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UNLABELLED: Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content. Better Evidence for Selecting Transplant Fluids (BEST-Fluids), a pragmatic, registry-based, double-blind, randomized trial, sought to determine whether using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce DGF. We sought to evaluate the generalizability of the trial cohort by reporting the baseline characteristics and representativeness of the trial participants in detail. METHODS: We compared the characteristics of BEST-Fluids participants with those of a contemporary cohort of deceased donor kidney transplant recipients in Australia and New Zealand using data from the Australia and New Zealand Dialysis and Transplant Registry. To explore potential international differences, we compared trial participants with a cohort of transplant recipients in the United States using data from the Scientific Registry of Transplant Recipients. RESULTS: During the trial recruitment period, 2373 deceased donor kidney transplants were performed in Australia and New Zealand; 2178 were eligible' and 808 were enrolled in BEST-Fluids. Overall, trial participants and nonparticipants were similar at baseline. Trial participants had more coronary artery disease (standardized difference [d] = 0.09; P = 0.03), longer dialysis duration (d = 0.18, P < 0.001), and fewer hypertensive (d = -0.11, P = 0.03) and circulatory death (d = -0.14, P < 0.01) donors than nonparticipants. Most key characteristics were similar between trial participants and US recipients, with moderate differences (|d| ≥ 0.2; all P < 0.001) in kidney failure cause, diabetes, dialysis duration, ischemic time, and several donor risk predictors, likely reflecting underlying population differences. CONCLUSIONS: BEST-Fluids p

Purpose: Risk scores may aid risk quantification and decision-making in kidney transplantation. The Living Kidney Donor Profile Index (LKDPI) was developed to choose between living donors. The original LKDPI is moderately discriminatory (Harrel's C Statistic=0.59,95% CI 0.55-0.61) but poorly calibrated in Australia/New Zealand. We developed a risk prediction score for overall graft survival in adult recipients of a living kidney donor transplant in an Australian and New Zealand population. Method(s): Using data from the Australia and New Zealand Dialysis and Transplant Registry, we included adult recipients of living kidney donor transplants over 2004-2018. We constructed Cox models for overall graft survival. We refit the original USA variables and then constructed a new model (ANZ LKDPI) considering all available potential covariates. Model performance was validated by assessing discrimination and calibration. Result(s): 4049 living donors were included. The C-statistic for the re-fit model was 0.57(95%CI 0.54-0.59). The remodeled score included the new variables history of hypertension and HLA-A mismatches. Variables excluded were donor:recipient weight ratio, HLA-B, both male, and ABO incompatibility. The ANZ LKDPI had similar discrimination (C=0.56,95%CI 0.54-0.58). The model fit and calibration was better. Conclusion(s): The ANZ LKDPI had similar discrimination to the original and the refitted LKDPI. The discrimination was low for both scores and so should be used with caution to decide between donors. The new score is better calibrated for our population so could be used to predict individual graft prognosis. (Figure Presented).

Background: End-stage kidney disease secondary to hyperoxaluria presents a major challenge for transplant physicians given concern regarding disease recurrence. Few contemporary studies have reported long-term outcomes following transplantation in this population. Method(s): This study examined the outcomes of all adult patients with end-stage kidney disease secondary to hyperoxaluria who received a kidney or combined liver-kidney transplant in Australia and New Zealand between 1965 and 2015. Patients with hyperoxaluria were propensity score matched to control patients with reflux nephropathy. The primary outcome was graft survival. Secondary outcomes included graft function, acute rejection, and patient survival. Result(s): Nineteen transplants performed in 16 patients with hyperoxaluria were matched to 57 transplants in patients with reflux nephropathy. Graft survival was inferior in patients with hyperoxaluria receiving a kidney transplant alone (subhazard ratio [SHR] = 3.83, 95% confidence interval [CI], 1.22-12.08, P = .02) but not in those receiving a combined liver-kidney transplant (SHR = 0.63, 95% CI, 0.08-5.21, P =. 67). Graft failure risk was particularly high in patients with hyperoxaluria receiving a kidney transplant alone after more than 1 year of renal replacement therapy (SHR = 8.90, 95% CI, 2.35-33.76, P = .001). Posttransplant estimated glomerular filtration rate was lower in patients with hyperoxaluria (10.97 mL/min/1.73 m2, 95% CI, 0.53-21.42, P = .04). There was no difference between groups in the risk of acute rejection or death with a functioning graft. Conclusion(s): Compared to reflux nephropathy, hyperoxaluria was associated with inferior graft survival in patients receiving a kidney transplant alone. Long-term graft function was lower in patients with hyperoxaluria, but the risks of acute rejection and death were not different.Copyright © 2020 Elsevier Inc.

Aim: To examine reasons underlying non-retrieval and non-utilisation of donor pancreata for solid pancreas transplantation in Australia and New Zealand (ANZ) and identify potentially useable organs from this cohort. Background(s): Deceased donor pancreas non-utilisation has increased in Australia, UK and the USA. Pancreas non-retrieval has increased in Australia and is high in New Zealand. We hypothesised that deceased donor pancreata in ANZ were not being optimally identified, retrieved or utilised. Method(s): Deceased donors from 2007 to 2016 from the Australian and New Zealand Organ Donor (ANZOD) registry were analysed for reasons underlying non-authorisation of pancreas donation, and for pancreas non-retrieval or non-utilisation. These groups were then screened using Transplantation Society of Australia and New Zealand (TSANZ) deceased-donor criteria to identify potentially suitable solid-organ pancreas donors. Their characteristics were then compared to actual donors. Result(s): 2998 donors had authorisation requested for pancreas donation during the study period. Donor medical unsuitability (37%) was the commonest reason for non-retrieval followed by donor age (25%) and logistics (14%). Several potential solid-organ pancreas donors (n = 222) comprising 18/71 non-authorised (25%), 197/1765 non-retrieved (11%), and 7/131 non-utilised pancreata (5%) were identified. When compared to actual donors, only donor region of origin, history of hypertension and cause of death were significantly different. Increasing donor upper-age limit to 50 years old resulted in an additional 62/1967 (3%) potential solid-organ pancreas donors. Conclusion(s): Potential additional solid-organ pancreas donors exist within the non-authorised, non-retrieved and non-utilised pancreas donor groups in ANZ. Further research into increasing solid-organ pancreas donor upper-age limits, and minimising logistical barriers to pancreas retrieval are necessary to minimise non-retrieval and non-utilis

