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Background There is an increase in elderly patients receiving kidney transplant internationally. This study describes elderly kidney transplant recipient outcomes in Australia and New Zealand. Methods The study included all adult first kidney transplant recipients in Australia and New Zealand from 2000 to 2015. Survival and graft outcomes were compared between elderly (≥70 years) and younger (18-69 years) recipients using Cox proportional hazards regression. Results Overall, 10651 kidney transplant recipients were included, of which 279 (2.6%) were elderly adults. The proportion of elderly recipients increased from 0.6 to 4.4% from 2000 to 2015. Compared with younger recipients, elderly recipients were more likely to receive kidneys from deceased donors, elderly donors, and expanded criteria donors. Elderly recipients experienced poorer patient survival with 1- and 5-year survival ranging from 96% to 97% and 79% to 81%, respectively, compared with 97% to 99% and 90% 95% in younger recipients, respectively. Elderly recipients experienced comparable rates of delayed graft function and, in living donor kidney recipients, lower rates of acute rejection. Conclusions Kidney transplantation in the elderly population is increasing. Although elderly recipients had inferior survival and graft outcomes, elderly recipients generally received poorer quality kidneys. The outcomes achieved in this cohort of elderly adults are encouraging, and improving elderly recipient outcomes should be an important focus for research.

BACKGROUND Kidney transplant recipients are at increased risk of developing and dying from keratinocyte cancer. Risk factors for keratinocyte cancer death have not been previously described. METHODS In a cohort of kidney transplant recipients transplanted in Queensland 1995-2014, we identified keratinocyte cancer deaths by searching national transplant and state death registries to March 2020. Standardized keratinocyte cancer mortality rates and mortality ratios were calculated. We used a competing risks model to identify factors associated with keratinocyte cancer death and calculated relative risks (RRs) and 95% confidence intervals (CIs). RESULTS There were 562 deaths in 1866 kidney transplant recipients (62% males; 86% Caucasian) with 25 934 person-years of follow-up, of which 36 were due to squamous cell carcinoma (SCC) and 1 to basal cell carcinoma (BCC) with standardized mortality rates of 78 (95% CI 53-111) and 2 (95% CI 0.1-11) per 100,000 person-years respectively. The standardized mortality ratio for keratinocyte cancer was 23 (95% CI 23-24). Besides Caucasian ethnicity (associated with 100% of keratinocyte cancer deaths), male sex (RR 3.24 95% CI 1.26-8.33), and older age at transplantation (≥ 50 versus

Introduction Impaired physical fitness is prevalent in people with chronic kidney disease (CKD), associating with an increased risk of mortality, falls, and hospitalization. A plethora of physical fitness outcomes have been reported in randomized trials. This study aimed to assess the scope and consistency of physical fitness outcomes and outcome measures reported in trials in CKD. Methods A systematic review of randomized trials reporting physical fitness outcomes in adults with CKD (not requiring kidney replacement therapy) receiving hemodialysis (HD) or peritoneal dialysis and kidney transplant recipients was conducted. Studies were identified from MEDLINE, Embase, and the Cochrane Library from 2000 to 2019. The scope, frequency, and characteristics of outcome measures were categorized and analyzed. Results From 111 trials, 87 tests/measurements were used to evaluate 30 outcomes measures that reported on 23 outcomes, categorized into five domains of physical fitness: neuromuscular fitness (reported in 76% of trials), exercise capacity (64%), physiological-metabolic (49%), body composition (36%), and cardiorespiratory fitness (30%). Neuromuscular fitness was examined by 37 tests/measurements including the physical function component of questionnaires (27%), one-repetition maximum (9%), and hand-grip strength (9%). Outcome measures were assessed by lab-based (58% of all trials), field-based (31%), and patient-reported measures (11%), and commonly evaluated at 12 (30%), 26 (23%) and 52 weeks (10%), respectively. Conclusion There is large heterogeneity in the reporting of physical fitness outcomes, with inconsistencies particularly in the definitions of outcome measures. Standardization in the assessment of physical fitness will likely improve the comparability of trial outcomes and enhance clinical recommendations., Graphical abstract

BACKGROUND Bayesian forecasting-based limited sampling strategies (LSSs) for tacrolimus have not been evaluated for the prediction of subsequent tacrolimus exposure. This study examined the predictive performance of Bayesian forecasting programs/services for the estimation of future tacrolimus area under the curve (AUC) from 0 to 12 hours (AUC0-12) in kidney transplant recipients. METHODS Tacrolimus concentrations were measured in 20 adult kidney transplant recipients, 1 month post-transplant, on 2 occasions one week apart. Twelve samples were taken predose and 13 samples were taken postdose at the specified times on the first and second sampling occasions, respectively. The predicted AUC0-12 (AUCpredicted) was estimated using Bayesian forecasting programs/services and data from both sampling occasions for each patient and compared with the fully measured AUC0-12 (AUCmeasured) calculated using the linear trapezoidal rule on the second sampling occasion. The bias (median percentage prediction error [MPPE]) and imprecision (median absolute prediction error [MAPE]) were determined. RESULTS Three programs/services were evaluated using different LSSs (C0; C0, C1, C3; C0, C1, C2, C4; and all available concentrations). MPPE and MAPE for the prediction of fully measured AUC0-12 were

AIM With improved life expectancy over time, the burden of kidney failure resulting in kidney replacement therapy (KRT) in older persons is increasing. This study aimed to describe the age distribution at dialysis initiation in Australia and New Zealand (ANZ) across centres and over time. METHODS Adults initiating dialysis as first KRT in ANZ from 1999 to 2018 reported to the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry were included. The primary outcomes were the age distribution and the proportion of older persons (75 years and older) initiating dialysis across centres and over time. Secondary outcomes were characterization of the older population compared with younger people and differences in dialysis modality and treatment trajectories between groups. RESULTS Over the study period, 55 382 people initiated dialysis as first KRT, including 10 306 older persons, in 100 centres. Wide variation in age distribution across states/countries was noted, although the proportion of older persons at dialysis initiation did not significantly change over time (from 13% in 1999 to 19% in 2003, then remaining stable thereafter). Older persons were less likely to be treated with home therapies compared with younger people. Older persons were mostly Caucasians; had higher socioeconomic position, more cardiovascular comorbidities and higher eGFR at baseline; and resided in major cities. Higher proportions of older persons per centre were noted in privately funded facilities. CONCLUSION Wide variations were noted in the proportions of older persons initiating dialysis across centres and states/country, which were associated with different case-mix across regions, particularly in terms of ethnicity, remoteness and socioeconomic advantage.

