Renal Allograft Recipients Research Articles

Combined Molecular Mismatch Approaches to Predict Immunological Events Within the First Year After Renal Transplantation.

Several molecular mismatch assessment approaches exist, but data on their combined use are limited. In this study, we aimed to define distinct risk groups for rejection based on the combination of three molecular mismatch assessment approaches (i.e., eplet mismatch count, the number of highly immunogenic eplets and PIRCHE-II score) in 439 consecutive immunological standard risk transplantations. For each molecular mismatch assessment approach, ROC analyses were used to define cut-offs for prediction of (sub) clinical rejection according to Banff 2019 classification within the first year post-transplant as a reference. If all three scores were below the cut-off, the patient was assigned to the low-risk group (19% of patients); if all three scores were above the cut-off, the patient was assigned to the high-risk group (21% of patients). The one-year incidence of (sub) clinical rejection was 12% in the low-risk group and 33% in the high-risk group (p = 0.003). Internal validation of the assigned risk groups for prediction of other outcomes revealed a high consistency: clinical rejection (6% vs. 24%; p = 0.004), ATG-treated rejection (1% vs. 16%; p < 0.001) and development of de novo HLA-DSA at 5 years post-transplant (6% vs. 25%; p = 0.003). The molecular mismatch risk group was an independent predictor for (sub) clinical rejection (high-risk vs. low-risk: hazard ratio 3.11 [95%-CI 1.50-6.45]; p = 0.002). We conclude that combining molecular mismatch approaches allows us to distinguish low- and high-risk groups among standard renal allograft recipients. Independent validation in other patient populations and different ethnicities is required.

Renal Allograft Macrophage Infiltration in Antibody-Mediated Renal Allograft Rejection

Abstract Introduction/Objective Macrophages are involved in the pathogenesis and contribute to acute and chronic renal allograft injury. We evaluated CD163+ (M2) macrophage graft tissue infiltration and its correlation with clinical and histological prognostic factors. Urinary soluble CD163, circulating total, and monocyte-derived microparticles (MMPs) in plasma were also estimated and correlated with tissue M2 macrophage infiltration. Methods/Case Report The study included forty-five renal allograft recipients with for-cause graft biopsy, with Antibody-mediated Rejection (ABMR) (n=30) or no evidence of rejection (NER) (n=15), from Jan 2021-Dec 2023, along with fifteen age-matched healthy controls (HC). On immunohistochemistry, CD163 positive cells were counted in glomeruli and tubulointerstitium. Urinary sCD163 was done by ELISA. Flow cytometry quantified plasma MPs (AnnexinV+) and MMPs (CD14+/ AnnexinV+). Results (if a Case Study enter NA) The mean age of renal allograft recipients was 35±9yrs (all males). Mean s.creatinine in ABMR and NER was 3±2.6 and 2±0.5 mg/dl, respectively. ABMR had significantly more glomerular (16.2±13.7/10 glomeruli) and tubulointerstitial (183±108/10hpf) M2 macrophage (CD163+) cell infiltration than NER (4.8±4.7/10 glomeruli; 133.5±108/10hpf). Urinary sCD163 in ABMR was also significantly raised (0.89±0.63ng/ml) than in NER. It was not detectable in HC. Plasma MMPs were elevated in ABMR [25% of total MPs (1.62x104)] as compared to NER [8.2 % of total MPs (1.4x104)] and HC [7.8% of total MPs (1.2x104)]. In ABMR, the glomerular CD163+ cells correlated with urinary sCD163 levels (r=0.350, p=0.050) and circulating MMPs (r=0.526, p=0.002). Conclusion We found that in renal allograft recipients with ABMR, there is significantly higher graft biopsy glomerular CD163+ (M2) macrophage infiltration and elevated urinary sCD163 levels as compared to NER. The plasma circulating MMPs were also elevated in ABMR. Our findings suggest that monocyte activation plays a significant role in the pathogenesis and injury in ABMR. Non-invasive markers of monocyte activation can distinguish ABMR from NER in allograft recipients presenting with allograft dysfunction.

Early CYP3A5 Genotype-Based Adjustment of Tacrolimus Dosage Reduces Risk of De Novo Donor-Specific HLA Antibodies and Rejection among CYP3A5-Expressing Renal Transplant Patients.