Aim: We developed a risk prediction score for overall graft survival in adult recipients of a living kidney donor transplant in an Australian and New Zealand population. Background(s): Risk scores may aid risk quantification and decision-making in kidney transplantation. The Living Kidney Donor Profile Index (LKDPI) was developed to choose between living donors. The original LKDPI is not discriminatory (C = 0.59, 95% CI 0.55-0.62) or well calibrated in Australia/New Zealand. Method(s): Using data from the Australia and New Zealand Dialysis and Transplant Registry, we included adult recipients of living kidney donor transplants over 2004-2018. We constructed Cox models for overall graft survival. We refit the original USA variables and constructed a new model considering all available potential covariates. Model performance was examined by partial validation, bootstrapping, Harrell's C-statistic (C) and Akaike information criterion (AIC). Result(s): 4049 living donors were included; 58.2% were female, 10.4% had hypertension and 18.7% were obese. For the original USA LKDPI the variables of both male and donor: recipient weight ratio were mis-specified. The C-statistic for the re-fit model was 0.57 (95%CI 0.54-0.59). When remodelling the score, the new variables included were history of hypertension and HLA-A mismatches. Variables excluded were donor: recipient weight ratio, HLA-B, both male, and ABO incompatibility. The Aus/NZ LKDPIC-statistic was 0.56 (95%CI 0.54-0.58). Calibration was similar but the Aus/NZ LKDPI had better model fit (AIC: 10402 vs. 11 023). Conclusion(s): The Aus/NZ LKDPI had similar discrimination to the original LKDPI and the LKDPI with adjusted coefficients. The discrimination was low for both scores and so should be used with caution to decide between donors. The new score is better calibrated for our population so could be used to predict graft prognosis.

Background: SPKT in Australia uses recipient criteria that are highly selective compared to those internationally, including a conservative recipient upper-age limit. Mortality rates due to comorbidity are high, therefore early referral is encouraged (eGFR <=25ml/min) to allow early identification of issues precluding transplantation. Aim(s): To describe the characteristics and early outcomes of patients referred to our unit for SPKT. Method(s): All referrals to our centre from 1/6/2010-30/6/2018 were reviewed. Patient characteristics including age, dialysis status, eGFR, and geographic origin were examined. Early outcomes (within 6 months after first initial assessment) were assessed including death, in principle acceptance/non-acceptance, and presence of clinical issues precluding transplantation. Result(s): During the study period, 290 referrals were received (48% females, mean age 40.3yrs (SD +/- 8.1)) with 240 (83%) referred from other centres. States referring were VIC 76.9%, SA 14.8%, TAS 7%, NSW/QLD/NT 1.3%. After excluding pancreas without kidney referrals, 75/279 (27%) were already on dialysis at referral. For those pre-dialysis (73%) mean eGFR was 21ml/min (SD +/-8). Of the 260 patients who attended the initial review, 16% were deemed unsuitable while 209 (80%) were accepted in principle. The remaining 4% had an acceptance decision deferred. Median time from referral to appointment was 95 days (range 67- 140). Seven (2.4%) died prior to review or soon after initial assessment (mean age 40.3, SD +/- 5.5 years). Sixty-six (32%) had clinical issues precluding transplantation (eg. heart disease, smoking, overweight, psychosocial issues). Conclusion(s): Patients referred for SPK transplantation to our centre are generally young and have a high mortality rate. A significant proportion are referred late, having already commenced dialysis. Many have complex clinical issues needing resolution before they can progress to transplantation.

Background: Current solid organ pancreas transplantation protocols have differing donor criteria for donor pancreas acceptance and recipient eligibility criteria for transplant workup. We quantified this variation and compared current Australia and New Zealand (ANZ) solid pancreas transplant eligibility criteria with current international practice. Material/Methods: A survey of donor and recipient eligibility criteria for solid pancreas transplantation was disseminated to 85 transplant units in 23 countries. Responses were grouped by regions (ANZ, North America, Eurotransplant, Europe, United Kingdom) and analyzed for significant differences between regions and for ANZ compared to all other regions. Result(s): Responding UK pancreas transplant units reported the highest mean donor upper age limit (61 years old) and the highest mean donation after cardiac death donor (DCD) age limit (55 years old). All responding UK and USA units utilized DCD pancreas donors and accepted suitable type 2 diabetes (T2DM) recipients for pancreas transplantation; however, this was less common among responding European or Eurotransplant units. ANZ mean standard and DCD pancreas donor upper age limits (47 and 35 years old, respectively) were lower compared to all other regions (54 years old and 48 years old, respectively). Conclusion(s): Pancreas donor age limits, DCD pancreas donor utilization, and transplanting T2DM recipients differ between responding pancreas transplant units. ANZ units have more conservative donor upper age limits compared to other responding units. Increased utilization of DCD pancreas donors and T2DM recipients while standardiz-ing pancreas donor age limits might increase donor numbers and improve access to solid pancreas transplan-tation both locally and abroad.Copyright © Ann Transplant.

The plant-derived toxin, aristolochic acid (AA), is the cause of Chinese Herb Nephropathy and Balkan Nephropathy. Ingestion of high dose AA induces acute kidney injury, while chronic low dose ingestion leads to progressive kidney disease. Ingested AA is taken up by tubular epithelial cells of the kidney, leading to DNA damage and cell death. Cyclophilin D (CypD) participates in mitochondrial-dependent cell death, but whether this mechanism operates in acute or chronic AA-induced kidney injury is unknown. We addressed this question by exposing CypD-/- and wild type (WT) mice to acute high dose, or chronic low dose, AA. Administration of 5 mg/kg AA to WT mice induced acute kidney injury 3 days later, characterised by loss of kidney function, tubular cell damage and death, and neutrophil infiltration. All of these parameters were significantly reduced in CypD-/- mice. Chronic low dose (2 mg/kg AA) administration in WT mice resulted in chronic kidney disease with impaired renal function and renal fibrosis by day 28. However, CypD-/- mice were not protected from AA-induced chronic kidney disease. In conclusion, CypD facilitates AA-induced acute kidney damage, but CypD does not contribute to the transition of acute kidney injury to chronic kidney disease during ongoing AA exposure.Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Aim: To assess the possibility of increasing solid-organ pancreas utilisation for transplantation in Australia and New Zealand (ANZ). Background(s): Solid-organ pancreas transplantation rates in ANZ are lower compared to the UK and USA (1.45 vs 3.05 and 3.09 pmp respectively in 2019). To understand this, we examined local donor characteristics associated with pancreas non-retrieval and non-transplantation. We also applied the Pancreas Donor Risk index (PDRI) to our cohort which has been validated elsewhere to quantify the impact of donor quality on pancreas graft survival. Method(s): Data-linkage between ANZDATA, ANZOD, and the Australia and New Zealand Islet and Pancreas Transplant registry for all solid pancreas transplants from 2007-2016 was obtained. Donor characteristics predictive of pancreas non-retrieval were assessed while donor, recipient and transplant characteristics associated with graft and patient survival were also addressed. PDRI was calculated for all pancreas donors and analysed as an independent covariate. Result(s): 2592 donors authorised to donate pancreas and 385 solid pancreas transplants comprised the study cohort. Medically unstable donor (37%), older age (25%), and logistical factors (14%) were the main reasons for non-retrieval. One- and five-year pancreas graft survival were 90% and 87% respectively. Increased donor age was associated with lower likelihood of pancreas transplantation (OR 0.84, 95% CI 0.81-0.88, p<0.001) and lower pancreas graft survival (HR 1.22, 95% CI 1.05-1.43, p=0.01). PDRI was 0.85-1.15 for most pancreas donors. Given the conservative cohort, PDRI was not associated with local pancreas graft survival. Conclusion(s): A more selective solid pancreas donor cohort exists for ANZ compared to the USA and UK. Selectively extending ANZ solid pancreas donor suitability criteria could significantly increase ANZ pancreas utilisation without a major compromise in transplant outcomes.