Thrombotic microangiopathy (TMA) is characterised by abnormalities in the walls of arterioles and capillaries, precipitated by hereditary or acquired characteristics, and culminating in microvascular thrombosis because of dysregulated complement activity. A number of drugs can precipitate TMA, including vascular endothelial growth factor (VEGF) inhibitors, because of their effects on endothelial repair. Pazopanib is a VEGF inhibitor used for the treatment of renal cell carcinoma (RCC); it is uncommonly associated with TMA. A 52-year-old male, 5 years post his second kidney transplant secondary to immunoglobulin (Ig) A nephropathy, presented with hypertension, fluid overload, and worsening graft function (peak creatinine 275 μmol/L, baseline 130–160 μmol/L) and nephrotic range proteinuria 2 months after commencing pazopanib for metastatic RCC. His maintenance immunosuppression included ciclosporin, mycophenolate, and prednisolone. Haematological parameters were unremarkable. Allograft biopsy demonstrated glomerular and arteriolar changes consistent with chronic active TMA, with overlying features of borderline cellular rejection. He was treated with intravenous methylprednisolone 250 mg for 3 days and commenced on irbesartan 75 mg daily. Drug-induced TMA from pazopanib was suspected, particularly given the documented association with other tyrosine kinase inhibitors (TKIs). In consultation with his medical oncologist, pazopanib was ceased, and an alternate TKI cabozantinib was commenced. Serum creatinine remained

Organ transplant recipients have over 100-fold higher risk of developing skin cancer than the general population and are in need of further preventive strategies. We assessed the possible preventive effects of omega-3 polyunsaturated fatty acid (PUFA) intake from food on the two main skin cancers, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) in kidney and liver transplant recipients. Adult kidney or liver transplant recipients transplanted for at least 1 year and at high risk of skin cancer were recruited from the main transplant hospital in Queensland, 2012–2014 and followed until mid-2016. We estimated their dietary total long-chain omega-3 PUFAs and α-linolenic acid intakes at baseline using a food frequency questionnaire and ranked PUFA intakes as low, medium, or high. Relative risks (RRsadj) of skin cancer adjusted for confounding factors with 95% confidence intervals (CIs) were calculated. There were 449 transplant recipients (mean age, 55 years; 286 (64%) male). During follow-up, 149 (33%) patients developed SCC (median 2/person; range 1–40) and 134 (30%), BCC. Transplant recipients with high total long-chain omega-3 PUFA compared with low intakes showed substantially reduced SCC tumour risk (RRadj 0.33, 95% CI 0.18–0.60), and those with high α-linolenic acid intakes experienced significantly fewer BCCs (RRadj 0.40, 95% CI 0.22–0.74). No other significant associations were seen. Among organ transplant recipients, relatively high intakes of long-chain omega-3 PUFAs and of α-linolenic acid may reduce risks of SCC and BCC, respectively.

Various treatments of keratotic skin lesions and early skin cancers are performed in organ transplant recipients (OTRs) at high risk of skin malignancies but the frequency of their use is unknown. We prospectively assessed the frequency of use of cryotherapy, diathermy, and topical therapies and also investigated their associations with background incidence of histologically-confirmed squamous-cell carcinoma (SCC) and basal cell carcinoma (BCC) in a cohort of OTRs in Queensland, Australia. Median follow-up ranged from 1.7 to 3.2 years across organ transplant groups. Among 285 kidney, 125 lung and 203 liver transplant recipients [382 (62%) male, 380 (62%) immunosuppressed > 5 years, 394 (64%) previously diagnosed with skin cancer], 306 (50%) reported treatment of skin lesions with major types of non-excision therapies during follow-up: 278 (45%) cryotherapy or diathermy; 121 (20%) topical treatments. Of these 306, 150 (49%) developed SCC at double the incidence of those who did not receive these treatments, as assessed by incidence rate ratio (IRR) adjusted for age, sex, type of organ transplant, skin color and history of skin cancer at baseline, calculated by multivariable Poisson regression (IRRadj = 2.1, 95% confidence interval (CI) 1.4–3.1). BCC incidence was not associated with these therapies. Skin lesions in OTRs that are treated with cryotherapy, diathermy, or topical treatment warrant judicious selection and careful follow-up.

Genetic kidney disease is increasingly identified as a cause of chronic kidney disease (CKD) in patients who have previously had no known etiology.1 Following advances in genetic sequencing and understanding, more than 500 monogenic etiologies have been identified as causes of CKD, and there are likely many additional genes yet to be identified.1 Kidney transplantation is currently the most effective form of kidney replacement therapy, and living kidney transplants continue to have the greatest short- and long-term patient and allograft survival.2 However, living-related kidney transplantation in patients with an unknown cause of end-stage kidney disease (ESKD) is clinically and ethically complex, as a donating family member may also have undiagnosed genetic kidney disease in a presymptomatic state. By removing a kidney, the time to ESKD for the donor is potentially shortened.

This registry-based study evaluated the contribution of center characteristics to kidney transplant outcomes in adult first kidney transplant recipients in Australia and New Zealand between 2004 and 2014. Primary outcomes were mortality and graft failure, and secondary outcomes were transplant complications. Overall, 6970 transplants from 17 centers were included. For deceased donor transplants, 5-year patient and graft survival rates varied considerably (81.0-93.9% and 72.2-88.3%, respectively). Variations in mortality and graft failure were partially reduced after adjustment for patient characteristics (1% and 20% reductions) and more markedly reduced after adjustment for center characteristics (41% and 55% reductions). For living donor transplants, 5-year patient and graft survival rates varied (89.7-100% and 79.2-96.9%, respectively). Centers with high average total ischemic times (>14 h) were associated with higher mortality for both deceased (adjusted hazard ratio [(AHR] 2.24, 95% CI 1.21-4.13) and living donor transplants (AHR 1.76, 95% CI 1.02-3.04). Small center size (

To describe the baseline characteristics and treatment of Australian patients diagnosed with atypical haemolytic uraemic syndrome (aHUS) reported to the Global aHUS Registry. Descriptive analysis of the Australian cohort with aHUS (n = 106) was undertaken for demographics, disease characteristics and prior treatment with eculizumab; comparing with the global cohort (n = 1688) for certain pre-specified disease characteristics. In Australia, almost two-thirds of patients diagnosed with aHUS were female and over 80% of patients were Caucasians, with similar proportions reported in the global cohort. Less than 6% of patients in the Australia and global cohorts were reported to have a history of autoimmune disease (4% vs 2%, respectively; P = 0.21) or cancer (5% vs 5%, respectively; P = 0.93), conditions that have been associated with secondary HUS. In the Australian cohort, 26% had received a kidney transplant and 68% of patients had received eculizumab. Kidneys were the most common organ involvement, followed by gastrointestinal tract (26%) and cardiovascular system (19%), with 35% of patients reported to have had at least 2 organs involved within 6 months prior to baseline visit or entry into the registry. Complement factor H (CFH) was the most common pathogenic complement gene variant in the Australian patients. Data from the aHUS registry confirms and defines region-specific disease characteristics among a selected group of Australian children and adults with aHUS reported to the registry. Ongoing and more inclusive data will provide further information about temporal trends and treatment outcomes, representing a unique opportunity for clinicians and researchers to further develop knowledge surrounding this rare disease. This article is protected by copyright. All rights reserved.

Background Home-based dialysis therapies, home hemodialysis (HHD) and peritoneal dialysis (PD) are underutilized in many countries and significant variation in the uptake of home dialysis exists across dialysis centers. This study aimed to evaluate the patient- and center-level characteristics associated with uptake of home dialysis. Methods The Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry was used to include incident dialysis patients in Australia and New Zealand from 1997 to 2017. Uptake of home dialysis was defined as any HHD or PD treatment reported to ANZDATA within 6 months of dialysis initiation. Characteristics associated with home dialysis uptake were evaluated using mixed effects logistic regression models with patient- and center-level covariates, era as a fixed effect and dialysis center as a random effect. Results Overall, 54 773 patients were included. Uptake of home-based dialysis was reported in 24 399 (45%) patients but varied between 0 and 87% across the 76 centers. Patient-level factors associated with lower uptake included male sex, ethnicity (particularly indigenous peoples), older age, presence of comorbidities, late referral to a nephrology service, remote residence and obesity. Center-level predictors of lower uptake included small center size, smaller proportion of patients with permanent access at dialysis initiation and lower weekly facility hemodialysis hours. The variation in odds of home dialysis uptake across centers increased by 3% after adjusting for the era and patient-level characteristics but decreased by 24% after adjusting for center-level characteristics. Conclusion Center-specific factors are associated with the variation in uptake of home dialysis across centers in Australia and New Zealand.