Our previous retrospective single-center cohort study found, at 3-year follow-up, a trend toward low tacrolimus trough levels and an increased risk of de novo donor-specific anti-HLA antibodies (DSAs) and of antibody-mediated rejection (ABMR) in CYP3A5-expressing patients. Determining CYP3A5-expression status immediately after renal transplant would allow early genotype-based dosage adjustment of tacrolimus and might prevent the occurrence of de novo DSAs and ABMR, improving transplant outcome. 160 renal allograft recipients who underwent renal transplant at the University Hospital Essen between May 2019 and May 2022 were genotyped for the CYP3A5 rs776746 polymorphism within the first two weeks after transplant, and genotype-based dose adjustment of tacrolimus was performed for the follow-up of 2 years. CYP3A5 expression was detected in 33 (21%) of the 160 patients. Tacrolimus trough levels were similar in CYP3A5 expressers and nonexpressers over the entire 2-year follow-up period. However, we observed a trend toward slightly higher tacrolimus trough levels in CYP3A5 expressers, who, as expected, required tacrolimus dosages twice as high as did nonexpressers during follow-up. Calcineurin inhibitor (CNI) nephrotoxicity-free survival rates were comparable between CYP3A5 expressers and nonexpressers (p = 0.49). Rejection-free survival rates (p = 0.89), de novo anti-HLA antibody-free survival rates (p = 0.57) and de novo DSA-free survival rates (p = 0.61) did not differ between the two groups. Early detection of CYP3A5-expression status and resultant genotype-based adjustment of tacrolimus dosage after renal transplant protected patients from transplant rejection and de novo DSA formation and was not associated with increased incidence of CNI toxicity among CYP3A5 expressers.

Association of Therapeutic Monitoring of Tacrolimus with Laboratory Markers of Kidney Function in Receptors of Kidney Allograft

Introduction: Kidney transplantation is the most commonly performed type of transplant in Brazil. Tacrolimus is one of the primary drugs used in post-transplant immunosuppressive therapy, and one of its main adverse effects is nephrotoxicity. Laboratory tests to assess renal function are of great importance in monitoring post-kidney transplant patients, helping to diagnose events indicative of graft dysfunction. Objective: !e present study aimed to evaluate the association between laboratory changes in renal function and blood levels of tacrolimus in post-kidney transplant patients. Methods: Observational, analytical and cross-sectional study. !e results of blood levels of tacrolimus and measurements of urea, creatinine and estimated Glomerular Filtration Rate (eGFR) were analyzed, as well as the sociodemographic data of kidney transplant recipients followed at a university hospital who underwent laboratory tests between months from January 2021 to July 2022 in a period close to 1 year after the transplant. !e variables analyzed in the research were collected from the patient's medical records and subsequently analyzed; the statistical analyses considered p &lt; 0.05. !e project was approved by the Ethics Committee of the Walter Cantídio University Hospital under opinion number 5,436,434 and CAAE number 57396622.1.0000.5045. Results: !e sample was mainly composed of males, mixed race, with an average age of 51.5 years (SD ± 12.5) and from cities in the interior of Ceará. Regarding the percentage of patients with laboratory changes, 50.62% (n = 45) showed changes in tacrolimus blood levels. 56.79% (n = 46) had changes in serum creatinine levels, 49.38% (n = 40) had changes in serum urea levels, and 59.26% (n = 48) had altered eGFR. !e correlation analyses suggested a low signi#cance between variations of the variables studied. Conclusion: !e results indicate no relationship between variations in tacrolimus blood concentrations and the appearance of changes in the results of classic renal biomarkers at the end of the #rst year post-transplant. However, it is necessary to carry out new studies to understand better the impact of changes in blood levels of tacrolimus on the renal function of renal allograft recipients.

410.4: A prospective observational study to assess the role of donor derived cell free DNA (dd-cfDNA) in predicting active rejection in renal allograft recipients.

410.4: A prospective observational study to assess the role of donor derived cell free DNA (dd-cfDNA) in predicting active rejection in renal allograft recipients.

