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Introduction: Kidney transplant recipients (KTR) have a three‐to‐four‐fold increased risk of developing urothelial carcinoma (UC) compared to the general population. BK polyoma virus (BKV) infection is known to affect approximately 15% of KTR. In vitro models support a potential pathogenic role for BKV in the development of UC. We describe a series of UC in kidney transplant recipients. Methods: Electronic patient records were searched to identify KTR with UC who had undergone kidney only or simultaneous kidney and pancreas transplantation in a single UK center between 2009 and 2015. Where available, stored pathological samples were retrieved, re‐examined and stained for SV40 as a marker of BKV using standard staining protocols for kidney biopsy samples. Results: Fourteen KTR had developed UC post‐transplant. Of these, 10 KTR had a history of BKV infection post‐transplant. Six of these 10 KTR developed a rare micropapillary tumor subtype of UC which is typically only found in <1% of UC cases. All six micropapillary tumor samples stained positive for SV40, including samples from metastases. Three tumor samples were available from the four KTR with no history of BKV infection and were not micropapillary subtype and were negative for SV40. Three micropapillary tumors from immunocompetent patients were examined as controls and were negative for SV40. Conclusions: These findings would support a pathogenic role for BK virus in the development of rare micropapillary subtype urothelial tumors in the kidney transplant population. [ABSTRACT FROM AUTHOR]

Background: Reports of HLA incompatible (HLAi) kidney transplant outcomes are inconclusive, especially in the context of lower level Donor Specific Antibodies (DSA). Methods: Multi‐centre national cohort study of HLAi kidney transplant recipients matched in 1:2 ratio with HLA compatible (HLAc) kidney transplant recipients. HLAi defined as DSA identified by Luminex. Antibody mediated rejection (AMR) and transplant‐survival were analysed using Kaplan–Meier plots. Propensity score (PS) matching was used to compare recipient and transplant survival between groups. Results: We included 61 HLAi and 122 HLAc recipients; mean age 46 years; 60% female. MFIT0: 3327 (IQR 1352–6458), 23 (38%) were Flow cytometry crossmatch positive (FC‐XMPOS). DSAPOS/FC‐XMPOS transplantation carried an increased risk of AMR at 1 year (52%) compared to DSAPOS/FC‐XMNEG (27%) and HLAc (0%). Unadjusted death censored graft loss at 3 years was 13% (HLAi) and 8% (HLAc). Three‐year patient survival was 95% in HLAc, 84% in DSAPOS/FC‐XMNEG and 69% in DSAPOS/FC‐XMPOS recipients; 58% of HLAi deaths were infection‐related. HLA incompatibility was associated with a decreased 3‐year survival in our PS‐matched cohort. Conclusion: In kidney transplantation, DSA and positive FC‐XM carries an increased risk of AMR. Despite inferior transplant and survival outcomes compared to HLAc transplantation, it remains a realistic option for highly sensitized patients facing prolonged waiting times and reduced survival on dialysis. Summary at a glance: Compared to HLA compatible transplantation, HLA incompatible kidney transplantation, especially in the presence of a positive FC‐XM, is associated with an increased risk of rejection, inferior graft function and death. For many highly sensitized recipients a compatible transplant is not on offer and HLA incompatible transplantation can be an appropriate alternative to remaining on dialysis. [ABSTRACT FROM AUTHOR]

