Alicia T. Morrish

Antibacterial honey for the prevention of peritoneal-dialysis-related infections (HONEYPOT): a randomised trial.

BACKGROUND There is a paucity of evidence to guide the best strategy for prevention of peritoneal-dialysis-related infections. Antibacterial honey has shown promise as a novel, cheap, effective, topical prophylactic agent without inducing microbial resistance. We therefore assessed whether daily application of honey at the exit site would increase the time to peritoneal-dialysis-related infections compared with standard exit-site care plus intranasal mupirocin prophylaxis for nasal carriers of Staphylococcus aureus. METHODS In this open-label trial undertaken in 26 centres in Australia and New Zealand, participants undergoing peritoneal dialysis were randomly assigned in a 1:1 ratio with an adaptive allocation algorithm to daily topical exit-site application of antibacterial honey plus standard exit-site care or intranasal mupirocin prophylaxis (only in carriers of nasal S aureus) plus standard exit-site care (control group). The primary endpoint was time to first infection related to peritoneal dialysis (exit-site infection, tunnel infection, or peritonitis). The trial is registered with the Australian New Zealand Clinical Trials Registry, number 12607000537459. FINDINGS Of 371 participants, 186 were assigned to the honey group and 185 to the control group. The median peritoneal-dialysis-related infection-free survival times were not significantly different in the honey (16·0 months [IQR not estimable]) and control groups (17·7 months [not estimable]; unadjusted hazard ratio 1·12, 95% CI 0·83-1·51; p=0·47). In the subgroup analyses, honey increased the risks of both the primary endpoint (1·85, 1·05-3·24; p=0·03) and peritonitis (2·25, 1·16-4·36) in participants with diabetes. The incidences of serious adverse events (298 vs 327, respectively; p=0·1) and deaths (14 vs 18, respectively; p=0·9) were not significantly different in the honey and control groups. 11 (6%) participants in the honey group had local skin reactions. INTERPRETATION The findings of this trial show that honey cannot be recommended routinely for the prevention of peritoneal-dialysis-related infections. FUNDING Baxter Healthcare, Queensland Government, Comvita, and Gambro.

Establishing a clinical trials network in nephrology: experience of the Australasian Kidney Trials Network

Chronic kidney disease is a major public health problem globally. Despite this, there are fewer high-quality, high-impact clinical trials in nephrology than other internal medicine specialties, which has led to large gaps in evidence. To address this deficiency, the Australasian Kidney Trials Network, a Collaborative Research Group, was formed in 2005. Since then, the Network has provided infrastructure and expertise to conduct patient-focused high-quality, investigator-initiated clinical trials in nephrology. The Network has not only been successful in engaging the nephrology community in Australia and New Zealand but also in forming collaborations with leading researchers from other countries. This article describes the establishment, development, and functions of the Network. The article also discusses the current and future funding strategies to ensure uninterrupted conduct of much needed clinical trials in nephrology to improve the outcomes of patients affected by kidney diseases with cost-effective interventions.

Association between Serum Hepcidin-25 and Primary Resistance to Erythropoiesis Stimulating Agents in Chronic Kidney Disease: A Secondary Analysis of the HERO Trial

Pentoxifylline has been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin‐stimulating agent (ESA)‐hyporesponsive anaemia in the Handling Erythropoietin Resistance with Oxpentifylline multicentre double‐blind, randomized controlled trial. The present sub‐study evaluated the effects of pentoxifylline on the iron‐regulatory hormone hepcidin in patients with ESA‐hyporesponsive CKD.

