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Abstract Background Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. Methods U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. Results Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41–58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. Conclusions Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. Trial registration Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Abstract Background Modulating 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. Methods Sixty 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. Discussion This 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 registration Australian 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 .

Abstract Background Estimation of GFR (eGFR) using formulae based on serum creatinine concentrations are commonly used to assess kidney function. Physical exercise can increase creatinine turnover and lean mass; therefore, this method may not be suitable for use in exercising individuals. Cystatin-C based eGFR formulae may be a more accurate measure of kidney function when examining the impact of exercise on kidney function. The aim of this study was to assess the agreement of four creatinine and cystatin-C based estimates of GFR before and after a 12-month exercise intervention. Methods One hundred forty-two participants with stage 3–4 chronic kidney disease (CKD) (eGFR 25–60 mL/min/1.73 m2) were included. Subjects were randomised to either a Control group (standard nephrological care [n = 68]) or a Lifestyle Intervention group (12 months of primarily aerobic based exercise training [n = 74]). Four eGFR formulae were compared at baseline and after 12 months: 1) MDRDcr, 2) CKD-EPIcr, 3) CKD-EPIcys and 4) CKD-EPIcr-cys. Results Control participants were aged 63.5[9.4] years, 60.3% were male, 42.2% had diabetes, and had an eGFR of 40.5 ± 8.9 ml/min/1.73m2. Lifestyle Intervention participants were aged 60.5[14.2] years, 59.5% were male, 43.8% had diabetes, and had an eGFR of 38.9 ± 8.5 ml/min/1.73m2. There were no significant baseline differences between the two groups. Lean mass (r = 0.319, p

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.

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.

Abstract 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.

Background. Kidney transplant recipients (KTRs) receiving the mammalian target of rapamycin inhibitor sirolimus may display a reduced risk of skin cancer development compared to KTRs receiving calcineurin inhibitors. Despite studies investigating the effects of these 2 drug classes on T cells in patient blood, the effect these drugs may have in patient skin is not yet known. Methods. Fifteen patients with chronic kidney disease (not recipients of immunosuppressive drugs), and 30 KTRs (15 receiving a calcineurin inhibitor, and 15 receiving sirolimus) provided matched samples of blood, sun exposed (SE) and non-SE skin. The abundance of total CD8+ and CD4+ T cells, memory CD8+ and CD4+ T cells, and regulatory T (Treg) cells in each sample was then assessed by flow cytometry. Results. Sirolimus treatment significantly increased absolute numbers of CD4+ T cells, memory CD8+- and CD4+ T cells, and Treg cells in SE skin versus paired samples of non-SE skin. No differences were found in the absolute number of any T cell subset in the blood. Correlation analysis revealed that the percentage of T cell subsets in the blood does not always accurately reflect the percentage of T-cell subsets in the skin of KTRs. Furthermore, sirolimus significantly disrupts the balance of memory CD4+ T cells in the skin after chronic sun exposure. Conclusions. This study demonstrated that immunosuppressive drug class and sun exposure modify the abundance of multiple T-cell subsets in the skin of KTRs. Correlation analysis revealed that the prevalence of Treg cells in KTR blood does not accurately reflect the prevalence of Treg cells in KTR skin.

The incidence of BK virus infection in kidney transplant recipients has increased over recent decades, coincident with the use of more potent immunosuppression. More importantly, posttransplant BK virus replication has emerged as an important cause of graft damage and subsequent graft loss. Immunosuppression has been accepted as a major risk for BK virus replication. However, the specific contribution of individual immunosuppressive medications to this risk has not been well established. The purpose of this paper is to provide an overview of the recent literature on the influence of the various immunosuppressant drugs and drug combinations on posttransplant BK virus replication. Evidence supporting the various immunosuppression reduction strategies utilised in the management of BK virus will also be briefly discussed.

