Prolonged Delayed Graft Function Research Articles

Histopathological Features and Role of Allograft Kidney Biopsy Among Recipients With Prolonged Delayed Graft Function: A Review.

Delayed graft function (DGF) is an early posttransplant complication predictive of adverse outcomes. This "acute kidney injury of transplantation" is often defined as allograft dysfunction requiring renal replacement within 7 d posttransplantation. DGF is an important area of study because it is emerging with efforts to expand the donor pool and address the supply-demand gap in kidney transplantation. DGF is often caused by severe kidney injury mechanisms because of multiple donors, recipients, and immunologic factors. The role of kidney biopsy, particularly in prolonged DGF, is an ongoing area of research and inquiry for clinicians and researchers alike to better define, manage, and predict outcomes of this early posttransplant event. This review aims to provide an in-depth, comprehensive summary of the literature to date on the histopathology of DGF and the role of kidney transplant biopsies in prolonged DGF.

The impact of preservation solutions for static cold storage on kidney transplantation outcomes: Results of a Brazilian nationwide multicenter study.

This study evaluated the current practices of selecting cold storage preservation solutions in Brazil and their impact on delayed graft function (DGF) incidence and 1-year outcomes in kidney transplant recipients. A retrospective cohort study was conducted, including 3,134 brain-dead deceased donor kidney transplants performed between 2014 and 2015 in 18 Brazilian centers. The most commonly used preservation solution was Euro-collins (EC, 55.4%), followed by Histidine-tryptophan-ketoglutarate (HTK, 30%) and Institut Georges Lopez (IGL-1, 14.6%). The incidence of DGF was 54.4%, with 11.7% of patients requiring dialysis for more than 14 days, indicating prolonged DGF. Upon adjusting for confounding variables, HTK demonstrated a significantly lower risk of DGF than EC (OR 0.7350.82500.926), as did IGL-1 (OR 0.6050.7120.837). Similar protective effects were observed for prolonged DGF when comparing HTK (OR 0.4780.5990.749) and IGL-1 (OR 0.4780.6810.749) against EC. No significant association was found between preservation solutions and 1-year death-censored graft survival. In conclusion, EC was the most frequently used cold storage perfusion solution, demonstrating a higher incidence and duration of DGF compared with HTK and IGL-1, but with no impact on 1-year graft survival.

Renal Function at Discharge Among Kidney Recipients Experiencing Delayed Graft Function and Its Associations With Long-term Outcomes.

Using Organ Procurement and Transplantation Network data, we examined DGF, and used recipient serum creatinine at discharge as a correlate of renal function and DGF severity (mild: <2.5 mg/dL; severe: ≥2.5 mg/dL). The associations between donor and recipient factors and DGF severity were quantified using logistic regression. We also examined the associations between DGF severity and long-term recipient outcomes, adjusting for potential confounders. A predictive model using donor and recipient factors had a reasonably good ability to discriminate mild (low creatinine) versus severe (high creatinine) DGF (c-statistic of 0.70). In Cox regression, DGF and creatinine at discharge were both independently associated with long-term outcomes, yet their effects differed depending on the outcome (graft function, death-censored graft function, recipient mortality). Our findings suggest that having DGF, but with relatively good renal function (creatinine <2.5) at discharge, may be less deleterious on graft and recipient survival compared with severe, prolonged DGF, which was associated with a decreased median graft survival of ~2.6 y compared with no DGF with low creatinine at discharge. Our novel DGF severity stratification identified unique factors associated with DGF severity, along with DGF's association with long-term graft and patient survival. The adverse cost and outcome implications of severe DGF warrant additional investigation to improve kidney transplantation practice.

