Graft Function In Renal Transplantation Research Articles

Necroptosis-related genes allow novel insights into predicting graft loss and diagnosing delayed graft function in renal transplantation

Ischemia–reperfusion injury (IRI) is an inevitable pathophysiological phenomenon in kidney transplantation. Necroptosis is an undoubtedly important contributing mechanism in renal IRI. We first screened differentially expressed necroptosis-related genes (DENRGs) from public databases. Eight DENRGs were validated by independent datasets and verified by qRT-PCR in a rat IRI model. We used univariate and multivariate Cox regression analyses to establish a prognostic signature, and graft survival analysis was performed. Immune infiltrating landscape analysis and gene set enrichment analysis (GSEA) were performed to understand the underlying mechanisms of graft loss, which suggested that necroptosis may aggravate the immune response, resulting in graft loss. Subsequently, a delayed graft function (DGF) diagnostic signature was constructed using the Least Absolute Shrinkage and Selection Operator (LASSO) and exhibited robust efficacy in validation datasets. After comprehensively analyzing DENRGs during IRI, we successfully constructed a prognostic signature and DGF predictive signature, which may provide clinical insights for kidney transplant.

Association of IL-1β rs16944 and IL-1RN rs2234663 gene polymorphisms with graft function in renal transplant recipients

BackgroundAfter renal transplantation, renal graft function affects both patient and graft survival. There is growing evidence of the genetic association between interleukin-1β (IL-1β) or its receptor antagonist (IL-1RN) and graft function in renal transplantation. The objective of this study is to investigate the role of the recipient IL-1β and IL-1RN gene polymorphisms and their haplotypes on renal graft outcome.MethodsUsing PCR, IL-1β (− 511C/T) and IL-1RN (86 bp VNTR) gene polymorphisms were determined in 31 renal allograft recipients; eight cases with stable allograft function and 23 cases with early renal dysfunction as well as 26 age- and gender-matched healthy controls.ResultsA statistically significant difference in IL-1 β (− 511C/T) gene polymorphisms and IL-1RN/IL-1β haplotypes was observed on comparing renal allograft recipients with stable allograft function and those with early renal allograft dysfunction. However, the difference in the frequency distribution of IL-1RN gene polymorphisms, between these two groups, did not reach statistical significance. Also, no statistically significant difference was observed in comparing these two gene polymorphisms and their haplotypes between renal allograft recipients and healthy controls.ConclusionThe IL-1β − 511 CT/TT polymorphic genotypes and IL-1RN/IL-1β polymorphic haplotypes are associated with early renal allograft dysfunction. These are observational data that can be repeated in larger studies. If the results obtained are consistent, this might open doors to personalized medicine where clinicians can take necessary measures to identify the renal transplant recipients’ genotypes at risk of mounting an increased inflammatory response and hence administer the appropriate immunosuppressive protocol.

Calcineurin Inhibition in Deceased Organ Donors: A Systematic Review and Meta-analysis of Preclinical Studies.

Preconditioning deceased organ donors with calcineurin inhibitors (CNIs) may reduce ischemia-reperfusion injury to improve transplant outcomes. We searched MEDLINE, EMBASE, Cochrane Library, and conference proceedings for animal models of organ donation and transplantation, comparing donor treatment with CNIs with either placebo or no intervention, and evaluating outcomes for organ transplantation. Reviewers independently screened and selected studies, abstracted data, and assessed the risk of bias and clinical relevance of included studies. Where possible, we pooled results using meta-analysis; otherwise, we summarized findings descriptively. Eighteen studies used various animals and a range of CNI agents and doses and evaluated their effects on a variety of transplant outcomes. The risk of bias and clinical applicability were poorly reported. Pooled analyses suggested benefit of CNI treatment on early graft function in renal transplants (3 studies; serum creatinine: ratio of means [RoM] 0.54; 95% confidence interval [CI], 0.34-0.86) but not for liver transplants (2 studies; serum alanine transaminase: RoM 0.61; 95% CI, 0.30-1.26; and serum aspartate aminotransferase: RoM 0.58; 95% CI, 0.26-1.31). We found no reduction in graft loss at 7 d (2 studies; risk ratio 0.54; 95% CI, 0.08-3.42). CNI treatment was associated with reduced transplant recipient levels of interleukin-6 (4 studies; RoM 0.36; 95% CI, 0.19-0.70), tumor necrosis factor-alpha (5 studies; RoM 0.36; 95% CI, 0.12-1.03), and cellular apoptosis (4 studies; RoM 0.30; 95% CI, 0.19-0.47). Although this compendium of animal experiments suggests that donor preconditioning with CNIs may improve early kidney graft function, the limited ability to reproduce a true clinical environment in animal experiments and to assess for risk of bias in these experiments is a serious weakness that precludes current clinical application.