The effect of pentoxifylline on oxidative stress in chronic kidney disease patients with erythropoiesis-stimulating agent hyporesponsiveness: Sub-study of the HERO trial

Objective: Pentoxifylline has previously been shown to increase haemoglobin levels in patients with chronic kidney disease (CKD) and erythropoietin-stimulating agent (ESA)-hyporesponsive anaemia in the HERO multi-centre double-blind, randomized controlled trial. The present study evaluated the effects of pentoxifylline on oxidative stress in ESA-hyporesponsive CKD patients. Methods: This sub-study of the HERO trial compared 15 patients in the pentoxifylline arm (400 mg daily) and 17 in the matched placebo arm on oxidative stress markers: plasma total F2-isoprostanes, protein carbonyls, glutathione peroxidase (GPX), and superoxide dismutase (SOD) activities. Results: Pentoxifylline did not significantly alter total F2-isoprostanes (adjusted mean difference (MD) 35.01 pg/ml, P = 0.11), SOD activity (MD 0.82 U/ml, P = 0.07), GPX activity (MD −6.06 U/l, P = 0.09), or protein carbonyls (MD −0.04 nmol/mg, P = 0.52). Replicating results from the main study, pentoxifylline significantly increased haemoglobin concentration compared with controls (MD 7.2 g/l, P = 0.04). Conclusions: Pentoxifylline did not alter oxidative stress biomarkers, suggesting that alternative mechanisms may be responsible for the agents ability to augment haemoglobin levels in CKD patients with ESA-hyporesponsive anaemia.

The Effect of Exit-Site Antibacterial Honey Versus Nasal Mupirocin Prophylaxis on the Microbiology and Outcomes of Peritoneal Dialysis-Associated Peritonitis and Exit-Site Infections: A Sub-Study of the Honeypot Trial.

♦ Background: The HONEYPOT study recently reported that daily exit-site application of antibacterial honey was not superior to nasal mupirocin prophylaxis for preventing overall peritoneal dialysis (PD)-related infection. This paper reports a secondary outcome analysis of the HONEYPOT study with respect to exit-site infection (ESI) and peritonitis microbiology, infectious hospitalization and technique failure. ♦ Methods: A total of 371 PD patients were randomized to daily exit-site application of antibacterial honey plus usual exit-site care (N = 186) or intranasal mupirocin prophylaxis (in nasal Staphylococcus aureus carriers only) plus usual exit-site care (control, N = 185). Groups were compared on rates of organism-specific ESI and peritonitis, peritonitis- and infection-associated hospitalization, and technique failure (PD withdrawal). ♦ Results: The mean peritonitis rates in the honey and control groups were 0.41 (95% confidence interval [CI] 0.32 – 0.50) and 0.41 (95% CI 0.33 – 0.49) episodes per patient-year, respectively (incidence rate ratio [IRR] 1.01, 95% CI 0.75 – 1.35). When specific causative organisms were examined, no differences were observed between the groups for gram-positive (IRR 0.99, 95% CI 0.66 – 1.49), gram-negative (IRR 0.71, 95% CI 0.39 – 1.29), culture-negative (IRR 2.01, 95% CI 0.91 – 4.42), or polymicrobial peritonitis (IRR 1.08, 95% CI 0.36 – 3.20). Exit-site infection rates were 0.37 (95% CI 0.28 – 0.45) and 0.33 (95% CI 0.26 – 0.40) episodes per patient-year for the honey and control groups, respectively (IRR 1.12, 95% CI 0.81 – 1.53). No significant differences were observed between the groups for gram-positive (IRR 1.10, 95% CI 0.70 – 1.72), gram-negative (IRR: 0.85, 95% CI 0.46 – 1.58), culture-negative (IRR 1.88, 95% CI 0.67 – 5.29), or polymicrobial ESI (IRR 1.00, 95% CI 0.40 – 2.54). Times to first peritonitis-associated and first infection-associated hospitalization were similar in the honey and control groups. The rates of technique failure (PD withdrawal) due to PD-related infection were not significantly different between the groups. ♦ Conclusion: Compared with standard nasal mupirocin prophylaxis, daily topical exit-site application of antibacterial honey resulted in comparable rates of organism-specific peritonitis and ESI, infection-associated hospitalization, and infection-associated technique failure in PD patients.