To examine if skin autofluorescence (sAF) differed in early adulthood between individuals with type 1 diabetes and age-matched controls and to ascertain if sAF aligned with risk for kidney disease. Young adults with type 1 diabetes (N = 100; 20.0 ± 2.8 years; M:F 54:46; FBG-11.6 ± 4.9 mmol/mol; diabetes duration 10.7 ± 5.2 years; BMI 24.5(5.3) kg/m2) and healthy controls (N = 299; 20.3 ± 1.8 years; M:F-83:116; FBG 5.2 ± 0.8 mmol/L; BMI 22.5(3.3) kg/m2) were recruited. Skin autofluorescence (sAF) and circulating AGEs were measured. In a subset of both groups, kidney function was estimated by GFRCKD-EPI CysC and uACR, and DKD risk defined by uACR tertiles. Youth with type 1 diabetes had higher sAF and BMI, and were taller than controls. For sAF, 13.6% of variance was explained by diabetes duration, height and BMI (Pmodel = 1.5 × 10–12). In the sub-set examining kidney function, eGFR and sAF were higher in type 1 diabetes versus controls. eGFR and sAF predicted 24.5% of variance in DKD risk (Pmodel = 2.2 × 10–9), which increased with diabetes duration (51%; Pmodel –16) and random blood glucose concentrations (56%; Pmodel –16). HbA1C and circulating fructosamine albumin were higher in individuals with type 1 diabetes at high versus low DKD risk. eGFR was independently associated with DKD risk in all models. Higher eGFR and longer diabetes duration are associated with DKD risk in youth with type 1 diabetes. sAF, circulating AGEs, and urinary AGEs were not independent predictors of DKD risk. Changes in eGFR should be monitored early, in addition to uACR, for determining DKD risk in type 1 diabetes.

Highlights •CKD is associated with very high risk of CAD. CAD management is complicated in CKD patients, due to comorbid conditions and potential side effects during interventions. •There are few trials related to CAD with focus on CKD patients, particularly in those with advanced CKD. •Additional prospective studies focusing on diagnosis, prevention, and treatment of CAD are needed in CKD.

Mycophenolic acid (MPA) is commonly used following renal transplant. Saliva MPA concentrations may reflect the pharmacologically active form of MPA in plasma. Therapeutic drug monitoring using saliva is convenient and non-invasive. This study examined the correlation between total and free plasma and saliva MPA concentrations following enteric-coated mycophenolate sodium (EC-MS) administration in renal transplant recipients. Total and free plasma and saliva MPA concentrations were measured simultaneously in 20 adult renal transplant recipients 1–2 months’ post-transplant. Thirteen samples were taken pre-dose and at specified time points up until 12 h post-dose. When considering all time points, correlation between total plasma and saliva MPA was r2 = 0.51 and between free plasma and saliva MPA concentrations r2 = 0.41. The correlation between total plasma MPA area under the concentration–time curve (AUC) or free plasma AUC and saliva MPA AUC was r2 = 0.25 and r2 = 0.13, respectively. The correlation between total plasma MPA AUC and total plasma MPA trough (C0) concentrations was r2 = 0.51, and between total plasma MPA AUC and saliva MPA trough concentrations, r2 = 0.03. Measurement of MPA concentration in saliva cannot currently replace plasma measurement for therapeutic drug monitoring of MPA following EC-MS administration. Additional studies are required to examine the relationship between MPA saliva concentrations and patient outcomes.

This review examines what is currently known about the pharmacokinetics and pharmacodynamics of commonly prescribed immunosuppressant medicines, tacrolimus, cyclosporine, mycophenolate and prednisolone, in elderly renal transplant recipients, and reported patient outcomes in this cohort. Renal transplantation is increasing rapidly in the elderly, however, currently, long-term patient outcomes are relatively poor compared to younger adults. Some studies have suggested that elderly recipients may have higher dose-adjusted exposure and/or lower clearance of the calcineurin inhibitors tacrolimus and cyclosporine; with one study reporting up to 50% reduction in tacrolimus exposure in the elderly. Elderly transplant recipients do not appear to have higher dosage-adjusted exposure to mycophenolic acid (MPA). The effects of ageing on the pharmacokinetics of prednisolone are unknown. Only one study has examined how aging effects drug target enzymes, reporting no difference in baseline inosine 5'-monophosphate dehydrogenase (IMPDH) activity and MPA-induced IMPDH activity in elderly compared to younger adult renal transplant recipients. In elderly transplant recipients, immunosenescence likely lowers the risk of acute rejection, but increases the risk of drug-related adverse effects. Currently, the three main causes of death in elderly renal transplant recipients are cardiovascular disease, infection and malignancy. One study has showed that renal transplant recipients aged over 65 years are seven times more likely to die with a functioning graft compared with young adults (aged 18–29 years). This suggests that an optimal balance between immunosuppressant medicine efficacy and toxicity is not achieved in elderly recipients, and further studies are needed to foster long-term graft and patient survival. Lower maintenance immunosuppressant targets in elderly recipients may decrease patient susceptibility to drug side effects, however, further studies are required and appropriate targets need to be established.

This review summarizes how possible age-related changes in tacrolimus and cyclosporine pharmacokinetics and pharmacodynamics may influence drug dosing and monitoring in the elderly, and highlights how micro-sampling may be useful in this cohort in the future. Advancing biological age leads to physiological changes that can affect drug absorption, distribution, metabolism and excretion, as well as immune system responsiveness. Some studies have shown that elderly recipients may have higher dose-adjusted exposure and/or lower clearance of the calcineurin inhibitors, suggesting that doses may need to be lowered in elderly recipients. Only one study has examined how aging effects drug target enzyme activity and demonstrated that age does not correlate with the calcineurin inhibitor half-maximal inhibitory concentration. Several studies have shown elderly kidney transplant recipients have increased risk of both morbidity and mortality, compared to younger adults due to increased susceptibility to immunosuppressant side effects, particularly cardiovascular disease, infection and malignancy. Current immunosuppressant dosing and monitoring protocols often make no adjustments for age. Lower maintenance immunosuppressant targets in elderly recipients may decrease patient susceptibility to drug side effects, however, further studies are required and appropriate targets need to be established. Blood draw by micro-sampling may be useful for drug monitoring in this cohort in the future, as blood collection is minimally invasive and less painful than venepuncture. Micro-sampling could also make further pharmacokinetic, pharmacodynamics and outcome studies in the elderly more feasible.

Half of the mortality in diabetes is seen in individuals DKD risk was assigned in youth with type 1 diabetes [n=100; 20.0±2.8 yrs; M:F-54:46, HbA1C-66.1(12.3) mmol/mol; diabetes duration-10.7±5.2 yrs; BMI-24.5(5.3) kg.m-2] and 10 year historical uACR, HbA1C and random blood glucose concentrations collected retrospectively. Glucose fluctuations in the absence of diabetes were also compared to streptozotocin diabetes in Apolipoprotein E-/- mice. Kidney biopsies were used to examine infiltration of KIM-1 expressing T cells in DKD and compared with other chronic kidney disease. Individuals at high risk for DKD had persistent elevations in uACR (uACRAUC0-10yrs, 29.7±8.8 vs 4.5±0.5; P-1.1.73m-2 higher estimated glomerular filtration rates (eGFRSCHWARTZ; Padj P

Background Infection remains a leading cause of death in kidney transplant recipients. This study aimed to assess the scope and consistency of infection outcomes reported in contemporary trials conducted in kidney transplant recipients. Methods A literature review of all randomized trials and trial protocols reporting infection outcomes in adult kidney transplant recipients were identified in the Cochrane Kidney and Transplant Specialized Register from January 2014 to July 2019. Characteristics and infection outcomes from the trials were analyzed. Results From 102 included trials, 772 outcome measures were extracted and categorized into 216 unique measures with a median of 3.2 outcome measures per trial (range: 1 to 9). Measures were further grouped into 32 outcomes based on site of infection (14 outcomes) and organism (18 outcomes). The most commonly reported site-specific outcome and organism-specific outcome was systemic infection (71% trials) and cytomegalovirus infection (62% trials), respectively. Outcome metric and methods of aggregation included mean, median, proportion, proportional change and number of patients with at least 1 episode. Across all trials, measures were assessed at 55 different time points with a range of 1 to 11 time points per trial. Conclusions Infection outcomes in kidney transplant recipients were frequently reported by site and organism but varied widely in terms of outcome, metrics, method of aggregation and time point of measurement. Establishment of core outcomes for infection based on the shared priorities of patients/caregivers and health professionals may improve the consistency, comparability and usefulness of trial evidence.Supplemental Visual Abstract; http://links.lww.com/TP/C169.

