Death-censored Graft Survival Rates Research Articles

Impact of the Mayo Adhesive Probability Score on Donor and Recipient Outcomes After Living-donor Kidney Transplantation: A Retrospective, Single-center Study of 782 Transplants.

This study was performed to assess the impact of the Mayo Adhesive Probability (MAP) score on donor and recipient outcomes after living-donor kidney transplantation (LDKT). We retrospectively analyzed 782 transplants involving LDKT between February 2008 and October 2019 to assess the correlation between the MAP score and outcome after LDKT. We divided the transplants into 2 groups according to the donor MAP score: 0 (MAP0) and 1-5 (MAP1-5). Compared with the MAP0 group, donors in the MAP1-5 group were significantly older, had higher body mass index, and were more likely to be men. The prevalences of hypertension, hyperlipidemia, and diabetes were also higher among donors in the MAP1-5 group than among donors in the MAP0 group. Operative time, estimated blood loss during donor nephrectomy, and percentage of glomerular sclerosis were significantly greater in the MAP1-5 group than in the MAP0 group. Donor and recipient perioperative complications were comparable between the 2 groups; death-censored graft survival rates also did not significantly differ between groups. Although the recipient mean estimated glomerular filtration rate (eGFR) from postoperative d 1 to 7 was significantly higher in the MAP0 group than in the MAP1-5 group (P = 0.007), eGFR reductions within 5 y after transplantation were similar between groups. There were no significant differences between groups in recipient mortality and biopsy-proven acute rejection episodes within 1 y after transplantation. Additionally, multivariate analysis showed that the only factors affecting recipient eGFR at postoperative d 7 were donor age, recipient age, and female sex (P < 0.001, <0.001, and =0.004, respectively). The MAP score did not influence surgical complications or graft survival; therefore, it should not affect donor selection.

MO939RECURRENCE AND OUTCOME OF ANTI-GLOMERULAR BASEMENT MEMBRANE GLOMERULONEPHRITIS AFTER KIDNEY TRANSPLANTATION: A BELGIAN MULTICENTER STUDY

Abstract Background and Aims Recurrence of anti-glomerular basement membrane (anti-GBM) glomerulonephritis in the kidney graft is a rare event, described in limited case reports and registry analysis. The aim of this study was to evaluate in a large cohort of patients with detailed data collection and long follow-up the risk of recurrence of anti-GBM disease and graft loss caused by recurrence, the risk factors associated with clinical recurrence and the long-term patient and graft survival. Method Multicenter retrospective study. Inclusion criteria: patients with anti-GBM glomerulonephritis transplanted with a kidney between 1977 and 2015. Exclusion criteria: systemic vasculitis (except ANCA), lupus erythematosus and cryoglobulinemia. Clinical recurrence was defined as reappearance of signs of glomerulonephritis along with histological signs of proliferative glomerulonephritis and linear IgG staining on kidney biopsy, with or without anti-GBM antibodies. Results Fifty-three patients were included. Clinical recurrence in a first kidney transplant occurred in only one patient five years after transplantation -a prevalence rate of 1.9%- in the context of cessation of immunosuppressive drugs. The graft was lost due to recurrence. Histological recurrence with linear IgG staining on kidney biopsy in the absence of histologic signs of proliferative glomerulonephritis was observed in four patients, in the context of cellular rejection. Two patients lost their kidney graft from severe acute rejection; the others fully recovered. Patient survival was 100%, 94% and 89% at 5, 10 and 15 years, respectively. Overall, death-censored first graft survival rates were 88%, 83% and 79% at 5, 10 and 15 years, respectively. Conclusion Recurrence rate of anti-GBM glomerulonephritis after transplantation is very low, and associated with graft loss. The long-term patient and graft survival rates are excellent.

Renal Biopsy and Clinical Outcomes in Patients With ABO-Incompatible Renal Transplant: Experience From a Tertiary Care Hospital.

