Kidney Transplant Outcomes in elderly Recipients: An Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry Study.

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

Investigating barriers to immunosuppressant medication adherence in renal transplant patients.

AIM: Immunosuppressant medication non-adherence can result in allograft rejection and loss. The aim of this study was to investigate the prevalence of non-adherence and barriers to adherence with immunosuppressant medications, in an adult renal transplant cohort. METHODS: Kidney transplant recipients completed a self-report survey consisting of five validated questionnaires (Basel Assessment of Adherence to Immunosuppressive Medications Scale (BAASIS), Beliefs about Medicines Questionnaire, Immunosuppressant Therapy Barrier Scale, Brief-Illness Perception Questionnaire, and Multidimensional Health Locus of Control Scale), and provided sociodemographic information. Adherence was categorised according to BAASIS, with adherence barriers compared between the groups. RESULTS: One hundred and sixty-one patients in total completed the survey. Eighty-six participants (55%) were categorised as non-adherent, with 45% delaying doses, and 25% skipping doses. Non-adherent patients were more likely to forget doses (P = 0.005), and more likely to skip doses when their daily routine changed (P < 0.001) or when short of money (P = 0.03). Additionally, non-adherent patients had less self-reported understanding about their graft than adherent patients (P = 0.008). Adherence was not associated with a patient's medicine beliefs or perception of locus of control. CONCLUSION: Over half the patients self-reported non-adherence. The main modifiable barriers leading to non-adherence were forgetfulness and skipped doses. Personalised interventions focused on habit forming may improve adherence in this population.

Therapeutic monitoring of mycophenolate in transplantation: is it justified?

Mycophenolate mofetil (MMF) is the preferred antimetabolite in solid organ transplantation. It is a prodrug that undergoes pre-systemic metabolism to mycophenolic acid (MPA), the active drug moiety. MMF is typically administered as a fixed dose without routine monitoring of MPA concentrations. However, a role for therapeutic drug monitoring (TDM) of MPA has been suggested based on the drug's narrow therapeutic window and considerable between-subject variability. Dose-normalized MPA area under the concentration-time curve (AUC) has been observed to vary >/=10-fold. Some of this variability may be accounted for by patient variability in renal and liver function, serum albumin and haemoglobin levels, body mass, concomitant medication exposure and genetic polymorphisms in enzymes responsible for drug metabolism and transport, but much is unexplained. Widespread adoption of MPA TDM has been limited by the impracticality of full 0 to 12 hour AUC measurement (AUC(0-12)), poor correlation between pre-dose MPA concentration and AUC(0-12), ongoing questions regarding the utility of free versus total MPA measurements and lack of evidence correlating MPA exposure with clinical outcomes. Two recent randomized studies evaluating the role of MPA TDM in renal transplant recipients have reported conflicting results. Promising areas of ongoing study include use of Bayesian forecasting to predict MPA dosage and measurement of inosine monophosphate dehydrogenase activity. This review provides an overview of the pharmacokinetics of MMF in solid organ transplantation, and discusses the benefits and limitations of MPA monitoring. Areas that require additional research are identified.

Modification of cardiovascular risk in hemodialysis patients: an evidence-based review.

Cardiovascular disease accounts for 40% to 50% of deaths in dialysis populations. Overall, the risk of cardiac mortality is 10-fold to 20-fold greater in dialysis patients than in age and sex-matched controls without chronic kidney disease. The aim of this paper is to review critically the evidence that cardiac outcomes in dialysis patients are modified by cardiovascular risk factor interventions. There is limited, but as yet inconclusive controlled trial evidence that cardiovascular outcomes in dialysis populations may be improved by antioxidants (vitamin E or acetylcysteine), ensuring that hemoglobin levels do not exceed 120 g/L (especially in the setting of known cardiovascular disease), prescribing carvedilol in the setting of dilated cardiomyopathy, and by using cinacalcet in uncontrolled secondary hyperparathyroidism. Similarly, there are a number of negative controlled trials, which have demonstrated that statins, high-dose folic acid, angiotensin-converting enzyme inhibitors, multiple risk factor intervention via multidisciplinary clinics, and high-dose or high-flux dialysis are ineffective in preventing cardiovascular disease. Although none of these studies could be considered conclusive, the negative trials to date should raise significant concerns about the heavy reliance of current clinical practice guidelines on extrapolation of findings from cardiovascular intervention trials in the general population. It may be that cardiovascular disease in dialysis populations is less amenable to intervention, either because of the advanced stage of chronic kidney disease or because the pathogenesis of cardiovascular disease in dialysis patients is different from that in the general population. Large, well-conducted, multicenter randomized-controlled trials in this area are urgently required.