Delayed Graft Function Duration in Deceased Donor Kidney Transplants

Delayed graft function (DGF) is an important prognostic indicator after kidney transplantation. Depending on the severity of the ischemia-reperfusion injury, DGF can have several clinical presentations, with different renal function recovery times. Both the presence and duration of DGF can have an impact on kidney transplantation outcomes. However, the definition of the cutoff point, above which the outcomes are worse, varies widely in the literature. To investigate the impact of DGF and its duration on patient and graft survivals, a single-center retrospective study including all deceased donor kidney transplants was performed between November 2008 and December 2015 (n=188). Through the analysis on the receiver operating characteristic curve, the cutoff point that determined the worst outcome was reached. DGF patients were then divided according to the duration of DGF (<8 days or ≥8 days). The overall incidence of DGF was 62.2%. Higher HLA mismatches was an independent risk factor for prolonged DGF. DGF ≥8 days was associated with acute rejection and this one was associated with patient death in 3 years. DGF with a duration of more than 8 days associated with higher HLA mismatches increases the risk of acute rejection, but graft loss and patient survival are not affected by DGF, regardless of its duration.

Transplant and Recipient Factors in Prediction of Kidney Transplant Outcomes: A UK-Wide Paired Analysis.

Background: In kidney transplantation, the relative contribution of various donor, procedure and recipient-related factors on clinical outcomes is unknown. Previous paired studies have largely focused on examining factors predicting early outcomes, where the effect of donor factors is thought to be most important. Here, we sought to examine the relationship between early and long-term outcomes in a UK-wide paired kidney analysis. Methods: UK Transplant Registry data covering 24,090 kidney transplants performed between 2001–2018, where both kidneys from each donor were transplanted, were analysed. Case-control studies were constructed using matched pairs of kidneys from the same donor discordant for outcome, to delineate the impact of transplant and recipient factors on longer-term outcomes. Results: Multivariable conditional logistic regression identified HLA mismatch as an important predictor of prolonged delayed graft function (DGF), in the context of a paired study controlling for the influence of donor factors, even when adjusting for early acute rejection. Prolonged DGF, but not human leucocyte antigen (HLA) mismatch, strongly predicted 12-month graft function, and impaired 12-month graft function was associated with an increased risk of graft failure. Conclusions: This study indicates prolonged DGF is associated with adverse long-term outcomes and suggests that alloimmunity may contribute to prolonged DGF by a mechanism distinct from typical early acute rejection.

Kidney Transplant Outcomes after Prolonged Delayed Graft Function.

Background: The protracted recovery of renal function may be an actionable marker of post-transplant adverse events, but a paucity of data are available to determine if the duration of graft recovery serves to stratify risk. Materials and Methods: Single-center data of adult-isolated deceased-donor kidney transplant (KTX) recipients between 1 July 2015 and 31 December 2018 were stratified by delayed graft function (DGF) duration, defined as time to serum creatinine < 3.0 mg/dL. Results: Of 355 kidney transplants, the time to creatinine < 3.0 mg/dL was 0–3 days among 96 cases (DGF ≤ 3), 4–10 days among 85 cases (DGF4-10), 11–20 days among 93 cases (DGF11-20), and ≥21 days for 81 cases (DGF ≥ 21). DGF ≥ 21 recipients were significantly more likely to be male, non-sensitized, and receive kidneys from donors that were older, with donation after circulatory death, non-mandatory share, hypertensive, higher KDPI, higher terminal creatinine, and longer cold and warm ischemia time. On multivariate analysis, DGF ≥ 21 was associated with a 5.73-fold increased odds of 12-month eGFR < 40 mL/min compared to DGF ≤ 3. Lesser degrees of DGF had similar outcomes. Conclusions: Prolonged DGF lasting over 20 days signifies a substantially higher risk for reduced eGFR at 1 year compared to lesser degrees of DGF, thus serving as a threshold indicator of increased risk.