A Randomized, Placebo-Controlled Trial of Pentoxifylline On Erythropoiesis Stimulating Agent Resistance in Anaemic Patients with Chronic Kidney Disease - the Hero Trial

Aims: To identify the indications for fistulograms and determine correlation between indication and radiological findings. Background: Dialysis access stenosis is the most common cause of access dysfunction. Clinical monitoring or vascular access surveillance abnormalities prompt a fistulogram. At our institution, fistulogram is primarily used to confirm stenosis. Methods: A retrospective observational study was conducted on 245 fistulograms performed at our institution over a two year period from January 2012 to December 2013. The indication for referral, fistulogram findings, type of fistula and demographic data were obtained. Results: Total of 75.5% (185 of 245) fistulograms performed confirmed stenosis. The most frequent clinical indication was high venous pressures – 18.4% (45 of 245) and the most common surveillance indication was abnormal access flow (Transonic®) – 17.1% (42 of 245). The average age was 57 years, with 35.9% Aboriginal and 28.2% Torres Straight Islander ethnicity. The most common type of vascular access was radiocephalic fistula (49.8%) followed by brachiocephalic fistula (43.3%). Further analysis of variables, using bivariate logistic regression analysis, failed to reveal any significant correlation between indications for referral and finding of stenosis. However, increased venous pressure tends to be associated with stenosis (Odds ratio 2.0, 95% CI = 0.84–4.7, P = 0.12). Both venous hypertension (Odds ratio 0.10, 95% CI = 0.011–1.0, P = 0.052) and development of collaterals (Odds ratio 0.077, 95% CI = 0.0084–0.70, P = 0.023) were associated with negative fistulograms. Conclusions: At our institution, the majority of fistulograms demonstrated access stenosis, based on established referral indications. Both venous hypertension and development of collaterals as referral indications were associated with less likelihood of finding vascular access stenosis in this cohort.Aim: To examine the value of neutrophil-lymphocyte ratio (NLR) as a marker of inflammation and predictor of all-cause mortality in patients with end-stage kidney disease (ESKD). Background: NLR is a marker of systemic inflammation that has been shown to predict mortality in patients with coronary and peripheral vascular disease. In contrast to albumin, NLR is unlikely to be affected by nutritional status. Its prognostic value in ESKD patients is unclear. Methods: We retrospectively reviewed all consecutive haemodialysis patients between January 2007 and December 2011 at a single centre. We recorded patients full blood count and other biochemistry three months after commencement of dialysis. Correlations between NLR and other metabolic and inflammatory markers were evaluated using Pearsons r coefficient. The prognostic value of NLR was tested using Kaplan Meier, univariate and multivariate Cox analyses adjusted for Australian and New Zealand Dialysis and Transplant Registry data. Results: 140 haemodialysis patients were included with median follow-up of 36 months and overall mortality of 41% (58 patients). Neutrophil-lymphocyte ratio was positively correlated with C-reactive protein (r = 0.48, P < 0.01) and negatively correlated with haemoglobin (r = -0.32, P < 0.01) and albumin (r = -0.40, P < 0.01). In Kaplan Meier analysis, NLR (stratified into tertiles) was associated with all-cause mortality (log-rank, P = 0.01). In multivariate Cox analysis, NLR was independently associated with all-cause mortality (HR 1.09, 95% CI 1.01– 1.17 P = 0.03). Other predictors of all-cause mortality in multivariate analysis were low albumin (HR 0.89, 95% CI 0.89–0.94 P < 0.01) and history of cardiovascular disease (HR 2.29, 95% CI 1.25–4.48 P = 0.01). Conclusions: Neutrophil-lymphocyte ratio correlates with other markers of systemic inflammation in ESKD patients and is associated with poor survival. The extent to which other confounding factors affect these results is unknown.Aim: To determine whether: (1) systemic expression of endogenous secretory RAGE (esRAGE) after the induction of diabetes can prevent the development of diabetic nephropathy (DN) in mice with streptozotocin-induced diabetes; (2) the protective effects of esRAGE are attributable to interruption of signaling via the HMGB1receptors (TLR2, TLR4 and RAGE). Background: We have reported that systemic overexpression of esRAGE attenuates diabetic kidney injury. esRAGE is a soluble decoy receptor that can competitively bind ligands for TLRs/RAGE, including HMGB1. Here we test the hypothesis that the protective effects of esRAGE are attributable to interruption of signaling via the HMGB1 receptors (TLR2, TLR4 and RAGE). Methods: DN was induced in WT, TLR4−/− and TLR2−/− mice by intraperitoneal injection of streptozotocin. At 2 weeks after streptozotocin injection, mice received an IP injection of 5 × 1011 vector genome copies (VGC) rAAV encoding either esRAGE or HSA, or saline-control. Samples were collected at week 12 post-induction of diabetes. Results: Diabetic mice that received rAAV-esRAGE, rAAV-HSA or saline developed equivalent degrees of hyperglycaemia. Diabetic WT-mice given rAAVHSA or saline developed significant albuminuria versus non-diabetic WT-mice (ACR309 ± 213 & 313 ± 215 versus 55 ± 10, P < 0.05–0.01), whilst rAAVesRAGE treated-diabetic-mice were protected (118 ± 42, P < 0.05). WT diabetic-mice developed histological damage including glomerular hypertrophy, podocyte injury, macrophage accumulation and interstitial fibrosis. These changes were significantly attenuated in diabetic mice given rAAV-esRAGE versus rAAV-HSA (P < 0.05–0.01).While both TLR2−/− mice and TLR4−/−mice were partially protected against diabetic nephropathy, esRAGE treatment provided additional protection to TLR2−/− mice, but not TLR4−/− mice. A further study of esRAGE treatment in RAGE−/− mice is underway. Conclusions: High-level expression of serum esRAGE after the induction of diabetes provided partial protection against the development of DN in mice with streptozotocin-induced diabetes, which may operate through the TLR4 pathway.

