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Dear Editor, Since the widespread adoption of multidetector computed tomography (MDCT) angiography for pre-operative assessment of living kidney donors, significant variability in renal vascular anatomy has been identified. Given the frequency of living kidney donation at the Irish National Kidney Transplant Service, we recognized an opportunity to assess the incidence of variant renal anatomy in first degree relatives undergoing potential living donor workup. Complex living donor kidneys are used successfully at many centers and still outperform deceased donor kidneys in the long-term.[3] We wish to open up the discussion of the concordance of complex vascular anatomy among first degree relatives as we believe this will be of interest to your readership. [Extracted from the article]

Polygenic risk scores (PRSs) calculated from genome‐wide association studies (GWASs) of non‐melanoma skin cancer (NMSC) in a general, non‐transplant setting have recently been shown to predict risk of and time to post‐renal transplant skin cancer. In this study, we set out to test these findings in a cohort of heart, lung, and liver transplant patients to see whether these scores could be applied across different organ transplant types. Using the PRS from Stapleton et al (2018), PRS was calculated for each sample across a European ancestry heart, lung, and liver transplant cohorts (n = 523) and tested as predictor of time to NMSC post‐transplant. The top PRS, squamous cell carcinoma (SCC) pT1 x 10−5, (n SNPs = 1953), SCC pT1 x 10−6, and SCC pT1 x 10−6 (n SNPs = 1061) were significantly predictive in the time to NMSC, SCC, and basal cell carcinoma (BCC) analysis across organ (P =.006,.02, and.02, respectively). We observed here a similar direction of effect and effect size [NMSC HR = 1.31(1.08‐1.59)] to that in the original discovery study with increased polygenic burden leading to a faster time to developing NMSC. In summary, we found that PRS of NMSC calculated from GWAS of NMSC in non‐transplant populations independently replicated in this cohort of heart, lung, and liver transplant. [ABSTRACT FROM AUTHOR]

Cutaneous squamous cell carcinoma (SCC) is a malignancy that arises from epidermal keratinocytes. Although the majority of cutaneous SCC cases are easily treated without further complication, some behave more aggressively and carry a poor prognosis. These 'high-risk' cutaneous SCCs commonly originate in the head and neck and have an increased tendency toward recurrence, local invasion, and distant metastasis. Factors for high-risk cutaneous SCC include large size (>2 cm), a deeply invasive lesion (>2 mm), incomplete excision, high-grade/desmoplastic lesions, perineural invasion (PNI), lymphovascular invasion, immunosuppression, and high-risk anatomic locations. Both the National Comprehensive Cancer Network® (NCCN®) and the American Joint Committee on Cancer (AJCC) identify several of these high-risk features of cutaneous SCC. The purpose of this article was to review the high-risk features included in these guidelines, as well as their notable discrepancies and omissions. We also provide a brief overview of current prophylactic measures, surgical options, and adjuvant therapies for high-risk cutaneous SCC. © 2016 Wiley Periodicals, Inc. Head Neck 39: 578-594, 2017 [ABSTRACT FROM AUTHOR]

Socioeconomic status ( SES) has been linked to worse end-stage kidney disease survival. The effect of SES on survival on chronic dialysis, including the impact of transplantation, was examined. A retrospective, observational study investigated the association of SES with dialysis patient survival, with censoring at time of transplantation. Adult patients commencing dialysis from 1990 to 2009 in an Irish tertiary center received a spatial SES score using the 2011 Pobal Haase- Pratschke Deprivation Index and were compared by quartile. Cox proportional hazard models and Kaplan- Meier survival analysis examined any association of SES with survival. The 1794 patients included had a median follow-up of 3.8 years. Patients in the lowest SES area quartile were significantly younger than the highest, mean age 56.7 vs. 59 years, P = 0.006, respectively. There was no association between SES area score and survival in an unadjusted model (hazard ratio [ HR] 1.00, 95% confidence interval [ CI] 0.99-1.01). Survival in the highest SES area quartile was superior to the lowest SES in a multivariable adjusted model including age, gender, and dialysis modality ( HR 0.83, 95% CI 0.70-0.99, P = 0.04). These results were only mildly attenuated by censoring at time of transplantation (highest SES area quartile deprived vs. lowest SES area quartile, HR 0.85, 95% CI 0.70-1.03, P = 0.09). Superior patient survival was identified in the highest SES areas compared with the lowest following age-adjusted analyses, despite the older population in the most affluent areas. Further research should focus on identifying modifiable targets for intervention that account for this socioeconomic-related survival advantage. [ABSTRACT FROM AUTHOR]

