Long-term Outcome Of Kidney Transplantation Research Articles

Association of PIRCHE-II score with anti-donor T-cell response and risk of de novo donor-specific antibody production in kidney transplant recipients

BackgroundDe novo donor-specific antibodies (dnDSAs) affect long-term outcomes of kidney transplantation (KT). A higher Predicted Indirectly ReCognizable Human Leukocyte Antigen (HLA) Epitopes (PIRCHE-II) score correlates with various clinical outcomes, including dnDSA formation. However, a detailed analysis of the relationship between the PIRCHE-II score and anti-donor T-cell response is lacking. Therefore, this study investigated the relationship between PIRCHE-II scores associated with dnDSA formation and mixed lymphocyte reaction results of anti-donor T-cell response. MethodsData of 105 adult living-donor KT recipients were retrospectively assessed. ResultsOf the 105 patients, 13.3 % developed dnDSAs during the observation period. The PIRCHE-II score at the HLA-DQ locus (PIRCHE-DQ) was significantly higher in patients with dnDSA formation than in those without. The incidence of dnDSA formation was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group. The proportion of patients with increased anti-donor T-cell response was significantly higher in the PIRCHE-DQ ≥ 77 group than in the PIRCHE-DQ < 77 group before KT and at 4 and 5 years after KT. ConclusionsPIRCHE-DQ may predict dnDSA formation and anti-donor T-cell response. Reducing the immunosuppressive drug dose in cases of high PIRCHE-DQ might not be prudent.

Impact of Donor-Recipient Relationship on Long-Term Outcomes in Living-Related Donor Kidney Transplantation.

BACKGROUND This study aimed to evaluate the impact of the donor-recipient relationship on the long-term outcomes of living-related kidney transplantation (LRKT), a topic that has been previously underreported. MATERIAL AND METHODS A total of 598 LRKTs performed between 2001 and 2021were analyzed and classified into 5 groups based on the donor-recipient relationship: 228 from mothers (M-to-C), 160 from fathers (F-to-C), 115 from siblings, 55 from spouses, and 40 from offspring. Graft survival, postoperative complications within the first year, serum creatinine (Scr), and hazard ratio (HR) for all-cause graft loss were assessed. RESULTS The overall 1-, 3-, 5-, 7-, and 10-year graft survival rates were 96.0%, 92.4%, 86.4%, 79.9%, and 69.9%, respectively. The graft survival rate in the sibling group was slightly higher than those in the M-to-C and F-to-C groups, and the differences between the groups were insignificant. The survival rates of grafts donated by spouses and offspring were lower than in other groups, and the incidence of graft loss within the first postoperative year was higher in the offspring group. In comparison to the sibling group, spouse and offspring donations increased the graft loss risk (HR, 3.3; 95% CI, 1.6-6.9) and 3.8 (1.7-8.4), respectively, followed by M-to-C and F-to-C donations (HR, 1.9; 95% CI: 1.2-3.4) and 1.8 (1.1-3.1), respectively, which were associated with elevated postoperative Scr levels. CONCLUSIONS Spouse and offspring donations significantly increased the risk of graft loss compared to donations from siblings, followed by M-to-C and F-to-C pairings, which were associated with higher postoperative Scr levels.

V-311.2: Perfusion techniques and long-term outcomes in kidney transplantation: A systematic review and meta-analysis.

V-311.2: Perfusion techniques and long-term outcomes in kidney transplantation: A systematic review and meta-analysis.

Pregnancies after kidney transplantation “the journey of hope”. Experience of the University Hospital of Batna, Algeria