Renal transplant with ABO-incompatible donors expands the donor pool. Earlier studies have focused the use of protocol biopsies in ABO-incompatible transplant patients. Our study described outcomes of indication (for cause) renal biopsies and clinical outcomes in patients with ABO-incompatible renal transplant. This retrospective study included 164 patients from January 2012 to June 2019. Biochemical parameters, serial immunoglobulin G anti-ABO titers, and class I and II donor-specific antibody findings were obtained from hospital records, and renal graft biopsies were reviewed according to the Banff 2017 update. We analyzed the results of 65 biopsies from 54 patients. Biopsy-proven acute antibody-mediated rejection (12.8%) was found to be more prevalent than acute cellular rejection (1.8%). Patients with antibodymediated rejection all had microvascular inflammation (g+ptc score of 2 or more, where g+ptc is the sum of the glomerulitis and peritubular capillaritis scores) and were positive for C4d. Acute tubular injury per se was seen in 10.3% of patients; 65% of these patients had C4d positivity in peritubular capillaries, and only 1 patient developed chronic active antibody-mediated rejection on follow-up. Patient and death-censored graft survival rates were 92% and 98% at 1 year after transplant and 88% and 91% at 3 years, respectively. Patients with an episode of antibody-mediated rejection had lower rates of patient (76.5%) and deathcensored graft survival (84.6%) at 1 year. The microvascular inflammation score (g+ptc score of 2 or higher) is more reliable than diffuse C4d positivity to determine antibody-mediated rejection in ABO-incompatible transplants because diffuse C4d positivity may also be seen in etiologies unrelated to antibody-mediated rejection. Acute tubular injury with C4d positivity without microvascular injury does not confirm antibody-mediated rejection. We suggest that Banff classification be updated in ABO-incompatible transplants to include diagnostic criteria for the diagnosis of antibody-mediated rejection.

Organ Preservation Solutions in Transplantation: A Literature Review.

Renal transplant with ABO-incompatible donors expands the donor pool. Earlier studies have focused the use of protocol biopsies in ABOincompatible transplant patients. Our study described outcomes of indication (for cause) renal biopsies and clinical outcomes in patients with ABO-incompatible renal transplant. This retrospective study included 164 patients from January 2012 to June 2019. Biochemical parameters, serial immunoglobulin G anti-ABO titers, and class I and II donor-specific antibody findings were obtained from hospital records, and renal graft biopsies were reviewed according to the Banff 2017 update. We analyzed the results of 65 biopsies from 54 patients. Biopsy-proven acute antibody-mediated rejection (12.8%) was found to be more prevalent than acute cellular rejection (1.8%). Patients with antibodymediated rejection all had microvascular inflammation (g+ptc score of 2 or more, where g+ptc is the sum of the glomerulitis and peritubular capillaritis scores) and were positive for C4d. Acute tubular injury per se was seen in 10.3% of patients; 65% of these patients had C4d positivity in peritubular capillaries, and only 1 patient developed chronic active antibody-mediated rejection on follow-up. Patient and death-censored graft survival rates were 92% and 98% at 1 year after transplant and 88% and 91% at 3 years, respectively. Patients with an episode of antibody-mediated rejection had lower rates of patient (76.5%) and deathcensored graft survival (84.6%) at 1 year. The microvascular inflammation score (g+ptc score of 2 or higher) is more reliable than diffuse C4d positivity to determine antibody-mediated rejection in ABO-incompatible transplants because diffuse C4d positivity may also be seen in etiologies unrelated to antibody-mediated rejection. Acute tubular injury with C4d positivity without microvascular injury does not confirm antibody-mediated rejection. We suggest that Banff classification be updated in ABOincompatible transplants to include diagnostic criteria for the diagnosis of antibody-mediated rejection.

Rapid Steroid Withdrawal after Renal Transplantation Reduces Mortality: Five Year Follow-Up of a Randomized Controlled Trial (Harmony Study) Confirms Long Term Efficacy and Safety