The evidence supporting an initial mycophenolate mofetil (MMF) dose of 2 g daily in tacrolimus-treated renal transplant recipients is limited. In a non-contemporaneous single-centre cohort study we compared the incidence of leukopaenia, rejection and graft dysfunction in patients initiated on MMF 1.5 g and 2 g daily. Baseline characteristics and tacrolimus trough levels were similar by MMF group. MMF doses became equivalent between groups by 12-months post-transplant, driven by dose reductions in the 2 g group. Leukopaenia occurred in 42.4% of patients by 12-months post-transplant. MMF 2 g was associated with a 1.80-fold increased risk of leukopaenia compared to 1.5 g. Rejection occurred in 44.8% of patients by 12-months post-transplantation. MMF 2 g was associated with half the risk of rejection relative to MMF 1.5 g. Over the first 7-years post-transplantation there was no difference in renal function between groups. Additionally, the development of leukopaenia or rejection did not result in reduced renal function at 7-years post-transplant. Leukopaenia was not associated with an increased incidence of serious infections or rejection. This study demonstrates the initial MMF dose has implications for the incidence of leukopaenia and rejection. Since neither dose produced superior long-term graft function, clinical equipoise remains regarding the optimal initial mycophenolate dose in tacrolimus-treated renal transplant recipients.

Cyclophilins have important homeostatic roles, but following tissue injury, cyclophilin A (CypA) can promote leukocyte recruitment and inflammation, while CypD can facilitate mitochon-drial-dependent cell death. This study investigated the therapeutic potential of a selective cyclo-philin inhibitor (GS-642362), which does not block calcineurin function, in mouse models of tubular cell necrosis and renal fibrosis. Mice underwent bilateral renal ischemia/reperfusion injury (IRI) and were killed 24 h later: treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. In the second model, mice underwent unilateral ureteric obstruction (UUO) surgery and were killed 7 days later; treatment with 10 or 30 mg/kg/BID GS-642362 (or vehicle) began 1 h before surgery. GS-642362 treatment gave a profound and dose-dependent protection from acute renal failure in the IRI model. This protection was associated with reduced tubular cell death, including a dramatic reduction in neutrophil infiltration. In the UUO model, GS-642362 treatment signifi-cantly reduced tubular cell death, macrophage infiltration, and renal fibrosis. This protective effect was independent of the upregulation of IL-2 and activation of the stress-activated protein kinases (p38 and JNK). In conclusion, GS-642362 was effective in suppressing both acute kidney injury and renal fibrosis. These findings support further investigation of cyclophilin blockade in other types of acute and chronic kidney disease.Copyright © 2020 by the authors.

Data about pregnancy outcomes for simultaneous pancreas-kidney transplant recipients (SPKR) are limited. We compared pregnancy outcomes in SPKR to Kidney Transplant Recipients (KTR) from 2001-17 using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and the Australian and New Zealand Pancreas Islet Transplant Registry (ANZPITR). A total of 19 pregnancies to 15 SPKR mothers, and 348 pregnancies to 235 KTR mothers were reported. Maternal ages were similar (SPKR 33.9 +/- 3.9 years; KTR 32.1 +/- 4.8 years, p =.10); however, SPKR had a shorter transplant to first-pregnancy interval compared to KTR (SPKR 3.3 years, IQR (1.7, 4.1); KTR 5 years, IQR (2.6, 8.7), p =.02). Median difference in creatinine pre- and post-pregnancy was similar between the groups (KTR -3 micromol/L, IQR (-15, 6), SPKR -3 micromol/L, IQR (-11, 3), p =.86). Maternal, fetal and kidney transplant outcomes were similar despite higher rates of pre-existing peripheral vascular and coronary artery diseases in SPKR. Live birth rates (>20 weeks) were comparable (SPKR 93.8% vs. KTR 96.8%, p =.06). KTR with either type 1 or type 2 diabetes mellitus (24 births) had similar outcomes compared to SPKR. In this national cohort, pregnancy outcomes were similar between SPKR and KTR mothers; however, findings should be interpreted with caution due to small sample sizes.Copyright © 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Aims: To review the Victorian increased viral risk donor (IVRD) program 22 months post-implementation. Background(s): IVRDs with at-risk behaviours for blood borne virus infection and negative nucleic acid testing (NAT) have a low absolute risk of window period infection but were historically under-utilised. A new system of allocation of these donors (defined by Public Health Service [PHS] 2013 criteria and open window periods) to pre-consented recipients was developed. Method(s): We retrospectively examined the characteristics of IVRDs (July 31 2018-May 31, 2020). Data for comparison with non-IVRDs was available for the first 7 months. Continuous data was expressed as median (IQR). Result(s): 40% of waitlisted recipients were pre-consented to accept IVRD kidneys. Thirty-two IVRDs (58 kidneys) were utilised, comprising 13.5% of all kidney donors. Only 9% of allocated IVRDs had neither kidney accepted. Injecting drug use (59%) was the commonest at-risk behaviour. NAT was performed 3 (2-4) days post-admission. 9 (28%) IVRDs had positive HCV Ab but negative NAT. 50% of recipients of these 9 IVRDs developed abnormal HCV serology, but no viraemia was detected in any IVRD recipients to date at 1 and 3 months post-transplantation. 3-month eGFR (CKD-EPI) was 65 (53-79) mL/min/1.73 m2. Compared with non-IVRDs, IVRDs were younger (37 (30-44) vs 51 (35-61) years; P < 0.01), with lower kidney donor profile index (KDPI) (26 (17-40) vs 59 (25-78); P < 0.001), and none had a KDPI >80% (0% vs 19%; P < 0.05). Waiting time was significantly shorter for blood group O IVRD vs non-IVRD recipients (26 (18-29) vs 38 (34-42) months; P = 0.001). Conclusion(s): IVRDs appear to offer better quality kidneys and may reduce waiting time with no transmission to date. Increasing the pre-consent rate may improve utilisation and benefit more waitlisted recipients.