Background. The aim of the present study was to determine whether the deceased donor kidney side (left or right kidney) was predictive of subsequent kidney transplant outcomes.Methods. A retrospective analysis was undertaken of the left–right deceased donor kidney pairs transplanted into recipients with end-stage renal failure in Queensland between 1 April 1994 and 31 March 2004.Results. A total of 201 left–right deceased donor kidney pairs were transplanted into 402 patients. The baseline characteristics of the recipients in the two groups were comparable, except that the patients receiving right kidneys had lower body mass indices and shorter cold ischaemic times. No differences were seen between the left and right kidney recipient groups with respect to operative duration (3.02 ± 0.67 vs 3.12 ± 0.72 h, P = 0.16), warm ischaemic time (0.62 ± 0.18 vs 0.65 ± 0.21, P = 0.09), delayed graft function (4 vs 6%, respectively, P = 0.26) or a composite vascular, haemorrhagic, ureteric and infective post-operative complication end-point (22 vs 22%, P = 0.90). Estimated glomerular filtration rates were almost identical at 1 month (52.7 ± 39.6 vs 51.0 ± 24.0 ml/min/1.73 m2, P = 0.34) and remained comparable thereafter. Respective death-censored graft survival rates for left and right kidney recipients were 100 and 100% at 1 year, 99.4 and 96.4% at 3 years and 96.3 and 95.5% at 5 years, respectively (P = 0.67).Conclusions. Although left and right deceased donor kidneys present different operative challenges, the present results suggest that the probability of early post-operative complications, delayed graft function, impaired early and medium-term renal allograft function or death-censored graft failure is comparable between left and right kidney recipients. [ABSTRACT FROM AUTHOR]

Background. Cardiovascular disease is the major cause of death in the end-stage renal disease population. Novel risk factors such as homocysteine (Hcy) are of considerable interest in this group as hyperhomocysteinaemia is highly prevalent in the setting of renal impairment. Folic acid–vitamin B group therapies are only partially effective treatments. Hcy is highly protein-bound and thus poorly dialysed. Dialyzers with albumin-leaking properties have been shown to result in lowering of plasma Hcy. As the FX-class (Advanced Fresenius Polysulfone dialyzer) has greater clearance of larger molecular weight substances but is non-albumin-leaking, we explored the capacity of this new technology membrane to reduce plasma Hcy levels.Methods. A prospective randomized cross-over trial in 35 prevalent haemodialysis patients, one group receiving 12 weeks dialysis using FX dialyzer then 12 weeks with standard high flux dialysis (SHF) and the other group SHF followed by FX dialyzer. All patients received vitamin B6 25 mg and folic acid 5 mg daily throughout the study.Results. The primary outcome was plasma Hcy pre-dialysis at week 12. FX vs SHF showed no significant difference, 25±6.6 vs 25.9±5.8 µg/l, Δ95% CI = −2.77 to 4.59, P = 0.31. There was a non-significant trend toward a decrease in Hcy in both groups (27.43±7.68 to 25.91±5.78 µmol/l for SHF, P = 0.23 and 26.0±4.58 to 25.0±6.61 µmol/l for FX, P = 0.28). Analysis by repeated measures method demonstrated a statistically significantly lower Hcy with FX vs SHF dialyzer (adjusted β = −1.30, 95% CI = −2.41 to −0.19, P = 0.022). Kt/Vurea was higher in FX vs SHF (1.35±0.18 vs 1.22±0.2; P = 0.013). Folate and B6 levels did not change.Conclusions. The primary outcome analysis did not show any significant difference in pre-Hcy comparing FX and SHF membranes. Although our secondary analysis demonstrated a statistically significant difference between membranes, the magnitude of the difference (1.3 μmol/l) is not clinically significant. Thus the use of the FX dialyzer did not result in a clinically significant benefit in relation to improving pre-dialysis Hcy compared with standard high-flux dialysis. [ABSTRACT FROM AUTHOR]

Objective. Cardiac events (CE; cardiac death, non-fatal myocardial infarction and acute coronary syndrome) are the principal causes of death in patients with chronic kidney disease (CKD). We sought to devise and validate a cardiac risk score to risk-stratify patients with CKD.Methods. Clinical history and biochemical data were obtained in 167 CKD patients. CE were recorded over a median follow-up of 22 months. The hazard ratio (HR) of each independent variable using Cox regression analysis was used to derive a cardiac risk score for the prediction of events. The cardiac risk score was then applied to a validation population of 99 CKD patients to confirm its validity in predicting CE.Results. CE occurred in 20 patients in the derivation group. The independent predictors of CE were cardiac history (HR 9.83, P = 0.001), body mass index (BMI; HR 1.15, P = 0.002), dialysis duration (HR 1.24, P = 0.004) and serum phosphate (HR 4.29, P = 0.001). The resulting cardiac risk score (range 26–67) gave an area under the receiver operating characteristic curve of 0.86. CE occurred in 25 patients in the validation group; the ROC curve area was similar (0.84, P = 0.11). An optimal cardiac risk score cut-off of 50 assigned high risk to 29% of the derivation and 35% of the validation group (P = 0.26). CE occurred in 35 and 57% of the high-risk derivation and validation groups, respectively (P = 0.09), and in 2 and 8% of the low-risk groups (P = 0.15).Conclusion. Application of a cardiac risk score using cardiac history, dialysis duration, BMI and phosphate identifies CKD patients at risk of future CE. [ABSTRACT FROM AUTHOR]

Objective The acceptability of being offered a choice from a suite of digital health service options to support optimal diet and exercise behaviors in adults with complex chronic conditions was evaluated. This study sought to understand many areas of acceptability including satisfaction, ease of use, usefulness and user appropriateness and perceived effectiveness. Methods This mixed-methods study was embedded within a randomized-controlled feasibility trial providing digital health services managing diet and exercise for adults from specialist kidney and liver disease clinics. Post study surveys and semistructured interviews were used to determine patients’ acceptability of the trial interventions. Quantitative (surveys) and qualitative (surveys and interviews) results were merged using integrative analysis and mapped to each construct of the modified version of the Theoretical Framework of Acceptability. Results Seventeen interviews (intervention group) and 50 surveys ( n = 24 intervention, n = 26 comparator) completed from a possible 67 participants were analyzed. In the intervention group, the survey results revealed high areas of acceptability for the digital health services including overall support received, ease of use, timely advice and feeling safe. The interviews also revealed high areas of acceptability including convenience, ability to adopt healthier behaviors and having regular interactions with health professionals. However, the interviews also revealed lower areas of acceptability as a result of absence of individualization, low digital literacy, and limitations from life circumstances. Conclusions Recipients of digital health services that supported diet and exercise interventions found these useful, effective, and safe. Individualized care, technical support and patient confidence remain important to improve the acceptability of digital health service interventions.

Background. Serum creatinine concentration is an unreliable and insensitive marker of chronic kidney disease (CKD). To improve CKD detection, the Australasian Creatinine Consensus Working Committee recommended reporting of estimated glomerular filtration rate (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD) formula with every request for serum creatinine concentration. The aim of this study was to evaluate the impact of automated laboratory reporting of eGFR on the quantity and quality of referrals to nephrology services in Southeast Queensland, Australia. Methods. Outpatient referrals to a tertiary and regional renal service, and a single private practice were prospectively audited over 3–12 months prior to and 12 months following the introduction of automated eGFR reporting and concomitant clinician education. The appropriateness of referrals to a nephrologist was assessed according to the Kidney Check Australia Taskforce (KCAT) criteria. Significant changes in the quantity and/or quality of referrals over time were analysed by exponentially weighed moving average (EWMA) charts with control limits based on ±3 standard deviations. Results. A total of 1019 patients were referred to the centres during the study period. Monthly referrals overall increased by 40% following the introduction of eGFR reporting, and this was most marked for the tertiary renal service (52% above baseline). The appropriateness of nephrologist referrals, as adjudicated by the KCAT criteria, fell significantly from 74.3% in the 3 months pre-eGFR reporting to 65.2% in the 12 months thereafter (P < 0.05). Nevertheless, a greater absolute number of CKD patients were appropriately being referred for nephrologist review in the post-eGFR period (24 versus 15 per month). Patients referred following the introduction of eGFR were significantly more likely to be older (median 63.2 versus 59.3 years, P < 0.05), diabetic (25 versus 18%, P = 0.05) and have stage 3 CKD (48% versus 36%, P < 0.01). Conclusion. The introduction of automated eGFR calculation has led to an overall increase in referrals with a small but significant decrease in referral quality. The increase in referrals was seen predominantly in older and diabetic patients with stage 3 CKD and appeared to result in net benefit. [ABSTRACT FROM AUTHOR]