Background: We previously reported excellent efficacy and improved safety aspects of rapid steroid withdrawal (RSWD) in the randomized controlled one year “Harmony” trial, in which 587 predominantly deceased-donor kidney transplant recipients were randomized either to basiliximab or rabbit ATG induction therapy and compared to standard immunosuppressive therapy consisting of basiliximab, low tacrolimus once daily, mycophenolate mofetil, and corticosteroids. Methods: Following the end of the original one-year study period, patients were asked to participate in the observational follow-up (FU) study examining most of the end points of the original study. Hereby, de novo incidences between year one and three as well as year three and five were assessed at the three-/five-year visits, respectively. Findings: Biopsy-proven acute rejection and death-censored graft survival rates remained low and independent of RSWD. RSWD was an independent positive factor for patient survival (adjusted hazard ratio 0·554, 95% confidence interval 0·314 to 0·976; p=0·041). Survival rate was increased with 89·4 % or 90·4 % in RSWD patients (basiliximab or rabbit ATG) compared to 84·7 % in control patients (p = 0·064). The reduced incidence of post-transplantation diabetes mellitus in RSWD patients during the original one-year study period was not compensated by later incidences during FU. Also, incidences of other important outcome parameters such as opportunistic infections, malignancies, cardiovascular morbidity/risk factors, donor specific antibody formation, or kidney function did not differ during FU period. Unexpectedly, patient incidences of bacterial infections requiring hospitalization was reduced in the rabbit ATG group. Interpretation: The Harmony FU trial confirms excellent efficacy and beneficial safety aspects of RSWD under modern immunosuppressive therapy. This is the first randomized study demonstrating increased patient survival in RSWD patients. The results shown here support that RSWD should become the new gold standard approach in an immunologically low-risk, elderly, and severely diseased population of Caucasian kidney transplant recipients. Trial Registration: Follow-up study DRK5786; Original trial NCT 00724022). Funding: The FU trial was designed and run by the first and last author who received financial support from Astellas Pharma GmbH and Sanofi (Investigator Initiated Trial (NCT 00724022, follow up study DRK5786). Neither of the funders had any role in data collection, data analysis, data interpretation, or writing of the manuscript. An independent contract research organization (Coordination Center for Clinical Studies of the Technical University of Dresden, Dresden, Germany) was responsible for data collection, monitoring and statistical analyses. Declaration of Interest: CH received grant support, consulting fees, and lecture fees from Astellas, Sanofi, Genzyme, Roche Pharma, Novartis, and Wyeth/Pfizer. CK received consulting fees and lecture fees from Astellas, Chiesi, Novartis, Sanofi-Genzyme. JWM received grant support, consulting fees, and lecture fees from Vifor, GSK, Novartis, Astra-Zeneca and Boehringer Ingelheim. OW has received research grants for clinical studies, speaker’s fees, honoraria and travel expenses from Amgen, Alexion, Astellas, Basilea, Biotest, Bristol-Myers Squibb, Correvio, Chiesi, Gilead, Hexal, Janssen, Dr. F. Kohler Chemie, MSD, Novartis, Roche, Pfizer, Sanofi, Takeda, TEVA and UCB. BB received grant support, consulting fees and lecture fees from Astellas, Bayer, Chiesi and Novartis. All other authors declare no competing interests. Ethical Approval: The study was approved by the institutional review boards of all sites participating in the follow-up period.

Impact of donor obesity on allograft outcomes after kidney transplantation adjusted for kidney donor profile index - a national cohort study.

Obesity in deceased kidney donors is a known risk factor for poor allograft outcomes. The Kidney Donor Profile Index (KDPI) has been introduced to predict graft survival in deceased donor kidney transplantation (DDKT). Obesity, however, is not included in KDPI. We study the impact of donor obesity on DDKT outcomes after adjusting for organ quality by KDPI. The Organ Procurement Transplantation Network/United Network for Organ Sharing (OPTN/UNOS) data of DDKT from 2005 to 2017, with donor BMI≥18.5kg/m2 and weight >80kg were included. There was a total of 66382 DDKTs with 10917 death-censored graft failures. For KDPI≤30%, the 10-year death-censored graft survival (DCGS) rates among donor BMI<30, 30-35, 35-40, 40-45 and ≥45kg/m2 groups were 75.9%, 75.4%, 76.1%, 74.9% and 79.6%, respectively. For KDPI>30%, 10-year DCGS rates were 67.5%, 66.1%, 65.9%, 62.6% and 63.2%, respectively. After adjusting for known confounding factors including KDPI, donor obesity was not independently associated with an increased risk for graft failure. In DDKT with donor weight >80kg, donor obesity was not associated with a lower long term DCGS compared to non-obesity when KDPI≤30%.

Impact of acute kidney injury in deceased donors with high Kidney Donor Profile Index on posttransplant clinical outcomes: a multicenter cohort study.