Aim Whether socioeconomic status confers worse outcomes after kidney transplantation is unknown. Its influence on allograft and patient survival following kidney transplantation in Ireland was examined. Methods A retrospective, observational cohort study of adult deceased-donor first kidney transplant recipients from 1990 to 2009 was performed. Those with a valid Irish postal address were assigned a socioeconomic status score based on the Pobal Hasse- Pratschke deprivation index and compared in quartiles. Cox proportional hazards models and Kaplan-Meier survival analysis were used to investigate any significant association of socioeconomic status with patient and allograft outcomes. Results A total of 1944 eligible kidney transplant recipients were identified. The median follow-up time was 8.2 years (interquartile range 4.4-13.3 years). Socioeconomic status was not associated with uncensored or death-censored allograft survival (hazard ratio ( HR) 1.0, 95% confidence interval ( CI) 0.99-1.00, P = 0.33 and HR 1.0, 95% CI 0.99-1.00, P = 0.37, respectively). Patient survival was not associated with socioeconomic status quartile ( HR 1.0, 95% CI 0.93-1.08, P = 0.88). There was no significant difference among quartiles for uncensored or death-censored allograft survival at 5 and 10 years. Conclusion There was no socioeconomic disparity in allograft or patient outcomes following kidney transplantation, which may be partly attributable to the Irish healthcare model. This may give further impetus to calls in other jurisdictions for universal healthcare and medication coverage for kidney transplant recipients. [ABSTRACT FROM AUTHOR]

Aim Apolipoprotein A- I amyloidosis is a rare, autosomal dominant disorder characterized by progressive accumulation of amyloid fibrils in tissues, leading to renal and hepatic disease. We describe the clinical manifestations and pathologic features of kidney disease in three Irish families. Methods This observational study examines all known cases of chronic kidney disease due to hereditary apolipoprotein A- I amyloidosis in Ireland. Patients were identified by physician interview. In all of the affected individuals the disease was caused by the Gly26Arg heterozygous mutation. Immunohistochemistry confirmed that amyloid deposits were composed of apolipoprotein A- I fibrils. Family trees and clinical data were obtained via analysis of patient medical records. Results The vast majority of affected cases had demonstrable kidney disease, with variable liver disease. Renal disease most commonly manifested as slowly progressive renal impairment with mild proteinuria. In one kindred, a severe, debilitating peripheral neuropathy was common among affected family members. Histology demonstrated tubulointerstitial fibrosis with amyloid deposition in the medulla. There was very high penetrance within affected families. Of five patients who were transplanted, one transplant was lost after 5 years due to recurrent disease. One patient died from sepsis shortly after transplant. Conclusion Hereditary apolipoprotein A- I amyloidosis is characterized by slowly progressive renal disease. Amyloid is deposited in the renal medulla highlighting the need to examine the medulla on renal biopsy. Overall, kidney transplantation conferred a survival advantage. [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]

Vascular access for hemodialysis remains a challenge for nephrologists, vascular surgeons, and interventional radiologists alike. Arteriovenous fistula and synthetic grafts remain the access of choice for long-term hemodialysis; however, they are subject to complications from infection and repeated needle cannulation. Pseudoaneurysms are an increasingly recognized adverse event. At present, there are many minimally invasive methods to repair these wall defects. We present a graft pseudoaneurysm, which required a combination of endovascular stent graft placement and percutaneous thrombin injection for successful occlusion. [ABSTRACT FROM AUTHOR]

