Clinical Implications of Initial Renal Function After Deceased Donor Transplant

The aim of this study was to investigate whether slow graft function (SGF) after transplantation of deceased-donor kidneys affected the prevalence of anemia or the glomerular filtration rate (GFR). We retrospectively evaluated the records of 534 kidney transplant patients who were classified based on their initial renal function, namely, immediate graft function (IGF), slow graft function (SGF), or delayed graft function (DGF). Among the 534 kidney transplant patients studied, the occurrences of each condition were IGF 104, SGF 133, and DGF 297. Six months after transplantation, a greater percentage of DGF patients were anemic compared with the others (P = .028). However, at 12 months after transplantation, SGF patients showed more anemia than the IGF group. DGF and SGF patients displayed similar GFR values at 18 and 24 months after transplantation. However, IGF patients displayed higher GFRs, even when subjects who experienced acute rejection episodes were censored (P = .004). The incidence of acute rejection episodes was similar among SGF and DGF patients. Patients displaying SGF after deceased-donor transplantation showed a greater tendency to be anemic than those displaying IGF. This study also suggested that SGF patients were at risk for acute rejection episodes and/or significantly reduced kidney function as measured by GFR.     

Reduced graft function (with or without dialysis) vs immediate graft function--a comparison of long-term renal allograft survival.

BACKGROUND: Delayed graft function (DGF) is a common complication in cadaveric kidney transplants affecting graft outcome. However, the incidence of DGF differs widely between centres as its definition is very variable. The purpose of this study was to define a parameter for DGF and immediate graft function (IGF) and to compare the graft outcome between these groups at our centre. METHODS: The renal allograft function of 972 first cadaveric transplants performed between 1990 and 2001 in the Republic of Ireland was examined. The DGF and IGF were defined by a creatinine reduction ratio (CRR) between time 0 of transplantation and day 7 post-transplantation of <70 and >70%, respectively. Recipients with reduced graft function (DGF) not requiring dialysis were defined as slow graft function (SGF) patients. The serum creatinine at 3 months, 6 months, 1, 2 and 5 years after transplantation was compared between these groups of recipients. The graft survival rates at 1, 3 and 5 years and the graft half-life for DGF, SGF and IGF recipients were also assessed. RESULTS: Of the 972 renal transplant recipients, DGF was seen in 102 (10.5%) patients, SGF in 202 (20.8%) recipients and IGF in 668 (68.7%) patients. Serum creatinine levels were significantly different between the three groups at 3 and 6 months, 1, 2 and 5 years. Graft survival at 5 years for the DGF patients was 48.5%, 60.5% for SGF recipients and 75% for IGF patients with graft half-life of 4.9, 8.7 and 10.5 years, respectively. CONCLUSION: This study has shown that the CRR at day 7 correlates with renal function up to 5 years post-transplantation and with long-term graft survival. We have also demonstrated that amongst patients with reduced graft function after transplantation, two groups with significantly different outcomes exist.     

Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients

Sadeghi M, Daniel V, Naujokat C, Schmidt J, Mehrabi A, Zeier M, Opelz G. Decreasing plasma soluble IL‐1 receptor antagonist and increasing monocyte activation early post‐transplant may be involved in pathogenesis of delayed graft function in renal transplant recipients
Clin Transplant 2010: 24: 415–423. © 2009 John Wiley & Sons A/S. Abstract: Delayed graft function (DGF) increases the risk of acute allograft rejection and may affect long‐term graft survival. We compared pre‐transplant, early post‐transplant, and late post‐transplant serum creatinine (Cr) and plasma levels of neopterin, cytokines, and cytokine receptors/antagonists in patients with DGF (n = 39), slow graft function (SGF) (n = 43), or immediate graft function (IGF) (n = 30). Three and eight days post‐transplant, plasma neopterin (p < 0.001; p < 0.001), Soluble Interleukin‐6 (IL‐6) receptor (R) (p = 0.002; p = 0.001), and IL‐10 (p = 0.003; p = 0.001) were higher in DGF than IGF patients. One month post‐transplant, plasma neopterin (p < 0.001) and IL‐10 (p < 0.001) were higher in DGF than IGF patients. Three days post‐transplant, the results indicated reduced sIL‐1 receptor antognist (RA) production in DGF patients (p = 0.001). Simultaneously, plasma sIL‐6R and IL‐10 increased in DGF (p < 0.001; p = 0.003) and SGF (p = 0.007; p = 0.030) patients, indicating increased production of sIL‐6R and IL‐10. Lower sIL‐1 production in DGF than IGF patients early post‐transplant might promote the increased production of monocyte‐derived neopterin, sIL‐6R, and IL‐10. This monocyte/macrophage activation might induce inflammation in the graft and subsequently cause an impairment of graft function. Blocking of monocyte activity after renal transplantation may be considered a potential approach for improving graft outcome.     