BackgroundThis study evaluated the impact of acute kidney injury (AKI) on posttransplant clinical outcomes for deceased donor (DD) kidney transplantation (KT) using the Kidney Donor Profile Index (KDPI) system.MethodsOverall, 657 kidney transplant recipients (KTRs) receiving kidneys from 526 DDs from four transplant centers were included. We divided them into the high and low KDPI donor groups by 65%, the KDPI score, and both groups were subdivided into the AKI-DDKT and non-AKI-DDKT subgroups according to AKI in DDs.ResultsThere was no significant difference in the incidence of delayed graft function (DGF) between the high and low KDPI-KTR groups; however, the AKI-DDKT subgroup showed significantly higher incidence of DGF than the non-AKI-DDKT subgroup in both groups (p = 0.001, p < 0.001, respectively). The death-censored graft survival rate was significantly lower in the high KDPI-KTR group than in the low KDPI-KTR group (p = 0.005). Only in the high KDPI-KTR group, the death-censored graft survival rate was significantly lower in the KT from DDs with AKI stage 3 than KT from DDs with non-AKI or AKI stage 1 or 2 (p = 0.040). The interaction between AKI stage 3 in DDs and high KDPI on the allograft outcome was significant (p = 0.002).ConclusionKTs from DDs with AKI stage 3 showed an adverse impact on the allograft outcome in the high KDPI-KTR group. Therefore, DDs with a high KDPI score should be managed carefully so that severe AKI does not occur prior to KT.

Change in Estimated GFR and Risk of Allograft Failure in Patients Diagnosed With Late Active Antibody-mediated Rejection Following Kidney Transplantation.

There are challenges in designing adequate, well-controlled studies of patients with active antibody-mediated rejection (AMR) after kidney transplantation (KTx). We assessed the functional relationship between change in estimated glomerular filtration rate (eGFR) following the diagnosis of AMR and the risk of subsequent death-censored graft failure using the joint modeling framework. We included recipients of solitary KTx between 1995 and 2013 at 4 transplant centers diagnosed with biopsy-proven active AMR at least 1 year post-KTx, who had a minimum of 3-year follow-up. A total of 91 patients across participating centers were included in the analysis. Of the 91 patients, n = 54 patients (59%) met the death-censored graft failure endpoint and n = 62 patients (68%) met the all-cause graft failure composite endpoint. Kaplan-Meier death-censored graft survival rates at 12, 36, and 60 months postdiagnosis of AMR pooled across centers were 88.9%, 58.9%, and 36.4%, respectively. Spaghetti plots indicated a linear trend in the change in eGFR, especially in the first 12 months postdiagnosis of active AMR. A significant change in eGFR was observed within the first 12 months postdiagnosis of active AMR, getting worse by a factor of -0.757 mL/min/1.73 m2 per month during the 12-month analysis period (a delta of -9.084 mL/min/1.73 m2 at 1 y). Notably, an extrapolated 30% improvement in the slope of eGFR in the first 12 months was associated with a 10% improvement in death-censored graft failure at 5 years. If prospectively validated, this study may inform the design of pivotal clinical trials for therapies for late AMR.

Clinical significance of de novo donor-specific antibody in kidney transplant recipients with chronic antibody-mediated rejection.

BackgroundChronic antibody-mediated rejection (CABMR) is an important cause of late graft loss. De novo donor-specific antibody (dnDSA) is an important prognostic factor for long-term allograft outcomes. However, the prognosis of CABMR based on the presence of dnDSA is uncertain.MethodsWe retrospectively analyzed 35 kidney transplant recipients with CABMR between 2010 and 2018. Fourteen recipients had no detectable DSA, and 21 recipients had detectable DSA. We investigated the pathologic findings at diagnosis of CABMR, allograft function 12 months later, related factors for allograft failure, and allograft survival rate based on the presence of dnDSA.ResultsThe pathologic findings showed that acute and chronic changes were more severe in the dnDSA (+) group than in the dnDSA (–) group. There was no significant difference in the allograft function 12 months after the diagnosis of CABMR and in the amount of proteinuria at diagnosis between the two groups. However, the death-censored graft survival rate was lower in the high-proteinuria group than in the low-proteinuria group in both groups. The treatment rate of recipients was higher in the dnDSA (+) group than in the dnDSA (–) group; however, there was no significant difference in the death-censored graft survival rate between the two groups.ConclusionsAlthough the effect of dnDSA on the prognosis of CABMR is not clear, it would be important not to neglect treatment for CABMR with risk factors for allograft failure even without dnDSA. Continuous and rigorous surveillance of DSA and allograft function is needed in patients with CABMR.