REPRESENTATIVENESS OF HONEYPOT TRIAL PARTICIPANTS TO AUSTRALASIAN PD PATIENTS

Background: The HONEYPOT trial failed to establish the superiority of exit-site application of Medihoney compared with nasal mupirocin prophylaxis for the prevention of peritonitis in peritoneal dialysis (PD) patients. This study aimed to assess the representativeness of the patients in the HONEYPOT trial to the Australian and New Zealand PD population. Methods: This study compared baseline characteristics of the 371 PD patients in the HONEYPOT trial with those of 6,085 PD patients recorded on the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Results: Compared with the PD population, the HONEYPOT sample was older (standardized difference [d] = 0.19, p = 0.003), more likely to be treated with automated PD (d = 0.58, p < 0.001), had higher residual renal function (d = 0.26, p < 0.001) and a higher proportion of participants with end-stage kidney disease due to polycystic kidney disease (d = 0.17) and lower proportion due to diabetes (d = -0.17) and glomerulonephritis (d = -0.18) (p < 0.001), and lower proportions of indigenous people (d = -0.17, p < 0.001), current smokers (d = -0.10, p < 0.001), and people with prior histories of hemodialysis (d = -0.16, p < 0.001), diabetes mellitus (d = -0.18, p < 0.001), and coronary artery disease (d = -0.15, p < 0.001). Conclusions: HONEYPOT trial participants tended to be healthier than the Australian and New Zealand PD patient population. Although the differences between the groups were generally modest, it is possible that their cumulative effect may have had some impact on external generalizability, which is not an uncommon occurrence in clinical trials.

Association Between Serum Alkaline Phosphatase and Resistance to Erythropoiesis Stimulating Agents in Chronic Kidney Disease: a Post-Hoc Analysis of the Hero Trial