Marginal zone B cells are required for optimal humoral responses to allograft

Antibody-mediated rejection (AMR) is among the leading causes of graft failure in solid organ transplantation. However, AMR treatment options are limited by an incomplete understanding of the mechanisms underlying de novo donor-specific antibody (DSA) generation. The development of pathogenic isotype-switched DSA in response to transplanted allografts is typically attributed to follicular B cells undergoing germinal center reaction whereas the contribution of other B cell subsets has not been previously addressed. The current study investigated the role of recipient marginal zone B cells (MZ B cells) in DSA responses using mouse models of heart and renal allotransplantation. MZ B cells rapidly differentiate into antibody-secreting cells in response to allotransplantation. Despite the selective depletion of follicular B cells in heart allograft recipients, MZ B cells are sufficient for T-dependent IgM and early IgG DSA production. Furthermore, the presence of intact MZ B cell subset is required to support the generation of pathogenic isotype-switched DSA in renal allograft recipients containing donor-reactive memory helper T cells. These findings are the first demonstration of the role of MZ B cells in humoral alloimmune responses following solid organ transplantation and identify MZ B cells as a potential therapeutic target for minimizing de novo DSA production and AMR in transplant recipients.

441.4: To study the long-term impact of hepatitis C treatment in terms of viral load and liver fibrosis among the renal allograft recipients.

441.4: To study the long-term impact of hepatitis C treatment in terms of viral load and liver fibrosis among the renal allograft recipients.

P.107: Pattern of CYP3A5 and MDR-1 single nucleotide polymorphism and its impact on tacrolimus levels and clinical outcomes in living renal allograft recipient.

P.107: Pattern of CYP3A5 and MDR-1 single nucleotide polymorphism and its impact on tacrolimus levels and clinical outcomes in living renal allograft recipient.

260.11: Impact of HLA donor specific antibody vs non-donor specific antibodies by single antigen bead method in predicting outcome of living related renal allograft recipients.

260.11: Impact of HLA donor specific antibody vs non-donor specific antibodies by single antigen bead method in predicting outcome of living related renal allograft recipients.

Relevance of Proteinuria in Kidney Transplant Recipients and Allograft Outcomes

BackgroundThe onset of proteinuria in renal allograft recipients is frequently associated with an increased risk for both graft failure and mortality. We investigated the risk associated with post-transplant proteinuria and its time-dynamics in a select group treated for biopsy proven antibody-mediated rejection (ABMR). MethodsEighty-five patients who underwent transplantation were enrolled in our study and followed up from transplantation until October 31, 2020, death, or the date of the return to dialysis. We created two main groups: the ABMR group (n = 19) and an ABMR-negative control group with stable kidney function (n = 52) without donor-specific antibodies (DSA) and a subgroup with DSAs but stable graft function (n = 14) without ABMR. Differences in patient, donor, and transplant graft characteristics between the groups were assessed by Fisher's exact test for categorical variables. Death-censored graft loss was evaluated with the help of Kaplan-Meier analysis using log risk statistics. ResultsProteinuria decreased after treatment in the ABMR group (P < .0009). Pre-treatment every 10 mg/mmol increase in proteinuria was associated with a 7% increase in the risk for graft failure in the ABMR group. The estimated 3-year graft survival was 87.5% in the ABMR group, compared to 93% in the group without ABMR but with pre-formed DSA, and 100% in the DSA negative subgroup (log-rank probe P < .0666). ConclusionProteinuria is an independent predictor for graft failure, can be lowered by treatment for ABMR but ABMR is associated with lower graft survival in our study population.