Introduction. Renal transplantation is the treatment of choice for chronic end-stage renal failure. Transplantation restores the fertility of transplant recipients, which explains the increase in the number of successful pregnancies in this population. However, it remains a high maternal risk pregnancy fetal and/or neonatal which requires a multidisciplinary approach. Objective. The aim of this study is to provide the results of our experience on pregnancies in kidney transplant patients and to evaluate the impact of pregnancy on kidney graft function. Patients and methods. 79 pregnancies in kidney transplant recipients were analyzed and the long-term results of kidney transplantation were studied. We analyzed the results from clinical and biological data before, during and after pregnancy. Results. Average age of the patients was 35.3 ± 3 years and the time between transplantation and the start of pregnancy was 56.4 ± 31.5 months. There was no significant difference between biological data before and after pregnancy. We did not observe any acute rejection. The average maternal complications were preeclampsia in 30% of cases, low birth weight in 29% of cases, prematurity in 44% and cesarean sections in 57%. There was no impact of pregnancy on the kidney graft during follow-up. Conclusion. Despite the frequency of premature deliveries and comorbidities, monitoring and management of kidney transplant recipients revealed good functional results of the kidney graft.

Long-Term Outcomes of Nephrectomy Before Kidney Transplantation in Patients With Polycystic Kidney Disease

BackgroundPolycystic kidney disease (PKD) is the most common hereditary kidney disorder. In most patients, the disease progresses to end stage kidney disease, which is treated preferably by kidney transplantation. In certain clinical circumstances, a pretransplant nephrectomy is indicated. Data regarding long-term outcomes of pretransplant nephrectomy are limited. In this study, we aimed to compare patient and graft survival, as well as other long-term outcomes of kidney transplantation, between patients with PKD who had a pretransplant nephrectomy and those who have not. MethodsA retrospective analysis of 112 adult kidney transplant recipients with PKD, 36 (32.14%) of which underwent a pretransplant nephrectomy. ResultsIn a mean follow-up period of 79 and 129 months (for patients who underwent nephrectomy and patients who did not, respectively), no significant differences were found in patient and graft survival, after adjustment to age and donor type. In addition, rate of hospitalizations, urinary tract infections requiring hospitalization, diabetes mellitus, and erythrocytosis post-transplant were similar in both cohorts. ConclusionsPretransplant nephrectomy in patients with PKD is not associated with increased risk of mortality and other long-term complications following kidney transplantation.

COMPARAISON DES RESULTATS A LONG TERME DE LA TRANSPLANTATION RENALE ENTRE CONJOINTS ET DONNEURS VIVANTS APPARENTES: EXPERIENCE MONOCENTRIQUE AU MAROC

Objective: End-stage kidney disease is a serious medical condition that often requires a kidney transplant. This single-center study, conducted in Morocco, examines the long-term outcomes of kidney transplants from spouses and related living donors. The goal is to enhance access to organ transplantation by assessing the success of transplants using spouses as donors. Patients and methods:A total of 117 patients were eligible for a kidney transplant from their spouses kidneys. Out of these, 36 received a transplant and were compared to 56 patients who received a kidney from a related donor. Demographic, clinical, and immunological data, as well as long-term outcomes, including graft survival, were analyzed. Results: Recipientswerepredominantly male in both groups (69.6% versus 83.3%). Recipients in the related group wereyoungerthanthose in the unrelated group (39.80 versus 56.56 years). Relatedgraftsshowed more HLA matchingthanunrelatedgrafts (4.45 versus 1.64). The occurrence of DSA after transplantation wasslightlylower in the relatedgraft (16.1% versus 19.4%). Graftsurvival at 1, 3, 5, and 10 yearswassimilar in both groups, with a slight favorable trend for the related group. Conclusion: Kidney transplant survival rates are broadlysimilarbetweenspouses and related living donors. This suggeststhatspousal donation can compensate for the scarcity of cadaveric donation, particularly in Morocco.

Ex Vivo Surgical Removal Versus Conservative Management of Small Asymptomatic Kidney Stones in Living Donors and Long-term Kidney Transplant Outcomes.