Aims: To identify the indications for fistulograms and determine correlation between indication and radiological findings. Background: Dialysis access stenosis is the most common cause of access dysfunction. Clinical monitoring or vascular access surveillance abnormalities prompt a fistulogram. At our institution, fistulogram is primarily used to confirm stenosis. Methods: A retrospective observational study was conducted on 245 fistulograms performed at our institution over a two year period from January 2012 to December 2013. The indication for referral, fistulogram findings, type of fistula and demographic data were obtained. Results: Total of 75.5% (185 of 245) fistulograms performed confirmed stenosis. The most frequent clinical indication was high venous pressures – 18.4% (45 of 245) and the most common surveillance indication was abnormal access flow (Transonic®) – 17.1% (42 of 245). The average age was 57 years, with 35.9% Aboriginal and 28.2% Torres Straight Islander ethnicity. The most common type of vascular access was radiocephalic fistula (49.8%) followed by brachiocephalic fistula (43.3%). Further analysis of variables, using bivariate logistic regression analysis, failed to reveal any significant correlation between indications for referral and finding of stenosis. However, increased venous pressure tends to be associated with stenosis (Odds ratio 2.0, 95% CI = 0.84–4.7, P = 0.12). Both venous hypertension (Odds ratio 0.10, 95% CI = 0.011–1.0, P = 0.052) and development of collaterals (Odds ratio 0.077, 95% CI = 0.0084–0.70, P = 0.023) were associated with negative fistulograms. Conclusions: At our institution, the majority of fistulograms demonstrated access stenosis, based on established referral indications. Both venous hypertension and development of collaterals as referral indications were associated with less likelihood of finding vascular access stenosis in this cohort.Aim: To examine the value of neutrophil-lymphocyte ratio (NLR) as a marker of inflammation and predictor of all-cause mortality in patients with end-stage kidney disease (ESKD). Background: NLR is a marker of systemic inflammation that has been shown to predict mortality in patients with coronary and peripheral vascular disease. In contrast to albumin, NLR is unlikely to be affected by nutritional status. Its prognostic value in ESKD patients is unclear. Methods: We retrospectively reviewed all consecutive haemodialysis patients between January 2007 and December 2011 at a single centre. We recorded patients full blood count and other biochemistry three months after commencement of dialysis. Correlations between NLR and other metabolic and inflammatory markers were evaluated using Pearsons r coefficient. The prognostic value of NLR was tested using Kaplan Meier, univariate and multivariate Cox analyses adjusted for Australian and New Zealand Dialysis and Transplant Registry data. Results: 140 haemodialysis patients were included with median follow-up of 36 months and overall mortality of 41% (58 patients). Neutrophil-lymphocyte ratio was positively correlated with C-reactive protein (r = 0.48, P < 0.01) and negatively correlated with haemoglobin (r = -0.32, P < 0.01) and albumin (r = -0.40, P < 0.01). In Kaplan Meier analysis, NLR (stratified into tertiles) was associated with all-cause mortality (log-rank, P = 0.01). In multivariate Cox analysis, NLR was independently associated with all-cause mortality (HR 1.09, 95% CI 1.01– 1.17 P = 0.03). Other predictors of all-cause mortality in multivariate analysis were low albumin (HR 0.89, 95% CI 0.89–0.94 P < 0.01) and history of cardiovascular disease (HR 2.29, 95% CI 1.25–4.48 P = 0.01). Conclusions: Neutrophil-lymphocyte ratio correlates with other markers of systemic inflammation in ESKD patients and is associated with poor survival. The extent to which other confounding factors affect these results is unknown.Aim: To determine whether: (1) systemic expression of endogenous secretory RAGE (esRAGE) after the induction of diabetes can prevent the development of diabetic nephropathy (DN) in mice with streptozotocin-induced diabetes; (2) the protective effects of esRAGE are attributable to interruption of signaling via the HMGB1receptors (TLR2, TLR4 and RAGE). Background: We have reported that systemic overexpression of esRAGE attenuates diabetic kidney injury. esRAGE is a soluble decoy receptor that can competitively bind ligands for TLRs/RAGE, including HMGB1. Here we test the hypothesis that the protective effects of esRAGE are attributable to interruption of signaling via the HMGB1 receptors (TLR2, TLR4 and RAGE). Methods: DN was induced in WT, TLR4−/− and TLR2−/− mice by intraperitoneal injection of streptozotocin. At 2 weeks after streptozotocin injection, mice received an IP injection of 5 × 1011 vector genome copies (VGC) rAAV encoding either esRAGE or HSA, or saline-control. Samples were collected at week 12 post-induction of diabetes. Results: Diabetic mice that received rAAV-esRAGE, rAAV-HSA or saline developed equivalent degrees of hyperglycaemia. Diabetic WT-mice given rAAVHSA or saline developed significant albuminuria versus non-diabetic WT-mice (ACR309 ± 213 & 313 ± 215 versus 55 ± 10, P < 0.05–0.01), whilst rAAVesRAGE treated-diabetic-mice were protected (118 ± 42, P < 0.05). WT diabetic-mice developed histological damage including glomerular hypertrophy, podocyte injury, macrophage accumulation and interstitial fibrosis. These changes were significantly attenuated in diabetic mice given rAAV-esRAGE versus rAAV-HSA (P < 0.05–0.01).While both TLR2−/− mice and TLR4−/−mice were partially protected against diabetic nephropathy, esRAGE treatment provided additional protection to TLR2−/− mice, but not TLR4−/− mice. A further study of esRAGE treatment in RAGE−/− mice is underway. Conclusions: High-level expression of serum esRAGE after the induction of diabetes provided partial protection against the development of DN in mice with streptozotocin-induced diabetes, which may operate through the TLR4 pathway.