ABO-Incompatible Living-Donor Kidney Transplantation in a Developing Country: A Multicenter Experience in Malaysia

Malaysia has a low deceased-donor donation rate and has not embarked on a paired kidney exchange program; therefore, ABO-incompatible and HLA-incompatible transplantation remain the main contributor to the sustainability of the national kidney transplantation (KT) program. There were 26 cases of ABO-incompatible KTs performed from 2011 to 2018 in 3 major transplant centers, namely, Hospital Kuala Lumpur, University Malaya Medical Centre, and Prince Court Medical Centre. We collected perioperative and follow-up data through June 2019. The desensitization protocol varies and is center specific: the localized Japanese protocol and Swedish protocol with a target anti-A/B isoagglutinin titer of 16 or 32 on the day of transplant. The induction and tacrolimus-based maintenance protocol was nearly identical. The median follow-up time was 62.3 months (interquartile range, 37.0-79.7). Fifteen subjects had the highest predesensitization anti-A/B titer of ≥32 (57.7%). The acute cellular rejection and antibody-mediated rejection incidence were 12.5% (3 cases) and 8.3% (2 cases), respectively. Patient, graft, and death-censored graft survival rates were 96.2%, 92.3%, and 96.0%, respectively, 1 year post-living-donor KT (LDKT) and 96.2%, 87.2%, and 90.7%, respectively, 5 years post-LDKT. Our experience shows that ABO-incompatible LDKT using a suitable desensitization technique could be a safe and feasible choice for LDKT even with varied desensitization regimens for recipients with relatively high baseline isoagglutinin titers.

Impact of donor kidney weight to recipient body weight ratio on long-term graft outcomes in live donor kidney transplantation

Background: Kidney weight has been suggested as a surrogate marker for nephron numbers and renal function. Small donor kid ney sizes relative to recipient body size is an important contributor to short-term graft renal function, but the impact of size mis matching on long-term graft outcomes remains unknown. This study is aimed to evaluate the impact of the donor kidney weight to recipient body weight ratio (KW/BW) on long-term graft survival in live donor kidney transplantation. Methods: We performed a longitudinal cohort study in 1,397 patients who underwent live donor kidney transplantation between 2000 and 2016 at Severance Hospital. Following cold perfusion and back table surgery, the kidney was weighted on the same electronic weighting scale by the surgeon. Patients were grouped into four groups according to KW/BW quartiles. Results: During a median follow-up period of 127 months, 245 graft losses occurred (172 graft failures and 73 patient deaths). The 10-year death-censored graft survival rates were 86.9% in the lowest quartile, 90.4% in the second quartile, 90.5% in the third quartile, and 92.4% in the highest quartile (P=0.002). Multivariable analysis revealed that the lowest KW/BW (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.33-3.48; P=0.002) and second lowest KW/BW (HR, 1.69; 95% CI, 1.06-2.70; P=0.029) groups were significantly associated with death-censored graft failure compared with the highest KW/BW group. Patients with lower KW/BW exhibited consistently lower estimated glomerular filtration rates than those with higher KW/BW. Conclusions: Low KW/BW ratio is significantly associated with long-term graft outcome in live donor kidney transplantation.

Long-term Outcomes of Sequential Hematopoietic Stem Cell Transplantation and Kidney Transplantation: Single-center Experience.

Experience with sequential hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) is limited. We conducted a retrospective observational study of adult patients who underwent both HSCT and KT at our center, with a median follow-up of 11 y. In our 54 patients cohort (94% autologous HSCT), 36 (67%) patients received HSCT first followed by KT, while 18 (33%) received KT before HSCT. In both groups, AL amyloidosis represented 50% of hematologic diagnosis. Only 4 patients expired due to hematologic disease relapse (2 patients in each group) and only 3 allografts were lost due to hematologic disease recurrence (HSCT first n = 1 and KT first n = 2). Overall 1, 5, and 10 y death-censored graft survival rates were 94%, 94%, and 94%, respectively, for the HSCT first group and 89%, 89%, and 75%, respectively, for the KT first group. Overall 1, 5, and 10 y patients survival rates were 100%, 97% and 90%, respectively, for the HSCT first group and 100%, 76%, and 63%, respectively, for the KT first group. Our study supports safety of sequential KT and HSCT, with improved overall patient survival compared to recipients of HSCT remaining on dialysis and good long-term kidney allograft outcome.