Donors with small asymptomatic kidney stones have been increasingly accepted because of organ shortages and advances in endoscopic urology. This study aims to evaluate and compare long-term living-donor kidney transplant outcomes following ex vivo surgical removal versus conservative management of donors' gifted asymptomatic stones. Between January 2007 and December 2021, 119 kidney transplant recipients received stone-bearing kidneys, divided into the removal group (N = 63) and observation group (N = 56). We evaluated posttransplant stone events, urinary infections, kidney function, delayed graft function, length of hospital stay, and survival outcomes. After a median follow-up of 75.5 mo, the removal group had a 10.9% lower absolute incidence of stone events (7/56 [12.5%] versus 1/63 [1.6%]; hazard ratio, 0.08; 95% confidence interval, 0.01-0.77) and a 14.3% lower absolute incidence of urinary infections (16/56 [28.6%] versus 9/63 [14.3%]; hazard ratio, 0.42; 95% confidence interval, 0.19-0.95) than the observation group. The removal group also showed superior kidney graft function. The 2 groups had comparable length of hospital stay (11.0 versus 12.0 d; P = 0.297) and exhibited similar delayed graft function incidence (1/56 [1.8%] versus 2/63 [3.2%]; P = 1.000) and urinary stricture incidence (1/56 [1.8%] versus 3/63 [4.8%]; P = 0.621). Graft survival (P = 0.350) and patient survival (P = 0.260) were comparable between 2 groups. Subgroup analyses in recipients who received kidneys with stones <4 mm also reported similar results. Ex vivo surgical removal might outperform conservative management for donors' gifted asymptomatic kidney stones, improving long-term transplant outcomes and reducing stone events without increasing perioperative complications, even for stones <4 mm.

Management of deceased and living kidney donor with lithiasis: a multicenter retrospective studyon behalf of the renal transplant group of the Spanish urological association.

To maximize the availability of suitable grafts and ensure effective management, several reports have demonstrated successful outcomes when using kidney grafts with urolithiasis. This multicenterstudy reports onthe management and long-term outcomes of kidney transplantation using renal grafts with lithiasis. Retrospective data from three Spanish hospitals were analyzed for kidney transplants involving grafts with nephrolithiasis performedbetween December 2009 and August 2023. The study included adult patients, excluding those with incomplete records. It evaluated stone characteristics, complications, and outcomes in recipientsand in living kidney donors. Out of 38 analyzed kidney transplants, 57.9% were cadaveric and 42.1% were from living kidney donors. Most diagnoses were incidental during donor evaluation, with an average stone size of 7.06mm. After follow-up (median 26months), all recipients but one had functioning grafts, and there were no stone recurrences in bothrecipients andliving kidney donors. Conservative management was adopted in 28 cases, while 10 cases required ex-vivo flexible ureterorenoscopy for stone removal. Following conservative management, 5 patients needed additional treatments for stone-related events. Kidneys with lithiasis can be considered for transplantation in selected cases, resulting in good functional outcomes with no stone recurrence in recipients or living donors.

Long-term Outcomes After Kidney Transplantation From DBD Donors Aged 70 y and Older.

Transplantation of kidneys from elderly donations after brain death (DBD) donors has increased owing to organ shortages. We aimed to assess the impact on long-term kidney transplant outcomes from DBD donors aged 70 y and older compared with kidneys from younger donors. From 2007 to 2022, 2274 first single kidney transplantations from DBD donors were performed at our center. Data from 1417 kidney transplant recipients receiving a DBD organ were included and categorized into 3 groups according to donor age: 70 y and older (n = 444, median age 74 y), 60-69 y (n = 527, median age 64 y), and a reference group consisting of donors aged 45-54 y (n = 446, median age 50 y). Kaplan-Meier plots and multivariate Cox regression with correction for recipient, donor, and transplant characteristics were used to investigate patient and kidney graft survival outcomes. The median patient follow-up time was 9.3 y (interquartile range, 5.3-13.1). The adjusted hazard ratios for patient death in recipients of kidneys from DBD donors aged 70 y and older compared with 60-69 y and 45-54 y were 1.12 (95% confidence interval [CI], 0.92-1.36; P = 0.26) and 1.62 (95% CI, 1.26-2.07; P < 0.001), respectively. Compared with recipients of donors aged 60-69 y and 45-54 y, the adjusted hazard ratios for kidney graft loss in recipients of donors aged 70 y and older were 1.23 (95% CI, 1.02-1.48; P = 0.029) and 1.94 (95% CI, 1.54-2.45; P < 0.001), respectively. Transplantation of kidneys from DBD donors aged 70 y and older resulted in acceptable long-term outcomes and is encouraging.

