NEPHROLOGY 2014; 19 (Supp. 4), 17–57
MINI ORAL ABSTRACTS 001 SYSTEMIC OVEREXPRESSION OF ENDOGENOUS SECRETORY RAGE (ESRAGE) ATTENUATES DIABETIC KIDNEY INJURY THROUGH TLR4 NOT TLR2 SIGNALING X CHEN1, J MA1, I STRIBOS1, L MESSCHENDORP1, M PAUL1, EC CUNNINGHAM1, AF SHARLAND1, SJ CHADBAN1,2, H WU1,2 1 Collaborative Transplant Research Group, University of Sydney; 2Renal Medicine, Royal Prince Alfred Hospital, Australia 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.
002 INFLUENCE OF THE LONG INTERDIALYTIC PERIOD (IDP) ON THE INCIDENCE OF SERIOUS ARRHYTHMIAS AND SUDDEN CARDIAC DEATH (SCD) IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD) UNDERGOING HAEMODIALYSIS (HD) M WONG1,3, J KALMAN1,3, E PEDAGOGOS2,3, N TOUSSAINT2,3, S JOSEPH4, K HALLORAN1, J VOHRA1,3, P SPARKS1,3, J MORTON1,3 1 Department of Cardiology, Royal Melbourne Hospital, Melbourne, Victoria; 2 Department of Nephrology, Royal Melbourne Hospital, Melbourne, Victoria; 3 Department of Medicine, University of Melbourne, Parkville, Victoria; 4Department of Cardiology, Western Hospital, Melbourne, Victoria, Australia Aim: We used an implantable cardiac monitor (ICM) to define the incidence and timing of significant arrhythmias in a HD population. Background: CKD patients on HD have a high risk of SCD. A unique risk factor may be the longer IDP between HD sessions. Inherent in conventional HD (thrice-weekly) are two 48-hour (short) breaks and one 72-hour (long) break between the start of HD sessions. Methods: 50 CKD patients on HD had an ICM inserted with intensive followup. Patients with LVEF < 35% were excluded. The primary end-point was SCD or significant arrhythmias. Ambulatory 24-hour Holter measurements of ventricular repolarization (VR): QTc, T wave alternants (TWA) & autonomic tone (AT): heart rate variability & turbulence (HRV, HRT) were compared during the long vs short IDP. Results: Mean age 66 ± 11 years; 72% male; follow-up 8 ± 3 months. There were 4 SCD (8%), all during the long IDP. The terminal event was severe bradycardia with asystole in 3 (terminal event in 4th patient not available). Significant
arrhythmias occurred in 16 pts (32%) including: bradycardia (≤40 bpm ≥4 beats) in 7 (14%); sinus arrest (pauses ≥3s) in 4 (8%); 2°AV block in 1 (2%); nonsustained ventricular tachycardia (>16 beats 15rbc/cmm) was observed in 60% of the same group. Compared to DN, patients with NDKD alone had a significantly shorter diabetes duration, lower HbA1c and proteinuria, and higher eGFR at time of biopsy. Time to ESRF or death was longest in patients with NDKD alone (75 vs 24 and 52 months (DN and mixed respectively), P < 0.05). Patients with DN were twice as likely to reach ESRF as those with NDKD alone (63% vs 28%, P < 0.05). Conclusions: Patients with pure NDKD had better outcomes. Traditional clinical parameters are useful, however haematuria does not distinguish DN from NDKD. This project was supported by the 2013 New Zealand Diabetes Foundation Research Fellowship award.
082 CONDUCT AND OUTCOMES OF AN RCT OF PREVENTION OF ALBUMINURIA, HYPERTENSION AND DIABETES IN ABORIGINES WE HOY1, SA MOTT1, B MCLEOD2, S SHARMA2, G ALLCOCK2, C NIXON2, A MONTZ2, LJ MAPLE-BROWN2, N ANDRIANOPOULOS3, A TONKIN3, L BEILIN4, MM HUQ3, CM REID3 1 Centre for Chronic Disease, University of Queensland, Brisbane, QLD; 2Menzies School of Health Research, Darwin, NT; 3Monash University, Melbourne, Victoria; 4 University of Western Australia, Perth, WA, Australia Aim and background: To describe outcomes of an RCT to assess effects of Coversyl on the onset of albuminuria, hypertension and diabetes in currently unaffected people in a remote Aboriginal community, which has very high rates of chronic disease. Methods: Eligible were adults (18+ years) with BP 3.4 and/or diabetes, with treatment duration up to 5 years and at least 114 people in each arm. A 2004–2006 screen indicated that about 600 adults might be eligible.