Combined Liver-Kidney Transplantation With Preformed Anti–human Leukocyte Antigen Donor-Specific Antibodies

IntroductionThe impact of preformed donor-specific anti–human leukocyte antigen (HLA) antibodies (pDSAs) after combined liver-kidney transplantation (CLKT) is still uncertain.MethodsWe conducted a retrospective study in 8 European high-volume transplant centers and investigated the outcome of 166 consecutive CLKTs, including 46 patients with pDSAs.ResultsPatient survival was lower in those with pDSAs (5-year patient survival rate of 63% and 78% with or without pDSA, respectively; P = 0.04). The presence of pDSAs with a mean fluorescence intensity (MFI) ≥ 5000 (hazard ratio 4.96; 95% confidence interval: 2.3–10.9; P < 0.001) and the presence of 3 or more pDSAs (hazard ratio 6.5; 95% confidence interval: 2.5–18.8; P = 0.05) were independently associated with death. The death-censored liver graft survival was similar in patients with or without pDSAs. Kidney graft survival was comparable in both groups. (The 1- and 5-year death-censored graft survival rates were 91.6% and 79.5%, respectively, in patients with pDSAs and 93% and 88%, respectively, in the donor-specific antibody [DSA]-negative group, P = not significant). Despite a higher rate of kidney graft rejection in patients with pDSAs (5-year kidney graft survival rate without rejection of 87% and 97% with or without pDSAs, respectively; P = 0.04), kidney function did not statistically differ between both groups at 5 years post-transplantation (estimated glomerular filtration rate 45 ± 17 vs. 57 ± 29 ml/min per 1.73 m2, respectively, in patients with and without pDSAs). Five recipients with pDSAs (11.0%) experienced an antibody-mediated kidney rejection that led to graft loss in 1 patient.ConclusionOur results suggest that CLKT with pDSAs is associated with a lower patients’ survival despite good recipients’, liver and kidney grafts’ outcome.

Two Decades of Deceased Donor Kidney Transplantation at Ahmedabad, India.

Gujarat, Tamil Nadu, Telangana, Maharashtra, Kerala, Chandigarh, and Karnataka are states in India with active programs for deceased donor kidney transplant. We report our experience of 2 decades of deceased donor kidney transplant at the Institute of Kidney Diseases and Research Center, Dr. H. L. Trivedi Institute of Transplantation Sciences, Ahmedabad, Gujarat, India. This single-center retrospective study comprised data from 831 deceased donor kidney transplant recipients between January 1, 1997 and December 31, 2018. Mean recipient age was 38 ± 14 years; 564 were male, and 267 were female. Mean donor age was 45.3 ± 17.13 years; 565 were men, and 266 were women. Between January 1, 1997 and March 15, 2020, 5838 kidney transplants were completed, including 4895 living donor kidney transplants, 943 deceased donor kidney transplants, and 440 kidney paired donation transplants. Over the mean follow-up time of 8 ± 5.4 years, patient survival rate was 70% (n = 581) and death-censored graft survival rate was 84% (n = 698). Delayed graft function was shown in 210 patients (25%) and biopsy-proven acute rejection rate in 180 patients (21%). Our experience of favorable outcomes with deceased donor kidney transplants has expanded the donor pool in many ways, including transplant from expanded criteria donors to younger recipients; transplant from older donors to older recipients; donation after cardiac death; successful intercity organ procurement; dual-kidney transplant; en bloc transplant from a pediatric deceased donor; and transplant from brain death deceased donors who died from neurotoxic snakebite, recurrent primary brain tumor, bacterial meningitis, or head injury, or with disseminated intravascular coagulation and deranged renal functions. The pathway to increase organ donation was investigated. Deceased donor kidney transplant can achieve acceptable graft function with patient/graft survival, which may encourage the use of this approach to increase the number of available organs.

Clinical outcomes of the first 300 cases of kidney transplantation: a single-center retrospective cohort study

BackgroundKidney transplantation (KT) is regarded as the most effective treatment for end-stage renal disease. The annual number of KT cases in South Korea has increased rapidly as more centers are implementing a transplantation program. The objective of this study was to determine clinical outcomes of the first 300 consecutive cases of KT in a single center.MethodsClinical data of 300 cases of KT at Seoul National University Bundang Hospital from January 2004 to March 2018 were obtained from a prospectively collected database and retrospectively reviewed.ResultsThe mean age of patients was 47.7±12.9 years, and 59% of patients were male. There were 225 living donors and 75 deceased donors. A total of 42 cases were from ABO-incompatible donors. During a mean follow-up of 68.6±43.5 months, 38 patients (12.7%) experienced rejection. The most common cause was acute T-cell mediated rejection (9.0%). Eighteen patients experienced graft loss. One-year and 5-year death-censored graft survival rates were 99% and 96.6%, respectively. One-year and 5-year patient survival rates were 98.3% and 96.6%, respectively. Multivariate analysis revealed that graft weight-to-recipient weight ratio and rejection were significant factors affecting graft survival.ConclusionsThis single-center review demonstrates clinical outcomes comparable to other major centers. Such good outcomes were obtained by good patient selection, dedicated transplant physicians, and adequate use of immunosuppressive therapy.