Background The need for kidney transplantation drives efforts to expand organ donation. The decision to accept organs from donors with acute kidney injury (AKI) can result in a clinical dilemma in the context of conflicting reports from published literature. Material and methods This observational study included all deceased donor kidney transplants performed in Australia and New Zealand between 1997 and 2017. The association of donor-AKI, defined according to KDIGO criteria, with all-cause graft failure was evaluated by multivariable Cox regression. Secondary outcomes included death-censored graft failure, death, delayed graft function (DGF) and acute rejection. Results The study included 10,101 recipients of kidneys from 5,774 deceased donors, of whom 1182 (12%) recipients received kidneys from 662 (11%) donors with AKI. There were 3,259 (32%) all-cause graft failures, which included 1,509 deaths with functioning graft. After adjustment for donor, recipient and transplant characteristics, donor AKI was not associated with all-cause graft failure (adjusted hazard ratio [HR] 1.11, 95% CI 0.99–1.26), death-censored graft failure (HR 1.09, 95% CI 0.92–1.28), death (HR 1.15, 95% CI 0.98–1.35) or graft failure when death was evaluated as a competing event (sub-distribution hazard ratio [sHR] 1.07, 95% CI 0.91–1.26). Donor AKI was not associated with acute rejection but was associated with DGF (adjusted odds ratio [OR] 2.27, 95% CI 1.92–2.68). Conclusion Donor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

BackgroundModulating the microbiota in the large intestine of kidney transplant recipients through prebiotic supplementation may prevent infectious complications from occurring. To date, there have been no interventional trials which have investigated this novel treatment in kidney transplantation. The aim of PREBIOTIC is to assess the feasibility of performing a randomised controlled trial of prebiotics in reducing infections and gastrointestinal symptoms in kidney transplant recipients.MethodsSixty kidney transplant patients will be recruited to a double-blind, placebo-controlled, randomised feasibility trial. Patients will be provided with prebiotic therapy or placebo for 4 to 6 weeks. Outcomes will include recruitment, adherence, tolerance, retention, laboratory parameters (including serum indoxyl sulphate, ρ-cresyl sulphate and stool collection), patients’ self-assessed quality of life, gastrointestinal symptoms and clinical outcomes.DiscussionThis trial will assess the feasibility of prebiotic supplementation in kidney transplant recipients. Prebiotics not only may alter the gut microbiota and their inherent metabolism and production of uraemic toxins but also may prevent infections from occurring in kidney transplant recipients.Trial registrationAustralian New Zealand Clinical Trials Registry number ACTRN12618001057279p. The date of registration was 25th June 2018,https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375370&isReview=true.

Background: There are few studies that have examined whether dysbiosis occurs in kidney donors and transplant recipients following kidney transplant surgery. Aim: To ascertain whether changes occur in the gastrointestinal microbiota of the kidney donor and recipient following kidney transplantation. Methods: Kidney transplant recipients and their donors were prospectively enrolled in a pilot study to collect one faecal sample prior to, and another faecal sample between four to eight weeks following surgery. Gastrointestinal microbiota richness, Shannon diversity measures and functional assessments of kidney donors and recipients were analysed via metagenomic sequencing. Results: The study included 12 donors (median age 56 years, 6 females) and 12 recipients (median age 51 years, 3 females). Donor microbiota showed no significant changes in gastrointestinal microbiota richness, Shannon diversity, or functional assessments before and after nephrectomy. Recipient microbiota was altered post-transplant, reflected in reductions of the mean (±SD) richness values (156 ± 46.5 to 116 ± 38.6, p = 0.002), and Shannon diversity (3.57 ± 0.49 to 3.14 ± 0.52, p = 0.007), and a dramatic increase in Roseburia spp. abundance post-transplant (26-fold increase from 0.16 ± 0.0091 to 4.6 ± 0.3; p = 0.006; FDR = 0.12). Functionally, the post-transplant microbial community shifted towards those taxa using the glycolysis pathway (1.2-fold increase; p = 0.02; FDR = 0.26) for energy metabolism, while those functions involved with reactive oxygen species degradation decreased (2.6-fold; p = 0.006; FDR = 0.14). Conclusion: Live donor kidney transplantation and standard care post-transplant result in significant alterations in gut microbiota richness, diversity, composition and functional parameters in kidney transplant recipients but not in their kidney donors.

Solid organ transplant recipients (SOTRs) have elevated risks for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), especially in high UVR environments. We assessed whether polygenic risk scores can improve the prediction of BCC and SCC risks and multiplicity over and above the traditional risk factors in SOTRs in a high UV setting. We built polygenic risk scores for BCC (n = 594,881) and SCC (n = 581,431) using UK Biobank and 23andMe datasets, validated them in the Australian QSkin Sun and Health Study cohort (n > 6,300), and applied them in SOTRs in the skin tumor in allograft recipients cohort from Queensland, Australia, a high UV environment. About half of the SOTRs with a high genetic risk developed BCC (absolute risk = 45.45%, 95% confidence interval = 33.14–58.19%) and SCC (absolute risk = 44.12%, 95% confidence interval = 32.08–56.68%). For both cancers, SOTRs in the top quintile were at >3-fold increased risk relative to those in the bottom quintile. The respective polygenic risk scores improved risk predictions by 2% for BCC (area under the curve = 0.77 vs. 0.75, P = 0.0691) and SCC (area under the curve = 0.84 vs. 0.82, P = 0.0260), over and above the established risk factors, and 19.03% (for BCC) and 18.10% (for SCC) of the SOTRs were reclassified in a high/medium/low risk scenario. The polygenic risk scores also added predictive accuracy for tumor multiplicity (BCC R2 = 0.21 vs. 0.19, P = 3.2 × 10–3; SCC R2 = 0.30 vs. 0.27, P = 4.6 × 10–4).