Chronic Kidney Disease in a Tertiary Care Hospital in Nepal

Introduction: Chronic kidney disease (CKD) is an increasingly recognized major public health problem globally and in Nepal. It has a high prevalence in the population and is associated with high morbidity, mortality and health care costs. Here, we aimed to study the socio-demographic profiles, etiologies of CKD and associated co-morbidities in patients attending a referral hospital. Methods: We conducted a hospital based, descriptive, observational, cross-sectional study among adult patients with CKD attending Tribhuvan University Teaching Hospital (TUTH), Kathmandu. Patients younger than 16 years and renal allograft recipients were excluded from the study. A diagnosis of CKD was established by the treating nephrologist based on KDIGO 2012 clinical practice guideline. Prior informed consent was taken. Data was collected on clinical features, socio-demographic profiles, major co-morbidities, presumed etiology of CKD and hematological and biochemical parameters of the patients. SPSS version 24 (Chicago, IL, USA) was used for the analysis of data. The study protocol was approved by the Institutional Review Board (IRB) of Institute of Medicine (IOM). Results: A total of 401 patients with CKD were included in the study. The mean age of the patient was 50.92 years (SD=17.98), male to female ratio was 1.8:1. Among these patients, 86% were Hindu, 24.4% were farmers, 57% were from the Hilly region of Nepal, 51% were active smokers, and 51.6% were alcohol consumers. Chronic glomerulonephritis (CGN) (36.2%; n= 145), diabetes mellitus (31.9%; n= 128) and hypertension (21.7%; n=87) were the three most common identified causes of CKD. Among the biopsy proven CGN patients, IgA nephropathy was the most common cause. In a large proportion of patients (68.3%) cause of CGN was not known. Most of the patients were in CKD stage 5 (27%), and stage 5D (55.8%). Coronary artery disease (CAD) (in 7% patients), heart failure (in 2.7%) and stroke (in 2.2%) were the most common comorbidities. Anemia was prevalent in CKD from stage 3 onwards, the severity increased with increasing stage (p &lt;0.001). Hemodialysis was the predominant mode of renal replacement therapy (RRT) used by 98.2% of CKD 5D patients. Conclusion: Nepalese patients of CKD are younger; males are more affected than females. CGN, diabetes and hypertension are three most common causes of CKD; IgA nephropathy is the most common cause of biopsy proven CGN leading to CKD. Anemia is common from CKD stage 3 onwards. The most common associated co-morbidity is CAD.

Early and late assessment of renal allograft dysfunction using intravoxel incoherent motion (IVIM) and diffusion-weighted imaging (DWI): a prospective study.

To evaluate the ability of the Intravoxel Incoherent Motion (IVIM) and monoexponentially ADC in renal allograft function in the early and late phases of transplantation, and to predict their effectiveness in discrimination of the graft pathology. This is a prospective study included participants scanned with quantitative diffusion and perfusion sequences on a 3-T MR scanner (Philips, Ingenia); the ADC and IVIM parameters; were calculated. Correlations and regression analysis with the eGFR, transplantation periods, and pathology were assessed. This study included 105 renal allograft recipients (85 males, and 20 females with mean age = 32.4 ± 11.9years and age range = 22-61years). There was a significant positive correlation between the whole parameters of the ADC and IVIM with eGFR however, the cortical parameters showed higher significant correlation coefficients (p < 0.001). Regression analysis revealed the most significant model can predict eGFR groups included cortical pseudo diffusion (D*) and cortical ADC (p < 0.001). In graft dysfunction eGFR was 61.5ml/min and normal graft was 64ml/min. This model demonstrates a high performance of an AUC 96% [0.93-0.97]. In the late transplantation, there is a higher correlation with D* compared to ADC, p-values = 0.001. IVIM and ADC Values are significant biomarkers for renal allograft function assessment, cortical ADC, and D* had the highest performance even in situations with mild impairment that is not affect the eGFR yet as cases of proteinuria with normal eGFR. Furthermore, D* is superior to ADC in the late assessment of the renal transplant.

Pattern of CYP3A5 and MDR-1 single nucleotide polymorphism and its impact on Tacrolimus levels and clinical outcomes in living renal allograft recipient

Abstract Introduction Renal transplant is best form of renal replacement therapy. Most favored immunosuppression includes Tacrolimus, mycophenolate mofetil and steroids. Tacrolimus has narrow therapeutic index and requires therapeutic drug monitoring (TDM). However, there is wide variation in tacrolimus level with weight based fixed dosage regimens. This variability is due to polymorphism of major pathways of metabolism ie CYP3A5 and MDR1 genes. Fast metabolizer require higher dosage and slow metabolizer require lower dosage. Genotype based dosing strategy may be useful to achieve early therapeutic level and reduce infections and rejections. Methodology 160 transplant patients at tertiary care hospital in India were included in this study from 2016 to 2018. Genetic polymorphism analysis in CYP3A5 and MDR1 gene was carried out at time of transplant. All patients were given a fixed weight-based dosage of Tacrolimus. Data was analyzed in relation to genotype polymorphism. Results and discussion 69.2% of Wild variants of CYP 3A5 (Fast metabolizers) have low initial tacrolimus levels. 51.5% of Homo variants (Slow metabolizers) have high initial tac levels. However, all variants achieve optimum tacrolimus levels at same time (mean 12.4 days). There were higher number of infections among slow metabolizers. Conclusion A fixed dosing regimen with TDM result in high and low initial tacrolimus levels in slow and fast metabolizers respectively and more infections in slow metabolizers. However, graft rejections being fewer in number, were not different. A larger sample with genotype based dosing is required to test such a strategy.