Background: Donor cause of death has a significant impact on transplant survival in heart transplants recipients. The objective of this study was to determine if long-term renal allograft and patient survival differed between grafts donated by donors who died of spontaneous intracranial haemorrhage (SIH) compared with those with other causes of death (OCOD). Methods: Between 1990 and 2001, 1526 renal transplants were performed (711 SIH donors and 815 OCOD donors) at our unit. Serum creatinine levels at 1 yr, graft half-life and annual graft failure rate were measured for both groups. Renal graft and patient survivals between the groups were compared. Relative risk for SIH donors and other confounding variables was measured using Cox proportional hazards models. Results: Graft half-life results were obtained for SIH (8 yr) and OCOD (10.13 yr) recipients. Graft and patient survival at 5 and 10 yr was 68.5% and 39.3% respectively for the SIH group vs. 76.8% and 51.9% respectively for the OCOD group (p < 0.001). However, SIH graft recipients were significantly older with more females. After adjustment for differences in baseline variables between the groups, donor cause of death did not have an independent effect on long-term graft or patient survival. Conclusion: Spontaneous intracranial haemorrhage as a cause of donor death, failed to have a significant independent effect on long-term allograft and patient survival. [ABSTRACT FROM AUTHOR]

Background and purpose Methods Results Conclusion Late‐onset mitochondrial disorders are diagnostically challenging with significant heterogeneity in disease presentation. A case is reported of a 67‐year‐old gentleman who presented with a 3‐month history of seizures, recurrent encephalopathy, ataxia and weight loss, preceded by recent initiation of haemodialysis for end‐stage chronic kidney disease.Extensive work‐up including serological, cerebrospinal fluid, magnetic resonance imaging and electroencephalography was performed. Whole exome sequencing and muscle biopsy confirmed the diagnosis.Magnetic resonance imaging brain demonstrated a single non‐enhancing T2 fluid attenuated inversion recovery hyperintense cortical/subcortical signal change in the right temporal lobe and cerebellar atrophy. Given the subacute presentation of uncertain aetiology, he was empirically treated for autoimmune/paraneoplastic encephalitis. Despite radiological resolution of the cortical abnormality 2 weeks later, there was no clinical improvement. Further collateral history unveiled a mildly ataxic gait and longstanding hearing loss suggestive of a genetic cause. Whole exome sequencing revealed a likely pathogenic, heteroplasmic mitochondrial DNA variant in the MT‐TV gene, m.1659T>C, present at higher levels of heteroplasmy in muscle (91%) compared to other mitotic tissues. A high fat/protein diet and multivitamins including co‐enzyme Q10 were commenced. Treatment of the nutritional deficiency and avoidance of intermittent fasting due to unreliable oral intake secondary to encephalopathy probably contributed to the clinical improvement seen over the ensuing few months, with resolution of his encephalopathy and return to his baseline gait and weight.An adult case is reported with an acute neurological presentation mimicking encephalitis, caused by a heteroplasmic m.1659T>C MT‐TV variant, previously reported once in a child who displayed a different clinical phenotype. [ABSTRACT FROM AUTHOR]

Introduction: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic cause of chronic kidney disease (CKD) and end‐stage renal disease (ESRD). We aimed to compare renal transplant outcomes in people with ESRD due to ADTKD to those with other causes of renal failure. Methods: Patients with clinical characteristics consistent with ADTKD by the criteria outlined in the 2015 KDIGO consensus were included. We compared ADTKD transplant outcomes with those of 4633 non‐ADTKD renal transplant recipients. Results: We included 31 patients who met diagnostic criteria for ADTKD in this analysis, 23 of whom had an identified mutation (28 were categorized as definite‐ADTKD and 3 as suspected ADTKD). Five patients received a second transplant during follow‐up. In total, 36 grafts were included. We did not identify significant differences between groups in terms of graft or patient survival after transplantation. Twenty‐five transplant biopsies were performed during follow‐up, and none of these showed signs of recurrent ADTKD post‐transplant. Conclusion: In patients with ESRD due to ADTKD, we demonstrate that transplant outcomes are comparable with the general transplant population. There is no evidence that ADTKD can recur after transplantation. [ABSTRACT FROM AUTHOR]