Luminex single antigen bead (SAB) assays used to detect HLA antibodies may artificially increase sensitisation in highly sensitised patients (HSP). The presence of denatured HLA (dHLA) within the assay enables antibodies specific to cryptic HLA epitopes to bind, such antibodies are not clinically relevant. We sought to exclude dHLA reactivity in a cohort of very HSP, calculated reaction frequency (cRF) 95%–100% and determine the effect upon sensitisation. Such patients have limited access to suitable donors and small changes in their HLA antibody profile, particularly where their cRF is 100%, can increase their opportunity of a transplant. We determined the presence of dHLA by aligning antibody reactivity which did not correspond to known HLA class I epitope mismatches with the results of assays modified to detect class I dHLA. 130 class I dHLA reactions were identified within 11 HSP, all of whom had clear sensitising events. cRF was corrected for dHLA, mean cRF 98.2% (93–100) pre and 95.5% (87–100) post correction (p = 0.0156). An increase in the number of predicted compatible donors (p = 0.0078) after dHLA correction was demonstrated. Two manufacturers SAB assays were used. A reduction of patients with 100% cRF was observed for both manufactures. dHLA is contributing to sensitisation in HSP and is detrimental to their chances of receiving a compatible transplant. The observed dHLA reactivity varied according to kit manufacturers (p = 0.0001), this is potentially a useful finding for laboratories wishing to discriminate between nHLA and dHLA, but without the resources required to regularly perform dHLA assay and epitope analyses. [ABSTRACT FROM AUTHOR]

Recent reports have identified that the presence of non‐native conformation HLA to which antibody can bind upon Luminex HLA Class I single antigen beads, can vary in levels between different manufacturers kits and that the prozone effect may also be specific to particular products. We present a case in which both prozone and non‐native HLA reactive antibodies were observed, which raises important questions on how SAB assays are utilised, especially in the post‐transplant monitoring setting. A 56‐year old, highly sensitised female patient awaiting a regraft received a HLAi renal transplant. Post‐transplant monitoring showed discordant results between two SAB manufacturers assays, with one assay identifying a potential de novo HLA DSA. HLA Class I antibody reactivity was observed which was directed towards the Bw6 public epitope, which is present upon HLA molecules encoded for by numerous HLA‐B alleles. However in the day 19 post‐transplant sample reactivity spread beyond the Bw6 epitope. To investigate the possibility of a prozone type effect influencing the testing kit the day 19 post‐transplant sample was diluted 1:10 with PBS and reanalysed. After dilution the Bw6 reactivity was observed again, however the suspect de novo DSA still persisted. An analysis of the mismatched epitopes identified one manufacturer's assay as being confounded by the presence of denatured reactivity as well as prozone. [ABSTRACT FROM AUTHOR]

Background: In Scotland, standard maintenance immunosuppression following kidney transplantation consists of mycophenolate (MPA), tacrolimus and prednisolone irrespective of recipient age. We analyzed the tolerability of this immunosuppression regimen and the association with transplant outcomes. Methods: A national, multicentre retrospective analysis of patients transplanted in 2015 and 2016, comparing graft function, acute rejection, significant infection rates and immunosuppression dosing between patients aged 18 and 59 years (Group 1) and ≥60 years (Group 2). Results: Of the 490 patients, 26% were aged ≥60 years. Acute rejection (AR) rates at 1 year were 15% and 11% in Groups 1 and 2, respectively. Full‐dose MPA was poorly tolerated with 53% in Group 1 and 77% in Group 2 requiring dose reduction or cessation. Female gender and age ≥60 years were independent predictors for MPA dose changes. One year following MPA dose reduction, AR risk was low (5%) in Group 2, however, those remaining on full dose MPA had a 79% increased rate of serious infections. Conclusion: The majority of renal transplant recipients aged ≥60 fail to tolerate full‐dose MPA. In this group, MPA dose reduction is associated with low rejection rates, but full‐dose MPA is associated with high infection rates. We suggest that a tailored approach to immunosuppression in elderly recipients incorporating lower doses of MPA may be appropriate. SUMMARY AT A GLANCE: This national cohort study suggests that full‐dose mycophenolate (MPA) was not well tolerated in older kidney transplant patients, with over 75% of patients =60 years requiring dose reduction or discontinuation. Continuation of full‐dose MPA was associated with a substantially greater risk of infection in the older patients, which was not observed in younger patients. [ABSTRACT FROM AUTHOR]