Sensitive HLA antibody testing and the risk of antibody-mediated rejection and graft failure.

Solid phase detection and identification of HLA antibodies in kidney transplantation currently relies on single antigen bead (Luminex®) assays, which is more sensitive than the previously used enzyme-linked immunosorbent assays (ELISA). To evaluate the impact of more sensitive HLA testing on antibody-mediated rejection (AMR) occurrence and allograft survival, we analysed 1818 renal allograft recipients transplanted between March 2004 and May 2021. In 2008, solid phase testing switched from ELISA to Luminex. We included 393 (21.6%) transplantations before and 1425 (78.4%) transplantations after transition from ELISA- to Luminex-based testing. For this study, bio-banked ELISA era samples were tested retrospectively with Luminex. Significantly less pretransplant DSA were found in patients transplanted with pre-existing HLA antibodies in the Luminex (109/387) versus the ELISA period (43/90) (28% vs. 48%, p < 0.01). Throughout histological follow-up, 169 of 1818 (9.3%) patients developed AMR. After implementing Luminex-based testing, the rate of AMR significantly decreased (p = 0.003). However, incidence of graft failure did not significantly differ between both eras. In conclusion, less patients with pretransplant DSA were transplanted since the implementation of Luminex HLA testing. Transition from ELISA- to Luminex-based HLA testing was associated with a significant decrease in AMR occurrence post-transplantation. Since the decline of AMR did not translate into improved graft survival, Luminex-based testing has the added value of preventing low-risk AMR cases. Therefore, Luminex' high sensitivity must be balanced against waiting time for a suitable organ.

#1718 Infectious complications among early versus late pulse steroid therapy among renal transplant recipients

Abstract Background and Aims Renal transplant recipients are at risk for infectious complications, with opportunistic infections predominating early after transplant and community acquired infections occurring in late transplant period. Pulse steroid is a form of heightened immunosuppression given to a transplant recipient, usually for treatment of rejection. This study aimed to investigate the effects of early and late pulse steroid therapy on the development of infectious complications in renal transplant recipients. Method Study population was drawn from patients undergoing kidney transplantation in the period between 1st January, 2016 and 31st December, 2020 in the study centre. Early and late pulse steroid therapy was defined based on whether pulse steroid was received within or after 90 days from date of transplant respectively. Patients receiving either early or late (but not both) pulse steroids who were more than or equal to 18 years of age and had at least 90 days of follow up were included in the study. Patients were followed up till 31st December, 2021 or till their death (whichever came earlier). Results Total of 516 patients underwent renal transplantation in the study centre in the specified period, out of whom 128 patients (24.8%) fulfilled the inclusion criteria without fulfilling the exclusion criteria. Out of these 128 patients, 83 (64.8%) and 45 (35.2%) patients received early and late pulse steroids respectively. The 2 groups were similar with respect to respect to baseline characteristics and use of other immunosuppressive agents. The mean values (95% confidence interval) for overall infections in early and late pulse steroid categories were 0.46 (0.31-0.61) and 1.16 (0.55-1.78) episodes per year respectively (p = 0.28). Sepsis occurred at higher rate in patients receiving late pulse steroids, with mean values (95% confidence interval) for sepsis in early and late pulse steroid categories being 0.02 (0.00-0.06) and 0.30 (0.04- 0.57) episodes per year respectively (p = 0.01). Viral infections also occurred at higher rate in patients receiving late pulse steroids, with mean values (95% confidence interval) for viral infections in early and late pulse steroid categories being 0.04 (0.02- 0.09) and 0.23 (0.03-0.43) episodes per year respectively (p = 0.01). Rates of other types of infection did not significantly differ between the 2 categories. A greater proportion of patients receiving late pulse steroids died (4.8% and 17.8% in early and late pulse steroid categories respectively, p = 0.02). Conclusion Late pulse steroid therapy is associated with more episodes of sepsis and viral infections compared to early pulse steroid therapy, although rate of overall infections do not significantly differ between the two groups. This study highlights the importance of surveillance for infections after pulse steroid therapy in renal allograft recipients.