The effect of pentoxifylline on oxidative stress markers: substudy of the hero trial

Aims: To identify the indications for fistulograms and determine correlation between indication and radiological findings. Background: Dialysis access stenosis is the most common cause of access dysfunction. Clinical monitoring or vascular access surveillance abnormalities prompt a fistulogram. At our institution, fistulogram is primarily used to confirm stenosis. Methods: A retrospective observational study was conducted on 245 fistulograms performed at our institution over a two year period from January 2012 to December 2013. The indication for referral, fistulogram findings, type of fistula and demographic data were obtained. Results: Total of 75.5% (185 of 245) fistulograms performed confirmed stenosis. The most frequent clinical indication was high venous pressures – 18.4% (45 of 245) and the most common surveillance indication was abnormal access flow (Transonic®) – 17.1% (42 of 245). The average age was 57 years, with 35.9% Aboriginal and 28.2% Torres Straight Islander ethnicity. The most common type of vascular access was radiocephalic fistula (49.8%) followed by brachiocephalic fistula (43.3%). Further analysis of variables, using bivariate logistic regression analysis, failed to reveal any significant correlation between indications for referral and finding of stenosis. However, increased venous pressure tends to be associated with stenosis (Odds ratio 2.0, 95% CI = 0.84–4.7, P = 0.12). Both venous hypertension (Odds ratio 0.10, 95% CI = 0.011–1.0, P = 0.052) and development of collaterals (Odds ratio 0.077, 95% CI = 0.0084–0.70, P = 0.023) were associated with negative fistulograms. Conclusions: At our institution, the majority of fistulograms demonstrated access stenosis, based on established referral indications. Both venous hypertension and development of collaterals as referral indications were associated with less likelihood of finding vascular access stenosis in this cohort.Aim: To examine the value of neutrophil-lymphocyte ratio (NLR) as a marker of inflammation and predictor of all-cause mortality in patients with end-stage kidney disease (ESKD). Background: NLR is a marker of systemic inflammation that has been shown to predict mortality in patients with coronary and peripheral vascular disease. In contrast to albumin, NLR is unlikely to be affected by nutritional status. Its prognostic value in ESKD patients is unclear. Methods: We retrospectively reviewed all consecutive haemodialysis patients between January 2007 and December 2011 at a single centre. We recorded patients full blood count and other biochemistry three months after commencement of dialysis. Correlations between NLR and other metabolic and inflammatory markers were evaluated using Pearsons r coefficient. The prognostic value of NLR was tested using Kaplan Meier, univariate and multivariate Cox analyses adjusted for Australian and New Zealand Dialysis and Transplant Registry data. Results: 140 haemodialysis patients were included with median follow-up of 36 months and overall mortality of 41% (58 patients). Neutrophil-lymphocyte ratio was positively correlated with C-reactive protein (r = 0.48, P < 0.01) and negatively correlated with haemoglobin (r = -0.32, P < 0.01) and albumin (r = -0.40, P < 0.01). In Kaplan Meier analysis, NLR (stratified into tertiles) was associated with all-cause mortality (log-rank, P = 0.01). In multivariate Cox analysis, NLR was independently associated with all-cause mortality (HR 1.09, 95% CI 1.01– 1.17 P = 0.03). Other predictors of all-cause mortality in multivariate analysis were low albumin (HR 0.89, 95% CI 0.89–0.94 P < 0.01) and history of cardiovascular disease (HR 2.29, 95% CI 1.25–4.48 P = 0.01). Conclusions: Neutrophil-lymphocyte ratio correlates with other markers of systemic inflammation in ESKD patients and is associated with poor survival. The extent to which other confounding factors affect these results is unknown.Aim: To determine whether: (1) systemic expression of endogenous secretory RAGE (esRAGE) after the induction of diabetes can prevent the development of diabetic nephropathy (DN) in mice with streptozotocin-induced diabetes; (2) the protective effects of esRAGE are attributable to interruption of signaling via the HMGB1receptors (TLR2, TLR4 and RAGE). Background: We have reported that systemic overexpression of esRAGE attenuates diabetic kidney injury. esRAGE is a soluble decoy receptor that can competitively bind ligands for TLRs/RAGE, including HMGB1. Here we test the hypothesis that the protective effects of esRAGE are attributable to interruption of signaling via the HMGB1 receptors (TLR2, TLR4 and RAGE). Methods: DN was induced in WT, TLR4−/− and TLR2−/− mice by intraperitoneal injection of streptozotocin. At 2 weeks after streptozotocin injection, mice received an IP injection of 5 × 1011 vector genome copies (VGC) rAAV encoding either esRAGE or HSA, or saline-control. Samples were collected at week 12 post-induction of diabetes. Results: Diabetic mice that received rAAV-esRAGE, rAAV-HSA or saline developed equivalent degrees of hyperglycaemia. Diabetic WT-mice given rAAVHSA or saline developed significant albuminuria versus non-diabetic WT-mice (ACR309 ± 213 & 313 ± 215 versus 55 ± 10, P < 0.05–0.01), whilst rAAVesRAGE treated-diabetic-mice were protected (118 ± 42, P < 0.05). WT diabetic-mice developed histological damage including glomerular hypertrophy, podocyte injury, macrophage accumulation and interstitial fibrosis. These changes were significantly attenuated in diabetic mice given rAAV-esRAGE versus rAAV-HSA (P < 0.05–0.01).While both TLR2−/− mice and TLR4−/−mice were partially protected against diabetic nephropathy, esRAGE treatment provided additional protection to TLR2−/− mice, but not TLR4−/− mice. A further study of esRAGE treatment in RAGE−/− mice is underway. Conclusions: High-level expression of serum esRAGE after the induction of diabetes provided partial protection against the development of DN in mice with streptozotocin-induced diabetes, which may operate through the TLR4 pathway.