Background There has been limited study of the prevalence of gastrointestinal symptoms and their impact on the quality of life (QOL) in kidney transplant recipients. The aim of this study was to examine the prevalence and predictors of gastrointestinal symptoms and the association with QOL in kidney transplant recipients. Methods All chronic kidney transplant recipients at the Princess Alexandra Hospital were provided with 3 questionnaires, the Gastrointestinal Quality of Life Index (GIQLI), the Gastrointestinal Symptoms Rating Scale (GSRS), and Structured Assessment of Gastrointestinal Symptoms (SAGIS) scale, to ascertain QOL impairment and to screen gastrointestinal symptom severity. Linear regression was used to determine the predictors of gastrointestinal QOL and gastrointestinal symptom severity. Results Of the 343 participants, the median age was 47 (interquartile range [IQR] 36–55) years, 58% were men, 79% were white, 39% had chronic glomerulonephritis, 83% had received their first graft, and median time since transplant was 6.3 (IQR 1.8–13.1) years. Using GSRS, 88% of participants reported at least 1 gastrointestinal symptom, most commonly indigestion (57%) and diarrhea (54%). Using GIQLI, 42% and 38% of participants reported mild and moderate QOL impairment, respectively. Gastrointestinal symptoms were predicted by female sex (coefficient −0.11, 95% CI −0.21 to −0.02) and mycophenolate (coefficient 0.0001, 95% CI 0.0001 to 0.0002), and were associated with poorer QOL (coefficient −0.38, 95% CI −0.45 to −0.30). Similar findings were observed using SAGIS for gastrointestinal symptoms. Conclusions Gastrointestinal symptoms are frequent in kidney transplant recipients, particularly in women and those receiving mycophenolate, and are strongly associated with poorer QOL., Graphical abstract

Background Many countries have suspended kidney transplantation programs during the COVID‐19 pandemic because of concerns for patient safety and the shortage of healthcare resources. This study aimed to describe patient, family member and potential donor perspectives on the suspension and resumption of kidney transplant programs due to COVID‐19. Methods We conducted seven online focus groups involving 31 adult kidney transplant candidates (n=22), caregivers (n=4) and potential donors (n=5). Transcripts were analyzed thematically. Results We identified five themes: cascading disappointments and devastation (with subthemes of shattering hope, succumbing to defeat, regret and guilt); helplessness and vulnerability (fear of declining health, confronted by the threat of and change in dialysis, disconnected from healthcare, susceptibility to infective complications); stress from uncertainty (confusion from conflicting information, unable to forward plan), exacerbating burdens (incurring extra financial costs, intensifying caregiver responsibilities), and sustaining health through the delay (protecting eligibility, relying on social support, adapting to emerging modalities of care). Conclusions During the suspension of kidney transplantation programs, patients felt medically vulnerable because of declining health, susceptibility to infection and reduced access to care. There is a need to address health vulnerabilities, disappointment, uncertainty and additional burdens arising from the suspension of kidney transplantation programs.

Aim Haemodialysis treatment prescription varies widely internationally. This study explored patient- and centre-level characteristics associated with weekly haemodialysis hours. Methods Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry data were analysed. Characteristics associated with weekly duration were evaluated using mixed-effects linear regression models with patient- and centre-level covariates as fixed effects, and dialysis centre and state as random effects using the 2017 prevalent in-centre haemodialysis (ICHD) and home haemodialysis (HHD) cohorts. Evaluation of patterns of weekly duration over time analysed the 2000 to 2017 incident ICHD and HHD cohorts. Results Overall, 12 494 ICHD and 1493 HHD prevalent patients in 2017 were included. Median weekly treatment duration was 13.5 (interquartile range [IQR] 12-15) hours for ICHD and 16 (IQR 15-20) hours for HHD. Male sex, younger age, higher body mass index, arteriovenous fistula/graft use, Aboriginal and Torres Strait Islander ethnicity and longer dialysis vintage were associated with longer weekly duration for both ICHD and HHD. No centre characteristics were associated with duration. Variability in duration across centres was very limited in ICHD compared with HHD, with variation in HHD being associated with state. Duration did not vary significantly over time for ICHD, whereas longer weekly HHD treatments were reported between 2006 and 2012 compared with before and after this period. Conclusion This study in the Australian and New Zealand haemodialysis population showed that weekly duration was primarily associated with patient characteristics. No centre effect was demonstrated. Practice patterns seemed to differ across states/countries, with more variability in HHD than ICHD.

Background and Aims Impaired physical fitness is prevalent across the spectrum of kidney disease and is associated with an increased risk of mortality, progression to end-stage kidney disease, falls and hospitalisation. Physical fitness outcomes have been extensively reported in randomised trials involving patients with kidney disease. This study aimed to assess the scope and consistency of physical fitness outcomes and outcome measures reported in kidney disease trials. Method A systematic review of randomised trials reporting physical fitness outcomes in adults with chronic kidney disease not requiring kidney replacement therapy, receiving maintenance haemodialysis or peritoneal dialysis, and kidney transplant recipients was conducted. The scope, frequency and characteristics of physical fitness outcome measures were categorised and analysed. Trials were identified from MEDLINE, Embase and the Cochrane Library from March 2000 to March 2019. Results From 115 relevant trials, 171 outcome measures for 32 outcomes were identified and categorised into five domains of physical fitness: exercise capacity (reported in 83% of trials), physiological-metabolic (57%), neuromuscular fitness (52%), body composition (45%) and cardiorespiratory fitness (19%). Exercise capacity had 53 different outcome measures and at 15 separate time points. The most common outcome measures were the 6-minute walk test (29%), peak oxygen uptake (20%), 1-repetition maximum (19%) and hand-grip strength (11%), with marked inconsistency in the reporting of outcomes between trials. Outcomes were assessed by field-based tests (65%), lab-based tests (31%) and patient-reported measures (4%). Conclusion There is large heterogeneity in the reporting of physical fitness outcomes, with inconsistencies in the use of validated, relevant and patient-important outcome measures.

Background In Australia, Lupus Nephritis (LN) affects a culturally diverse population of patients. We established the Lupus Nephritis Australian Registry (LUNAR) to better understand the population of patients receiving Myfortic and other immunosuppressants, and to analyse the safety and efficacy of the treatments they received. Methods A non-interventional, multicentre, registry of patients with biopsy-proven ISN/RPS class III, IV or V LN, treated with Myfortic or other immunosuppressants, was established. We collected baseline demographic and 6-monthly follow-up data over a 5-year period (2013–2018), including clinical data, laboratory tests and safety outcomes. Results 149 patients were enrolled in LUNAR across 8 sites, with 83.7% female and a mean age of 38.8 years. Most patients were Caucasian (45.2%) – patients of Asian ethnicity (29.6%) and Aboriginal/Torres Strait Islander or Maori/Pacific Islander descent (10.4%) were significantly over-represented compared to the general population. The mean and median duration of SLE was 8.6 and 6 years, respectively (range 0–42 years), and of LN was 5.4 and 3.9 years, respectively (range 0–30 years). Most patients had class IV LN on their initial kidney biopsy (59.3%), with 21.5% having class III and 11.1% having class V LN. Immunosuppressants used prior to screening included corticosteroids (68.9%), mycophenolate mofetil ((MMF) 61.5%), Myfortic (41.5%) and cyclophosphamide (32.6%). At enrolment or during the study, most patients were treated with Myfortic (76.3%), MMF (65.2%) and/or hydroxychloroquine (67.4%). Rituximab and azathioprine were each started in 8.9% of patients during the study period. Kidney function was stable/improved for most patients over the study period and mycophenolate-based therapy was well-tolerated. Conclusions LUNAR is the first study outlining the demographics, outcomes and practice patterns in the management of patients with LN in Australia. Acknowledgements Supported by funding from Novartis Pharmaceuticals.