Randomized, controlled trial of topical exit-site application of honey (Medihoney) versus mupirocin for the prevention of catheter-associated infections in hemodialysis patients.

The clinical usefulness of hemodialysis catheters is limited by increased infectious morbidity and mortality. Topical antiseptic agents, such as mupirocin, are effective at reducing this risk but have been reported to select for antibiotic-resistant strains. The aim of the present study was to determine the efficacy and the safety of exit-site application of a standardized antibacterial honey versus mupirocin in preventing catheter-associated infections. A randomized, controlled trial was performed comparing the effect of thrice-weekly exit-site application of Medihoney versus mupirocin on infection rates in patients who were receiving hemodialysis via tunneled, cuffed central venous catheters. A total of 101 patients were enrolled. The incidences of catheter-associated bacteremias in honey-treated (n = 51) and mupirocin-treated (n = 50) patients were comparable (0.97 versus 0.85 episodes per 1000 catheter-days, respectively; NS). On Cox proportional hazards model analysis, the use of honey was not significantly associated with bacteremia-free survival (unadjusted hazard ratio, 0.94; 95% confidence interval, 0.27 to 3.24; P = 0.92). No exit-site infections occurred. During the study period, 2% of staphylococcal isolates within the hospital were mupirocin resistant. Thrice-weekly application of standardized antibacterial honey to hemodialysis catheter exit sites was safe, cheap, and effective and resulted in a comparable rate of catheter-associated infection to that obtained with mupirocin (although the study was not adequately powered to assess therapeutic equivalence). The effectiveness of honey against antibiotic-resistant microorganisms and its low likelihood of selecting for further resistant strains suggest that this agent may represent a satisfactory alternative means of chemoprophylaxis in patients with central venous catheters.

Elevated white cell count at commencement of peritoneal dialysis predicts overall and cardiac mortality.

BACKGROUND: Higher total white blood cell counts (WCC) have been shown in the general population to be strongly and independently predictive of coronary heart disease and all-cause mortality. The aim of the present study was to evaluate the prognostic value of WCC in patients commencing peritoneal dialysis (PD). METHODS: A cohort of 323 patients (mean age 55.1 +/- 17.7 years, 54% male, 81% Caucasian) commencing PD at the Princess Alexandra Hospital between January 1, 1998 and March 31, 2003 were prospectively followed until death, completion of PD therapy, or otherwise to the end of the study (January 2, 2004), at which point data were censored. Individuals with failed renal transplants (N= 17) and those with acute infections at the time of PD onset (N= 12) were not included. A multivariate Cox's proportional hazards model was applied to calculate hazard ratios and adjusted survival curves for time to death or cardiac death, adjusting for baseline demographic, clinical, and laboratory characteristics. RESULTS: Median actuarial patient survival was 3.9 years [95% confidence interval (CI) 3.2-4.7 years]. The highest quartile of WCC (>9.4 x 10(9)/L) was significantly and independently associated with increased risks of both death from all causes [adjusted hazard ratio (HR) 2.27, 95% CI 1.09-4.74, P < 0.05] and cardiac death (HR 3.75, 95% CI 1.2-11.8, P < 0.05). Other adverse risk factors included older age, lower serum albumin, and the presence of coronary artery disease. Similar associations were found between mortality and PMN count, but not lymphocyte count. CONCLUSION: Elevated baseline WCC or PMN count at the commencement of PD (in the absence of acute infection) strongly predicts all-cause and cardiovascular mortality. These data suggest that new PD patients with higher WCC may warrant closer monitoring and extra attention to modifiable cardiovascular risk factors.