Mycophenolate Dose Reduction in Tacrolimus-based Regimens and Long-term Kidney Transplant Outcomes in Australia and New Zealand.

Mycophenolate dose reduction (MDR) is associated with acute rejection and transplant failure in kidney transplant recipients (KTRs). The optimal dose to prevent rejection and reduce complications remains poorly defined in tacrolimus-based regimens. We assessed adult KTRs from 2005 to 2017 initiated on mycophenolate mofetil 2 g/d, tacrolimus, and prednisolone from the Australia and New Zealand Dialysis and Transplant Registry. KTRs with rejection within the first 30 d posttransplant were excluded. The primary outcome was time to first rejection between 30 d and 2 y posttransplant. Mycophenolate dose was modeled as a time-varying covariate using Cox proportional hazards regression. Secondary outcomes included assessment of early MDR to <1.5 g/d within the first 6 mo posttransplant and subsequent patient and death-censored graft survival. In the primary analysis, 3590 KTRs were included. Compared with mycophenolate dose of ≥2 g/d, both 1.0-<1.5 and <1 g/d were associated with an increased risk of rejection during the 2 y posttransplant (hazard ratio [HR] 1.67; 95% confidence interval [CI], 1.29-2.16; P < 0.001 and HR 2.06; 95% CI, 1.36-3.13; P = 0.001, respectively) but not 1.5-<2 g/d (HR 1.20; 95% CI, 0.94-1.53; P = 0.14). Early MDR to <1.5 g/d occurred in 45.3% of KTRs and was an independent risk factor for death-censored graft failure (HR 1.32; 95% CI, 1.05-1.66; P = 0.016) but not death (HR 1.18; 95% CI, 0.97-1.44; P = 0.10), during a median follow-up of 5.0 (interquartile range, 2.6-8.5) y. Early MDR was a risk factor for subsequent rejection and graft failure in KTRs receiving contemporary tacrolimus-based regimens.

Immune monitoring in pediatric kidney transplant.

Long-term outcomes in pediatric kidney transplantation remain suboptimal, largely related to chronic rejection. Creatinine is a late marker of renal injury, and more sensitive, early markers of allograft injury are an active area of current research. This is an educational review summarizing existing strategies for monitoring for rejection in kidney transplant recipients. We summarize supporting currently available clinical tests, including surveillance biopsy, donor specific antibodies, and donor-derived cell free DNA, as well as the potential limitations of these studies. In addition, we review the current avenues of active research, including transcriptomics, proteomics, metabolomics, and torque tenovirus levels. Advancing the use of noninvasive immune monitoring will depend on well-designed multicenter trials that include patients with stable graft function, include biopsy results on all patients, and can demonstrate both association with a patient-relevant clinical endpoint such as graft survival or change in glomerular filtration rate and a potential timepoint for intervention.

Maximizing matching, equity and survival in kidney transplantation using molecular HLA immunogenicity quantitation

HLA matching improves long-term outcomes of kidney transplantation, yet implementation challenges persist, particularly within the African American (Black) patient demographic due to donor scarcity. Consequently, kidney survival rates among Black patients significantly lag behind those of other racial groups. A refined matching scheme holds promise for improving kidney survival, with prioritized matching for Black patients potentially bolstering rates of HLA-matched transplants.To facilitate quantity, quality and equity in kidney transplants, we propose two matching algorithms based on quantification of HLA immunogenicity using the hydrophobic mismatch score (HMS) for prospective transplants. We mined the national transplant patient database (SRTR) for a diverse group of donors and recipients with known racial backgrounds. Additionally, we use novel methods to infer survival assessment in the simulated transplants generated by our matching algorithms, in the absence of actual target outcomes, utilizing modified unsupervised clustering techniques.Our allocation algorithms demonstrated the ability to match 87.7% of Black and 86.1% of White recipients under the HLA immunogenicity threshold of 10. Notably, at the lowest HMS threshold of 0, 4.4% of Black and 12.1% of White recipients were matched, a marked increase from the 1.8% and 6.6% matched under the prevailing allocation scheme. Furthermore, our allocation algorithms yielded similar or improved survival rates, as illustrated by Kaplan–Meier (KM) curves, and enhanced survival prediction accuracy, evidenced by C-indices and Integrated Brier Scores.