Reversal of Prolonged Delayed Graft Function Following Kidney Transplantation with a Belatacept-Based Regimen

Reversal of Prolonged Delayed Graft Function Following Kidney Transplantation with a Belatacept-Based Regimen

MO954DONOR TYPE INFLUENCE IN EARLY POST KIDNEY TRASPLANTATION HYPERTRANSAMINASEMIA

Abstract Background and Aims The early increase in transaminases after kidney transplant (KT) is a frequent finding. It has been associated with the cross-talk produced between liver and kidney in ischemia-reperfusion situations. However, the influence of the donor type has not been evaluated. We analyze the incidence, relevance and possible correlations of postKT hypertransaminasemia. Method Retrospective study (2004-2018) to analyze the increase in serum AST/ALT during the first 3 months after KT in 119 KT recipients of deceased donors, either brain death (DBD n=59), controlled after cardiac death (cDCD n=21) or uncontrolled after cardiac death (uDCD n=39). All recipients received induction with thymoglobulin and maintenance immunosuppression with tacrolimus and mycophenolate. Results Recipients of uDCD group were younger, with a higher proportion of men and lower percentage of diabetics and retransplants. Delayed graft function duration was longer, although serum creatinine was similar at 3 months between groups. There were no differences between recipients in terms of past medical liver disease, postKT transfusion requirement or vasoactive drug use. There were also no differences in cumulative thymoglobulin dose, and uDCD recipients presented, as expected, lower levels of tacrolimus at one week postKT (Table). From all KT recipients, 37.3/45.3% presented with an increase in AST/ALT at 72 hours postKT. Regarding donor type, the percentage of recipients who experienced 72 hours postKT hypertransaminasemia was higher (69.2/82.1% in uDCD group vs 22/29.3% in DBD and 21.1/21.1% in cDCD, p&amp;lt;0.001). This liver function alteration resolved early, and one month after transplant, AST/ALT values in all groups returned to baseline (Figure). The multivariate analysis showed that uDCD recipients had x10 higher risk of developing early post-KT hypertransaminasemia than the other groups (for AST, OR 10.85 [2.463-47.826] and for ALT OR 11.15 [2.627-47.294]). However, when we tried to correlate this hypertransaminasemia with a prolonged delayed graft function (creatinine decrease&amp;gt; 14 days postKT) we did not find any association. Conclusion Early postKT hypertransaminasemia is a frequent and transient event that is related to the kidney donor type, being more frequent in recipients of donors in uncontrolled cardiac death.

Cytokine absorption during human kidney perfusion reduces delayed graft function-associated inflammatory gene signature.

Transplantation is the optimal treatment for most patients with end‐stage kidney disease but organ shortage is a major challenge. Normothermic machine perfusion (NMP) has been used to recondition marginal organs; however, mechanisms by which NMP might benefit organs are not well understood. Using pairs of human kidneys obtained from the same donor, we compared the effect of NMP with that of cold storage on the global kidney transcriptome. We found that cold storage led to a global reduction in gene expression, including inflammatory pathway genes and those required for energy generation processes, such as oxidative phosphorylation (OXPHOS). In contrast, during NMP, there was marked upregulation OXPHOS genes, but also of a number of immune and inflammatory pathway genes. Using biopsies from kidneys undergoing NMP that were subsequently transplanted, we found that higher inflammatory gene expression occurred in organs with prolonged delayed graft function (DGF). Therefore, we used a hemoadsorber (HA) to remove pro‐inflammatory cytokines. This attenuated inflammatory gene expression increased OXPHOS pathway genes and had potentially clinically important effects in reducing the expression of a DGF‐associated gene signature. Together, our data suggest that adsorption of pro‐inflammatory mediators from the perfusate represents a potential intervention which may improve organ viability.

Procurement Biopsies Can Predict Unfavorable Outcomes in Kidneys With Low MAPI Score Values