Immunosuppression for delayed or slow graft function in primary cadaveric renal transplantation: use of low dose tacrolimus therapy with post-operative administration of anti-CD25 monoclonal antibody

BACKGROUND: Patients who develop delayed graft function (DGF) following cadaveric renal transplantation have inferior survival to those who do not. Calcineurin inhibitors (CNI) may prolong recovery from DGF. Patients with DGF are therefore routinely treated with either polyclonal antilymphocyte preparations or monoclonal anti-CD3 monoclonal antibodies and delayed introduction of CNI. The purpose of this study was to evaluate the efficacy of the anti-CD25 monoclonal antibody basiliximab (BSLIX) started post-operatively in patients at high risk for DGF combined with low dose tacrolimus (TAC). METHODS: Patients who received a primary cadaveric renal transplant only after August 1998 were included in this retrospective study (n = 143). All patients received TAC and mycophenolate Mofetil (MMF) pre-operatively. At 6 h post-operatively, graft function was assessed clinically by urine output and serum creatinine. Those patients who had a urine output < 300 cc/6 h or a rising serum creatinine were presumed to be at risk for DGF (n = 46). These patients were treated with 20 mg BSLIX and had TAC dose reduced to maintain a trough blood level of < 5 ng/mL. Basiliximab was repeated at day 5. Patients not felt to be at risk for DGF were treated with standard TAC dose with trough level target of 9-12 ng/mL. Patients at risk were classified as DGF if they needed dialysis or as slow graft function (SGF) if they did not. The combined group (SGF/DGF) were analysed together. Patients with SGF/DGF had their TAC dose increased to achieve trough levels of 9-12 ng/mL when renal function improved. Patient groups were compared for demographics, need for dialysis, serum creatinine, glomerular filtration rate (GFR), TAC trough levels, MMF dosage, complications and 1- and 2-yr actuarial graft survival. RESULTS: Patients with SGF/DGF had a longer length of stay (8 vs. 5.7 d), were more likely to be black (41.3 vs. 25.7%), and required more post-operative haemodialysis (HD) (52.2 vs. 4.1%). SGF/DGF and non-SGF/DGF patients had similar rates of rejection (28.2 vs. 19.6%, p = 0.28) and steroid resistant rejection (SRR) (6.5 vs. 2.1%, p = 0.32). There were no differences in the rate of cytomegalovirus (CMV) infection (4.3 vs. 6.1%). Serum creatinine was higher and GFR lower at all time points in the SGF/DGF patients. The 1 and 2 yr actuarial survival in the non-SGF/DGF patients was 97.6 and 97.6% compared with 1 and 2 yrs actuarial survival of 94.1% and 80.0% in the SGF/DGF patients, p = 0.04. There were no differences in patient survival. There were no differences in actuarial survival for the SGF/DGF patients who received dialysis compared with those who did not receive dialysis. Comparison of patients who received HD (n = 28) to those who did not (n = 115), regardless of group demonstrated no difference in 1 and 2 yrs actuarial survival, 100 and 94.1% in HD patients vs. 98.2 and 92.5% in non-HD patients. CONCLUSIONS: The clinical diagnosis of SGF/DGF can be made 6 h post-operatively based on urine output and serum creatinine. Basiliximab can be started post-operatively in these patients and decreased levels of TAC can be used to achieve acceptably low rates of rejection in these patients. However, SGF/DGF patients, regardless of their need for dialysis, have worse function at 1 yr and lower 2-yr actuarial graft survival compared with non-SGF/DGF patients. Most of the poor survival can be attributed to the SGF group. Further strategies to either prevent SGF/DGF or to optimize treatment in these patients are needed.     

