Live donor study – implications of kidney donation on cardiovascular risk with a focus on lipid parameters including lipoprotein a

In this prospective observational cohort study, we evaluate the change in cardiovascular risk parameters, with a focus on lipids, in live kidney donors 1 year post donation. Body mass index, systolic/diastolic blood pressure, kidney function (chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration) and lipid parameters were measured at baseline and 1 year. Data on 87 live kidney donors were collected. Body mass index increased from 26.5 ± 2.7 pre to 27.4 ± 3.0 kg/m post donation (p < 0.0001). Chromium-51 ethylenediaminetetraacetic acid estimated glomerular filtration decreased from 111.8 ± 20.0 pre to 72.1 ± 13.1 mL/min/1.73 m post donation (p < 0.0001). Serum triglyceride levels increased from 0.8 (interquartile range 0.6–1.3) pre to 1.0 mmol/L (interquartile range 0.7–1.6) post donation (p = 0.0004). Statin use increased from 11.5% pre to 21% post donation (p < 0.005). Low-density lipoprotein remained stable, and other lipids (high-density lipoprotein, apolipoprotein B and lipoprotein a) did not change post donation

BK Virus in Kidney Transplant Recipients: The Influence of Immunosuppression

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

Agreement between cystatin-C and creatinine based eGFR estimates after a 12-month exercise intervention in patients with chronic kidney disease

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  <  0.01) and grip strength (r = 0.391, p  <  0.001) were associated with serum creatinine at baseline. However, there were no significant correlations between cystatin-C and the same measures. The Lifestyle Intervention resulted in significant improvements in exercise capacity (+ 1.9 ± 1.8 METs, p  <  0.001). There were no changes in lean mass in both Control and Lifestyle Intervention groups during the 12 months. CKD-EPIcys was considerably lower in both groups at both baseline and 12 months than CKD-EPIcr (Control = − 10.5 ± 9.1 and − 13.1 ± 11.8, and Lifestyle Intervention = − 7.9 ± 8.6 and − 8.4 ± 12.3 ml/min/1.73 m2), CKD-EPIcr-cys (Control = − 3.6 ± 3.7 and − 4.5 ± 4.5, and Lifestyle Intervention = − 3.6 ± 3.7 and − 2.5 ± 5.5 ml/min/1.73 m2) and MDRDcr (Control = − 9.3 ± 8.4 and − 12.0 ± 10.7, Lifestyle Intervention = − 6.4 ± 8.4 and − 6.9 ± 11.2 ml/min/1.73 m2). Conclusions: In CKD patients participating in a primarily aerobic based exercise training, without improvements in lean mass, cystatin-C and creatinine based eGFR provided similar estimates of kidney function at both baseline and after 12 months of exercise training. Trial registration: The trial was registered at www.anzctr.org.au (Registration Number ANZCTR12608000337370) on the 17/07/2008 (retrospectively registered)

Association of anthropometric measures with kidney disease progression and mortality: a retrospective cohort study of pre-dialysis chronic kidney disease patients referred to a specialist renal service

Background: Although elevated body mass index (BMI) is a predictor of better clinical outcomes in dialysis patients, the evidence in pre-dialysis chronic kidney disease (CKD) is conflicting. Clinical measures of central obesity may be better prognostic indicators, although investigation has been limited. The aim of this study was to assess the predictive value of anthropometric measures for kidney failure progression and mortality in stage 3-4 CKD. Methods: The study included newly referred stage 3-4 CKD patients at a single centre between 1/1/2008 and 31/12/2010. The associations between clinical measures of obesity (BMI, waist circumference [WC] and conicity index [ConI]) and time to a composite primary outcome of doubling of serum creatinine, commencement of renal replacement therapy or mortality were evaluated using the Kaplan-Meier method and multivariable Cox regression models. Results: Over a median follow-up period of 3.3 years, 229 (25.4 %) patients of a total population of 903 experienced the composite primary renal outcome. When compared to normal BMI (18.5-24.9 kg/m2, n = 174), the risk of the composite primary outcome was significantly lower in both the overweight (BMI 25-29.9 kg/m2, n = 293; adjusted hazard ratio [HR] 0.50, 95 % CI 0.33-0.75) and obese class I/II groups (BMI 30-39.9 kg/m2, n = 288; HR 0.62, 95 % CI 0.41-0.93), but not in the obese class III group (BMI ≥40 kg/m2, n = 72; HR 0.94, 95 % CI 0.52-1.69). All-cause mortality was also lower in the overweight group (HR 0.50, 95 % CI 0.30-0.83). WC and ConI were not associated with either the composite primary outcome or mortality. Conclusion: BMI in the overweight range is associated with reduced risks of kidney disease progression and all-cause mortality in stage 3-4 CKD. WC and ConI were not independent predictors of these outcomes in this population

Thrombotic Microangiopathy Associated with Pazopanib in a Kidney Transplant Recipient

