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.

The HONEYPOT randomized controlled trial statistical analysis plan.

BACKGROUND: The HONEYPOT study is a multicenter, open-label, blinded-outcome, randomized controlled trial designed to determine whether, compared with standard topical application of mupirocin for nasal staphylococcal carriage, exit-site application of antibacterial honey reduces the rate of catheter-associated infections in peritoneal dialysis patients. OBJECTIVE: To make public the pre-specified statistical analysis principles to be adhered to and the procedures to be performed by statisticians who will analyze the data for the HONEYPOT trial. METHODS: Statisticians and clinical investigators who were blinded to treatment allocation and treatment-related study results and who will remain blinded until the central database is locked for final data extraction and analysis determined the statistical methods and procedures to be used for analysis and wrote the statistical analysis plan. The plan describes basic analysis principles, methods for dealing with a range of commonly encountered data analysis issues, and the specific statistical procedures for analyzing the primary, secondary, and safety outcomes. RESULTS: A statistical analysis plan containing the pre-specified principles, methods, and procedures to be adhered to in the analysis of the data from the HONEYPOT trial was developed in accordance with international guidelines. The structure and content of the plan provide sufficient detail to meet the guidelines on statistical principles for clinical trials produced by the International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. CONCLUSIONS: Making public the pre-specified statistical analysis plan for the HONEYPOT trial minimizes the potential for bias in the analysis of trial data and the interpretation and reporting of trial results.

Staphylococcus aureus peritonitis in Australian peritoneal dialysis patients: predictors, treatment, and outcomes in 503 cases.

Staphylococcus aureus peritonitis is a serious complication of peritoneal dialysis (PD). Since reports of the course and treatment of S. aureus peritonitis have generally been limited to small, single-center studies, the aim of the current investigation was to examine the frequency, predictors, treatment, and clinical outcomes of this condition in all 4675 patients receiving PD in Australia between 1 October 2003 and 31 December 2006. 3594 episodes of peritonitis occurred in 1984 patients and 503 (14%) episodes of S. aureus peritonitis occurred in 355 (8%) individuals. 273 (77%) patients experienced 1 episode of S. aureus peritonitis, 52 (15%) experienced 2 episodes, 19 (5%) experienced 3 episodes, and 11 (3%) experienced 4 or more episodes. The predominant antibiotics used as initial empiric therapy were vancomycin (61%) and cephazolin (31%). Once S. aureus was isolated and identified, the prescription of vancomycin did not appreciably change for methicillin-sensitive S. aureus (MSSA) peritonitis (59%) and increased for methicillin-resistant S. aureus (MRSA) peritonitis (84%). S. aureus peritonitis was associated with a higher rate of relapse than non-S. aureus peritonitis (20% vs 13%, p < 0.001) but comparable rates of hospitalization (67% vs 70%, p = 0.2), catheter removal (23% vs 21%, p = 0.4), hemodialysis transfer (18% vs 18%, p = 0.6), and death (2.2% vs 2.3%, p = 0.9). MRSA peritonitis was independently predictive of an increased risk of permanent hemodialysis transfer [odds ratio (OR) 2.11, 95% confidence interval (CI) 1.17 - 3.82] and tended to be associated with an increased risk of hospitalization (OR 2.00, 95% CI 0.96 - 4.19). The initial empiric antibiotic choice between vancomycin and cephazolin was not significantly associated with clinical outcomes, but serious adverse outcomes were more likely if vancomycin was not used for subsequent treatment of MRSA peritonitis. In conclusion, S. aureus peritonitis is a serious complication of PD, involves a small proportion of patients, and is associated with a high rate of relapse and repeat episodes. Other adverse clinical outcomes are similar to those for peritonitis overall but are significantly worse for MRSA peritonitis. Empiric initial therapy with either vancomycin or cephazolin results in comparable outcomes, provided vancomycin is prescribed when MRSA is isolated and identified.

Oxpentifylline versus placebo in the treatment of erythropoietin-resistant anaemia: a randomized controlled trial.

BACKGROUND: The main hypothesis of this study is that Oxpentifylline administration will effectively treat erythropoietin- or darbepoietin-resistant anaemia in chronic kidney disease patients. METHODS/DESIGN: Inclusion criteria are adult patients with stage 4 or 5 chronic kidney disease (including dialysis patients) with significant anaemia (haemoglobin or= 200 IU/kg/week) or darbepoetin (>or= 1 microg/kg/week). Patients will be randomized 1:1 to receive either placebo (1 tablet daily) or oxpentifylline (400 mg daily) per os for a period of 4 months. During this 4 month study period, haemoglobin measurements will be performed monthly. The primary outcome measure will be the difference in haemoglobin level between the 2 groups at the end of the 4 month study period, adjusted for baseline values. Secondary outcome measures will include erythropoiesis stimulating agent dosage, Key's index (erythropoiesis stimulating agent dosage divided by haemoglobin concentration), and blood transfusion requirement. DISCUSSION: This investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their chronic kidney disease patients determine whether oxpentifylline represents a safe and effective strategy for treating erythropoiesis stimulating agent resistance in chronic kidney disease.

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.