BackgroundThere are few reports about the usefulness of Maryland Aggregate Pathology Index (MAPI) score in procurement biopsies. This study aimed to evaluate the association between histopathological analysis according to MAPI and unfavorable outcomes in the first year after kidney transplantation (KT). MethodsThis retrospective study included deceased-donor KT patients whose grafts were biopsied before transplantation and had low MAPI scores (<8) in frozen sections (FSs). Paraffin sections (PSs) were analyzed after KT. MAPI parameters were global glomerulosclerosis in more than 15% (2 patients), periglomerular fibrosis (4 patients), wall-lumen ratio of arteries >0.5 (2 patients), arteriolar hyalinosis (4 patients), and interstitial scar (3 patients). Multivariable models were used to analyze risk factors for delayed graft function (DGF), prolonged DGF, inferior renal function, and graft loss (P < .05). ResultsOne hundred fifty-nine KTs were included. Donors (n = 120) were predominantly men (70%) and young adults (37.68 ± 12.50 years old) who suffered a traumatic death (55.8%). Recipients were predominantly men (62.26%) and adults (45.70 ± 15.80 years old) with kidney disease of unknown etiology (39.6%). Low rates of agreement between FS and PS were observed for all MAPI criteria, with kappa values ranging from 0.28 to 0.51. Using FS, no histologic parameter was independently associated with outcomes. After adjustment, glomerulosclerosis was an independent risk factor for prolonged DGF (odds ratio = 6.18: 95% confidence interval, 1.27-30.18) and wall-lumen ratio >0.5 for inferior renal function at 1 year (odds ratio = 4.08; 95% confidence interval, 1.21-13.76). ConclusionProcurement biopsies can be useful to predict inferior outcomes even in kidneys with low MAPI scores.

Duration of delayed graft function and outcomes after kidney transplantation from controlled donation after circulatory death donors: a retrospective study.

The impact of the duration of delayed graft function (DGF) on graft survival is poorly characterized in controlled donation after circulatory death (DCD) donor kidney transplantation. A retrospective analysis was performed on 225 DCD donor kidney transplants between 2011 and 2016. When patients with primary nonfunction were excluded (n=9), 141 recipients (65%) had DGF, with median (IQR) duration of dialysis dependency of 6 (2-11.75)days. Longer duration of dialysis dependency was associated with lower estimated glomerular filtration rate at 1year, and a higher rate of acute rejection. On Kaplan-Meier analysis, the presence of DGF was associated with lower graft survival (log-rank test P=0.034), though duration of DGF was not (P=0.723). However, multivariable Cox regression analysis found that only acute rejection was independently associated with lower graft survival [HR (95% CI) 4.302 (1.617-11.450); P=0.003], whereas the presence of DGF and DGF duration were not. In controlled DCD kidney transplantation, DGF duration itself may not be independently associated with graft survival; rather, it may be that acute rejection associated with prolonged DGF is the poor prognostic factor.

Prolonged delayed graft function in an orthotopic liver transplantation recipient: a case report

Background: Patients undergoing orthotopic liver transplantation (OLT) can be a considerably complex population to manage post-operatively, as there are several potential complications that can arise during this period, with etiologies ranging from vascular, biliary, immune-mediated, infectious, or other causes. Any of these complications can be responsible for early graft dysfunction or delayed graft function (DGF). In each of these scenarios, the patient must be worked up in a timely manner, in order for the transplant surgeon to determine feasibility to manage the aforementioned complications conservatively, versus returning to the operating room, or even considering relisting the patient for a new organ. Methods: This is a single center, retrospective chart review of a single patient at Hahnemann University Hospital status post OLT demonstrating significantly prolonged DGF over the course of approximately four months. The data was abstracted retrospectively from the inpatient electronic medical record system, CERNER, to include sociodemographic, clinical, and management information. The primary objective of this case report is to describe the clinical and laboratory changes observed in this patient starting from post-operative day one, until normal graft function was achieved, while focusing on the non-surgical interventions performed during this time period. Results: A 56 year old male with a history of end-stage liver disease due to nonalchololic steatohepatitis with cirrhosis underwent OLT, with allograft obtained through donation after cadiac death and with biopsy proven 5 - 10% microsteatosis with no macrosteatosis, and positive hepatitis B virus and CMV serology. His post-operative course was complicated by persistent C. difficile diarrhea treated with antibiotics and eventual fecal transplantation, and multiple bile leaks originally found at the level of the donor cystic duct remnant, and later at the native cystic stump and at the anastomosis. This was reflected in laboratory results as a persistent cholestatic pattern with total bilirubin levels peaking at about 45 mg/dL with direct bilirubin fraction at about 30 mg/dL over one month after OLT. Biopsy of the allograft showed no signs of acute rejection and imaging consistent with normal vasculature and blood flow. This was managed over the course of the first four months post OLT with up to four ERCP procedures with biliary stents placement, and two visits to interventional radiology for percutaneous biliary drain placement due to hepatic collection and bacteremia. Cholestatic laboratory markers started to slowly decrease around week five after OLT, at which point the patient was deemed ready to be discharged to a local rehabilitation center, and finally they were normalized around the four-month mark. No other surgical interventions were performed during this period of time. Conclusion: Post-operative OLT patients are a complex demographic to manage clinically due to a wide array of potential complications, which can manifest either as early graft dysfunction or DGF. During these complications, there is always a question of whether the patient will need a surgical intervention or if a more conservative approach can be used to overcome said complications. This case report highlights how despite initial graft dysfunction post transplantation, demonstrated by abnormal liver function markers, a new graft can potentially achieve normal function even after prolonged periods of time via medical management and non-surgical interventions. This is clinically significant, as this approach could potentially save this fragile population an unnecessary surgical intervention, and/or prevent relisting. Further research is needed investigating this topic.