Graft and Patient Survival in Kidney Transplant with Deceased Donor Using KDRI (Kidney Donor Risk Index), KDPI (Kidney Donor Profile Index), and EPTS (Estimated Post-Transplant Survival) in Colombia.

BACKGROUND EPTS (Estimated Post-Transplant Survival), KDRI (Kidney Donor Risk Index), and KDPI (Kidney Donor Profile Index) were developed aiming to ameliorate donor-recipient longevity matching in kidney transplants. They are based on a prediction model made using the United States population; evidence of their use outside EEUU remains limited. The aim of this study was to describe the quality of deceased-donor kidneys and to determine recipient and graft survival, glomerular filtration rate, and incidence of delayed graft function in renal transplantation according to these indices in Cali, Colombia. MATERIAL AND METHODS In this historical cohort study, Kaplan-Meier method was used to analyze survival of recipient and graft according to the values of the indices categorized by quintiles. Glomerular filtration rate and incidence of delayed graft function were also analyzed according to KDRI and KDPI. RESULTS We included 380 patients. Medians of EPTS, KDRI, and KDPI were 24% (IQR 9-60), 0.8 (IQR 0.71-0.99), and 27% (IQR 13-49), respectively. Two-year survival was 97.8% in recipients with EPTS ≤20% and it decreased with higher values of the index. Recipient and graft survival were lower for all periods when donors had KDPI >80%. Incidence of delayed graft function was higher in patients whose donors had KDPI ≥60% (44% vs 21%). Glomerular filtration rate decreased with the highest values of KDPI for all periods. CONCLUSIONS Our study represents the initial evaluation of the usefulness of these indices in Colombia. Our results suggest that KDRI, KDPI, and EPTS may serve as valuable tools for kidney allocation in our setting. Further research with larger sample sizes is necessary to validate these indices in our population.

Predictors of Delayed Graft Function in Renal Transplantation

Purpose: This study aimed to analyze our data on delayed graft function (DGF) and to identify associated factors. Methods: This is a retrospective case-control study of all patients transplanted in our center over a period of 11 years (January 1, 2003, to December 31, 2014) comparing patients with immediate graft function (n = 332) to those with DGF (n = 165). DGF was defined as the need for hemodialysis within the first 7 days after transplantation. Donor and recipient characteristics as well as procedural factors were compared by univariate and multivariate logistic regression analyses. Results: Overall, 33% of patients had DGF. The rate of DGF declined from 2003 to 2011. In cases with DGF, donors and recipients were significantly older (p = 0.004 and p = 0.005, respectively), had longer cold ischemia times (p = 0.039), more revision surgeries (p < 0.001), and more HLA mismatches (p = 0.001), especially in the DR locus (p = 0.002). Neither donor nor recipient gender, waiting time, nor CMV status had any influence. In multivariable analysis, significant risk factors were ischemia time and mismatches at the HLA-DR loci. Conclusions: DGF is a common complication in renal transplantation which occurred in 33% of our cases. Important factors identified were donor and recipient age, ischemia time, HLA mismatching, and revision surgery.

Risk factors and consequences of delayed graft function in renal transplantation

Background/Aim: Delayed graft function (DGF) continues to be an important complication in patients who underwent kidney transplantation. Our study aimed to determine the rate of DGF and risk factors after renal transplantation at our center and explore DGF-related complications and outcomes. Methods: Patients over 18 years of age who underwent kidney transplantation between January 2015 and January 2020 were evaluated. DGF was defined as the need for at least one dialysis session within the first week after renal transplantation. The factors affecting DGF were analyzed as the primary outcome, and discharge and additional complications, as the secondary outcomes. Results: Data of 206 patients who underwent renal transplantation were analyzed, and delayed graft function (the need for at least one dialysis session within the first week after renal transplantation) was observed at a rate of 20.9%. A statistically significant relationship was observed between DGF and presence of diabetes mellitus, cadaver graft transplantation, higher cold ischemia time, need for postoperative erythrocyte suspension and fresh frozen plasma transfusion (P<0.05 for all). Graft loss was significantly higher in patients with DGF (P=0.001). Conclusion: After renal transplantation, delayed graft function continues to occur at a high rate. Prevention of delayed graft function development will reduce graft loss rates.