The COVID-19 pandemic has challenged the delivery of health services. Telehealth allows delivery of care without in-person contacts and minimizes the risk of vial transmission. We aimed to describe the perspectives of kidney transplant recipients on the benefits, challenges, and risks of telehealth. We conducted five online focus groups with 34 kidney transplant recipients who had experienced a telehealth appointment. Transcripts were thematically analyzed. We identified five themes: minimizing burden (convenient and easy, efficiency of appointments, reducing exposure to risk, limiting work disruptions, and alleviating financial burden); attuning to individual context (depending on stability of health, respect patient choice of care, and ensuring a conducive environment); protecting personal connection and trust (requires established rapport with clinicians, hampering honest conversations, diminished attentiveness without incidental interactions, reassurance of follow-up, and missed opportunity to share lived experience); empowerment and readiness (increased responsibility for self-management, confidence in physical assessment, mental preparedness, and forced independence); navigating technical challenges (interrupted communication, new and daunting technologies, and cognizant of patient digital literacy). Telehealth is convenient and minimizes time, financial, and overall treatment burden. Telehealth should ideally be available after the pandemic, be provided by a trusted nephrologist and supported with resources to help patients prepare for appointments.Copyright © 2021 The Authors. Transplant International published by John Wiley & Sons Ltd on behalf of Steunstichting ESOT

Background: Donor characteristics help guide donor pancreas acceptance for solid pancreas-kidney transplantation; however, these criteria vary worldwide. Such variation could result in nonuse of potentially transplantable organs. Using a registry cohort, we identified donor characteristics associated with donor pancreas retrieval and subsequent solid pancreas transplantation in Australia and New Zealand. Method(s): Australia and New Zealand Organ Donor registry donor data from 2007 to 2016 were used to define cohort 1 (all donors authorized for pancreas retrieval) and cohort 2 (all retrieved donor pancreata considered for solid pancreas transplantation). Donor factors significantly associated with donor pancreas retrieval (cohort 1) and solid pancreas transplantation of retrieved donor pancreata (cohort 2) were determined via multivariable logistic regression. Result(s): Nonretrieval and nonuse of solid organ donor pancreas increased throughout the study period, and nonauthorization for pancreas donation remained stable. Donor body mass index, sex, and viral serology were associated with donor pancreas retrieval but not transplantation. Donor age, cause of death, donation after brain death status, terminal serum creatinine, and donor region were associated with both donor pancreas retrieval and acceptance for solid pancreas transplantation with donation after brain death status being the strongest predictor for both outcomes. Conclusion(s): Donor age, cause of death, donation after brain death status, terminal serum creatinine, and donor region were associated with both donor pancreas retrieval and subsequent transplantation in Australia and New Zealand. Subsequent correlation of these factors with post-pancreas transplant outcomes would help guide pancreas transplant decisions and minimize nonuse of potentially usable donor pancreata.Copyright © 2021 Elsevier Inc.

Background: Risk indices such as the pancreas donor risk index (PDRI) and pre-procurement pancreas allocation suitability score (P-PASS) are utilised in solid pancreas transplantation however no review has compared all derived and validated indices in this field. We systematically reviewed all risk indices in solid pancreas transplantation to compare their predictive ability for transplant outcomes. Method(s): Medline Plus, Embase and the Cochrane Library were searched for studies deriving and externally validating risk indices in solid pancreas transplantation for the outcomes of pancreas and patient survival and donor pancreas acceptance for transplantation. Results were analysed descriptively due to limited reporting of discrimination and calibration metrics required to assess model performance. Result(s): From 25 included studies, discrimination and calibration metrics were only reported in 88% and 38% of derivation studies (n = 8) and in 25% and 25% of external validation studies (n = 12) respectively. 21 risk indices were derived with mild to moderate ability to predict risk (C-statistics 0.52-0.78). Donor age, donor body mass index (BMI) and donor gender were the commonest covariates within derived risk indices. Only PDRI and P-PASS were subsequently externally validated, with variable association with post-transplant outcomes. P-PASS was not associated with pancreas graft survival. Conclusion(s): Most of the risk indices derived for use in solid pancreas transplantation were not externally validated (90%). PDRI and P-PASS are the only risk indices externally validated for solid pancreas transplantation, and when validated without reclassification measures, are associated with 1-year pancreas graft survival and donor pancreas acceptance respectively. Future risk indices incorporating recipient and other covariates alongside donor risk factors may have improved predictive ability for solid pancreas transplant outcomes.Copyright © 2021, The Author(s).

Aim: Careful assessment of the potential donor-recipient relationship is recommended by guidelines to prevent undue coercion, and to ensure realistic expectations and genuine motivations. However, relationships are complex, nuanced and value-laden, and can be challenging to evaluate in living kidney donation. We aimed to describe the attitudes and approaches of transplant clinicians towards assessing the relationship between potential living kidney donors and their recipients. Method(s): Semi-structured interviews were conducted with 54 transplant clinicians (nephrologists, surgeons, coordinators, social workers, psychiatrists and psychologists) from 32 transplant centres across nine countries including Australia, United States, Canada and New Zealand. Transcripts were analyzed thematically. Result(s): Four themes were identified: protecting against vulnerability and premature decisions (ensuring genuine motivation, uncovering precarious dynamics and pre-empting conflict, shared accountability, relying on specialty psychosocial expertise, trusting intimate bonds, tempering emotional impulsivity); safeguarding against coercion (discerning power imbalance, justified inquiry, awareness of impression management); minimizing potential threat to relationships (preserving the bond, giving equitable attention to donors and recipients, ensuring realistic expectations); and ambiguities in making judgments (adjudicating appropriateness and authenticity of relationships, questioning professional intervening, uncertainties in subjective and emotional assessments). Conclusion(s): Clinicians felt ethically compelled to minimize the risk of undue coercion and to protect donors and recipients when evaluating the donor-recipient relationship. However, disentangling voluntariness and altruism from potential undisclosed pressures to enact societal and family duty, making decisions within this complex, multi-stakeholder context, and avoiding the imposition of undue paternalism and donor