A randomised, controlled trial of exit site application of medihoney for the prevention of catheter-associated infections in PD patients - Honeypot study

Aim: Patency after percutaneous balloon angioplasty (PTA) for haemodialysis fistula stenosis is highly variable. This study aimed to assess factors associated with patency following first episode of treatment with PTA. Background: Restenosis recurs commonly after PTA. Previous studies have shown that some intrinsic fistula and biochemical factors may influence patency after PTA. Methods: We retrospectively reviewed all endovascular procedures performed by nephrologists between 2007 and 2012 at a single centre. Anatomical, clinical, biochemical and medication information was subjected to cox regression analysis to identify factors influencing post-intervention patency. Results: 120 patients were identified as having first episode treatment with PTA. During a median follow-up period of 22.66 months (5.24–53 months), 171 follow-up procedures were performed. Post-intervention primary patency rates at 6, 12 and 18 months were 46%, 25% and 15% respectively. Cumulative (functional) patency rates at 6, 12 and 18 months were 97%, 94 and 92% respectively with 1.4 additional procedures per patient. In univariate cox regression analysis, the presence of multiple lesions (p = 0.037) was associated with early restenosis at 6 months, while upper arm fistulae were associated with early restenosis (p = 0.004) and shorter primary patency (p = 0.001). Other anatomical characteristics (fistula age, lesion length, pre-procedure stenosis), clinical history (diabetes, coronary and peripheral artery disease), medications, and biochemical parameters (HbA1c, CRP, albumin and lipids) did not influence patency. Conclusion: Multiple stenoses and upper arm fistulae may be associated with shorter patency after PTA. More large volume prospective studies are required to further assess factors associated with patency after PTA in haemodialysis fistulae, particularly the role of metabolic and inflammatory markers.