Outcome of ABO-incompatible living-donor kidney transplants : Aplea for crossover living-donor kidney transplantation

The lack of postmortem donated organs is the background to varyingly high rates of living-donor kidney transplants worldwide. ABO blood group-incompatible living-donor kidney transplants have also been established for at least 20years. The equivalence of the results of ABO-incompatible and ABO-compatible transplants has recently been questioned. In the sense of acritical reflection of our own kidney transplant program, we were interested in comparing ABO-incompatible with ABO-compatible living-donor kidney transplants. Aretrospective analysis of the long-term outcomes of all living-donor kidney transplants performed at our center since the first ABO-incompatible transplants were performed in 2005 up to and including 2022 was performed. Between 2005 and 2022, 1099 living kidney transplants were performed at the authors' center. Among them were 241ABO-incompatible transplants. Transplant survival was significantly lower after ABO-incompatible donation than after ABO-compatible donation. This effect consisted of an increased mortality of the recipients, especially in the early phase, and areduced longevity of the grafts. Including ABO-incompatible pairs for living-donor kidney transplants in crossover programs can improve medical outcomes and reduce costs.

Peri-operative and long-term outcomes of kidney transplantation in patients with cystic fibrosis.

There is a lack of data regarding the peri-operative and long-term outcomes of kidney transplantation in cystic fibrosis (CF) patients. Herein, we report the peri-operative and long-term outcomes of kidney transplantation in CF patients. All CF patients who received a kidney transplant at the national kidney transplant center between 1993 and 2022 were identified. Recipients of the contralateral donor kidney were selected as a control group. Primary outcomes included 1-, 5-, and 10- year death-censored graft survival and overall survival. Secondary outcomes included peri-operative morbidity, acute graft rejection, delayed graft function (DGF), and length of stay (LOS). Fourteen patients received a kidney transplant over the study period. Median age at transplantation was 35 (IQR 31, 40) years. The 1-, 5-, and 10-year death-censored graft survival was 92, 74, and 74% in the CF group compared to 100, 92, and 92% in the control group (p=.44). The 1-, 5-, and 10-year overall survival in the CF group was 85, 66, and 57% compared to 100, 92, and 82% in the control group (p=.036). There was no significant difference in peri-operative outcomes including LOS (10vs. 11 days, p=.84), ICU admission (1vs. 0 patients, p>.99), acute rejection episodes (2vs. 1 patients, p>.99), and DGF (1vs. 2 patients, p=.60). CF patients have good long-term graft survival, however, overall survival was worse compared to a matched cohort. These data provide important information for transplant surgeons when considering suitable donor allografts in this unique patient population.

Effect of delayed graft function on immediate and long-term kidney transplant outcomes

Objective: to analyze the immediate and long-term outcomes of kidney transplantation (KT) depending on the duration of delayed graft function (DGF). Materials and methods. The study conducted a retrospective analysis of KT outcomes in 312 patients operated on at Botkin Hospital from June 2018 to December 2022. Exclusion criteria were primary non-function, severe surgical complications that required emergency transplantectomy in the first week after KT and cases where a comprehensive approach to DGF prevention was applied. DGF was defined as the need for dialysis within the first 7 days of KT. The severity of this complication was assessed by the time it took the transplanted kidney function to normalize from mild DGF to severe. We analyzed the immediate and long-term outcomes of KT depending on the presence of initial function and the severity of DGF. Results. DGF developed in 25.3% of cases. The mean time for graft function normalization was 16.5 ± 6.8 days. Mild DGF occurred in 68% of cases, severe DGF was determined in the remaining cases (32%). The incidence of complications was statistically significantly higher in the severe DGF group: 14/25 (56%) vs. 15/54 (27.8%) (p = 0.047). There were also no significant differences in the rate of complications between recipients with immediate and mild DGF: 43/233 (18.4%) vs. 15/54 (27.8%) (p &gt; 0.05). Severe DGF lasting for more than 2 weeks had a statistically significant association with postoperative complications (p = 0.047) and with decreased long-term graft survival (log-rank p = 0.021). Conclusion. Development of severe DGF mainly depends on donor characteristics, timing and peculiarities of graft preservation. Nevertheless, other factors, such as acute calcineurin inhibitor nephrotoxicity, should not be ignored. Therefore, prevention of all potentially modifiable risk factors for DGF should go hand in hand with the expansion of the indications for donation.