Background In the era of organ shortage, home hemodialysis (HHD) has been identified as the possible preferential bridge to kidney transplantation. Data are conflicting regarding the comparability of HHD and transplantation outcomes. This study aimed to compare patient and treatment survival between HHD patients and kidney transplant recipients. Methods The Australia and New Zealand Dialysis and Transplant Registry was used to include incident HHD patients on Day 90 after initiation of kidney replacement therapy and first kidney-only transplant recipients in Australia and New Zealand from 1997 to 2017. Survival times were analyzed using the Kaplan–Meier product-limit method comparing HHD patients with subtypes of kidney transplant recipients using the log-rank test. Adjusted analyses were performed with multivariable Cox proportional hazards regression models for time to all-cause mortality. Time-to-treatment failure or death was assessed as a composite secondary outcome. Results The study compared 1411 HHD patients with 4960 living donor (LD) recipients, 6019 standard criteria donor (SCD) recipients and 2427 expanded criteria donor (ECD) recipients. While LD and SCD recipients had reduced risks of mortality compared with HHD patients [LD adjusted hazard ratio (HR) = 0.57, 95% confidence interval (CI) 0.46–0.71; SCD HR = 0.65 95% CI 0.52–0.79], the risk of mortality was comparable between ECD recipients and HHD patients (HR = 0.90, 95% CI 0.73–1.12). LD, SCD and ECD kidney recipients each experienced superior time-to-treatment failure or death compared with HHD patients. Conclusions This large registry study showed that kidney transplant offers a survival benefit compared with HHD but that this advantage is not significant for ECD recipients.

Objectives Patients with chronic kidney disease (CKD) are at a high risk of future autonomic dysfunction and cardiovascular disease. The aim of this study was to examine the effects of a 12-month lifestyle intervention (LI) involving regular aerobic exercise on cardiac autonomic function in CKD patients. Design Pooled exploratory analysis. Methods 113 eligible patients with stage 3–4 CKD (eGFR 25–60 ml/min/1.75m2) participated in a LI program, including an 8-week individualised gym-based exercise program followed by a 10-month home-based program. The control (CON) group underwent standard nephrological care. The following parameters were assessed prior to and following the 12-month study period: cardiorespiratory fitness (VO2peak) from a graded exercise test; cardiac autonomic function from time, frequency, and non-linear measures of heart rate variability (HRV), heart rate (HR) recovery following peak exercise, and chronotropic competence during exercise. Results Compared to the CON group, the LI group significantly increased VO2peak (CON = -1.0 vs. LI = +1.8 ml/kg/min, p < 0.01) while there was no significant improvement in any HRV measure (p = 0.85), HR recovery (p = 0.38) or chronotropic competence (p = 0.28). Changes in relative VO2peak were significantly associated with changes in a non-linear HRV measure, α1 (p < 0.01), independent of age and eGFR (r2 = 0.196, p = 0.03). Conclusions Despite the significant increase in cardiorespiratory fitness for the LI group, there were no changes in cardiac autonomic function. However, α1 may be a sensitive measure to assess VO2peak changes in this clinical cohort. Further research is required to investigate the role of different modalities of exercise training to enhance cardiac autonomic function in patients with CKD.

Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease. The Global aHUS Registry collects real-world data on the natural history of the disease. Here we characterize end-stage renal disease (ESRD)-free survival, the rate of thrombotic microangiopathy, organ involvement and the genetic background of 851 patients in the registry, prior to eculizumab treatment. A sex-specific difference was apparent according to age at initial disease onset as the ratio of males to females was 1.3:1 for childhood presentation and 1:2 for adult presentation. Complement Factor I and Membrane Cofactor Protein mutations were more common in patients with initial presentation as adults and children, respectively. Initial presentation in childhood significantly predicted ESRD risk (adjusted hazard ratio 0.55 [95% confidence interval 0.41-0.73], whereas sex, race, family history of aHUS, and time from initial presentation to diagnosis, did not. Patients with a Complement Factor H mutation had reduced ESRD-free survival, whereas Membrane Cofactor Protein mutation was associated with longer ESRD-free survival. Additionally extrarenal organ manifestations occur in 19%-38% of patients within six months of initial disease presentation (dependent on organ). Thus, our real-world results provide novel insights regarding phenotypic variables and genotypes on the clinical manifestation and progression of aHUS.

Background Membranoproliferative glomerulonephritis (MPGN) is an uncommon cause of end stage kidney disease (ESKD) and the clinical outcomes of patients with MPGN who commence kidney replacement therapy have not been comprehensively studied. Methods All adult patients with ESKD due to glomerulonephritis commencing kidney replacement therapy in Australia and New Zealand from January 1, 1996 to December 31, 2016 were reviewed. Patients with ESKD due to MPGN were compared to patients with other forms of glomerulonephritis. Patient survival on dialysis and following kidney transplantation, kidney recovery on dialysis, time to transplantation, allograft survival, death-censored allograft survival and disease recurrence post-transplant were compared between the two groups using Kaplan Meier survival curves and Cox proportional hazards regression. Results Of 56,481 patients included, 456 (0.8%) had MPGN and 12,660 (22.4%) had another form of glomerulonephritis. Five-year patient survival on dialysis and following kidney transplantation were similar between patients with ESKD from MPGN and other forms of glomerulonephritis (Dialysis: 59% vs. 62% p = 0.61; Transplant: 93% vs. 93%, p = 0.49). Compared to patients with other forms of glomerulonephritis, patients with MPGN had significantly poorer 5-year allograft survival (70% vs. 81% respectively, p = 0.02) and death censored allograft survival (74% vs. 87%, respectively; p p p Conclusions Compared with other forms of glomerulonephritis, patients with MPGN experienced comparable rates of survival on dialysis and following kidney transplantation, but significantly higher rates of allograft loss due to disease recurrence.

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. Although TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 (a disintegrin and metalloprotease thrombospondin, number 13) activity. A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. Although early confirmation of aHUS is often not possible, except in the minority of patients in whom auto-antibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

Thrombotic microangiopathy (TMA) arises in a variety of clinical circumstances with the potential to cause significant dysfunction of the kidneys, brain, gastrointestinal tract and heart. TMA should be considered in all patients with thrombocytopenia and anaemia, with an immediate request to the haematology laboratory to look for red cell fragments on a blood film. While TMA of any aetiology generally demands prompt treatment, this is especially so in thrombotic thrombocytopenic purpura (TTP) and atypical haemolytic uraemic syndrome (aHUS), where organ failure may be precipitous, irreversible and fatal. In all adults, urgent, empirical plasma exchange (PE) should be started within 4-8 h of presentation for a possible diagnosis of TTP, pending a result for ADAMTS13 activity (a disintegrin and metalloprotease thrombospondin, number 13). A sodium citrate plasma sample should be collected for ADAMTS13 testing prior to any plasma therapy. In children, Shiga toxin-associated haemolytic uraemic syndrome due to infection with Escherichia coli (STEC-HUS) is the commonest cause of TMA, and is managed supportively. If TTP and STEC-HUS have been excluded, a diagnosis of aHUS should be considered, for which treatment is with the monoclonal complement C5 inhibitor, eculizumab. While early confirmation of aHUS is often not possible, except in the minority of patients in whom autoantibodies against factor H are identified, genetic testing ultimately reveals a complement-related mutation in a significant proportion of aHUS cases. The presence of other TMA-associated conditions (e.g. infection, pregnancy/postpartum and malignant hypertension) does not exclude TTP or aHUS as the underlying cause of TMA.