UNLABELLED: Increased viral risk donors (IVRDs) with increased risk behaviors for blood-borne virus infection and negative nucleic acid testing have a low absolute risk of "window period" infection. Utilization and allocation of IVRD organs differ between jurisdictions. METHODS: We examined the characteristics and utilization of deceased donor IVRD kidneys and recipient outcomes within a 2-y period (July 31, 2018-July 31, 2020) postimplementation of a new opt-in allocation pathway for preconsented recipients in Victoria, Australia. RESULTS: Fifty-six kidneys from 31 IVRDs were utilized, comprising 13% of donors. Preconsent rate to accept IVRD kidneys increased to 41% of the waitlist in the 2 y postimplementation, and IVRDs having no kidneys utilized reduced to 0%. Compared with non-IVRD kidneys, kidney offer declines >10 per donor were less likely from IVRDs (3% vs 19%; P < 0.05). IVRDs were younger (median age 36 [IQR 30-44] vs 51 [35-60] y; P < 0.0001), with lower kidney donor profile index (25% [13-40%] vs 57% [29-75%]; P < 0.0001), and less hypertension (0% vs 22%; P < 0.01). Estimated glomerular filtration rate 3 mo post-transplant was superior (P < 0.01). Injecting drug use (61%) was the most common increased risk behavior. 29% of IVRDs were hepatitis C antibody positive but nucleic acid testing negative. No active infection was detected in any recipient post-transplant. CONCLUSIONS: The described opt-in system permits efficient allocation and utilization of kidneys from IVRDs, with superior quality and graft function. Education is crucial to facilitate informed consent and equity of access to this donor pool.

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHODS: In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin: creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULTS: Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin: creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSIONS: In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment with a

Background. Data regarding the long-term efficacy of everolimus-based immunosuppression for kidney transplantation are lacking. Existing randomized controlled trials are limited by short follow-up duration which limits capacity to assess impact on graft and patient survival. Methods. We linked individual trial participants to the Australian and New Zealand Dialysis and Transplant Registry. Using a 1-step meta-analysis approach, we investigated the 10-year risk of graft loss, mortality and graft function in 349 participants from 5 randomized trials of everolimus-based immunosuppression. Results. Two hundred forty-two patients randomized to everolimus and 107 control patients were followed for a median of 9 years (interquartile range, 7.1, 9.8 y). There were no significant differences in the risk of all-cause graft loss (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 0.69-1.94), mortality (adjusted HR, 1.51; 95% CI, 0.78-2.93) and death-censored graft loss in everolimus versus control (adjusted HR, 1.00; 95% CI, 0.50-2.01). For patients in the early initiation (de novo or <6-month conversion) everolimus trials (n = 279), decline in estimated glomerular filtration rate did not significantly differ with control (mean difference in the slope of estimated glomerular filtrate rate, 0.01 mL/min per 1.73 m2 [-0.06 to +0.09]). Conclusions. This registry-based analysis with long-term follow-up found no differences in graft and recipient survival or graft function for everolimus over current standard of care.Copyright © 2020 Lippincott Williams and Wilkins. All rights reserved.

Cyclophilin A (CypA) is a highly abundant protein in the cytoplasm of most mammalian cells. Beyond its homeostatic role in protein folding, CypA is a Damage-Associated Molecular Pattern which can promote inflammation during tissue injury. However, the role of CypA in kidney disease is largely unknown. This study investigates the contribution of CypA in two different types of kidney injury: acute tubular necrosis and progressive interstitial fibrosis. CypA (Ppia) gene deficient and wild type (WT) littermate controls underwent bilateral renal ischaemia/reperfusion injury (IRI) and were killed 24h later or underwent left unilateral ureteric obstruction (UUO) and were killed 7 days later. In the IRI model, CypA-/- mice showed substantial protection against the loss of renal function and from tubular cell damage and death. This was attributed to a significant reduction in neutrophil and macrophage infiltration since CypA-/- tubular cells were not protected from oxidant-induced cell death in vitro. In the UUO model, CypA-/- mice were not protected from leukocyte infiltration or renal interstitial fibrosis. In conclusion, CypA promotes inflammation and acute kidney injury in renal IRI, but does not contribute to inflammation or interstitial fibrosis in a model of progressive kidney fibrosis.Copyright © 2020 by the authors. Licensee MDPI, Basel, Switzerland.

Background: Cyclophilin D (CypD) facilitates mitochondrial-dependant cell death during pathological conditions. CypD-/-mice are protected from acute kidney injury (AKI) following ischaemia/reperfusion injury and show reduced renal fibrosis in the unilateral ureteric obstruction model. However, the contribution of CypD in aristolochic acid (AA) induced AKI or AA-induced chronic kidney disease (CKD) is unknown. We aim to determine the role of CypD in: 1) acute AA-induced nephropathy (AAN); and 2) chronic AAN. Method(s): Groups (n=10) of CypD-/-and wild type (WT) C57BL/6J mice were used. Study 1: Mice were given an intraperitoneal (IP) injection of 5mg/kg AA and killed 3 days later. Study 2: Mice were given IP injections of 2mg/kg AA every 2nd day and killed on day 28. Controls were untreated. Result(s): Study 1: Acute high dose AA caused renal failure in WT mice (39.7+/-7.1mmol/L vs 13.5+/-2.3mmol/L serum creatinine (SCr) in controls; P<0.0001) with evidence of tubular damage and cell death on PAS sections and increased cleaved caspase-3+ cells. Acute AAN also caused inflammation with infiltrating neutrophils and T cells and up-regulation of IL-36a mRNA levels. CypD-/-mice were protected from AA-induced acute renal dysfunction (18.9+/-9.5 mmol/L SCr; P<0.0001 vs WT AAN). CypD-/-mice showed reduced tubular damage and cell death on PAS and reduced cleaved caspase-3+ cells (both P<0.001 vs WT AAN), as well as reduced neutrophil infiltration and IL-36alpha mRNA levels (both P<0.001 vs WT AAN). Study 2: Chronic AA administration caused renal impairment in WT mice (34.3+/-9.9mmol/L SCr), with evidence of chronic tubular damage (KIM-1 & a-Klotho mRNA levels), increase in tubular cell death (cleaved caspase-3+ cells), and significant renal fibrosis (increased collagen IV deposition). However, CypD-/-mice were not protected from chronic AA-induced renal dysfunction (37.0+/-14.3 mmol/L SCr; P=NS) and showed no reduction in tubular damage, cell death or renal fibrosis. Conclusio