Risk factors for slow graft function after kidney transplants: a multivariate analysis

BACKGROUND: We previously defined an intermediate group of cadaver kidney transplant recipients who do not have immediate graft function (IGF), but do not have sufficient graft dysfunction to be classified as having delayed graft function (DGF). We showed that this group with slow graft function (SGF) had an increased risk of rejection and inferior long-term results vs. recipients with IGF. The aim of our current study was to determine risk factors for SGF, which have not been well defined (in contrast to risk factors for DGF). METHODS: Between January 1, 1984 and September 30, 1999, we performed 896 adult cadaver kidney transplants at the University of Minnesota. Recipients were analysed in three groups based on initial graft function: IGF [creatinine (Cr) < 3 mg/dL by post-operative day (POD) no. 5], SGF (Cr > 3 mg/dL on POD no. 5, but no need for dialysis), and DGF (need for dialysis in the first week post-transplant). A multivariate analysis looked specifically at risk factors for SGF, as compared with risk factors for DGF. Outcomes with regard to graft survival and acute rejection (AR) rates were determined for the three groups. RESULTS: Of the 896 recipients, 425 had IGF, 238 had SGF, and 233 had DGF. A multivariate analysis of risk factors for SGF showed donor age >50 yr (RR=3.3, p=0.0001) and kidney preservation time >24 h (RR=1.6, p=0.01) to be the most significant risk factors. A multivariate analysis of risk factors for DGF showed similar findings, although high panel-reactive antibodies (PRA) and donor Cr >1.7 mg/dL were also significant risk factors for DGF. Initial function of the graft significantly influenced the subsequent risk of AR: at 12 months post-transplant, the incidence of AR was 28% for those with IGF, 38% for those with SGF, and 44% for those with DGF (p=0.04 for SGF vs. DGF). Initial graft function also significantly influenced graft survival: the 5-yr death-censored graft survival rate was 89% for recipients with IGF, 72% for those with SGF, and 67% for those with DGF (p=0.01 for IGF vs. SGF; p=0.03 for SGF vs. DGF). CONCLUSIONS: SGF represents part of the spectrum of graft injury and post-transplant graft dysfunction. Risk factors for SGF are similar to those seen for DGF. Even mild to moderate graft dysfunction post-transplant can have a negative impact on long-term graft survival.     

Influence of dialysis on post-transplant events

INTRODUCTION: We examined the effect of haemodialysis (HD) or peritoneal dialysis (PD) on acute rejection, delayed graft function (DGF), graft and patient survival after cadaveric renal transplantation. MATERIALS AND METHODS: We carried out a retrospective analysis of 325 patients (cyclosporin [CyA]-based therapy) who had their first cadaver renal transplant between January 1991 and December 1996 and followed up for a mean of 61 +/- 26 months. They were divided into three groups: HD, PD and CD (where both PD and HD was used for at least 3 months). Delayed graft function was diagnosed if the patient needed dialysis in the first week post-transplant while primary non-function (PNF) was diagnosed if the kidney never achieved function. Graft rejection was confirmed by biopsy; early acute rejection (EAR) was defined as acute rejection occurring before 90 days and late acute rejection (LAR) as one after 90 d. RESULTS: A total of 183 patients had PD, 117 HD and 25 CD. The mean time period in which the patients were on dialysis for PD was 24 months, HD 34.5 months and CD 50.6 months (p < 0.01). The recipients were matched for age and gender. The donor variables (age, gender and cold ischaemia time) did not differ between the groups. The mean time for the development of first acute rejection following renal transplant in each group was as follows: PD group: 68.8 d, HD group: 81.3 d and CD group: 105 d (p = 0.08). The number of patients who developed EAR was 90 (49.2%) in PD group, 51 (43.6%) in HD group and 11 (56%) in CD group (p = 0.6); the number who developed LAR was nine in PD group (4.9%), six in HD group (5.1%) and one in CD group (4%) (p = 0.9). Fifty-six patients with PD had DGF compared with 58 with HD (p = 0.01). There was no difference in the number and severity of rejection episodes or DGF based on the duration of dialysis. The 5-yr survival of patients was 79% for PD, 81% HD and 78% CD groups (p = n.s), while the graft survival for PD group was 61%, HD group 63% and CD group 74% (p = n.s). SUMMARY: We could find no difference in the patient or graft survival between patients who had pre-transplant HD, PD or CD. There was no difference in the incidence of acute rejection episodes between the three groups of patients as well. However, we found a significantly higher rate of DGF in the HD versus PD patients.     