Background Arterial stiffness is an independent predictor of all-cause and cardiovascular mortality in patients with chronic kidney disease (CKD). There are limited prospective data however on progression of arterial stiffness in CKD, including evaluating associations with bone mineral markers such as fibroblast growth factor 23 (FGF23) and soluble α-klotho (sKl). Methods In this prospective, single-center, observational study, arterial stiffness [measured by pulse wave velocity (PWV)] and hormones influencing mineral homeostasis, including serum FGF23 and sKl, were compared between non-dialysis CKD stages 4/5 and healthy controls at baseline and 12 months (12 m). Abdominal aortic calcification (AAC) was quantitated using lateral lumbar radiography at baseline. Results Forty patients with CKD [mean estimated glomerular filtration rate (eGFR) 19.5 ± 6.7 mL/min/1.73m2] and 42 controls (mean eGFR 88.6 ± 12.9 mL/min/1.73m2) completed follow-up. There were no differences in age, gender and body mass index between groups. A significant increase in FGF23 [240.6 (141.9–1129.8) to 396.8 (160.3–997.7) pg/mL, p = 0.001] was observed in the CKD group but serum phosphate, corrected calcium, parathyroid hormone and sKl did not change significantly over 12 m. At baseline, CKD subjects had higher AAC prevalence [83.8% versus (vs.) 43.6%, p = 0.002] and higher aortic PWV [9.7(7.6–11.7) vs. 8.1 (7.2–9.7) m/s, p = 0.047] compared to controls. At 12 m, aortic PWV increased by 1.3 m/s (95% confidence interval, 0.56 to 2.08, p 10 m/s). Serum FGF23 was associated with AAC, abnormal PWV and progression of PWV at 12 m. Conclusions Arterial stiffness and serum FGF23, both of which are associated with increased cardiovascular risk, increased over one year in individuals with CKD. Additionally, a significant association was found between serum FGF23 and arterial calcification and stiffness. Larger clinical studies and further experimental work are warranted to delineate the temporal relationship as well as the pathological mechanisms linking FGF23 and vascular disease. Electronic supplementary material The online version of this article (10.1186/s12882-017-0705-4) contains supplementary material, which is available to authorized users.

Disorders in the regulation of the alternate complement pathway often result in complement-mediated damage to the microvascular endothelium and can be associated with both glomerulonephritis and atypical haemolytic uraemic syndrome. Inherited defects in complement regulatory genes or autoantibodies against complement regulatory proteins are predictive of the severity of the disease and the risk of recurrence post kidney transplantation. Heterozygous mutations in CD46, which codes for a transmembrane cofactor glycoprotein membrane cofactor protein, usually have a lower incidence of end-stage kidney disease and decreased risk of recurrent disease post transplant, as wild-type membrane cofactor protein is present in the transplanted kidney. However, some patients with CD46 mutations have a second variant in other complement regulatory genes increasing the severity of disease. The following case report illustrates the course of a young adult patient with end-stage kidney disease initially ascribed to seronegative systemic lupus erythematosus, who presented with biopsy-proven thrombotic microangiopathy following kidney transplantation. It highlights the complexity associated with disorders of complement regulation and the need for a high index of suspicion and genetic testing in patients who present with thrombotic microangiopathy post-transplant.

Background/Aims: Cardiac biomarkers are associated with cardiac abnormalities and adverse outcomes in dialysis patients. Our aim was to report the effect of the beta-blocker carvedilol on cardiac biomarkers in adult dialysis patients. Methods: The Beta-Blocker to Lower Cardiovascular Dialysis Events Feasibility Study was a randomized controlled trial comparing carvedilol to placebo. Serum and plasma were collected before the run-in, then 6 and 12 months post-randomization to measure B-type Natriuretic Peptide (BNP), N-terminal BNP (NT-ProBNP), high-sensitivity cardiac troponins I (hs-TnI) and T (hs-TnT), and galectin-3. Left ventricular global longitudinal strain (GLS) was measured by echocardiography at baseline. Results: Seventy-two participants were recruited of whom 49 completed the run-in and were randomized to carvedilol (n=26) or placebo (n=23). Baseline echocardiography demonstrated median (inter-quartile range) GLS of -14.27% (-16.63 to -11.93). NTproBNP and hs-TnT correlated with GLS (Spearman’s rho=0.34 [p=0.018] and rho=0.28 [p=0.049], respectively). Median change scores from baseline to 12 months did not differ significantly between participants with complete biomarker data randomized to carvedilol (n=15) or placebo (n=16) for any biomarkers. Conclusions: NT-proBNP and hs-TnT were associated with GLS. However, changes in levels of the biomarkers from baseline to 12 months were not different between groups randomized to carvedilol and placebo.

Azathioprine, a purine antimetabolite immunosuppressant, photosensitizes the skin and causes the production of mutagenic reactive oxygen species. It is postulated to increase the risk of squamous cell carcinoma (SCC) and other skin cancers in organ transplant recipients (OTRs), but evidence from multiple, largely single-center studies to date has been inconsistent. We aimed to resolve the issue of azathioprine's carcinogenicity by conducting a systematic review of the relevant literature and pooling published risk estimates to evaluate the risks of SCC, basal cell carcinoma (BCC), keratinocyte cancers (KCs) overall and other skin cancers in relation to azathioprine treatment. Twenty-seven studies were included in total, with risk estimates from 13 of these studies able to be pooled for quantitative analysis. The overall summary estimate showed a significantly increased risk of SCC in relation to azathioprine exposure (1.56, 95% confidence interval [CI] 1.11-2.18). No significant associations between azathioprine treatment and BCC (0.96, 95% CI 0.66-1.40) or KC (0.84, 95% CI 0.59-1.21) risk were observed. There was significant heterogeneity between studies for azathioprine risk estimates and the outcomes of SCC, BCC and KC. The pooled findings of available evidence support the contention that treatment with azathioprine increases the risk of SCC in OTRs.

The incidence of infectious complications, compared with the general population and the pre-transplant status of the recipient, increases substantially following kidney transplantation, causing significant morbidity and mortality. The potent immunosuppressive therapy given to prevent graft rejection in kidney transplant recipients results in an increased susceptibility to a wide range of opportunistic infections including bacterial, viral and fungal infections. Over the last five years, several advances have occurred that may have changed the burden of infectious complications in kidney transplant recipients. Due to the availability of direct-acting antivirals to manage donor-derived hepatitis C infection, this has opened the way for donors with hepatitis C infection to be considered in the donation process. In addition, there have been the development of medications targeting the growing burden of resistant cytomegalovirus, as well as the discovery of the potentially important role of the gastrointestinal microbiota in the pathogenesis of post-transplant infection. In this narrative review, we will discuss these three advances and their potential implications for clinical practice.

Chronic kidney disease (CKD) is a major risk factor for valvular heart disease (VHD). Mitral annular and aortic valve calcifications are highly prevalent in CKD patients and commonly lead to valvular stenosis and regurgitation, as well as complications including conduction system abnormalities and endocarditis. VHD, especially mitral regurgitation and aortic stenosis, is associated with significantly reduced survival among CKD patients. Knowledge related to VHD in the general population is not always applicable to CKD patients because the pathophysiology may be different, and CKD patients have a high prevalence of comorbid conditions and elevated risk for periprocedural complications and mortality. This Kidney Disease: Improving Global Outcomes (KDIGO) review of CKD and VHD seeks to improve understanding of the epidemiology, pathophysiology, diagnosis, and treatment of VHD in CKD by summarizing knowledge gaps, areas of controversy, and priorities for research.

Background: Prednisolone displays significant pharmacokinetic variability and exposure-outcome relationships in renal transplant recipients, suggesting a role for drug monitoring in some scenarios. It is highly protein-bound, and the free form is pharmacologically active but cumbersome to measure. Saliva concentrations might reflect free plasma prednisolone and present an alternative measurement. The aim of this study was to examine the correlation between total and free plasma and saliva prednisolone in adult renal transplant recipients.Methods: Total and free plasma and saliva prednisolone concentrations were measured in 20 patients receiving oral prednisolone 1-2 months after transplant, between pre-dose and 12 hours post-dose. Prednisolone was determined using high-performance liquid chromatography mass spectrometric detection. The Pearson coefficient was used to assess the association between plasma and salivary prednisolone concentrations and area under the concentration-time curves (AUC(0-12)).Results: When considering all time points, the total and free plasma prednisolone concentrations correlated well (r(2) = 0.81), but there was poor correlation between saliva and free (r(2) = 0.003) and total (r(2) = 0.01) plasma concentrations. When concentrations before the maximum free prednisolone plasma value were excluded, the correlation between free plasma and saliva concentrations improved (r(2) = 0.57). There was a moderate correlation between free and total plasma prednisolone AUC(0-12) (r(2) = 0.62) using all time points, but a poor correlation between free and total plasma prednisolone AUC(0-12) and saliva AUC(0-12) (r(2) = 0.07; r(2) = 0.17).Conclusions: Total and free plasma prednisolone measurements correlated poorly with saliva measurements; however, correlation improved when concentrations early in the dosing interval were excluded.