RENAL ALLOGRAFT OUTCOME FROM HYPERTENSIVE DONOR: COMPARISON BETWEEN LIVING AND DECEASED DONOR

Korean Organ Transplantation Registry Study Introduction: Donor shortage is a serious problem in renal transplantation, and hypertensive living donor is potential candidates to expand donor pool. However, it is not unclear that renal allograft outcome from hypertensive living donor is similar compared to normotensive living donor or deceased donor. Methods: 4311 renal transplant recipients from the KOTRY database were enrolled from Jul 2014 to Dec 2018. We tried to investigate the renal allograft survival rate and estimated glomerular filtration rate (eGFR) of renal transplant recipients from hypertensive living donor (n = 280), compared to those from living normotensive donor (n = 2723) and deceased donor with or without hypertension (n = 262 and n = 1046, respectively). Results: Renal transplant recipients from hypertensive living donor exhibited significantly worse death-censored graft survival rate than those from normotensive living donor (p = 0.028). The allograft survival rate was not different between normotensive and hypertensive deceased donors (p = 0.649). In multivariate Cox-regression model, the renal allograft from normotensive donor was significantly associated with better survival rate compared to recipients from normotensive living donor (95% CI 0.18-0.91; p = 0.028). The recipients of hypertensive living donor did not show better graft survival rate compared to those of deceased donor with and without hypertension. The renal allograft from hypertensive donor was associated with lower eGFR than those from normotensive living and deceased donor without hypertension during entire follow up. The presence of donor proteinuria and more than 50 years-old recipients further increased the risk of renal allograft loss in hypertensive living donor transplantation. However, these relationships were not observed in hypertensive deceased donor transplantaion. Conclusion: Renal allograft from hypertensive living donor had increased the risk of renal allograft loss and associated with lower eGFR.This study was supported by the Korean Society for Transplantation, and funded by the Research of Korea Centers for Disease Control and Prevention.

Reduced Recurrence of Primary IgA Nephropathy in Kidney Transplant Recipients Receiving Everolimus With Corticosteroid: A Retrospective, Single-Center Study of 135 Transplant Patients

BackgroundLong-term kidney allograft survival remains a major clinical challenge. Recurrent glomerulonephritis disease, including recurrence of IgA nephropathy (IgAN), is a significant barrier to long-term kidney allograft survival. We performed a retrospective, observational study to evaluate the role of everolimus (EVR) in the risk of recurrent IgAN. MethodsThe study included data from 135 patients aged ≥16 years with biopsy-proven IgAN on native kidneys who underwent a kidney transplant (KT) between December 2002 and December 2018. ResultsPatients who underwent de novo KT received mycophenolate mofetil (MMF) (n = 107) or EVR (n = 28). The mean recipient age in the MMF and EVR groups was 44.9 ± 13.7 and 41.1 ± 10.1, respectively. The median (interquartile range) follow-up period was 90.9 (64.9-115.3) and 21.2 (11.4-30.6) months, respectively (< .0001). All patients received continuous corticosteroid and tacrolimus therapy. The death-censored graft survival rate after KT and the recurrence-free survival rate did not differ significantly between the groups. Univariate and multivariate Cox regression analyses identified EVR for de novo KT as an independent predictive factor for recurrence-free survival (P = .024). ConclusionsOur findings suggest that EVR-based regimens with tacrolimus and corticosteroid therapy for de novo KT reduce the recurrence of IgAN compared with MMF-based regimens with tacrolimus and corticosteroid therapy.

Monitoring of CMV-specific cell-mediated immunity with a commercial ELISA-based interferon-γ release assay in kidney transplant recipients treated with antithymocyte globulin.