Prolonged Delayed Renal Graft Function Secondary to Venous Hypertension.

The case of a 39-year-old highly sensitized woman who underwent second renal transplantation after being on warfarin because of a history of frequent thromboses of her left femoral arteriovenous graft (AVG) is reported here. The patient received a flow cytometric positive crossmatch kidney transplant from a deceased donor. Her posttransplant course was complicated by prolonged delayed graft function (DGF) lasting for 9 months. Antibody-mediated rejection occurred in the immediate postoperative period. This resolved after treatment, and resolution was confirmed by repeat biopsy. Despite this, she had persistent DGF and remained dialysis dependent. A computed tomography scan due to the development of perinephric hematoma after posttransplant biopsy demonstrated venous collateralization around the allograft. At 7 months posttransplant, a venogram during declotting of AVG revealed chronic thrombus in the inferior vena cava (IVC) above the level of native renal veins with a venous gradient of 26 mmHg. After declotting of the graft, iliac venoplasty, and subsequent IVC stent, her renal function continues to improve with a most recent creatinine of 1.4 mg/dL at 36 months posttransplant. Venous hypertension secondary to IVC thrombosis in presence of patent femoral AVG should be considered as a rare cause of prolonged DGF.

Effect of an Early Switch to Belatacept Among Calcineurin Inhibitor-Intolerant Graft Recipients of Kidneys From Extended-Criteria Donors.

Transplant recipients receiving a kidney from an extended-criteria donor (ECD) are exposed to calcineurin inhibitor (CNI) nephrotoxicity, as demonstrated by severe delayed graft function and/or a low GFR. Belatacept is a nonnephrotoxic drug that is indicated as an alternative to CNIs. We reported 25 cases of conversion from a CNI to belatacept due to CNI intolerance within the first 6 mo after transplantation. The mean age of the recipients was 59 years, and 24 of 25 patients received ECD kidneys. At the date of the medication switch, 12 of 25 patients displayed a calculated GFR (cGFR) <15 mL/min, six patients remained on dialysis, and the biopsies showed evidence of acute tubular damage associated with severe vascular or tubulointerstitial chronic lesions. Three patients did not recover renal function, and three patients died during the follow-up period. Among the remaining patients, renal function improved: The cGFR was 18.28 ± 12.3 mL/min before the medication switch compared with 34.9 ± 14.5 mL/min at 1 year after conversion to belatacept (p = 0.002). Tolerance of and compliance with belatacept were good, and only one patient experienced acute rejection. Belatacept is an effective therapy that preserves renal function in kidney transplant patients who are intolerant of CNIs.