Infectious complications are common following kidney transplantation and rank in the top five causes of death in patients with allograft function. Over the last 5 years, there has been emerging evidence that changes in the gastrointestinal microbiota following kidney transplantation may play a key role in the pathogenesis of transplant-associated infections. Different factors have emerged which may disrupt the interaction between the gastrointestinal microbiota and the immune system, which may lead to infective complications in kidney transplant recipients. Over the last 5 years, there has been emerging evidence that changes in the gastrointestinal microbiota following kidney transplantation may play a key role in the pathogenesis of transplant-associated infections. This review will discuss the structure and function of the gastrointestinal microbiota, the changes that occur in the gastrointestinal microbiota following kidney transplantation and the factors underpinning these changes, how these changes may lead to transplant-associated infectious complications and potential treatments which may be instituted to mitigate this risk.

BACKGROUND AND OBJECTIVES: The burden of infectious disease is high among kidney transplant recipients because of concomitant immunosuppression. In this study the incidence of infectious-related mortality and associated factors were evaluated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: In this registry-based retrospective, longitudinal cohort study, recipients of a first kidney transplant in Australia and New Zealand between 1997 and 2015 were included. Cumulative incidence of infectious-related mortality was estimated using competing risk regression (using noninfectious mortality as a competing risk event), and compared with age-matched, populated-based data using standardized incidence ratios. RESULTS: Among 12,519 patients, (median age 46 years, 63% men, 15% diabetic, 6% Indigenous ethnicity), 2197 (18%) died, of whom 416 (19%) died from infection. The incidence of infection-related mortality during the study period (1997–2015) was 45.8 (95% confidence interval [95% CI], 41.6 to 50.4) per 10,000 patient-years. The incidence of infection-related mortality reduced from 53.1 (95% CI, 45.0 to 62.5) per 10,000 person-years in 1997–2000 to 43.9 (95% CI, 32.5 to 59.1) per 10,000 person-years in 2011–2015 (P

Introduction Recurrence of atypical hemolytic uremic syndrome (aHUS) in renal allografts is common, leading to dialysis and graft failure. Pretransplant versus posttransplant initiation of eculizumab treatment in patients with aHUS has not been rigorously investigated. We hypothesized eculizumab pretransplant would reduce dialysis incidence posttransplant. Methods Of patients enrolled in the Global aHUS Registry (n = 1549), 344 had ≥1 kidney transplant. Of these, 188 had received eculizumab. Eighty-eight patients (47%) were diagnosed with aHUS and received eculizumab before, and during, their most recent transplant (group 1). A total of 100 patients (53%; group 2) initiated eculizumab posttransplantation. This second group was subdivided into those diagnosed with aHUS before (n = 52; group 2a) or after (n = 48; group 2b) their most recent transplant. Results Within 5 years of transplantation, 47 patients required dialysis; the risk of dialysis after transplantation was significantly increased in group 2b (hazard ratio [HR] 4.6; confidence interval [CI] 1.7–12.4) but not 2a (HR 2.3; CI 0.9–6.2). Graft function within 6 months of transplantation was significantly better in group 1 (median estimated glomerular filtration rate of 60.6 ml/min per 1.73 m2) compared with 31.5 and 9.6 ml/min per 1.73 m2 in groups 2a (P = 0.004) and 2b (P = 0.0001), respectively. One meningococcal infection (resolved with treatment) and 3 deaths (deemed unrelated to eculizumab) were reported. Conclusions Outcomes for transplant patients with aHUS treated with eculizumab were improved compared with previous reports of patients with aHUS not treated with eculizumab. Our findings suggest delayed aHUS diagnosis and therefore treatment is associated with an increased risk of dialysis posttransplantation and reduced allograft function., Graphical abstract

Introduction High-intensity interval training (HIIT) increases mitochondrial biogenesis and cardiorespiratory fitness in chronic disease populations, however has not been studied in people with chronic kidney disease (CKD). The aim of this study was to compare the feasibility, safety, and efficacy of HIIT with moderate-intensity continuous training (MICT) in people with CKD. Methods Fourteen individuals with stage 3-4 CKD were randomized to 3 supervised sessions/wk for 12 weeks, of HIIT (n = 9, 4 × 4 minute intervals, 80%-95% peak heart rate [PHR]) or MICT (n = 5, 40 minutes, 65% PHR). Feasibility was assessed via session attendance and adherence to the exercise intensity. Safety was examined by adverse event reporting. Efficacy was determined from changes in cardiorespiratory fitness (VO2 peak), exercise capacity (METs), and markers of mitochondrial biogenesis (PGC1α protein levels), muscle protein catabolism (MuRF1), and muscle protein synthesis (p-P70S6k Thr389 ). Results Participants completed a similar number of sessions in each group (HIIT = 33.0[7.0] vs MICT = 33.5[3.3] sessions), and participants adhered to the target heart rates. There were no adverse events attributable to exercise training. There was a significant time effect for exercise capacity (HIIT = +0.8 ± 1.2; MICT = +1.3 ± 1.6 METs; P = 0.01) and muscle protein synthesis (HIIT = +0.6 ± 1.1; MICT = +1.4 ± 1.7 au; P = 0.04). However, there were no significant (P > 0.05) group × time effects for any outcomes. Conclusion This pilot study demonstrated that HIIT is a feasible and safe option for people with CKD, and there were similar benefits of HIIT and MICT on exercise capacity and skeletal muscle protein synthesis. These data support a larger trial to further evaluate the effectiveness of HIIT.

BackgroundResidual kidney function (RKF) is associated with improved survival and quality of life in dialysis patients. Previous studies have suggested that initiation of peritoneal dialysis (PD) may slow RKF decline compared to the pre-dialysis period. We sought to evaluate the association between PD initiation and RKF decline in the Initiating Dialysis Early And Late (IDEAL) trial.MethodsIn thispost hocanalysis of the IDEAL randomized controlled trial, PD participants were included if results from 24-hour urine collections had been recorded within 30 days of dialysis initiation, and at least one value pre- and one value post-dialysis commencement were available. The primary outcome was slope of RKF decline, calculated as mean of urinary creatinine and urea clearances. Secondary outcomes included slope of urine volume decline and time from PD initiation to anuria.ResultsThe study included 151 participants (79 early start, 72 late start). The slope of RKF decline was slower after PD initiation (-2.69±0.18mL/min/1.73m2/yr) compared to before PD (-4.09±0.33mL/min/1.73m2/yr; change in slope +1.19 mL/min/1.73m2/yr, 95%CI 0.48–1.90, pConclusionsInitiation of PD was associated with a slower decline of RKF compared to the pre-dialysis period.

In this prospective observational cohort study, we evaluate the change in cardiovascular risk parameters, with a focus on lipids, in live kidney donors 1 year post donation. Body mass index, systolic/diastolic blood pressure, kidney function (chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration) and lipid parameters were measured at baseline and 1 year. Data on 87 live kidney donors were collected. Body mass index increased from 26.5 ± 2.7 pre to 27.4 ± 3.0 kg/m(2) post donation (p