The use of thromboelastography to assess post-operative changes in coagulation and predict graft function in renal transplantation

BackgroundEnd stage renal disease (ESRD) is associated with elevated fibrinogen levels and fibrinolysis inhibition. However, there is a paucity of data on how renal transplantation impacts coagulation. we hypothesize that renal transplantation recipients with good functioning grafts will have improved fibrinolytic activity following surgery. MethodsKidney recipients were analyzed pre-operatively and on post-operative day 1(POD1) using three different TEG assays with and without two concentration of tissue-plasminogen activator (t-PA). TEG indices and percent reduction in creatinine from pre-op to POD1 were measured, with >50% defining “good” graft function. Follow up was done at 6, 12, and 24 months. ResultsPercent lysis(LY30) on POD1 the t-PA TEG was significantly correlated to change creatinine from pre-op to POD-1(p = 0.006). A LY30 ≥ 23% was associated with good early graft function, and lower creatinine at 24-months(p = 0.028) compared to recipients with low POD1 LY30. ConclusionsPost-operative tPA-TEG LY30 is associated with favorable early and late outcomes in kidney transplant.

Timely surgical intervention for ureteric complications ensures adequate graft function in renal transplantation: a 10-year review.

Ureteric complications can cause significant morbidity in renal and simultaneous pancreas-kidney (SPK) transplantation. This 10-year review identified transplant patients with ureteric complications necessitating surgical intervention in an Australian tertiary centre. The hospital records were scrutinized in detail to identify all patients who underwent renal or SPK transplantation from 1 June 2009 to 31 May 2019 with subsequent surgical management of ureteric complications. A case series of patients with ureteric complications was generated and findings were analysed. A total of 893 renal and SPK transplants were performed over the 10-year period. Ten of these (1.12%; seven renal and three SPK) had ureteric complications. All were managed surgically. Five of the 10 had ureteric leaks (0.56%); three had ureteric strictures (0.34%), one had ureteric obstruction from extraluminal compression (0.11%) and one had both leak and stricture (0.11%). All 10 patients underwent ureteric reimplantation. Two patients required more than one operation for their ureteric complication. No graft loss or surgical mortality occurred. All 10 patients currently have functioning kidney transplants and none require maintenance dialysis. We report a low rate (1.12%) of ureteric complications in our renal and SPK transplants. Our standard practice of definitive correction by ureteric reimplantation is proving successful. The authors confirm that appropriate surgery is a viable and durable option in renal transplant patients with excellent graft outcomes.

250 Delayed Graft Function in Renal Transplantation

250 Delayed Graft Function in Renal Transplantation

Specific expression of heme oxygenase-1 by myeloid cells modulates renal ischemia-reperfusion injury

Renal ischemia-reperfusion injury (IRI) is a major risk factor for delayed graft function in renal transplantation. Compelling evidence exists that the stress-responsive enzyme, heme oxygenase-1 (HO-1) mediates protection against IRI. However, the role of myeloid HO-1 during IRI remains poorly characterized. Mice with myeloid-restricted deletion of HO-1 (HO-1M-KO), littermate (LT), and wild-type (WT) mice were subjected to renal IRI or sham procedures and sacrificed after 24 hours or 7 days. In comparison to LT, HO-1M-KO exhibited significant renal histological damage, pro-inflammatory responses and oxidative stress 24 hours after reperfusion. HO-1M-KO mice also displayed impaired tubular repair and increased renal fibrosis 7 days after IRI. In WT mice, HO-1 induction with hemin specifically upregulated HO-1 within the CD11b+ F4/80lo subset of the renal myeloid cells. Prior administration of hemin to renal IRI was associated with significant increase of the renal HO-1+ CD11b+ F4/80lo myeloid cells in comparison to control mice. In contrast, this hemin-mediated protection was abolished in HO-1M-KO mice. In conclusion, myeloid HO-1 appears as a critical protective pathway against renal IRI and could be an interesting therapeutic target in renal transplantation.