The 25-hydroxyvitamin D level in Kidney Transplant Recipients and Its Association With Renal Function and Other Cardio-Metabolic Risk Markers

Vitamin D is the main hormone that plays a critical role in controlling mineral homeostasis. Transplant recipients frequently have altered levels of 25-hydroxyvitamin D (25[OH] D) and 1, 25-hydroxyvitamin (1, 25[OH] D). To explore the status of vitamin D level in renal allograft recipients and its association with renal function and cardio-metabolic risk markers. One hundred two adult kidney transplant recipients (KTRs) were included. Clinical history and information about transplantation and immunosuppression were recorded. Blood and urine samples were collected for relevant laboratory tests, including chronic kidney disease (CKD)-mineral and bone disorder markers (Ca, PO4, and 25[OH] D). The mean age was 35 ± 8 years, with a male/female ratio of 89/11%. The transplant duration was 34 ± 26 (4.5-112) months. All donors involved were living-related: fathers comprised 44%, wives 16%, sisters 13%, mothers 11%, and the others 16% (ie, brothers, sons, daughters, uncles, aunts). The immunosuppression regimen included prednisolone and tacrolimus in all, with mycophenolate mofetil in 96%. The estimated glomerular filtration rate showed CKD distribution from stage 1 to 5 in 6%, 29%, 44%, 15%, and 6%, respectively. Vitamin D level was lower in 22% (<20 ng/mL), insufficient (20-30 ng/mL) in 48%, and adequate (>30 ng/mL) in 30%. We compared different clinical and laboratory variables in 3 different vitamin D groups but found no difference in cardio-renal risk factors (P = Not Significant). Similarly, no correlation was seen between vitamin D levels and other clinical and metabolic factors. According to conventional cutoffs, the vitamin D (25[OH] D) level is inadequate in 70% of renal allograft recipients. The hormone level has no apparent association with renal function and major cardio-metabolic risk factors.

Clinicopathologic Spectrum and Outcomes of Infections Diagnosed on Graft Biopsies and Nephrectomy in Live Renal Allograft Recipients: An Institutional Experience.

Modern immunosuppressive regimens have reduced rejection episodes in renal allograft recipients but have increased the risk of opportunistic infections. Infections are considered to be the second leading cause of death after cardiovascular complications in renal allograft recipients. Data on opportunistic infections affecting the allograft itself are scarce. The present study describes the spectrum of renal opportunistic infections and their outcomes diagnosed on renal allograft biopsies and nephrectomy specimens. Our retrospective observational study was conducted from December 2011 to December 2021. We analyzed infectious episodes diagnosed on renal allograft biopsies or graft nephrectomy specimens. We obtained clinical, epidemiological, and laboratory details for analyses from hospital records. BK virus nephropathy was the most common opportunistic infection affecting the allograft, accounting for 47% of cases, followed by bacterial graft pyelonephritis (25%). Mucormycosis was the most common fungal infection. The diagnosis of infection from day of transplant ranged from 14 days to 39 months. Follow-up periods ranged from 1 to 10 years. Mortality was highest among patients with opportunistic fungal infection (62%), followed by viral infections, and graft failure rate was highest in patients with graft pyelonephritis (50%). Among patients with BK polyomavirus nephropathy, 45% had stable graft function compared with just 33% of patients with bacterial graft pyelonephritis. BK polyoma virus infection was the most common infection affecting the renal allograft in our study. Although fungal infections caused the highest mortality among our patients, bacterial graft pyelonephritis was responsible for maximum graft failure. Correctly identifying infections on histology is important so that graft and patient life can be prolonged.

Kidney Retransplantation in Children.

