survivin over-expression was induced by gene-delivery. Survivin haploinsufficiency in syngeneic grafts was associated with exuberant I/R tissue injury, which triggered inflammation eventually resulting in graft loss. Conversely, survivin over-expression in the grafts minimized I/R injury and dysfunction in syngeneic grafts and in a clinically relevant fully MHC-mismatched allogeneic combination. In the latter, survivin over-expression translated into limited anti-donor adaptive immune response and less long-term allograft injury with protection from renal parenchymal damage. Our data support survivin over-expression in the graft as a novel target for protocols aimed at limiting tissue damage at the time of transplant ultimately modulating the recipient immune system.

Clinical efficacy of rituximab for acute rejection in kidney transplantation: a meta-analysis

This meta-analysis was undertaken to compare the efficacy and safety of pretransplant treatment with rituximab in sensitized patients receiving kidney transplantation. PubMed, EMBASE, and Cochrane databases were searched to identify studies that used pretransplantation rituximab in eligible patients. The major outcomes included antibody-mediated rejections (AMR) after kidney transplantation and one-year graft survival rate. The meta-analysis was performed using fixed-effects model. Seven studies were identified including a total of 589 patients, of whom 312 were treated without rituximab, while 277 were treated with rituximab. In our meta-analysis, patients treated with rituximab had significantly fewer AMR after kidney transplantation [odds ratio (OR) 0.52, 95 % CI 0.28, 0.98, P = 0.04] and higher rate of one-year graft survival rates (OR 3.02, 95 % CI 1.14, 8.02, P = 0.03), indicating that rituximab is effective against acute rejection and enhances graft survival in kidney transplantation. No differences were noted in other efficacy and safety parameters in these two patient groups. We demonstrated that preinduction with rituximab could significantly improve AMR and graft survival rates in sensitized patients undergoing kidney transplantation. Future prospective controlled studies are warranted to further understand rituximab's role in kidney transplantation.

Complications and Graft Survival in Kidney Transplants With Vascular Variants: Our Experience and Literature Review

IntroductionIn the literature several reconstructive techniques for vascular anastomoses in case of kidney graft vascular variants are reported. This article reports our experience in kidney transplants with vascular anomalies. Materials and methodsBetween January 1996 and June 2012, 154 cadaveric kidney transplantations were performed at our center. In 35 case, vascular variants were found. Among the arterial variants we observed 27 double arteries, 2 cases with 3 arteries, and 1 case with 4 arteries. All cases of Venous variants were double veins. Based on the type of reconstructive technique used, we divided transplants into group A (n = 22) separate multiple arterial anastomoses; group B (n = 8) anastomosis on the aortic patch; group C (n = 4) single anastomosis in case of 2 arteries with a common ostium at the aortic origin. The venous variants were treated with ligation of the vein of smaller caliber. ResultsKidney preparation to the back table lasted on average 50 minutes with no significant differences between the 3 groups and no significant timing increase compared to renal transplants without vascular anomalies (mean warm ischemia 40 minutes, range 30–60 minutes). The mean cold ischemia time was limited to 16 hours from the removal and the mean warm ischemia was 50 minutes (range 30–70 minutes). There were no differences in timing between group C and single anastomoses, whereas groups A and B showed mean warm ischemia time was slightly increased compared to group C (P < .05). There were no significant differences in terms of delayed upturn of graft function and graft survival between groups A, B, and C and compared to transplants without vascular anomalies. ConclusionsIn our series we observed similar results performing the reimplantation on aortic patch and separate multiple arterial anastomoses. Considering our experience, we believe that vascular variants are not an indication to exclude a graft for transplantation.

The effect of donor‐recipient gender mismatch on short‐ and long‐term graft survival in kidney transplantation: a systematic review and meta‐analysis

There is no limitation of gender matching in renal transplantation. This study was intended to evaluate its effect on short- and long-term graft survival. PubMed, the Web of Knowledge, Medline, the Cochrane Library, and two additional Chinese databases were searched. The data were then abstracted and meta-analyzed. 14 studies involving 445 279 patients were included. Each study reported data on the four gender matches (male donor-male recipient, MDMR; male donor-female recipient, MDFR; female donor-male recipient, FDMR; female donor-female recipient, FDFR). The pooled risk ratios (RRs) for 0.5-, 1-, 2-, 3-, 5-, and 10-yr graft survival rates showed that the FDMR group had the worst outcomes, and when recipients were female, short-term graft survival was worse, but long-term graft survival was better. The differences between groups changed with time. FDMR patients showed poor graft survival. The female recipients had worse short-term graft survival but the best long-term graft survival. This study introduces an important consideration into donor-recipient matching in renal transplantation.