Many countries have suspended kidney transplantation programmes 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 programmes due to COVID-19. We conducted seven online focus groups involving 31 adult kidney transplant candidates (n = 22), caregivers (n = 4) and potential donors (n = 5). Transcripts were analysed thematically. 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 health care, 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). During the suspension of kidney transplantation programmes, 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 programmes.Copyright © 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd

Background: Cyclophilins are a family of enzymes which regulate protein folding. Of these enzymes, cyclophilin D (CypD) facilitates mitochondrial-dependant cell death during pathological conditions. CypD-/-mice are protected from acute kidney injury (AKI) following renal ischaemia/reperfusion injury, and exhibit less renal fibrosis in the unilateral ureteric obstruction model. However, the contribution of CypD in the transition of AKI to chronic kidney disease (CKD) is not known. The aim of this study was to determine the role of CypD in promoting the transition of AKI to CKD using the aristolochic acid-induced nephropathy (AAN) model. Method(s): Groups (n=10) of wild type (WT) and CypD-/-mice on the C57BL/6J background were given intraperitoneal injections of 2mg/kg aristolochic acid every 2nd day for 28 days. Mice were killed on day 28. Controls were untreated. Result(s): AAN caused >2.5-fold rise in serum creatinine (sCr) in WT mice (34.3+/-9.9mmol/L vs 13.5+/-2.3mmol/L in controls; P<0.0001), with evidence of tubular damage (KIM-1 & alpha-Klotho mRNA levels; P<0.0001), increase in tubular cell death (cleaved caspase-3+ cells; P<0.0001), and significant renal fibrosis (collagen IV immunostaining, and collagen I & alpha-SMA mRNA levels; all P<0.0001 vs controls). CypD-/-mice were not protected from AA-induced renal dysfunction (sCr 37.0+/-14.3 mmol/L; P=N.S.), and showed no reduction in tubular damage, cell death or renal fibrosis. Further analysis showed that AAN in WT mice caused loss of peritubular CD31+ capillaries (P<0.0001), and infiltration of macrophages (CD68 & CD206 mRNA levels; P<0.0001) and T-cells (CD3 & IL-2 mRNA levels; P<0.0001). CypD-/-mice were not protected from peritubular capillary loss or macrophage infiltration in AAN. However, CypD-/-mice showed reduced T-cell infiltration and activation (CD3 & IL-2 mRNA levels; P<0.0001), including Th1 cells (T-bet mRNA levels; P<0.05). Conclusion(s): CypD does not contribute to the transition of AKI to CK

BACKGROUND: Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease who are at risk for progression is not known. METHOD(S): In this randomized, controlled trial, we randomly assigned adults with stage 3 or 4 chronic kidney disease and no history of gout who had a urinary albumin: creatinine ratio of 265 or higher (with albumin measured in milligrams and creatinine in grams) or an eGFR decrease of at least 3.0 ml per minute per 1.73 m2 of body-surface area in the preceding year to receive allopurinol (100 to 300 mg daily) or placebo. The primary outcome was the change in eGFR from randomization to week 104, calculated with the Chronic Kidney Disease Epidemiology Collaboration creatinine equation. RESULT(S): Enrollment was stopped because of slow recruitment after 369 of 620 intended patients were randomly assigned to receive allopurinol (185 patients) or placebo (184 patients). Three patients per group withdrew immediately after randomization. The remaining 363 patients (mean eGFR, 31.7 ml per minute per 1.73 m2; median urine albumin: creatinine ratio, 716.9; mean serum urate level, 8.2 mg per deciliter) were included in the assessment of the primary outcome. The change in eGFR did not differ significantly between the allopurinol group and the placebo group (-3.33 ml per minute per 1.73 m2 per year [95% confidence interval {CI}, -4.11 to -2.55] and -3.23 ml per minute per 1.73 m2 per year [95% CI, -3.98 to -2.47], respectively; mean difference, -0.10 ml per minute per 1.73 m2 per year [95% CI, -1.18 to 0.97]; P = 0.85). Serious adverse events were reported in 84 of 182 patients (46%) in the allopurinol group and in 79 of 181 patients (44%) in the placebo group. CONCLUSION(S): In patients with chronic kidney disease and a high risk of progression, urate-lowering treatment

Introduction: Increased viral risk donors (IVRDs) with at-risk behaviours for blood borne virus infection and negative nucleic acid testing (NAT) have a low absolute risk of window period infection. A program allocating these kidneys to pre-consented recipients was recently implemented in the state of Victoria, Australia. We reviewed the performance after twelve months in operation. Material(s) and Method(s): We retrospectively examined the characteristics of IVRDs (defined by Public Health Service (PHS) 2013 criteria and open window periods) (31/07/2018-31/07/2019). Data for comparison with non-IVRDs was available for the first 7 months. Kidney function, serological and NAT results of recipients at 1 and 3 months post-transplantation were analysed. Continuous data was expressed as median (IQR). Results and Discussion: 33% of waitlisted patients were pre-consented at 12 months post-implementation, increasing from 24% at 7 months. Sixteen IVRDs (28 kidneys) were utilised, comprising 12.6% of all utilised kidney donors. Risk factors included people who inject drugs (57%), increased risk sexual behaviour (31%), imprisonment (6%) and multiple risk factors (6%). NAT was performed 3.0 (1.0-4.3) days after admission. Four IVRDs had abnormal serology results (3 HCV Ab positive, 1 HBcAb and HCV Ab positive) but negative NAT. All recipients but one of HCV Ab positive IVRDs seroconverted, but no viraemia was detected in recipients from all IVRDs to date. Adherence to post-transplant surveillance testing in recipients was 85%. eGFR (CKD-EPI) was 67 (54-77) and 68 (53-81) mL/min/1.73m2 at 1 and 3 months post-transplantation. Compared with non-IVRDs, IVRDs were significantly younger (36 (28-43) versus 53 (36-61) years; P<0.01). Kidney donor profile index (KDPI) was significantly lower (21 (10-39) versus 62 (27-77); P<0.01), more likely <=20 (50% versus 18%; P<0.05) and none had a KDPI >85 (0% versus 12%; P=0.35). Waiting time was significantly shorter for blood group O recipients