Pediatric kidney transplant recipients will likely require a retransplant in their lifetime. Although the significant advances in clinical management and newer immunosuppressive agents have had a significant effect to improve short-term allograft function, it is apparent that long-term allograft function remains suboptimal. Therefore, it is likely that most pediatric renal allograft recipients will require 1 or more retransplants during their lifetime. In the West, an increasing number of patients on the deceased donor wait list are awaiting a retransplant; in the US, 15% of current annual transplants are retransplants. Unfortunately, the use of a second or subsequent grafts in pediatric recipients has inferior long-term graft survival rates compared with initial grafts, with decreasing rates with each subsequent graft. Multiple issues influence the outcome of retransplant, with the most significant being the cause of the prior transplant failure. Nonadherenceassociated graft loss poses unresolved ethical issues that may affect a patient's access to retransplant. Graft nephrectomy prior to retransplant may benefit selected patients, but the effect of an in situ failed graft on the development of panel reactive antibodies remains to be definitively determined. It is important that these and other factors discussed in this presentation be taken into consideration during the counseling of families on the optimal approach for their child who requires a retransplant.

Fixed low dose versus concentration-controlled initial tacrolimus dosing with reduced target levels in the course after kidney transplantation: results from a prospective randomized controlled non-inferiority trial (Slow & Low study)

Optimal initial tacrolimus dosing and early exposure of tacrolimus after renal transplantation is not well studied. In this open-label, 6 months, multicenter, randomized controlled, non-inferiority study, we randomly assigned 432 renal allograft recipients to receive basiliximab induction, mycophenolate and steroids and either standard prolonged-release tacrolimus (trough levels: 7-9ng/ml; Standard Care arm), or an initial 7-day fixed 5mg/day dose of prolonged-release tacrolimus followed by lower tacrolimus predose levels (trough levels: 5-7ng/ml; Slow & Low arm). The primary end point was the combined incidence rate of biopsy-proven acute rejections (BPAR; including borderline), graft failure, or death at 6 months with a non-inferiority margin of 12.5%. (EudraCT-Nr: 2013-001770-19. The combined primary endpoint in the Slow & Low arm was non-inferior compared to the Standard Care arm (22.1% versus 20.7%; difference: 1.4%, 90% CI-5.5% to 8.3%). The overall rate of BPAR including borderlines was similar (Slow & Low 17.4% versus Standard Care 16.6%). Safety parameters such as delayed graft function, kidney function, donor specific HLA-antibodies, infections, or post-transplantation diabetes mellitus did not differ. This is the first study to show that an initial fixed dose of 5mg per day followed by lower tacrolimus exposure is non-inferior compared to standard tacrolimus therapy and equally efficient and safe within 6 months after renal transplantation. These data suggest that therapeutic drug monitoring for prolonged release tacrolimus can be abandoned until start of the second week after transplantation. Investigator-initiated trial, financial support by Astellas Pharma GmbH.

Clinicopathological Correlation of Polyomavirus Nephropathy in Renal Allograft Recipients According to the Banff 2018 Classification.

Polyomavirus nephropathy (PVN) is a rare kidney disease caused by the BK virus, a strain of polyomavirus. The disease primarily affects transplant recipients, which is related to intensive immunosuppression protocol and can lead to kidney allograft failure. The objective of this study is to analyze histopathological features of PVN using the Banff 2018 PVN classification and to determine clinical features and outcomes of patients with PVN in each histologic class. The study included 44 patients who had been diagnosed with PVNby renal allograft biopsy in a large tertiary care hospital in Thailand from January 2011 to January 2020. The kidney biopsy slides were reviewed for Banff 2018 PVN classification and other histologic features. Patient demographic information, clinical data, and laboratory results were retrospectively collected. Nine (20.45%), 27 (61.36%), and eight (18.18%) cases of PVN were Class I, Class II, and Class III, respectively. The time from transplant to PVN diagnosis for Classes I, II, and III was four, 19, and 33.5months, respectively. Class III had the worst clinical outcomes in terms of deterioration of allograft function, the lowest rate of resolution, and the highest rate of graft failure. PVN classification provides prognostic information in renal allograft biopsy. Our study confirmed the validity of the three-tier histologic PVN classification put forward by the Banff Working Group in 2018.