Pre-transplant crossmatch-negative donor-specific anti-HLA antibody predicts acute antibody-mediated rejection but not long-term outcomes in kidney transplantation: an analysis of the Korean Organ Transplantation Registry.

Pre-transplant donor-specific anti-human leukocyte antigen antibody (HLA-DSA) is a recognized risk factor for acute antibody-mediated rejection (ABMR) and allograft failure. However, the clinical relevance of pre-transplant crossmatch (XM)-negative HLA-DSA remains unclear. We investigated the effect of XM-negative HLA-DSA on post-transplant clinical outcomes using data from the Korean Organ Transplantation Registry (KOTRY). This study included 2019 living donor kidney transplant recipients from 40 transplant centers in South Korea: 237 with HLA-DSA and 1782 without HLA-DSA. ABMR developed more frequently in patients with HLA-DSA than in those without (5.5% vs. 1.5%, p<0.0001). Multivariable analysis identified HLA-DSA as a significant risk factor for ABMR (odds ratio = 3.912, 95% confidence interval = 1.831-8.360; p<0.0001). Furthermore, the presence of multiple HLA-DSAs, carrying both class I and II HLA-DSAs, or having strong HLA-DSA were associated with an increased incidence of ABMR. However, HLA-DSA did not affect long-term clinical outcomes, such as allograft function and allograft survival, patient survival, and infection-free survival. Pre-transplant XM-negative HLA-DSA increased the risk of ABMR but did not affect long-term allograft outcomes. HLA-incompatible kidney transplantation in the context of XM-negative HLA-DSA appears to be feasible with careful monitoring and ensuring appropriate management of any occurrence of ABMR. Furthermore, considering the characteristics of pre-transplant XM-negative HLA-DSA, the development of a more detailed and standardized desensitization protocol is warranted.

Predicting long-term outcomes of kidney transplantation in the era of artificial intelligence

The ability to accurately predict long-term kidney transplant survival can assist nephrologists in making therapeutic decisions. However, predicting kidney transplantation (KT) outcomes is challenging due to the complexity of the factors involved. Artificial intelligence (AI) has become an increasingly important tool in the prediction of medical outcomes. Our goal was to utilize both conventional and AI-based methods to predict long-term kidney transplant survival. Our study included 407 KTs divided into two groups (group A: with a graft lifespan greater than 5 years and group B: with poor graft survival). We first performed a traditional statistical analysis and then developed predictive models using machine learning (ML) techniques. Donors in group A were significantly younger. The use of Mycophenolate Mofetil (MMF) was the only immunosuppressive drug that was significantly associated with improved graft survival. The average estimated glomerular filtration rate (eGFR) in the 3rd month post-KT was significantly higher in group A. The number of hospital readmissions during the 1st year post-KT was a predictor of graft survival. In terms of early post-transplant complications, delayed graft function (DGF), acute kidney injury (AKI), and acute rejection (AR) were significantly associated with poor graft survival. Among the 35 AI models developed, the best model had an AUC of 89.7% (Se: 91.9%; Sp: 87.5%). It was based on ten variables selected by an ML algorithm, with the most important being hypertension and a history of red-blood-cell transfusion. The use of AI provided us with a robust model enabling fast and precise prediction of 5-year graft survival using early and easily collectible variables. Our model can be used as a decision-support tool to early detect graft status.