Background We examined, through genome-wide association studies ( GWAS), the correlation between recipient genetic variation and renal function at five yr. Methods Our cohort contained 326 Irish, first time, kidney-only, deceased donor, transplant recipients on calcineurin inhibitors (263 had a functioning graft at five yr) between 1993 and 2002. Outcomes were creatinine at five yr and long-term graft function. Results Two variants were identified showing borderline genome-wide significance - one on chromosome 18 (p = 4.048e-08, rs6565887) and another on chromosome 14 (p = 7.631e-08, rs3811321). Individually, the two SNPs explained up to 8.8% and 11.29% of five-yr creatinine variance, respectively, while together they explained up to 17.4% of trait variance. Both variants were predictors of long-term allograft function (p = 0.004, 70% vs 30% survival at 10 yr). The chromosome 14 variant is located in the intergenic region of the T- Cell Receptor Alpha locus. Conclusions Using a genome-wide approach, we have identified two associations with five-yr creatinine levels in renal transplant recipients treated with calcineurin inhibitors. Independent replication is now warranted to clarify the clinical significance of these results. [ABSTRACT FROM AUTHOR]

Phelan PJ, O'Kelly P, Tarazi M, Tarazi N, Salehmohamed MR, Little DM, Magee C, Conlon PJ. Renal allograft loss in the first post-operative month: causes and consequences. Abstract: Early transplant failure is a devastating outcome after kidney transplantation. We report the causes and consequences of deceased donor renal transplant failure in the first 30 d at our center between January 1990 and December 2009. Controls were adult deceased donor transplant patients in the same period with an allograft that functioned >30 d. The incidence of early graft failure in our series of 2381 consecutive deceased donor transplants was 4.6% (n = 109). The causes of failure were allograft thrombosis (n = 48; 44%), acute rejection (n = 19; 17.4%), death with a functioning allograft (n = 17; 15.6%), primary non-function (n = 14; 12.8%), and other causes (n = 11; 10.1%). Mean time to allograft failure was 7.3 d. There has been a decreased incidence of all-cause early failure from 7% in 1990 to <1% in 2009. Patients who developed early failure had longer cold ischemia times when compared with patients with allografts lasting >30 d (p < 0.001). Early allograft failure was strongly associated with reduced patient survival (p < 0.001). In conclusion, early renal allograft failure is associated with a survival disadvantage, but has thankfully become less common in recent years. [ABSTRACT FROM AUTHOR]

ABSTRACT: Allograft thrombosis is a devastating early complication of renal transplantation that ultimately leads to allograft loss. We report here on our experience of nine cases of immediate re-transplantation following early kidney transplant thrombosis at a single centre between January 1990 and June 2009. The mean age was 42.9 years at time of transplant. For seven patients, the allograft thrombosis was their first kidney transplant and seven of the nine cases had a deceased donor transplant. The initial transplants functioned for a mean of 1.67 days and the patients received a second allograft at a mean of 3.1 days after graft failure. All of the re-transplants worked immediately. Four allografts failed after a mean of 52.5 months (2-155 months). Two of these died with a functioning allograft, one failed owing to chronic allograft nephropathy and one owing to persistent acute cellular rejection. The remaining five patients still have a functioning allograft after a mean of 101.8 months (7-187 months). One year allograft and patient survival after re-transplantation were 87.5% and 100% respectively (after 5 years, both were 57%). Immediate re-transplantation following early kidney transplant thrombosis can be a success. It may be considered in selected cases after allograft thrombosis. [ABSTRACT FROM AUTHOR]

The article describes the case of co-existent adult polycystic kidney disease (APKD) and Alport syndrome in a teenage boy whose family demonstrated preserved renal function until later life despite having APKD. Topics covered include polygenic inheritance involving PKD1 and other genes, X-linked COL4A5 mutation and co-existent mutations in cystic genes.