Predicting delayed kidney graft function with gene expression in preimplantation biopsies and first-day posttransplant blood

The purpose of this study was to investigate possible markers for predicting delayed graft function (DGF). To this end we analyzed, in pre-implantation biopsies (PIB) and in first-day post-Tx peripheral blood mononuclear cells (PBMC), the expression of five genes (ACSL4, CUBN, DEFB1, FABP3, GK) through real-time TaqMan PCR assays. These genes were selected from a large scale gene expression study in PIB. DEFB1, FABP3 and GK expression levels in PIB were lower in cases with DGF and, in a multivariate analysis which included these genes and clinical variables, only FABP3 expression remained independently associated with DGF. FABP3 expression lower than −1.32 units of relative expression conferred an odds ratio for DGF of 41.1. Compared to the PBMC of recipients without DGF, recipients with prolonged DGF (pDGF) had lower ACSL4 and higher DEFB1 expression levels. In a multivariate analysis, including PBMC gene expression levels of ACSL4, DEFB1 and TLR4 (data from a previous study with the same patients) and clinical variables, only TLR4 remained independently associated with pDGF. In summary, this study revealed FABP3 expression in PIB as a marker for DGF and disclosed new genes possibly involved in the pathogenesis of DGF.

Prolonged Delayed Graft Function Is Associated with Inferior Patient and Kidney Allograft Survivals.

It is unclear if there is an association between the duration of delayed graft function (DGF) and kidney transplant (KT) outcomes. This study investigated the impact of prolonged DGF on patient and graft survivals, and renal function one year after KT. This single center retrospective analysis included all deceased donor KT performed between Jan/1998 and Dec/2008 (n = 1412). Patients were grouped in quartiles according to duration of DGF (1–5, 6–10, 11–15, and >15 days, designated as prolonged DGF). The overall incidence of DGF was 54.2%. Prolonged DGF was associated with retransplantation (OR 2.110, CI95% 1.064–4.184,p = 0.033) and more than 3 HLA mismatches (OR 1.819, CI95% 1.117–2.962,p = 0.016). The incidence of acute rejection was higher in patients with DGF compared with those without DGF (36.2% vs. 12.2%, p<0.001). Compared to patients without DGF, DGF(1–5), DGF(6–10), and DGF(11–15), patients with prolonged DGF showed inferior one year patient survival (95.2% vs. 95.4% vs. 95.5% vs. 93.4% vs. 88.86%, p = 0.003), graft survival (91% vs. 91.4% vs. 92% vs. 88.7% vs. 70.5%, p<0.001), death-censored graft survival (95.7% vs. 95.4% vs. 96.4% vs. 94% vs. 79.3%, p<0.001), and creatinine clearance (58.0±24.6 vs. 55.8±22.2 vs. 53.8±24.1 vs. 53.0±27.2 vs. 36.8±27.0 mL/min, p<0.001), respectively. Multivariable analysis showed that prolonged DGF was an independent risk factor for graft loss (OR 3.876, CI95% 2.270–6.618, p<0.001), death censored graft loss (OR 4.103, CI95% 2.055–8.193, p<0.001), and death (OR 3.065, CI95% 1.536–6.117, p = 0.001). Prolonged DGF, determined by retransplantation and higher HLA mismatches, was associated with inferior renal function, and patient and graft survivals at one year.

Early Sirolimus Conversion as Rescue Therapy in Kidneys With Prolonged Delayed Graft Function in Deceased Donor Renal Transplant