Monitoring for cytomegalovirus (CMV)-specific cell-mediated immunity (CMV-CMI) may be useful for individualizing valganciclovir (VGCV) prophylaxis after kidney transplantation (KT). We performed a commercial ELISA-based interferon (IFN)-γ release assay (QTF-CMV) from posttransplant months 2-5 (362 points) in 120 CMV-seropositive KT recipients that received antithymocyte globulin as induction therapy and VGCV prophylaxis (median of 92days). Forty-seven patients (39.3%) had CMV infection after discontinuation of prophylaxis. The QTF-CMV assay was reactive, nonreactive, and indeterminate in 264 (72.9%), 90 (24.9%), and 8 points (2.2%). The QTF-CMV assay at prophylaxis discontinuation exhibited suboptimal accuracy for predicting protective CMV-CMI (sensitivity: 77.4%; specificity: 34.3%; positive predictive value [PPV]: 64.1%; negative predictive value [NPV]: 50.0%), with no differences in 1-year CMV infection rates between patients with negative (nonreactive or indeterminate) or reactive results (45.8% vs 36.1%; P=.244). Specificity and PPV to predict protective CMV-CMI improved by elevating the IFN-γ cutoff value to 1.13IU/mL (65.7% and 71.4%) and 7.0IU/mL (85.7% and 76.2%), although NPVs decreased. The QTF-CMV assay as per manufacturer's interpretative criteria performed poorly to predict protection from CMV infection following discontinuation of VGCV prophylaxis among ATG-treated CMV-seropositive KT recipients. This performance is slightly improved by modifying the IFN-γ positivity threshold.

The combination of area under the curve and percentage change in estimated glomerular filtration rate predicts long-term outcome of kidney transplants.

The development of surrogate markers for long-term outcomes of kidney transplant (KT) is a focus of attention. We examined the possibility of using a combination of the area under the curve of estimated glomerular filtration rate (eGFR) for 2years (AUCeGFR2yrs ) and percent change in eGFR between 1 and 2years after KT (% changeeGFR1/2yr ) as a surrogate marker. We compared the predictive power of death-censored graft failure with various combinations. The combination of >2% vs ≤2% for % changeeGFR1/2yr and >1300 vs ≤1300mL/min/month for AUCeGFR2yr had the highest Harrell C-index (0.647; 95% confidence interval [95% CI], 0.604-0.690). The death-censored graft survival rate of the group with ≤2% changeeGFR1/2yr and ≤1300mL/min/month AUCeGFR2yr was significantly lower than those of other groups. The AUC/% change eGFR had comparable predictive power to the previously identified marker ≥30% decline in eGFR between years 1 and 3 after KT (≤-30% changeeGFR1/3yr ) (Harrell's C-index=0.645 [95% CI 0.628-0.662] for ≤-30% changeeGFR1/3yr ). The proposed combination might be useful as a surrogate marker in KT trials because it requires a shorter surveillance period than the established marker while having comparable predictive power.

Kidneys From Elderly Deceased Donors-Is 70 the New 60?

There is a growing shortage of kidney donors leading to extended transplant waiting times associated with increased mortality. To expand the donor pool, clinicians nowadays regularly accept organs from elderly donors, including those aged ≥70 years. There is only limited and conflicting data whether kidneys from these elderly donors allow for satisfactory allograft outcome rates. To asses this question, the 5-year death censored graft survival of 116,870 adult first deceased donor kidney allograft recipients that were transplanted at European centers between 1997 and 2016 and reported to the “Collaborative Transplant Study” were analyzed using Kaplan–Meier analysis and country stratified Cox regression. The combinations of the two transplant periods 1997–2006 and 2007–2016 with the donor age categories 18–49, 50–59, 60–69, and ≥70 years were considered. From 1997–2006 to 2007–2016, the median donor age increased from 50 to 55 years and the proportion of kidneys from ≥60-year-old donors rose from 24.1 to 38.8%. At the same time, the proportion of kidneys from ≥70-year-old donors more than doubled (6.7 vs. 15.4%). Between 1997–2006 and 2007–2016, the 5-year graft survival improved in all donor age categories. During 2007–2016, the 5-year death censored graft survival of kidneys from ≥70-year-old donors was comparable to that of kidneys from 60 to 69-year-old donors during 1997–2006. This was true both for younger recipients (18–64 years) and older recipients (≥65 years). Among the younger recipients, 45–64-year-old recipients showed the best death censored graft survival rates for kidneys from old donors. In the country-stratified Cox regression analysis, compared to the reference of grafts from 18 to 49-year-old donors, the hazard ratio for grafts from ≥70-year-old donors during 2007–2016 was 1.92, exactly the same as the hazard ratio for grafts from 60 to 69-year-old donors during 1997–2006. Our analysis indicates that within only one further decade (1997–2006 vs. 2007–2016) the 5-year death censored graft survival of kidneys from ≥70-year old donors improved to the level of kidneys from 60 to 69-year-old donors in the previous decade.