Impact of acute kidney injury and renal recovery status in deceased donor to kidney transplant outcome: results from the Thai national transplant registry

The influence of acute kidney injury (AKI) and renal recovery in deceased donor (DD) on long-term kidney transplant (KT) outcome has not previously been elucidated in large registry study. Our retrospective cohort study included all DDKT performed in Thailand between 2001 and 2018. Donor data was reviewed case by case. AKI was diagnosed according to the KDIGO criteria. Renal recovery was defined if DD had an improvement in AKI to the normal or lower stage. All outcomes were determined until the end of 2020. This study enrolled 4234 KT recipients from 2198 DD. The KDIGO staging of AKI was as follows: stage 1 for 710 donors (32.3%), stage 2 for 490 donors (22.3%) and stage 3 for 342 donors (15.6%). AKI was partial and complete recovery in 265 (17.2%) and 287 (18.6%) before procurement, respectively. Persistent AKI was revealed in 1906 KT of 990 (45%) DD. The ongoing AKI in DD significantly increases the risk of DGF development in the adjusted model (HR 1.69; 95% CI 1.44–1.99; p < 0.001). KT from DD with AKI and partial/complete recovery was associated with a lower risk of transplant loss (log-rank P = 0.04) and recipient mortality (log-rank P = 0.042) than ongoing AKI. KT from a donor with ongoing stage 3 AKI was associated with a higher risk of all-cause graft loss (HR 1.8; 95% CI 1.12–2.88; p = 0.02) and mortality (HR 2.19; 95% CI 1.09–4.41; p = 0.03) than stage 3 AKI with renal recovery. Persistent AKI, but not recovered AKI, significantly increases the risk of DGF. Utilizing kidneys from donors with improving AKI is generally safe. KT from donors with persistent AKI stage 3 results in a higher risk of transplant failure and recipient mortality. Therefore, meticulous pretransplant evaluation of such kidneys and intensive surveillance after KT is recommended.

Association of high intra-patient variability in tacrolimus exposure with calcineurin inhibitor nephrotoxicity in kidney transplantation

Tacrolimus intra-patient variability (IPV) is a novel predictive marker for long-term kidney transplantation outcomes. We examined the association between IPV and calcineurin inhibitor (CNI) nephrotoxicity and the impact of pharmacogenes on CNI nephrotoxicity and IPV. Among kidney transplant recipients at our hospital between January 2013 and December 2015, the records of 80 patients who underwent 1-year protocol renal allograft biopsy and agreed to donate blood samples for genetic analysis were retrospectively reviewed. The cohort was divided into the low and high IPV groups based on a coefficient variability cutoff value (26.5%). In multivariate analysis, the IPV group was involved in determining CNI nephrotoxicity (HR 4.55; 95% CI 0.05–0.95; p = 0.043). The 5-year graft survival was superior in the low IPV group than in the high IPV group (100% vs 92.4% respectively, p = 0.044). Analysis of the time above therapeutic range (TATR) showed higher CNI nephrotoxicity in the high IPV with high TATR group than in the low IPV with low TATR group (35.7% versus 6.7%, p = 0.003). Genetic analysis discovered that CYP3A4 polymorphism (rs2837159) was associated with CNI nephrotoxicity (HR 28.23; 95% CI 2.2–355.9; p = 0.01). In conclusion, high IPV and CYP3A4 polymorphisms (rs2837159) are associated with CNI nephrotoxicity.

Qualifying a Novel Clinical Trial Endpoint (iBOX) Predictive of Long-Term Kidney Transplant Outcomes.

New immunosuppressive therapies that improve long-term graft survival are needed in kidney transplant. Critical Path Institute's Transplant Therapeutics Consortium received a qualification opinion for the iBOX Scoring System as a novel secondary efficacy endpoint for kidney transplant clinical trials through European Medicines Agency's qualification of novel methodologies for drug development. This is the first qualified endpoint for any transplant indication and is now available for use in kidney transplant clinical trials. Although the current efficacy failure endpoint has typically shown the noninferiority of therapeutic regimens, the iBOX Scoring System can be used to demonstrate the superiority of a new immunosuppressive therapy compared to the standard of care from 6months to 24months posttransplant in pivotal or exploratory drug therapeutic studies.