BackgroundIncreasing rate of delayed graft function (DGF) is seen with the use of Donation after circulatory death (DCD) and extended criteria donor (ECD) kidneys. Use of calcineurin inhibitors (CNIs) may add to insult by causing acute and chronic nephrotoxicity ultimately leading to primary non-function (PNF). We report our experience of early sirolimus (SRL) conversion in such cases in an attempt to salvage graft function. MethodsRetrospective study to analyze the impact of early conversion of SRL in patients with prolonged DGF. Two groups were identified: a study (SRL) group with 14 patients and a historic control (CNI) group with 28 patients case-matched based on donor and recipient characteristics. ResultsSRL group included 8 ECD donors with mean DGF duration of 42.3 ± 38.3 days and were converted to SRL 46.6 ± 20.6 days post-transplantation. CNI group had DGF duration of 26.5 ± 9.9 days (P = .03).Mean recipient eGFR (mL/min per 1.73 m2) was 12.2 ± 4.3 pre-SRL and 26.0 ± 11.5, 34.1 ± 17.3 and 28.6 ± 14.3 at 3, 12 and 24 months post-SRL conversion respectively. Seven patients achieved sustained good graft function (mean Cr at 1 year of 140 μmol/L). The mean eGFR of the case-matched control group was 31.7 ± 11.7, 36.3 ± 14.1, and 34.9 ± 13.9 over the same time period (P = .104, .540, and .217). ConclusionConversion to SRL in patients with prolonged DGF may help salvage renal graft function and achieve long-term graft survival in some cases where conventional treatment has failed. We suggest a prospective study of this targeted group to validate such benefit.

Belatacept Conversion in Kidney Transplant Recipients for Prolonged DGF.

Introduction Prolonged delayed graft function (PDGF), which we define as need for HD or a serum creatinine >2 mg/dL >14 days post-transplant, has a negative impact on long-term graft outcome. Tacrolimus may prolong PDGF. We investigated belatacept conversion from tacrolimus as a novel treatment strategy for PDGF. Methods Retrospective single center analysis of the first 11 patients converted to belatacept for PDGF (Group 1) compared to a historical control group of 22 PDGF patients who remained on tacrolimus (Group 2) matched for type of kidney transplant, cause of ESRD, and CIT. A renal allograft biopsy was done to rule out rejection as a cause of PDGF. Included patients demonstrated only acute tubular necrosis on their biopsies. Objectives: compare eGFR and rates of acute rejection and infection during the first 6 months post-transplant. Results Demographic and transplant characteristics were similar.Table: No Caption available.Biopsies to evaluate PDGF occurred on mean POD (SD) 36 (15.7) and 20.2 (19.8) for Groups 1 and 2, respectively (P = 0.03). Mean POD of belatacept conversion was 45.6 (range 18-74). Mean number of HD treatments (SD) for Groups 1 and 2 were 10.7 (10.7) and 13 (7.3), respectively (P = 0.47). Mean eGFR mL/min/1.73m2 (SD) for Groups 1 and 2 were 52.8 (31.6) and 47.2 (24.6; P = 0.59) at 3-months and 59.6 (26.7) and 47.4 (21; P = 0.19) at 6-months post-transplant, respectively. One Banff type 2a clinical rejection occurred in a patient in Group 2; subclinical rejection occurred in 3 patients in Group 1 (all type 1a) and 3 patients in Group 2 (1 type 1a and 2 type 2a). Infectious events were similar. Conclusion Belatacept conversion for PDGF is a novel strategy that resulted in a numerically higher eGFR at 6 months post-transplant compared to a tacrolimus historical control group. Expansion of this cohort with longer follow-up is necessary to further define the efficacy and safety of this strategy. DISCLOSURES:Wojciechowski, D.: Grant/Research Support, BMS. Chandran, S.: Grant/Research Support, BMS. Vincenti, F.: Grant/Research Support, BMS.

Vasculopathy in the kidney allograft at time of transplantation delays recovery of graft function after deceased-donor kidney transplantation