Thrombotic microangiopathy (TMA) is characterised by abnormalities in the walls of arterioles and capillaries, precipitated by hereditary or acquired characteristics, and culminating in microvascular thrombosis because of dysregulated complement activity. A number of drugs can precipitate TMA, including vascular endothelial growth factor (VEGF) inhibitors, because of their effects on endothelial repair. Pazopanib is a VEGF inhibitor used for the treatment of renal cell carcinoma (RCC); it is uncommonly associated with TMA. A 52-year-old male, 5 years post his second kidney transplant secondary to immunoglobulin (Ig) A nephropathy, presented with hypertension, fluid overload, and worsening graft function (peak creatinine 275 μmol/L, baseline 130–160 μmol/L) and nephrotic range proteinuria 2 months after commencing pazopanib for metastatic RCC. His maintenance immunosuppression included ciclosporin, mycophenolate, and prednisolone. Haematological parameters were unremarkable. Allograft biopsy demonstrated glomerular and arteriolar changes consistent with chronic active TMA, with overlying features of borderline cellular rejection. He was treated with intravenous methylprednisolone 250 mg for 3 days and commenced on irbesartan 75 mg daily. Drug-induced TMA from pazopanib was suspected, particularly given the documented association with other tyrosine kinase inhibitors (TKIs). In consultation with his medical oncologist, pazopanib was ceased, and an alternate TKI cabozantinib was commenced. Serum creatinine remained &lt;200 μmol/L 3 months after admission. This is the first reported biopsy-proven case of TMA attributed to pazopanib in a kidney transplant recipient. With increasing clinical indications for and availability of TKIs, clinicians need to be aware of their association with TMA events in kidney transplant recipients, who are already susceptible to TMA due to abnormal vasculature, infectious triggers, ischaemia-reperfusion injury, and use of calcineurin inhibitor

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

Effect of vitamin D supplementation on blood pressure:a systematic review and meta-analysis incorporating individual patient data

D-PRESSURE Collaboration: et al.[Importance]: Low levels of vitamin D are associated with elevated blood pressure (BP) and future cardiovascular events. Whether vitamin D supplementation reduces BP and which patient characteristics predict a response remain unclear.[Objective]: To systematically review whether supplementation with vitamin D or its analogues reduce BP.[Data Sources]: We searched MEDLINE, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and http://www.ClinicalTrials.com augmented by a hand search of references from the included articles and previous reviews. Google was searched for gray literature (ie, material not published in recognized scientific journals). No language restrictions were applied. The search period spanned January 1, 1966, through March 31, 2014.[Study Selection]: We included randomized placebo-controlled clinical trials that used vitamin D supplementation for a minimum of 4 weeks for any indication and reported BP data. Studies were included if they used active or inactive forms of vitamin D or vitamin D analogues. Cointerventions were permitted if identical in all treatment arms.[Data Extraction and Synthesis]: We extracted data on baseline demographics, 25-hydroxyvitamin D levels, systolic and diastolic BP (SBP and DBP), and change in BP from baseline to the final follow-up. Individual patient data on age, sex, medication use, diabetes mellitus, baseline and follow-up BP, and 25-hydroxyvitamin D levels were requested from the authors of the included studies. For trial-level data, between-group differences in BP change were combined in a random-effects model. For individual patient data, between-group differences in BP at the final follow up, adjusted for baseline BP, were calculated before combining in a random-effects model.[Main Outcomes and Measures]: Difference in SBP and DBP measured in an office setting.[Results]: We included 46 trials (4541 participants) in the trial-level meta-analysis. Individual patient data were obtained for 27 trials (3092 participants). At the trial level, no effect of vitamin D supplementation was seen on SBP (effect size, 0.0 [95% CI, −0.8 to 0.8] mm Hg; P = .97; I2 = 21%) or DBP (effect size, −0.1 [95% CI, −0.6 to 0.5] mm Hg; P = .84; I2 = 20%). Similar results were found analyzing individual patient data for SBP (effect size, −0.5 [95% CI, −1.3 to 0.4] mm Hg; P = .27; I2 = 0%) and DBP (effect size, 0.2 [95% CI, −0.3 to 0.7] mm Hg; P = .38; I2 = 0%). Subgroup analysis did not reveal any baseline factor predictive of a better response to therapy.[Conclusions and Relevance]: Vitamin D supplementation is ineffective as an agent for lowering BP and thus should not be used as an antihypertensive agent.Peer reviewe

Australian University Nursing and Allied Health Students’ and Staff Physical Activity Promotion Preparedness and Knowledge: A Pre-Post Study Using an Educational Intervention

The promotion of physical activity (PA) by health professionals is a key strategy to increase PA levels in the population. In this study, we investigated PA promotion, preparedness, and knowledge among university nursing and allied health students and staff, as well as PA resource usage within curricula, before and after an educational intervention. Students and staff from 13 health disciplines at one Australian university were invited to complete an online survey, and a curriculum audits were conducted before and after PA teaching resources were promoted by academic PA champions (n = 14). A total of 299 students and 43 staff responded to the survey pre-intervention, and 363 and 32 responded to the post-intervention, respectively. PA promotion role perception (≥93%) and confidence to provide general PA advice (≥70%) were high throughout the study. Knowledge of PA guidelines was poor (3–10%). Students of physiotherapy, sport and exercise science, as well as more active students, were more likely to be aware of the PA guidelines (p < 0.05). Over 12 months, PA promotion preparedness and knowledge did not change significantly, nor was there a change in the amount of PA content delivered, despite a significant increase in the use of the teaching resources across a number of disciplines (p = 0.007). Future research should be carried out to investigate the implementation of the resources over time and to develop additional strategies for PA promotion and education scaffolded across curricula