Day 1 post-operative fasting hyperglycemia may affect graft survival in kidney transplantation

Early post-operative hyperglycemia is commonly encountered in patients without pre-existing diabetes mellitus who are undergoing kidney transplantation. The aim of this study was to determine the effect of early post-operative hyperglycemia on graft and patient survival after kidney transplantation in our center. This was a single-center retrospective review of solitary kidney recipients transplanted in our center between January 1998 and December 2007. Of a total of 432 patients, 377 were eligible for the study. Fasting plasma glucose (FPG) levels at day 1 (D1) and day 5 (D5) after transplantation were recorded. Hyperglycemia was defined as FPG ≥ 7.0 mmol/l. Outcome events recorded included deaths and graft failures. The mean age at transplantation was 43.2 ± 9.5 years and 50.4% were male. The mean FPG levels at D1 and D5 were 7.5 ± 1.3 mmol/L and 5.3 ± 1.3 mmol/L, respectively; 64.2% of recipients had FPG ≥ 7.0 mmol/L on D1 and this was reduced to 8.5% on D5. Recipients with D1 FPG ≥ 7.0 mmol/L had significantly poorer graft survival (39 events) compared to those without D1 hyperglycemia (6 events), with a hazard ratio of 3.708 (95% CI, 1.568-8.766, P=0.003). There was a trend towards better patients survival in recipients with D1 FPG <7.0 mmol/L (P=0.056). D1 post-transplantation hyperglycemia may be associated with increased risk of graft failure. It is thus important to closely monitor glucose levels during the early post-transplantation period so that high risk patients can be identified and appropriate measures can be implemented to improve the long-term outcome.

Influence of Delayed Graft Function and Acute Rejection on Outcomes After Kidney Transplantation From Donors After Cardiac Death

Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.

Long-Term Graft Function in Elderly Living-Donor Kidney Transplantation

Background: Donor age adversely affects graft survival in kidney transplantation. The aim of our study is to evaluate long-term graft function in elderly living-donor kidney transplantation. Methods: We retrospectively reviewed graft function of living-donor kidney transplant between June 1984 and February 2010. A total of 2,687 living-donor kidney transplants were performed at our center during this period. Donor age was classified into 5 groups; 1) < 25 yrs (n=337) 2) 25-34 yrs (n=959) 3) 35-44 yrs (n=694) 4) 45-54 yrs (n=473) 5) ≥55 yrs (n=224) Graft survival was calculated using the Kaplan-Meier method. Graft function was evaluated using MDRD estimated glomerular filtration rate (eGFR). Results: Ten-year graft survival rates were as follows according to donor age; 1) < 25 yrs (75.4%) 2) 25-34 yrs (74.9%) 3) 35-44 yrs (78.5%) 4) 45-54 yrs (68.5%) 5) ≥55 yrs (63.5%). Graft survival was significantly lower among older donor recipients (≥ 45yrs) than that among younger donor recipients. At 1, 5, 10, and 15 year post-transplant, values of eGFR were significantly lower among older donor recipients (≥ 45yrs) (Figure 1).[Figure 1.]Conlusion: Long-term graft function as well as graft survival in older living donor (≥ 45yrs) recipients was inferior to those in younger living donor recipients.

Optimized outcomes for renal allografts with cold ischemic times of 20 h or greater

Prolonged cold ischemia time (CIT) has been associated with inferior graft survival in kidney transplantation (KT). The aim of this study was to evaluate the impact of prolonged CIT on short- and long-term outcomes and to determine the possible ways to optimize the use of these organs. All kidney transplants from April 2001 to December 2010 with CIT ≥ 20 h were considered. Donor and recipient data were analyzed with uni- and multivariate Cox proportional hazard analyses. Graft and patient survival were calculated using the Kaplan-Meier method. One hundred and eighty-one patients were transplanted with 184 grafts. Median recipient age and waiting time on dialysis were 52.5 and 4.9 years, respectively. After a median follow-up of 4.9 years, 148 of 181 patients are alive, 143 of them with functioning grafts. One-, three, and five-year graft and patient survival rates were 90, 87, and 79 %, and 96, 91, and 85 %, respectively. Donor age (p < 0.0001), retransplantation (p = 0.0025), and induction therapy with interleukin-2 antagonists (p = 0.0487) were predictors of graft survival by univariate analysis. Donor age and retransplantation remained significant by multivariate analysis (p < 0.001 and p = 0.0046, respectively). Donor age (p = 0.0176) and creatinine level at 1-month post-KT (p = 0.0271) were predictors of patient survival by univariate analysis. Only donor age reached multivariate significance (p = 0.0464). The calculated donor age cut off was 60 years. Satisfactory long-term kidney transplant outcomes in the setting of CIT ≥ 20 h can be achieved with grafts from donors <60 years in first-time recipients. Induction therapy should preferably be with an interleukin-2 antagonist.