Background: Cyclophilins are enzymes that regulate protein folding. During various pathological conditions, cyclophilin A (CypA) has been shown to promote leukocyte recruitment and inflammation. However, the contribution of CypA in acute kidney injury (AKI) and renal fibrosis is poorly understood. The aim of this study was to determine the role of CypA in renal tubular damage, inflammation, and fibrosis using the: (1) renal ischaemia/reperfusion injury (IRI), and (2) unilateral ureteric obstruction (UUO) models. Method(s): Groups (n=10) of wild type (WT) and CypA-/-mice on the 129 background were subjected to either: (1) bilateral renal IRI (19min at 37degreeC) and killed 24 hours post reperfusion, or (2) UUO surgery and killed on day 7. Controls were sham operated. Result(s): Renal IRI induced AKI with a >6-fold rise in serum creatinine (sCr) in WT mice (41+/-13.8 vs 6.3+/-1.7umol/L in sham; P<0.0001) and marked tubular damage based on the tubular injury score, increased KIM-1 mRNA levels, and tubular cell death (TUNEL+ cells; all P<0.0001 vs sham). CypA-/-mice were protected from renal dysfunction with a 50% improvement of sCr (20.7+/-3.5umol/L; P<0.0001), less histologic tubular damage (P<0.01), lower KIM-1 mRNA levels (P<0.01), and less tubular cell death (P<0.001). Renal IRI caused upregulated mRNA levels of inflammatory molecules (TNF-alpha and IL-36-alpha; P<0.05), and neutrophil infiltration (Ly6G+ cells; P<0.0001). CypA-/-mice had a clear reduction in inflammatory molecules (P<0.05) and less infiltrating neutrophils (P<0.001). UUO in WT mice resulted in significant renal fibrosis (3-fold increase in collagen IV deposition by immunostaining; P<0.001 vs sham), with significant infiltrates of macrophages (F4/80+ cells), T cells (CD3+ cells) and neutrophils (Ly6G+ cells) (all P<0.0001 vs sham). CypA-/-mice were not protected from renal fibrosis or leukocyte infiltration in the UUO model. Conclusion(s): CypA contributes to leukocyte infiltration and inflammation

Over the last decade, organ donation and transplantation rates have increased in Australia and worldwide. Donor and recipient characteristics for most organ types have generally broadened, resulting in the need to consider more complex data in transplant decision-making. As a result of some of these pressures, the Australian software used for donor and recipient data management is currently being updated. Because of the in-built capacity for improved data management, organ allocation processes will have the opportunity to be significantly reviewed, in particular the possible use of risk indices (RIs) to guide organ allocation and transplantation decisions. We aimed to review RIs used in organ allocation policies worldwide and to compare their use to current Australian protocols. Significant donor, recipient, and transplant variables in the indices were summarized. We conclude that Australia has the opportunity to incorporate greater use of RIs in its allocation policies and in transplant decision-making processes. However, while RIs can assist with organ allocation and help guide prognosis, they often have significant limitations which need to be properly appreciated when deciding how to best use them to guide clinical decisions.Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.

Background: Risk indices (RI) using donor and recipient characteristics assist in organ allocation and acceptance decisions by predicting post-transplant outcomes such as graft and patient survival. While RI have been derived for use in pancreas transplantation (PTx), they are not widely utilised. We intend to review the ability of available RI to predict PTx outcomes. Method(s): Medline Plus, Embase via OVID and the Cochrane Library were searched for studies describing derivation or use of RI in PTx up to 1st November 2017. Primary outcomes of interest were pancreas graft and patient survival, with secondary outcomes of organ acceptance. Data extraction was performed using the Checklist for Critical Appraisal and data extraction for Systematic Reviews of Prediction Modelling Studies (CHARMS) and risk of bias assessment was done via the Quality in Prognostic Studies (QUIPS) tool. Result(s): 2418 abstracts were screened with 32 studies entering full-text analysis. Of these 32 studies, 8 were abstracts with no full-text retrievable despite contacting authors. 10/32 studies derived 23 models predicting outcomes of interest. 2/23 models were RI that were externally validated in 24/32 studies. 21/23 models were derived without external validation. RI were the pancreas donor risk index (PDRI) and the pancreas pre-procurement score (P-PASS). Apart from their covariates, common covariates in other models included recipient age and body mass index (BMI), dialysis duration pre-transplant, history of diabetes, transplant type, and immunosuppression regimen. Risk of bias was generally low in the studies with model derivation. Conversely, abstracts tended to have high risk of bias. Deficiencies in reporting included handling of missing data, covariates and follow-up duration. Discrimination and calibration was only described in 10 and 2 studies respectively. Heterogeneity was present in model derivation method, outcome definitions and study results. PDRI was significantly associ

BACKGROUND: The US Kidney Donor Risk Index (KDRI) and the UK KDRI were developed to estimate the risk of graft failure following kidney transplantation. Neither score has been validated in the Australian and New Zealand (ANZ) population. METHOD(S): Using data from the Australia and New Zealand Organ Donor (ANZOD) and Dialysis and Transplant (ANZDATA) Registries, we included all adult deceased donor kidney-only transplants performed in ANZ from 2005 to 2016 (n=6405). The KDRI was calculated using both the US donor-only and UK formulae. Three Cox models were constructed (Model 1: KDRI only; Model 2: Model 1+transplant characteristics; Model 3: Model 2+recipient characteristics) and compared using Harrell's C-statistics for the outcomes of death-censored graft survival and overall graft survival. RESULT(S): Both scores were strongly associated with death-censored and overall graft survival (P<0.0001 in all models). In the KDRI-only models, discrimination of death-censored graft survival was moderately good with C-statistics of 0.63 and 0.59 for the US and UK scores, respectively. Adjusting for transplant characteristics resulted in marginal improvements of the US KDRI to 0.65 and the UK KDRI to 0.63. The addition of recipient characteristics again resulted in marginal improvements of the US KDRI to 0.70 and the UK KDRI to 0.68. Similar trends were seen for the discrimination of overall graft survival. CONCLUSION(S): The US and UK KDRI scores were moderately good at discriminating death-censored and overall graft survival in the ANZ population, with the US score performing slightly better in all models.Copyright © The Author(s) 2019. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.