Induction Immunosuppressive Therapy Use in Deceased Donor Kidney Transplantation: 11-Year Experience in Veracruz, Mexico

BackgroundInduction therapy reduces the frequency of acute rejection and delayed graft function in renal transplantation. Basiliximab and Thymoglobulin are most commonly used agents for induction. MethodsA retrospective study of two transplant centers in Veracruz, Mexico compared induction therapy in deceased donor renal transplantation from 2003 to 2014. Efficacy and safety outcomes evaluated were primary graft nonfunction, delayed graft function, acute rejection episodes and hospitalizations during first year, and patient and graft survival. P < .05 was considered statistically significant. ResultsSeventy deceased kidney donors (40 male) were studied. Mean donor age was 32.9 ± 14.3 years, mean donor BMI 25.6 ± 4.3 kg/m2, and mean donor creatinine 1.13 ± 0.58 mg/dL. Main cause of death was trauma (62.9%). In total, 125 kidney transplantations were performed, with female predominance (53.6%) and mean age 33.8 ± 11.8 years. Of these, 66.4% used basiliximab and 33.6% Thymoglobulin. Thymoglobulin patients were significantly older, with lower weight and BMI, and were on dialysis longer than basiliximab patients. DGF was present in 19.3% of basiliximab patients vs 16.7% in Thymoglobulin patients, acute rejection occurred in 16.9% of basiliximab patients vs 19% Thymoglobulin patients. A total of 33.7% basiliximab patients were hospitalized during the first year vs 47.6% Thymoglobulin-induced patients (P > .05). Mean graft survival was 84.2 ± 5.3 months (73.8–94.7) basiliximab vs 32.4 ± 28.7 months (28.7–36.1) Thymoglobulin, Kaplan-Meier survival did not show statistically significant differences between groups (P = .276; CI 95%). ConclusionSimilar transplant outcomes were obtained using basiliximab or Thymoglobulin induction in our population.

The effect of pre-operative methylprednisolone on the incidence of delayed graft function in renal transplantation

Introduction: This study explores the effect of different corticosteroid administration timings on the incidence of slow/delayed graft function. Methods: One hundred and twelve kidney transplants from January 2011 to March 2014 were retrospectively analysed. Thirty-six cases were excluded because they were donor-specific antibody positive ( n=16), received thymoglobulin/plasma exchange ( n=11), were ABO-incompatible ( n=6) or suffered graft loss from vascular thrombosis within the first week post-transplant ( n=3). The study period straddled three eras of corticosteroid administration, from intra-operative intravenous (IV) hydrocortisone (Era 1; n=26), to intra-operative IV methylprednisolone (Era 2; n=38) and pre-operative IV methylprednisolone (Era 3; n=12). The primary endpoint was the incidence of slow/delayed graft function. Secondary outcomes included estimated glomerular filtration rate at discharge and 120 and 365 days, rejection (acute and one-year), wound complications, post-transplant diabetes, increase in low-density lipoprotein or body mass index, and cytomegalovirus or BK viraemia within one year. Results: On univariate analysis, pre-operative methylprednisolone was associated with lower incidence of slow/delayed graft function (17%, 55%, 58% in Eras 3, 2, 1 respectively; p=0.041), superior estimated glomerular filtration rate at discharge (median 56, 37 and 43 ml/min for Eras 3, 2, 1 respectively; p=0.033) and at 120 days (median 60, 52, and 46 ml/min for Eras 3, 2, 1 respectively; p=0.017). On multivariate analysis, pre-operative IV methylprednisolone ( vs. Eras 1 and 2 combined; odds ratio 4.79 (90% confidence interval 1.16–19.80); p=0.07) and living donor type ( vs. deceased; odds ratio 5.56 (90% confidence interval 2.25–13.77); p=0.002) were associated with lower incidence of slow/delayed graft function. Conclusion: Pre-operative methylprednisolone was associated with reduced slow/delayed graft function and improved early estimated glomerular filtration.

Propofol Prevents Renal Ischemia-Reperfusion Injury via Inhibiting the Oxidative Stress Pathways

Background/Aims: Renal ischemia/reperfusion injury (IRI) is a risk for acute renal failure and delayed graft function in renal transplantation and cardiac surgery. The purpose of this study is to determine whether propofol could attenuate renal IRI and explore related mechanism. Methods: Male rat right kidney was removed, left kidney was subjected to IRI. Propofol was intravenously injected into rats before ischemia. The kidney morphology and renal function were analyzed. The expression of Bax, Bcl-2, caspase-3, cl-caspase-3, GRP78, CHOP and caspase-12 were detected by Western blot analysis. Results: IR rats with propofol pretreatment had better renal function and less tubular apoptosis than untreated IR rats. Propofol pretreated IR rats had lower Bax/Bcl-2 ratio and less cleaved caspase-3. The protein expression levels of GRP78, CHOP and caspase-12 decreased significantly in propofol pretreated IR rats. In vitro cell model showed that propofol significantly increased the viability of NRK-52E cells that were subjected to hypoxia/reoxygenation (H/R) in a dose-dependent manner. The effect of propofol on the expression regulation of Bax, Bcl-2, caspase-3, GRP78, CHOP was consistent in both in vitro and in vivo models. Conclusion: Experimental results suggest that propofol prevents renal IRI via inhibiting oxidative stress.

The Utility of Serial Allograft Biopsies during Delayed Graft Function in Renal Transplantation under Current Immunosuppressive Regimens

Delayed graft function (DGF) of kidney transplants increases risk of rejection. We aimed to assess the utility of weekly biopsies during DGF in the setting of currently used immunosuppression and identify variables associated with rejection during DGF. We reviewed all kidney transplants at our institution between January 2008 and December 2011. All patients received rabbit antithymocyte globulin/Thymoglobulin (ATG) or Basiliximab/Simulect induction with maintenance tacrolimus + mycophenolate + corticosteroid therapy. Patients undergoing at least one weekly biopsy during DGF comprised the study group. Eighty-three/420 (19.8%) recipients during this period experienced DGF lasting ≥1 week and underwent weekly biopsies until DGF resolved. Biopsy revealed significant rejection only in 4/83 patients (4.8%) (one Banff 1-A and two Banff 2-A cellular rejections, and one acute humoral rejection). Six other/83 patients (7.2%) had Banff-borderline rejection of uncertain clinical significance. Four variables (ATG versus Basiliximab induction, patient age, panel reactive anti-HLA antibody level at transplantation, and living versus deceased donor transplants) were statistically significantly different between patients with and without rejection, though the clinical significance of these differences is questionable given the low incidence of rejection. Conclusions. Under current immunosuppression regimens, rejection during DGF is uncommon and the utility of serial biopsies during DGF is limited.

Delayed graft function in renal transplantation: risk factors and impact on prognosis - a single center analysis

Delayed graft function in renal transplantation: risk factors and impact on prognosis - a single center analysis

The Influence of Intraoperative Central Venous Pressure on Delayed Graft Function in Renal Transplantation: A Single-Center Experience

Introduction Delayed graft function (DGF) is a common complication in kidney transplantation. We sought to evaluate possible correlates for DGF including intraoperative parameters, focusing on fluid replacement and central venous pressure (CVP) values among patients undergoing kidney transplantation at our center. Methods One hundred fifty-five cadaveric donor transplantations performed at our center between 2001 and 2005 were selected for the study. We compared intraoperative parameters together with 15 other clinical and socio-demographic recipient and donor variables among patients experiencing DGF (n = 58) versus those with immediate graft function (IGF; n = 97). All significant variables at P < .05 upon univariate analysis were entered into a multivariate logistic regression model to identify risk factors for DGF. Results CVP at awakening of ≤8 mm Hg (odds ratio [OR] = 3.53; 95% confidence interval [CI], 1.63–7.63), fluid input during surgery ≤2.250 mL (OR = 2.12; 95% CI, 1.00–4.51), and recipient age ≥50 years (OR = 2.72; 95% CI, 1.11–6.68) were the strongest correlates of DGF. Conclusions Our data suggested that reduced intraoperative perfusion as measured using CVP monitoring might increase DGF risk. This study provides the rationale to further investigate the optimal CVP target during this surgery.

JNK signalling in human and experimental renal ischaemia/reperfusion injury

Ischaemia/reperfusion (I/R) is an important factor in delayed graft function in renal transplantation and is a determinant of long-term graft outcome. This study examined the role of c-Jun N-terminal kinase (JNK) signalling in human and experimental renal I/R injury. Biopsies obtained 15-20 min after reperfusion of human renal allografts were examined for JNK signalling by immunostaining for phospho-c-Jun. To examine the pathologic role of JNK signalling, a selective JNK inhibitor (CC-401) was administered to rats before or after the induction of a 30-min period of bilateral renal ischaemia followed by reperfusion. Renal function and tubular damage were analysed. Substantial JNK activation was evident in tubular epithelial cells in kidneys from deceased donors (n = 30) which was less prominent in kidneys from live donors (n = 7) (44.6 +/- 24.8% vs 29.1 +/- 20% p-c-Jun+, respectively; P < 0.05), whereas biopsies of thin basement membrane disease exhibited little, or no, p-c-Jun staining. The degree of p-c-Jun staining correlated with ischaemic time in deceased donor allografts, but not with graft function. Administration of CC-401 to rats prior to bilateral renal I/R prevented acute renal failure and largely prevented tubular damage, leucocyte infiltration and upregulation of pro-inflammatory molecules. However, delaying CC-401 treatment until 1 h after reperfusion (after the peak of JNK activation) had no protective effect. We have identified acute activation of the JNK signalling pathway following I/R in human kidney allografts. Experimental studies indicate that blockade of JNK signalling, commenced prior to this activation, can prevent acute tubular necrosis and renal dysfunction secondary to I/R injury.

Fate of the Mate: The Influence of Delayed Graft Function in Renal Transplantation on the Mate Recipient

Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of -11.2 mL/min, while the control group had a mean change of -0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these'at-risk'recipients should be developed and tested.

Incidence and Factors Associated With Delayed Graft Function in Renal Transplantation at Carlos Van Buren Hospital, January 2000 to June 2008

Delayed graft function (DGF) is defined as the need for dialysis within the first week after renal transplantation, and slow graft function as persistence of serum creatinine concentration of at least 3 mg/dL on day 5 after the procedure. In the present study, we analyzed the incidence and risk factors for DGF at our center. This retrospective study included 106 patients who underwent renal transplantation between January 2000 and June 2008. Of these, 11 patients were excluded. Two of the remaining 95 patients received organs from living donors, and 93 received cadaver organs. Variables analyzed included donor age, cause of death, cause of chronic renal failure, recipient age, method and time of long-term renal replacement therapy, residual diuresis, panel of reactive antibodies (PRA), HLA mismatch, sex compatibility, cold and warm ischemia times, biopsy-confirmed episodes of acute rejection, urine output in the operating room and in the first 24 hours after the procedure, and intraoperative induction therapy. Data were analyzed using the chi(2) and Fisher exact tests and analysis of variance, and are given as mean (SD) and frequency. Variables associated with DGF at univariate analysis (P < .05) were divided between risk factors and predictors of DGF for inclusion in logistic regression models. The incidence of DGF was 32.6%; slow graft function, 16.8%; and immediate graft function, 50.5%. Cold ischemia time longer than 20 hours (P = .02) and donor age (P = .008) were directly associated with DGF. Twenty-four-hour urine output was a strong predictor of DGF. Patients with DGF demonstrated a 25% incidence of an episode of acute rejection before discharge from the hospital. No difference in DGF was observed for use of intraoperative induction therapy.

Delayed graft function in renal transplantation

Delayed graft function is an important determinant of patient and graft survival. A complex of pathologic mechanisms intervenes in the pathophysiology of this outcome. This paper reviews the main processes involved in delayed graft function as they relate to five chronologically related stages: donor tissue quality, brain death and related stress, preservation variables, immune factors, and recipient variables. Dialyzed delayed graft function and nondialyzed slow graft function both have a negative impact on graft survival and on the incidence of acute rejection. Expanded-criteria donors, older donors, and non-heart-beating donors are more frequently used. The long-term results of the use of well-selected non-heart-beating donors are surprisingly good. The process of ischemia/reperfusion injury is already initiated in the brain-death donor and continues during preservation of the graft. Graft-infiltrating T cells, heat shock proteins, and heme oxygenase-1 are implicated in the process. Modifications in immunosuppressive therapy and pharmacologic modulations have an effect on delayed graft function. Delayed graft function plays a part in the incidence of acute rejection, impaired graft function, and survival of patients and grafts. This review discusses the current literature on several recent findings of pathophysiologic mechanisms of, and possible therapeutic interventions in, delayed graft function.