Recurrence from primary and secondary glomerulopathy after renal transplant

Glomerulonephritis is the primary cause of end-stage renal failure in 30-50% of kidney transplant recipients and recurrence of the initial disease is an important determinant of long-term graft outcome after transplantation. Although renal transplantation remains the best treatment option for patients with end stage renal diseases in most cases, diagnosis and management of recurrences of glomerulopathies are critical for the optimization and improvement of long-term kidney transplant graft survival and provide a unique opportunity to explore the pathogenesis of native kidney disease. This review aims to update knowledge for a large panel of recurrent primary and secondary glomerulonephritis after kidney transplantation, excluding diabetic nephropathy including primary focal and segmental glomerulosclerosis, membranous nephropathy, IgA nephropathy, membranoproliferative glomerulonephritis, lupus, vasculitis but also less usual secondary nephropathy related to sarcoidosis, AA and AL amyloidosis, monoclonal immunoglobulin deposition disease, and fibrillary glomerulonephritis.

Blood transfusions in the surgical patient: A gift of life, but at what cost?

DOI of original article: 10.1016/j.jss.2012.0 * Corresponding author. Department of Surge 2M, New York, NY 10003. Tel.: 212 844 8570; E-mail address: mleitman@chpnet.org (I. 0022-4804/$ e see front matter a 2013 Elsev doi:10.1016/j.jss.2012.02.031 From the discovery of circulation by Dr. William Harvey in 1628, to the first successful human-to-human blood transfusion by Dr. James Blundell in 1818, to the creation of the American Red Cross in 1941, our understanding of blood transfusion has evolved. The so-called hazards of transfusions have been documented since World War II and include infectious complications, hemolytic-related reactions, and, in more recent times, transfusion-related lung injuries and transfusion-induced immunomodulation [1,2]. This immunologic consequence of blood transfusions is not a novel concept. During the 1970s, the immunosuppressive effects of blood transfusion were first recognized when Opelz and Teraski [3] reported improvement in kidney transplant graft survival with an increased number of blood transfusions. This landmark study was the first to highlight the pro-inflammatory and immunosuppressive effects of transfused blood. Despite these

Mesenchymal stromal cells in renal ischemia/reperfusion injury

Ischemia/reperfusion (I/R) injury is an inevitable consequence of organ transplantation and a major determinant of patient and graft survival in kidney transplantation. Renal I/R injury can lead to fibrosis and graft failure. Although the exact sequence of events in the pathophysiology of I/R injury remains unknown, the role of inflammation has become increasingly clear. In this perspective, mesenchymal stromal cells (MSCs) are under extensive investigation as potential therapy for I/R injury, since MSCs are able to exert immune regulatory and reparative effects. Various preclinical studies indicate the beneficial effects of MSCs in ameliorating renal injury and accelerating tissue repair. These versatile cells have been shown to migrate to sites of injury and to enhance repair by paracrine mechanisms instead of by differentiating and replacing the injured cells. The first phase I studies of MSCs in human renal I/R injury and kidney transplantation have been started, and results are awaited soon. In this review, preliminary results and opportunities of MSCs in human renal I/R injury are summarized. We might be heading towards a cell-based paradigm shift in the treatment of renal I/R injury.

Antibody-mediated rejection in kidney transplantation: a review.

Antibody mediated rejection (AMR) poses a significant and continued challenge for long term graft survival in kidney transplantation. However, in the recent years, there has emerged an increased understanding of the varied manifestations of the antibody mediated processes in kidney transplantation. In this article, we briefly discuss the various histopathological and clinical manifestations of AMRs, along with describing the techniques and methods which have made it easier to define and diagnose these rejections. We also review the emerging issues of C4d negative AMR, its significance in long term allograft survival and provide a brief summary of the current management strategies for managing AMRs in kidney transplantation.

Kidney transplantation in highly sensitized patients: are there options to overcome a positive crossmatch?

Presensitization against a broad array of human leukocyte antigens (HLA) is associated with prolonged waiting times and inferior graft survival in kidney transplantation. Since the late 1960s, a positive lymphocytotoxic crossmatch has been considered a contraindication for kidney transplantation and solutions, such as enrollment of eligible patients in the Acceptable Mismatch Program of Eurotransplant and kidney paired donation in the case of living donor kidney transplantation, have been proposed to avoid this barrier. Alternatively, a positive crossmatch might not be considered as a contraindication for kidney transplantation and one can try to overcome this hurdle by desensitization. In principle, there are three different ways to overcome the crossmatch barrier by desensitization. The highly sensitized patient awaiting a cadaveric kidney transplant may be desensitized either immediately pretransplant when an organ is offered or in advance, during the time on the waiting list, to increase his chance of having a negative crossmatch at the time of transplantation. In the case of living donor kidney transplantation, the patient can be desensitized for days to weeks until the positive crossmatch with his intended living kidney donor becomes negative. "Heidelberg algorithm" is a combination of different measures, such as pretransplant risk estimation, good HLA match, inclusion of patients in the Eurotransplant Acceptable Mismatch program, and desensitization, which leads to timely transplantation and excellent survival rates in highly sensitized patients at a low rate of toxicity. We believe that all available options should be utilized in an integrated manner for the transplantation of kidney transplant recipients who are at a high risk of antibody-mediated rejection.