In 2016, Australia began reporting the Kidney Donor Performance Index (KDPI) with all deceased donor kidney transplant offers despite this not being used in organ allocation rules, offering a unique opportunity to explore the "labeling effect" of KDPI reporting. We reviewed all kidneys retrieved for transplant in Australia from 2015 to 2018 and analyzed the association of KDPI reporting with organ nonutilization, number of offer declines, and donor/recipient age and longevity matching. Analyses were stratified by organ failure risk: higher risk (KDPI > 80%), standard risk (KDPI 20% to 79%), and lower risk (KDPI 0% to 20%). There was no significant difference in organ nonutilization post KDPI reporting either overall or for higher-risk kidneys. KDPI reporting was associated with an increase in offer declines for both higher-risk (incidence risk ratio 1.45, P = .007) and standard-risk (incidence risk ratio 1.22, P = .021) kidneys but not for lower-risk organs. There was a significant increase in recipient age and expected posttransplant survival score for higher-risk kidneys but no differences among other groups. We conclude that although KDPI reporting in Australia has been associated with an increased number of offer declines for higher-risk kidneys, this has not resulted in increased nonutilization and may have contributed to more appropriate use of these organs.

The demand for kidney transplantation continues to exceed the availability of deceased donor kidneys. Balancing the overarching principles of the optimal use of (utility) and equal access to (equity) this scarce resource requires a sophisticated allocation system. This review will examine how various factors are addressed in allocation systems around the world to strike a balance between utility and equity.Copyright © 2018 Asian Pacific Society of Nephrology

Purpose: The aim of this study was to determine if measurement of B cell protective immunity was associated with susceptibility to sinopulmonary infection in kidney transplant recipients. Methods and Materials: A prospective cohort of 168 patients with stable graft function (median 4.1 years) underwent assessment of B-lymphocyte antigen CD19 (CD19+) cell number, immunoglobulin G concentration, and seroresponses to influenza vaccination upon study entry. Patients received a single dose of a trivalent, seasonal influenza vaccine. Result(s): After 2 years follow-up, 31 patients (18%) developed sinopulmonary infection. CD19+ cell number was strongly associated with future sinopulmonary infection. A higher proportion of patients with CD19+ cell counts below the fifth percentile for controls developed sinopulmonary infections than those above the fifth percentile, 30% (23 of 77 patients) compared with 9% (7 of 79 patients; P =.001). There was a trend toward a higher proportion of patients with reduced immunoglobulin G concentrations developing infections than in the normal range for controls, 29% (14 of 48 patients) compared with 15% (16 of 108 patients; P =.060). Influenza vaccination seroresponses were poor in patients and controls such that they could not be used to identify a subgroup of patients at high risk for the development of severe pulmonary infection. Conclusion(s): Monitoring B-cell numbers represents a simple, inexpensive means of stratifying transplant recipients' risk of sinopulmonary infection.Copyright © 2018 Elsevier Inc.

Graft-derived cell-free DNA (donor-derived cell-free DNA) is an emerging marker of kidney allograft injury. Studies examining the clinical validity of this biomarker have previously used the graft fraction, or proportion of total cell-free DNA that is graft-derived. The present study evaluated the diagnostic validity of absolute measurements of graft-derived cell-free DNA, as well as calculated graft fraction, for the diagnosis of graft dysfunction. Plasma graft-derived cell-free DNA, total cell-free DNA, and graft fraction were correlated with biopsy diagnosis as well as individual Banff scores. Sixty-one samples were included in the analysis. For the diagnosis of antibody mediated rejection, the receiver-operator characteristic area under the curves of graft-derived cell-free DNA and graft fraction were 0.91 (95% CI 0.82-0.98) and 0.89 (95% CI 0.79-0.98), respectively. Both measures did not diagnose borderline or type 1A cellular mediated rejection. Graft fraction was associated with a broader range of Banff lesions, including lesions associated with cellular mediated rejection, while graft-derived cell-free DNA appeared more specific for antibody mediated rejection. Limitations of this study include a small sample size and lack of a validation cohort. The capacity for absolute quantification, and lower barriers to implementation of this methodology recommend it for further study.Copyright © 2018 The American Society of Transplantation and the American Society of Transplant Surgeons

In 2016, Australia began reporting the Kidney Donor Performance Index (KDPI) with all deceased donor kidney transplant offers despite this not being used in organ allocation rules, offering a unique opportunity to explore the "labeling effect" of KDPI reporting. We reviewed all kidneys retrieved for transplant in Australia from 2015 to 2018 and analyzed the association of KDPI reporting with organ nonutilization, number of offer declines, and donor/recipient age and longevity matching. Analyses were stratified by organ failure risk: higher risk (KDPI > 80%), standard risk (KDPI 20% to 79%), and lower risk (KDPI 0% to 20%). There was no significant difference in organ nonutilization post KDPI reporting either overall or for higher-risk kidneys. KDPI reporting was associated with an increase in offer declines for both higher-risk (incidence risk ratio 1.45, P =.007) and standard-risk (incidence risk ratio 1.22, P =.021) kidneys but not for lower-risk organs. There was a significant increase in recipient age and expected posttransplant survival score for higher-risk kidneys but no differences among other groups. We conclude that although KDPI reporting in Australia has been associated with an increased number of offer declines for higher-risk kidneys, this has not resulted in increased nonutilization and may have contributed to more appropriate use of these organs.Copyright © 2019 The American Society of Transplantation and the American Society of Transplant Surgeons

Background: The aim of this study was to determine whether a composite score of simple immune biomarkers and clinical characteristics could predict severe infections in kidney transplant recipients. Method(s): We conducted a prospective study of 168 stable kidney transplant recipients who underwent measurement of lymphocyte subsets, immunoglobulins, and renal function at baseline and were followed up for 2 years for the development of any severe infections, defined as infection requiring hospitalization. A point score was developed to predict severe infection based on logistic regression analysis of factors in baseline testing. Result(s): Fifty-nine (35%) patients developed severe infection, 36 (21%) had two or more severe infections, and 3 (2%) died of infection. A group of 19 (11%) patients had the highest predicted infectious risk (>60%), as predicted by the score. Predictive variables were mycophenolate use, graft function, CD4+, and natural killer cell number. The level of immunosuppression score had an area under the receiver operating curve of 0.75 (95% CI: 0.67-0.83). Conclusion(s): Our level of immunosuppression score for predicting the development of severe infection over 2 years has sufficient prognostic accuracy for identification of high-risk patients. This data can inform research that examines strategies to reduce the risks of infection.Copyright © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd