Perioperative Care for Kidney Transplant Recipients

Transplantation carries significant mortality benefit compared to dialysis in end-stage kidney disease. Increased perioperative risk, however, results in a higher mortality in the first 3 months post-transplantation compared to remaining on haemodialysis. Consequently, optimal perioperative management is essential. Patients presenting for kidney transplantation require rapid assessment and preparation for theatre to minimise ischaemic times and improve mortality and graft outcomes. This task is often complicated by the presence of multiple medical comorbidities. Furthermore, early complications of hypotension, delayed graft function, renovascular and ureteric surgical complications and rejection render the perioperative phase of transplant challenging for the recipient and for the transplant team. In this chapter, we outline current practices in the assessment and management of kidney transplant recipients during the perioperative period, particularly focusing on their clinical application and the evidence underpinning them

Cardiovascular Disease in Dialysis Patients

Cardiovascular disease (CVD) is highly prevalent in the dialysis population, affecting up to 60% of cohorts. Cardiovascular mortality rates are reported to be ~14 per 100 patient-years, which are 10- to 20-fold greater than those of age- and gender-matched controls. CVD is the primary cause of death in up to 40% of dialysis patients in Australia, New Zealand and the United States. Dialysis patients endure a greater burden of both traditional risk factors for CVD and risk factors related to loss of kidney function that may account for the higher CVD morbidity and mortality. Many cardiology guidelines include chronic kidney disease (CKD) and end-stage kidney disease (ESKD) as coronary heart disease (CHD) risk equivalents. It is therefore important for clinicians to both recognise and optimise the cardiovascular health of patients receiving maintenance dialysis. This chapter will focus on risk factor modification, screening and prevention of CVD in dialysis patients

Fluid Convection, Generation and Reinfusion in Haemodiafiltration

Despite widespread use in clinical practice for over 30 years, many questions remain unanswered regarding fluid convection and reinfusion strategies in haemodiafiltration (HDF). Randomised controlled trials have failed to consistently demonstrate improved survival with convective therapies, but a dose-dependent improvement in outcome has been suggested. The ‘minimum’ and ‘ideal’ volumes of convection are undefined. Online generation of ultrapure dialysis fluid has allowed unprecedented convection volumes; however, delivery of fluid directly into the blood circuit requires strict monitoring. The replacement fluid may be reinfused at multiple points in the circuit. Post-dilution HDF is highly efficient in terms of solute clearance but is limited by haemoconcentration. Pre-dilution HDF prolongs filter life but requires significant convection volumes to achieve adequate solute clearance. Mid-dilution HDF utilises a specific dialyser, which is associated with additional cost and escalating transmembrane pressure. Mixed-dilution HDF appears to offer an attractive balance between solute clearance efficiency and haemoconcentration, however these findings need to be confirmed in large studies. The majority of trials comparing fluid reinfusion strategies have enrolled small numbers of patients over brief study periods. It is unclear whether high-quality evidence examining fluid convection and reinfusion will become available and practice may need to rely on observational data

The Role of Oxidative Stress and Systemic Inflammation in Kidney Disease and Its Associated Cardiovascular Risk

Chronic kidney disease (CKD) is a major global health burden, with a prevalence of 10–15% and high mortality rates. In particular, CKD portends a disproportionately high risk of cardiovascular disease beyond the traditional cardiovascular risk factors, with pathophysiological factors such as oxidative stress, inflammation and hyperuricaemia considered to exert an additional role in accelerated atherosclerosis. The presence of heightened oxidative stress and systemic inflammation in CKD is associated with increased mortality. The possible underlying mechanisms include gut dysbiosis, dialysis factors, infections, metabolic acidosis and hyperuricaemia. The state of oxidative stress and systemic inflammation are closely linked and perpetuate each other resulting in progression of CKD and cardiovascular disease. Potential interventions to alleviate the oxidative stress and inflammation in CKD include lifestyle modifications including dietary changes and exercise, optimization of dialysis procedure and pharmacotherapeutic agents including antioxidants. They present a potentially highly effective approach to add to the currently available traditional risk-modification strategies. To date, the majority of the published trials have had a small number of participants with a short duration of follow up. Therefore, no robust evidence has been established. Larger trials with meaningful clinical outcomes and longer follow up are required to evaluate such potential therapies

Adiponectin is associated with cardiovascular disease in male renal transplant recipients: baseline results from the LANDMARK 2 study

BACKGROUND: Adiponectin is a major adipocyte-derived protein with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. Adiponectin levels correlate inversely with renal function and higher levels are predictive of lower cardiovascular disease (CVD) in patients with normal renal function and chronic kidney disease. No data exists on the association between adiponectin and CVD in renal transplant recipients (RTR). METHODS: Standard biochemistry, clinical data and adiponectin were collected from 137 RTR recruited to the LANDMARK 2 study at baseline. The LANDMARK 2 study is an ongoing randomized controlled study that compares the outcome of aggressive risk factor modification for cardiovascular disease versus standard post-transplant care in renal transplant recipients with impaired glucose tolerance or diabetes mellitus. RESULTS: Mean patient age was 53.4 +/- 12 years and the median post-transplantation period was 5 (0.5-31.9) years. Mean serum adiponectin level was 12.3 +/- 7.1 microg/mL. On univariate analysis, adiponectin was positively associated with female gender (P = 0.01) and serum high-density lipoprotein (HDL) concentration (P < 0.001), and inversely with body mass index (P = 0.009), metabolic syndrome (P = 0.047), abnormal glucose tolerance (P = 0.01), C-reactive protein (P = 0.001) and serum triglyceride (P < 0.001). On stepwise multivariate analysis, adiponectin in males was negatively correlated with combined baseline CVD (P = 0.03), waist-hip ratio (P = 0.003) and glomerular filtration rate (P = 0.046), and positively with HDL (P < 0.001). In contrast, in females adiponectin was inversely associated with C-reactive protein (P = 0.001) and serum triglyceride. CONCLUSION: In conclusion, adiponectin is positively correlated with inflammation, dyslipidemia and abnormal glucose tolerance in RTR. Furthermore, hypoadiponectinemia correlated with increased baseline CVD in male RTR

Intravenous versus oral iron supplementation for correction of post-transplant anaemia in renal transplant patients

Background Post-transplant anaemia remains a common problem after kidney transplantation, with an incidence ranging from nearly 80% at day 0 to about 25% at 1 year. It has been associated with poor graft outcome, and recently has also been shown to be associated with increased mortality. Our transplant unit routinely administers oral iron supplements to renal transplant recipients but this is frequently accompanied by side effects, mainly gastrointestinal intolerance. Intravenous iron is frequently administered to dialysis patients and we sought to investigate this mode of administration in transplant recipients after noticing less anaemia in several patients who had received intravenous iron just prior to being called in for transplantation. Methods This study is a single-centre, prospective, open-label, randomised, controlled trial of oral versus intravenous iron supplements in renal transplant recipients and aims to recruit approximately 100 patients over a 12-month period. Patients will be randomised to receive a single dose of 500 mg iron polymaltose (intravenous iron group) or 2 ferrous sulphate slow-release tablets daily (oral iron group). The primary outcome is time to normalisation of haemoglobin post-transplant. Prospective power calculations have indicated that a minimum of 48 patients in each group would have to be followed up for 3 months in order to have a 90% probability of detecting a halving of the time to correction of haemoglobin levels to ≥110 g/l in iron-treated patients, assuming an α of 0.05. All eligible adult patients undergoing renal transplantation at the Princess Alexandra Hospital will be offered participation in the trial. Exclusion criteria will include iron overload (transferrin saturation >50% or ferritin >800 μg/l), or previous intolerance of either oral or intravenous iron supplements. Discussion If the trial shows a reduction in the time to correction of anaemia with intravenous iron or less side effects than oral iron, then intravenous iron may become the standard of treatment in this patient group

Probable tacrolimus toxicity from tibolone co-administration in a woman: a case report

Introduction: Tibolone is a synthetic steroid, used with increasing frequency to treat symptoms of menopause, including patients with solid-organ transplants who are taking concurrent immune suppression. To the best of our knowledge, there are no reported drug interactions between tibolone and tacrolimus, one of the principal immune suppressants used in kidney transplantation. Case presentation: We report the case of a 49-year-old Caucasian woman who had received a kidney transplant and who developed acute kidney injury secondary to tacrolimus toxicity 10 days after starting tibolone therapy. No alternative causes were found. Tibolone is known to be a weak competitive inhibitor of CYP3A4, which is involved in tacrolimus metabolism. Conclusions: Despite a careful evaluation, no alternative reason was found for the acute kidney injury, and her kidney function returned to the previous baseline within several days of cessation of the medication, and with no other specific treatment. Using the Drug Interaction Probability Scale we conclude that she experienced a probable drug interaction. We believe that transplant clinicians should utilise frequent therapeutic drug monitoring of tacrolimus in patients starting or stopping tibolone therapy

A comparison of graft and patient outcomes following kidney transplantation in extended hour and conventional haemodialysis patients

Differences in early graft function between kidney transplant recipients previously managed with either haemodialysis (HD) or peritoneal dialysis are well described. However, only two single-centre studies have compared graft and patient outcomes between extended hour and conventional HD patients, with conflicting results.This study compared the outcomes of all extended hour (≥24 hours/week) and conventional HD patients transplanted in Australia and New Zealand between 2000 and 2014. The primary outcome was delayed graft function (DGF), defined in an ordinal manner as either a spontaneous fall in serum creatinine of less than 10% within 24 hours, or the need for dialysis within 72 hours following transplantation. Secondary outcomes included the requirement for dialysis within 72 hours post-transplant, acute rejection, estimated glomerular filtration rate at 12 months, death-censored graft failure, all-cause and cardiovascular mortality, and a composite of graft failure and mortality.A total of 4,935 HD patients (378 extended hour HD, 4,557 conventional HD) received a kidney transplant during the study period. Extended hour HD was associated with an increased likelihood of DGF compared with conventional HD (adjusted proportional odds ratio 1.33; 95% confidence interval 1.06-1.67). There was no significant difference between extended hour and conventional HD in terms of any of the secondary outcomes.Compared to conventional HD, extended hour HD was associated with DGF, although long-term graft and patient outcomes were not different