A randomized controlled trial of topical exit site mupirocin application in patients with tunnelled, cuffed haemodialysis catheters.

BACKGROUND: Central venous catheters are frequently needed for the provision of haemodialysis, but their clinical usefulness is severely limited by infectious complications. The risk of such infections can be reduced by topical application of mupirocin to the exit sites of non-cuffed catheters or by the use of tunnelled, cuffed catheters. Whether mupirocin offers any additional protection against infection in patients with tunnelled, cuffed haemodialysis catheters has not been studied. METHODS: An open-label, randomized controlled trial was performed comparing the effect of thrice-weekly exit site application of mupirocin (mupirocin group) vs no ointment (control group) on infection rates and catheter survival in patients receiving haemodialysis via a newly inserted, tunnelled, cuffed central venous catheter. All patients were followed until catheter removal and were monitored for the development of exit site infections and catheter-associated bacteraemias. RESULTS: Fifty patients were enrolled in the study. Both the mupirocin (n=27) and control (n=23) groups were similar at baseline with respect to demographic characteristics, comorbid illnesses and causes of renal failure. Compared with controls, mupirocin-treated patients experienced significantly fewer catheter-related bacteraemias (7 vs 35%, P<0.01) and a longer time to first bacteraemia (log rank score 8.68, P<0.01). The beneficial effect of mupirocin was entirely attributable to a reduction in staphylococcal infection (log rank 10.69, P=0.001) and was still observed when only patients without prior nasal Staphylococcus aureus carriage were included in the analysis (log rank score 6.33, P=0.01). Median catheter survival was also significantly longer in the mupirocin group (108 vs 31 days, log rank score 5.9, P<0.05). Mupirocin use was not associated with any adverse patient effects or the induction of antimicrobial resistance. CONCLUSIONS: Thrice-weekly application of mupirocin to tunnelled, cuffed haemodialysis catheter exit sites is associated with a marked reduction in line-related sepsis and a prolongation of catheter survival.

Is C-reactive protein a useful predictor of outcome in peritoneal dialysis patients?

An elevated C-reactive protein (CRP) has recently been shown to be strongly predictive of mortality in hemodialysis patients. However, its predictive value in peritoneal dialysis (PD) patients has not been assessed. A cohort of 50 PD patients was followed prospectively for a 3-yr period, after initial determination of CRP. Patients with an elevated CRP (>6 mg/L; n = 29) had significantly reduced plasma prealbumin (0.36 +/- 0.02 versus 0.44 +/- 0.03 g/L; P: < 0.05), decreased total weekly creatinine clearance (C(Cr); 52.5 +/- 2.3 versus 63.1 +/- 3.2 L/1.73 m(2); P: < 0.01), and increased left ventricular thickness (1.24 +/- 0.05 versus 1.08 +/- 0.06 cm; P: < 0.05) at baseline compared with those who had a normal CRP (< or =6 mg/L; n = 21). Baseline CRP (log-transformed) correlated weakly with baseline Kt/V, C(Cr), and pre-albumin. With the use of a multivariate Cox's proportional hazards model to adjust for potential confounding factors, an elevated CRP was predictive of myocardial infarction (adjusted hazard ratio, 4.8; 95% confidence interval [CI], 1.0 to 23; P: = 0.048) and tended to be predictive of fatal myocardial infarction (adjusted hazard ratio, 6.0; 95% CI, 0.8 to 43; P: = 0.07). However, CRP was not significantly associated with all-cause mortality (adjusted hazard ratio, 2.1; 95% CI,0.8 to 5.4; P: = 0.15). In conclusion, CRP elevation occurs in a substantial proportion of PD patients and is independently predictive of future myocardial infarction. Such patients may warrant closer monitoring and attention to modifiable cardiovascular risk factors.