The purpose of this study was to evaluate the impact of donor and recipient characteristics on duration of delayed graft function (DGF) and 1-year serum creatinine (SCr), as a surrogate endpoint for allograft survival. We reviewed 120 first cadaver kidney transplants carried out consecutively at our center to examine the effect on 1-year SCr of the presence and duration of DGF. DGF rate was 68%, with a median duration of 12 days (range, 1-61). Forty-four (38%) patients presented DGF lasting 12 or more days (prolonged DGF group). Mean donor age was 43 ± 13 years, 37% had hypertension and in 59% the cause of brain death was cardiovascular accident. The mean cold ischemia time was 23 ± 5 hours. Twenty-seven (23%) donors were classified as expanded-criteria donors according to OPTN criteria. The mean recipient age was 51 ± 15 years. The recipients median time in dialysis was 43 months (range, 1-269) and 25% of them had panel reactive antibodies > 0%. Patients with prolonged DGF presented higher 1-year SCr in comparison with patients without DGF (1.7 vs. 1.3 mg/dL, respectively, p = 0.03). In multivariate logistic regression analysis, the only significant factor contributing to the occurrence of prolonged DGF was the presence of vascular lesions in the kidney allograft at time of transplantation (HR 3.6, 95% CI 1.2-10.2; p = 0.02). The presence of vasculopathy in the kidney allograft at time of transplantation was identified as an important factor independently associated with prolonged DGF. Prolonged DGF negatively impacts 1-year graft function.

Serum Lactic Dehydrogenase Levels as a Prognosis Marker for Clinical Outcomes in Donors after Cardiac Death Kidney Transplant Recipients

Objectives: The aim of this study was: 1) To investigate if lactic dehydrogenase (LDH) levels is a marker for delayed graft function (DGF) and primary non-function (PNF) in kidney transplantation from non-controlled donors after cardiac death (DCD). 2) To evaluate the main risk factors of DGF and PNF in this population and their relationship with serum LDH levels. Materials and methods: All DCD kidney transplantation recipients from January 2008 to December 2011 were included (N=174, mean age 50.5±10 years, 68% male). We examined donor [age, creatinine levels, warm (WIT) and cold ischemic time (CIT)] and demographic recipient parameters, serum LDH and Tacrolimus levels post-transplant and ecographic and doppler data. We investigated the relationship between these parameters and incidence of acute rejection, DGF, PNF and parameters of renal function at one, three, six and twelve month post-transplant. For statistical analysis Student t, Kruskal-Wallis and Chi-square tests were used. Logistic regression analysis was used to determine independent risk factors for DGF and PNF. Results: All patients received induction therapy (Basiliximab or Thymoglobulin) and Tacrolimus as main immunosuppressive. Significant creatinine decrease took place at 16 (11-23) days. Maximum Tacrolimus and LDH levels were 14.7 (5.42) ng/mL and 2700 (1841-4016) UI/L, respectively. A statistical correlation between first day post-transplant LDH levels and CIT were found (r=0.186, p=0.031), but it did not happen in case of WIT (r=0.320, p=0.739). Logistic regression analysis revealed that LDH levels at first day post-transplant >3800 UI/L (percentile 75) (RR 7.911, 95% CI 2.104-29.750, p=0.002) and warm ischemic time (RR 0.966, 95% CI 0.934-0.999, p=0.044) were independent predictors of PNF. Maximum LDH levels>2600 UI/L (percentile 50) was predictor of DGF (RR 10.667, 95% CI 1.103-103.50, p=0.041). Tacrolimus levels>15 ng/mL (RR 2.319, 95% CI 0.926-5.860, p=0.073) and biopsy-proven acute rejection (BPAR) (RR 7.175, 95% CI 1.902-27.063, p=0.040) had a significant association with prolonged DGF (>16 days). Neither BPAR (MDRD-4=47.5±16.0 vs 49.5±18.0 mL/min, p=0.641) nor DGF (MDRD-4=47.1±16.1 vs 52.0±19.4 mL/min, p=0.167) had influence in first year renal function. However, significant differences were found in case of prolonged DGF (MDRD-4=45.5±14.5 vs 58.8±19.8 mL/min, p=0.033). Conclusion: Serum LDH levels in immediate post-transplant period could be a good marker for PNF and DGF in non-controlled DCD renal transplant recipients. WIT is the main risk factor of PNF in our study. These renal grafts have a special vulnerability to several injuries like high Tacrolimus levels and acute rejection episodes, which could impair the DGF. A prolonged DGF could have a negative impact in renal function at first year post-transplant.