Similar impact of slow and delayed graft function on renal allograft outcome and function

Kidney transplant patients can be divided into three groups, according to the initial graft function. First-week dialyzed patients form the delayed graft function (DGF) group. Nondialyzed patients are divided into slow graft function (SGF) or immediate graft function (IGF) according to whether the day 5 serum creatinine was higher versus lower than 3 mg/dL, respectively. SGF patients showed worse graft survival, above higher incidence of acute rejection and lower renal function than IGF patients, although few reports have analyzed outcomes in these groups. We analyzed the impact of SGF on graft survival, first-year renal function, and incidence of acute rejection in 291 renal transplant patients. Creatinine was significantly worse at 12 months for SGF and DGF than for IGF patients (1.9 +/- 0.8 mg/dL, 1.8 +/- 0.7 mg/dL, 1.5 +/- 0.5 mg/dL, respectively; P < .05). There was no difference in first-year renal function between SGF and DGF. The acute rejection rate was higher among the SGF than the IGF group (45% vs 21%, P < .05), but not different from DGF patients (42%, P < .05). Graft survival was better among IGF than SGF or DGF patients, with no significant difference between the last two groups (3-year graft survival, 82%, 71%, 70%, respectively; log-rank test, P < .05). Kidney transplant recipients who develop SGF have a worse outcome than patients with IGF, similar to DGF patients. SGF patients show worse graft survival, worse renal function, and higher acute rejection rates than IGF patients, despite not needing dialysis.     

应用血肌酐下降率预测肾移植患者术后早期肾功能恢复情况

目的 探讨肾移植术后患者SCr下降率(CRRz)与早期移植肾功能恢复情况的相关性,建立早期预测移植.肾功能恢复的标准. 方法同种异体肾移植术后患者80例.分3组:①移植肾功能立即恢复(IGF)组53例,术后5 d SCr＜265.2 gmol/L;②移植肾功能缓慢恢复(SGF)组14例,术后5 d SCr＞265.2gmol/L,但1周内不需要透析治疗;③移植肾功能延迟恢复(DGF)组13例,术后1周内需要透析治疗.比较分析3组患者CRR:值和CRRz的99%可信区间(99%CI).结果 IGF组、SGF组和DGF组患者CRR2值分别为(46.8±14.6)%、(25.6±13.5)%和(0.7±17.7)%,99%C1分别为41%～52%、15%～36%和-14%～16%.3组间CRR2值两两比较,差异有统计学意义(P≤0.01).由3组CRR2的99%CI设定IGF、SGF、DGF的早期预测标准分别为CRR2≥40%、15%＜CRR2＜40%和CRR2≤15%.结论 CRR2与术后早期移植肾功能恢复情况有较好的相关性,可用于早期预测移植术后患者发生明功能延迟恢复的风险.     

Influence of genetic polymorphisms in GSTM1, GSTM3, GSTT1 and GSTP1 on allograft outcome in renal transplant recipients

Abstract: Introduction: Glutathione S‐transferases (GSTs) are important in protection against xenobiotic compounds and toxicity caused by immunosuppressants in renal transplant recipients. In the present study we hypothesize that genetic variability in GSTM1, GSTM3, GSTP1 and GSTT1 genes may be associated with allograft outcome. Methods: The study included 223 controls and 273 transplant recipients categorized into 184 stable graft function (SGF), 57 rejection episodes (RE) and 32 delayed graft function (DGF). The polymorphism was studied using multiplex PCR and PCR‐RFLP. Results: GSTM1 null genotype showed a 3.35‐fold higher risk for rejection in SGF vs. RE category [95% confidence interval (CI) 1.27–8.84, p = 0.014]. Mutant (G) allele of GSTP1 was associated with a 5.52‐fold risk for DGF (95% CI 1.37–22.17, p = 0.016). Kaplan–Meier analysis revealed significantly lower mean time to first RE in null genotype as compared with GSTM1 present patients (Log p = 0.002). The dose adjusted C₂ levels in null genotype was higher as compared with GSTM1 present patients at one (p = 0.007) and three months (p = 0.027) post transplantation. Conclusion: Patients with variant genotype of GSTM1 and GSTP1 were at higher risk for rejection and delayed functioning of the allograft, respectively, supporting the hypothesis for involvement of GST isoform variants in allograft outcome in renal transplant recipients.     