BackgroundThe metabolic syndrome is common across many complex chronic disease groups. Advances in health technology have provided opportunities to support lifestyle interventions. ObjectiveThe purpose of this study is to test the feasibility of a health technology-assisted lifestyle intervention in a patient-led model of care. MethodsThe study is a single-center, 26-week, randomized controlled trial. The setting is specialist kidney and liver disease clinics at a large Australian tertiary hospital. The participants will be adults with a complex chronic condition who are referred for dietetic assessment and display at least one feature of the metabolic syndrome. All participants will receive an individualized assessment and advice on diet quality from a dietitian, a wearable activity monitor, and standard care. Participants randomized to the intervention group will receive access to a suite of health technologies from which to choose, including common base components (text messages) and optional components (online and mobile app–based nutrition information, an online home exercise program, and group-based videoconferencing). Exposure to the optional aspects of the intervention will be patient-led, with participants choosing their preferred level of engagement. The primary outcome will be the feasibility of delivering the program, determined by safety, recruitment rate, retention, exposure uptake, and telehealth adherence. Secondary outcomes will be clinical effectiveness, patient-led goal attainment, treatment fidelity, exposure demand, and participant perceptions. Primary outcome data will be assessed descriptively and secondary outcomes will be assessed using an analysis of covariance. This study will provide evidence on the feasibility of the intervention in a tertiary setting for patients with complex chronic disease exhibiting features of the metabolic syndrome. ResultsThe study was funded in 2019. Enrollment has commenced and is expected to be completed by June 2022. Data collection and follow up are expected to be completed by December 2022. Results from the analyses based on primary outcomes are expected to be submitted for publication by June 2023. ConclusionsThe study will test the implementation of a health technology–assisted lifestyle intervention in a tertiary outpatient setting for a diverse group of patients with complex chronic conditions. It is novel in that it embeds patient choice into intervention exposure and will inform health service decision-makers in regards to the feasibility of scale and spread of technology-assisted access to care for a broader reach of specialist services. Trial RegistrationAustralian New Zealand Clinical Trial Registry ACTRN12620001282976; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378337 International Registered Report Identifier (IRRID)DERR1-10.2196/37556

BackgroundThe 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 methodsThis 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.ResultsThe 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).ConclusionDonor AKI stage was not associated with any kidney transplant outcome, except DGF. Use of kidneys with AKI for transplantation appears to be justified.

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 this post hoc analysis 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.

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.

Echocardiographic global longitudinal strain (GLS) is increasingly recognised as a more effective technique than conventional ejection fraction (EF) in detecting subtle changes in left ventricular (LV) function. This study investigated the prognostic value of GLS over EF in patients with advanced Chronic Kidney Disease (CKD).The study included 183 patients (57% male, 63% on dialysis) with CKD stage 4, 5 and 5Dialysis (D). 112 (61%) of patients died in a follow up of 7.8 ± 4.4 years and 41% of deaths were due to cardiovascular (CV) disease. GLS was calculated using 2-dimensional speckle tracking and EF was measured using Simpson's biplane method. Cox proportional hazard models were used to assess the association of measures of LV function and all- cause and CV mortality.The mean GLS at baseline was -13.6 ± 4.3% and EF was 45 ± 11%. GLS was a significant predictor of all-cause [Hazard Ratio (HR) 1.09 95%; Confidence Interval (CI) 1.02-1.16; p = 0.01] and CV mortality (HR 1.16 95%; CI 1.04-1.30; p = 0.008) following adjustment for relevant clinical variables including LV mass index (LVMI) and EF. GLS also had greater predictive power for both all- cause and CV mortality compared to EF. Impaired GLS (>-16%) was associated with a 5.6-fold increased unadjusted risk of CV mortality in patients with preserved EF.In this cohort of patients with advanced CKD, GLS is a more sensitive predictor of overall and CV mortality compared to EF. Studies of larger populations in CKD are required to confirm that GLS provides additive prognostic value in patients with preserved EF.

Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of these differentially expressed probe-set lists is consistent with the originating tissue and their functional enrichment consistent with allograft rejection. Finally, we demonstrate that the strategy described here can be used to derive useful hypotheses by validating a cell type-specific ratio in an independent cohort using the nanoString nCounter assay.