Analysis of Clinical Outcomes According to the Definition of Slow Graft Function in Deceased Donor Kidney Transplantation

BackgroundSlow graft function (SGF) is considered to be an intermediate state between immediate graft function (IGF) and delayed graft function (DGF). However, the criteria of SGF is still arbitrary, and the clinical outcomes of SGF are not fully understood.MethodsA total of 212 deceased donor kidney transplantation recipients were enrolled. Three schemas were adopted, which classified SGF according to the serum creatinine (Cr) level by a given postoperative day (POD). SGF was defined as Cr ≥ 3.0 mg/dL on POD5, Cr ≥ 2.5 mg/dL on POD7, and Cr ≥ 1.5 mg/dL on POD14 without dialysis in schema I, II, and III, respectively. Estimated glomerular filtration rate (eGFR) after transplantation, acute rejection, and graft survival were compared in each schema. Decreased renal function, defined as eGFR less than 30.0 mL/min/1.73m², was also compared.ResultsIn schema I and III, SGF had significantly lower eGFR at 3 months after transplantation compared with IGF (P < .017), and only schema III maintained the difference until 36 months after transplantation. The incidence of decreased renal function showed significant difference among groups in schema I and III (P < .05). Graft survival did not show significant difference among groups in all schemas. However, SGF and DGF groups showed a higher probability of decreased renal function than the IGF group (P < .017) in schema I and III.ConclusionsIn deceased donor kidney transplantation, certain definitions of SGF identified significantly worse clinical outcomes compared with IGF, suggesting similar impact with DGF. It is necessary to reach a consensus on a clearer definition of SGF with further studies.     

Impact of Slow and Delayed Graft Function on Kidney Graft Survival Between Various Subgroups Among Renal Transplant Patients

Objective

Renal allografts with excellent graft function show good long-term outcomes, while grafts with delayed function have been associated with poor long-term survivals, although few reports have analyzed outcomes among these groups. We compared first-week postoperative graft function among renal transplant patients to analyze the impact of slow graft function (SGF) and delayed graft function (DGF) on graft survival.

Materials and Methods

Renal transplantations were performed from 362 unrelated, 46 related, and 163 deceased donors. Kidney transplant patients were divided into 3 groups according to their initial graft function. First-week dialyzed patients formed the DGF group. Nondialyzed patients were divided into a SGF or an excellent graft function (EGF) cohort according to whether the serum creatinine at day 7 was higher vs lower than 2.5 mg/dL, respectively.

Results

Of the 570 renal transplant recipients, DGF was observed in 39 patients (6.8%), SGF in 64 (11.2%), and EGF in 467 (81.8%). There was no significant difference in SGF vs DGF between patients who received kidneys from unrelated vs related living or deceased donors. Graft survival was worse among the DGF than the SGF or EGF patients, with no significant difference between the last 2 groups. The 6-month graft survivals were 74%, 93%, and 96%; the 3-year graft survivals were 70%, 88%, and 90%, respectively (P < .001).

Conclusions

We observed a similar impact of EGF and SGF on kidney graft survival. Kidney transplant recipients who developed DGF showed worse graft survival than those with EGF or SGF.     

Machine perfusion following static cold storage preservation in kidney transplantation: donor‐matched pair analysis of the prognostic impact of longer pump time

The impact of machine perfusion (MP) time on kidney transplant outcome is mixed in previous studies using multivariable analyses. In an analysis of 66 pairs of donor‐matched adult, first transplant recipients (N = 132) with identical donor characteristics except for pump time, tests of association of shorter versus longer pump time (first versus second kidney removed) by delayed graft function(DGF), slow graft function(SGF), and biopsy proven acute rejection(BPAR) were performed using McNemar’s test. Freedom‐from‐BPAR, graft and patient survival, and renal function were also compared. Mean ± SD pump times for paired recipients with first and second kidneys were 22.7 ± 7.3 h and 31.2 ± 7.9 h, respectively (mean difference: 8.5 ± 4.5 h, P < .000001). There was no significant impact of pump time on DGF or SGF, with discordant pairs favoring less SGF with longer pump time (N.S.). The incidence of BPAR during the first 12 months post‐transplant yielded a borderline difference favoring longer pump time (P = .09), and freedom‐from‐BPAR during the first 12 months was significantly more favorable for longer pump times (95% vs. 84%, P = 0.04). No differences were observed in graft and patient survival, and renal function. While offering significantly favorable protection from BPAR, this analysis of donor‐matched recipient pairs corroborates longer MP (pump) times having no unfavorable effect on other clinical outcomes.     

Early Graft Function After Living Donor Kidney Transplantation Predicts Rejection But Not Outcomes

Poor early graft function (EGF) after deceased donor kidney transplantation (DDKT) has been intensely studied. Much less is known about poor EGF after living donor kidney transplantation (LDKT). Data were collected on 469 LDKTs performed between 1/1/97 and 12/31/01 to determine risk factors for and outcomes associated with poor EGF, defined as either delayed or slow graft function (DGF or SGF). The incidence of DGF and SGF were 4.7% and 10.7%, respectively. Diabetic etiology (OR 2.22; p = 0.021) and warm ischemia time (WIT) (OR 1.05 per min increment; p = 0.0025) emerged as independently associated with poor EGF. Neither functional graft survival nor 1-year graft function differed among the EGF groups. However, DGF and SGF strongly predisposed to acute rejection (AR), which compromised functional graft survival (p = 0.0007) and 1-year graft function. Therefore, we conclude that diabetic etiology of renal disease and WIT are the dominant risk factors for poor EGF after LDKT. Poor EGF did not directly compromise functional graft survival but strongly predisposed to AR. We suggest that immunosuppression should be intensified in the poor EGF setting to maximize LDKT longevity, as AR does impair functional graft survival.     

Effects of pre-transplant dialysis modality on early outcome of kidney transplantation from donation after cardiac death

Objective To compare the influence of hemodialysis (HD) and peritoneal dialysis (PD) on early outcome of patients underwent kidney transplantation from donation after cardiac death (DCD). Methods Patients admitted in the First People's Hospital of Foshan with DCD kidney transplant from January 1st, 2011 to June 30th, 2016 were analyzed retrospectively. Recipients were grouped into HD group (n=61) and PD group (n=28) according to their pre-transplant dialysis modality. Their short-term outcomes after DCD kidney transplant were compared, including recovery of renal function, short-term complications and laboratory data. Results Patients had longer dialysis duration and lower hemoglobin, serum albumin and phosphorus in PD group than those in HD group (all P＜0.05), but no significant difference shown in age, gender, body mass index, primary disease, blood pressure, and hepatitis B infection (all P＞0.05). HD patients with 6.00(4.00, 11.00) d recovery time of renal function, 18.00(17.00, 21.50) d hospital time, had 24.59% the delayed graft function (DGF), 3.28% acute rejection and 16.39% infection during hospitalization. While for PD patients the recovery time of renal function was 4.00(3.75, 7.00) d; hospital time was 19.00(15.00, 21.75) d; the incidence rate of DGF was 14.29%; acute rejection was 3.57%; and infection during hospitalization reached 17.86%. Above indexes were not significantly different between HD and PD groups (all P＞0.05). Repeated measure ments showed that, compared with those before transplant surgery, after 1 month, 3 months and 6 months HD and PD groups had decreased creatinine and phosphorus, and increased hemoglobinserum albumin and calcium; Serum albumin and calcium were different between the two groups (P＜0.001, P=0.040), whereas creatinine, hemoglobin and phosphorus did not show difference (all P＜0.05). After transplantation the trends of creatinine, hemoglobin, calcium and phosphorus were not different between the two groups (P values were 0.295, 0.310, 0.501 and 0.063, respectively). Conclusions No significant difference of the recovery regarding renal function, anemia, nutrition status and mineral metabolites was found between pre-transplant HD and PD modality in patients who underwent DCD kidney transplantations.     

Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes

Singh RP, Farney AC, Rogers J, Zuckerman J, Reeves‐Daniel A, Hartmann E, Iskandar S, Adams P, Stratta RJ. Kidney transplantation from donation after cardiac death donors: lack of impact of delayed graft function on post‐transplant outcomes.
Clin Transplant 2011: 25: 255–264. © 2010 John Wiley & Sons A/S. Abstract: Introduction: Delayed graft function (DGF) is more common in recipients of kidney transplants from donation after cardiac death (DCD) donors compared to donation after brain death (DBD) donors. Methods: Single‐center retrospective study to evaluate the impact of DGF on controlled (Maastricht category III) DCD donor kidney transplant outcomes. Results: From 10/01 to 6/08, 578 adult deceased donor kidney transplants were performed including 70 (12%) from DCD and 508 (88%) from DBD donors. Mean follow‐up was 36 months. DCD donor kidney transplants had significantly greater rates of DGF (57% DCD vs. 21% DBD, p < 0.0001)) and acute rejection (29% DCD vs. 16% DBD, p = 0.018) compared to DBD donor kidney transplants, but patient and graft survival rates were similar. DBD donor kidney transplants with DGF (n = 109) had significantly greater rates of death‐censored graft loss (12.5% DCD vs. 31% DBD), primary non‐function (0 DCD vs. 10% DBD) and higher 2 year mean serum creatinine levels (1.4 DCD vs. 2.7 mg/dL DBD) compared to DCD donor kidney transplants with DGF (n = 40, all p < 0.04). On univariate analysis, the presence of acute rejection and older donor age were the only significant risk factors for death‐censored graft loss in DCD donor kidney transplants, whereas DGF was not a risk factor. Conclusion: Despite higher rates of DGF and acute rejection in DCD donor kidney transplants, subsequent outcomes in DCD donor kidney transplants with DGF are better than in DBD donor kidney transplants experiencing DGF, and similar to outcomes in DCD donor kidney transplants without DGF.     

Delayed graft function requiring more than one‐time dialysis treatment is associated with inferior clinical outcomes

Delayed graft function (DGF) is a common complication of deceased donor kidney transplantation with negative impact on clinical outcomes. In a single‐center retrospective analysis, we compared patient and kidney survival, early renal function, and the incidence of acute rejection during the first year among all adult deceased donor kidney transplant patients without DGF, with DGF requiring one‐time and/or more than one‐time dialysis treatment between January 1, 2000, and December 31, 2008. Of 831 adult kidney transplant patients, 74 (8.9%) required one‐time and 134 (16.1%) more than one‐time dialysis treatment post‐transplantation, respectively. While DGF patients with one‐time dialysis treatment had comparable clinical outcomes to that of patients without DGF, patients with DGF requiring more than one‐time dialysis treatment had a 45% increased risk for death (HR 1.45, 95% CI 1.02, 2.05, p = 0.04) after adjustment for the differences in demographic and baseline characteristics. Furthermore, DGF patients with more than one‐time dialysis requirement displayed significantly lower renal function after recovery (OR 0.32, 95% CI 0.21, 0.49, p < 0.001, for eGFR ≥ 60 mL/min) and higher incidence of acute rejection during the first year (OR 1.66, 95% CI 1.11, 2.49, p = 0.015). Additional studies of therapeutic approaches to manage patients with prolonged DGF are needed.     

Predictors and outcomes of delayed graft function after living‐donor kidney transplantation

Delayed graft function (DGF) following deceased donor kidney transplantation is associated with inferior outcomes. Delayed graft function following living‐donor kidney transplantation is less common, but its impact on graft survival unknown. We therefore sought to determine risk factors for DGF following living‐donor kidney transplantation and DGF's effect on living‐donor kidney graft survival. We analyzed living‐donor kidney transplants performed between 2000 and 2014 in the UNOS dataset. A total of 64 024 living‐donor kidney transplant recipients were identified, 3.6% developed DGF. Cold ischemic time, human leukocyte antigen mismatch, donor age, panel reactive antibody, recipient diabetes, donor and recipient body mass index, recipient race and gender, right nephrectomy, open nephrectomy, dialysis status, ABO incompatibility, and previous transplants were independent predictors of DGF in living‐donor kidney transplants. Five‐year graft survival among living‐donor kidney transplant recipients with DGF was significantly lower compared with graft survival in those without DGF (65% and 85%, respectively, P < 0.001). DGF more than doubled the risk of subsequent graft failure (hazard ratio = 2.3, 95% confidence interval: 2.1–2.6; P < 0.001). DGF after living‐donor kidney transplantation is associated with inferior allograft outcomes. Minimizing modifiable risk factors may improve outcomes in living‐donor kidney transplantation.     

The impact of delayed graft function of the kidney on the pancreas allograft in simultaneous kidney-pancreas transplantation

It is unclear whether delayed graft function (DGF) of the kidney has any influence on pancreas graft function following simultaneous kidney-pancreas transplantation (SKPT). A subgroup analysis was conducted using data from a multicenter study to determine the impact of DGF of the kidney on pancreas graft function following SKPT. METHODS: Of the 297 SKPT patients, 24 (8%) had DGF of the kidney, defined as the need for dialysis during the first week posttransplant. Clinical parameters including patient and graft survival, incidence of acute rejection, and pancreas and renal function were compared between patients with and without DGF at 1 week, and at 1, 3, 6, and 12 months posttransplant. RESULTS: Demographic and transplant characteristics were similar between the two groups except for longer kidney and pancreas cold ischemia times, more males, and more primary cytomegalovirus (CMV) exposure in the DGF group (P <.05). No differences were seen in patient and graft survival rates, but the incidence of acute renal rejection was higher in patients with DGF (42%) than in those without DGF (15%, P =.001). More patients with DGF (25%) received oral hypoglycemic agents at 1-year posttransplant than in those without DGF (5%, P <.01). At 1 year, the mean serum creatinine was 1.8 mg/dL and 1.4 mg/dL in patients with and without DGF, respectively (P <.01). CONCLUSIONS: Patients with DGF of the kidney had a higher incidence of acute renal rejection and received oral hypoglycemic agents more often during the first year posttransplant compared to those who did not have DGF following SKPT.     

Genetic association of interleukin-1beta and receptor antagonist (IL-1Ra) gene polymorphism with allograft function in renal transplant patients

Cytokines are known to be important mediators during renal graft outcome. The present study was therefore, conducted to determine the impact of IL-1beta and its receptor antagonist polymorphism on allograft outcome. We evaluated single nucleotide polymorphism (SNPs) in interleukin-1 gene cluster, IL-1beta (promoter region -511 and exon-5 +3954) and IL-1Ra (86-bp VNTR) in 136 renal transplant recipients and 150 normal healthy controls by polymerase chain restriction based (PCR-RFLP) analysis. Recipients were HLA matched and clinically characterized including delayed graft function (DGF), rejection episode (RE) and stable graft function (SGF). Haplotypes and linkage disequilibrium (LD) were determined using SNPAnalyzer software. Significant difference was observed for the frequency distribution of the three sites of IL-1 gene among patients and controls (p<0.001, 0.022 and <0.001 respectively). When RE and DGF were compared to SGF, only IL-1Ra showed significant differences among RE and SGF (p=0.014) and DGF and SGF (p=0.020). The presence of 1/2 genotype showed 18 folds risk in RE and 10 folds in DGF (OR=18.000 and OR=10.667 respectively). The majority of recipients with SGF had 1-4 HLA mismatch whereas RE had 5-8 mismatches. Risk for rejection increased >6 folds (OR=6.571; p<0.01) for 5-8 mismatches. Haplotypes constructed with the combination of three polymorphisms in IL-1 gene cluster showed significant difference between RE and SGF group. LD value for IL-1beta (promoter region) and IL-1Ra and IL-1beta promoter and exon-5 gene in the control group indicated strong association among the variants (D'=0.37, p<0.0001 and D'=0.29, p=0.002). Our study demonstrate that genetically determined low production of IL-1Ra may be a risk factor for RE and DGF and that IL-1beta/IL-1Ra haplotype influences the impact of allograft outcome. These findings may significantly abet in better perception of the survival of the graft.     

Sub‐clinical acute rejection detected using protocol biopsies in patients with delayed graft function

Abstract Acute rejection in renal transplants is difficult to diagnose when patients have delayed graft function (DGF) in the early post‐transplant period. In this study protocol, renal transplant biopsies were performed in an attempt to detect sub‐clinical acute rejection episodes. Eighty‐three patients were eligible for the study, of whom 33 had DGF. All had protocol renal transplant biopsies performed under ultrasound control at 7 days post‐transplant, and those with DGF had further biopsies weekly until the graft functioned. All histologically confirmed acute rejection episodes were treated. Sub‐clinical acute rejection was detected in 6/33 (18%) patients with DGF compared to 2/50 (4 %) in the other patients (P < 0.05). Borderline rejection was present in 4/33 (12 %) and 4/50 (8 %) patients, respectively. Because of the high detection rate of sub‐clinical acute rejection and the low morbidity of renal transplant biopsies, their use is recommended in patients with DGF.