Results: On review of >855 people in 2008, 301 had developed disease, 175 were females without implanted contraception, 30 declined, 33 were non-resident and 169 consented. Of those, 35 never took drug, 38 dropped out within 3 months, while 96 participated for ≥1 year, 74 ≥ 2 years and 63 ≥ 3 years (total treatment time 309 person years). 65% took ≥50% of study medication. There were 20 endpoints in 17 people, (0.065/person yr) with no difference between study groups. However, SBP and DBP were lower in the treatment group who took ≥60% study drug use continuously over ≥7mths (P = 0.011, P = 0.022). Eight in the treatment and 10 in the placebo had serious adverse events (P = 0.428) and minor adverse events numbered 41:62 (P = 0.091) respectively, by group. Conclusions: Intercurrent disease development, prejudicial exclusion of fertile women, and high dropout rates hindered this trial. Despite apparent benefits of Coversyl, there was no significant effect on pre-specified outcomes.
083 THE DIFFERENTIAL EFFECT OF SOCIO-ECONOMIC STATUS ON BODY MASS INDEX AMONG ABORIGINAL CHILDREN & ADOLESCENTS S KIM1,2, P MACASKILL2, LA BAUR2,3, EM HODSON1,2, J DAYLIGHT1, R WILLIAMS1, N VUKASIN1, R KEARNS1, DM LYLE4, JC CRAIG1,2 1 Centre for Kidney Research, The Children’s Hospital at Westmead, Westmead, NSW; 2Sydney School of Public Health University of Sydney, Camperdown, NSW; 3 Discipline of Paediatrics and Child Health, Sydney Medical School, University of Sydney, Camperdown, NSW; 4Department of Rural Health, University of Sydney, Camperdown, NSW, Australia Aim: To determine relative changes in body mass index (BMI) between Aboriginal and non-Aboriginal children as they move through adolescence into young adulthood. Background: Earlier onset of obesity is associated with increased risk of chronic kidney disease (CKD) in adulthood. Aboriginal children have a higher prevalence of overweight and obesity with the contribution of socioeconomic status (SES) unclear. Methods: A prospective cohort study of Aboriginal and non-Aboriginal schoolchildren commenced in 2002 across 15 different screening centres involving 38 primary schools and 213 high schools across urban, regional and remote NSW. SES was recorded at baseline and participants’ BMI was measured every 2 years. We fitted a series of mixed linear regression models adjusting for age, sex, Aboriginality and SES. Results: 3418 (1949 Aboriginal) participants were screened over a total of 11, 387 participant years follow up. Obesity prevalence increased from 14.2% (mean age 11 years) at baseline to 17.2% at eight years follow up. Mean BMI SDS increased with age, with the increase in girls BMI SDS being significantly higher than boys (P for interaction < 0.01). SES had a differential effect on mean BMI SDS for Aboriginal children compared to non-Aboriginal children (P for interaction = 0.01). In the highest SES group, Aboriginal children had a BMI SDS 0.16 higher than non-Aboriginal children, whilst in the lowest SES group their BMI SDS was 0.17 lower. Conclusions: SES has a differential effect on adiposity for Aboriginal children, similar to that seen in low and middle income countries. Interventions to reduce the prevalence of obesity in the Aboriginal community are urgently needed, and must also focus on those who are socioeconomically advantaged, to maximise their impact. Subheadings (Arial, bold, font 12): Obesity, BMI, Aboriginal Health
084 CHRONIC KIDNEY DISEASE IN THE TOP END OF THE NORTHERN TERRITORY, 2002–2011 PD LAWTON1, J CUNNINGHAM1, N HADLOW2, Y ZHAO3, MD JOSE4 1 Menzies School of Health Research, Charles Darwin University, Darwin, Northern Territory; 2PathWest, Perth, Western Australia; 3Department of Health, Northern Territory Government, Darwin, Northern Territory; 4University of Tasmania, Hobart, Tasmania, Australia Aim: To determine the prevalence and progression of measured chronic kidney disease (CKD) across a region with a high incidence of treated end-stage kidney disease (ESKD). Background: The incidence of treated ESKD in the Northern Territory of Australia (NT) is three-to-four times national figures. Individual Indigenous community surveys have a much higher rate of treated ESKD and a very high prevalence of albuminuria compared to national rates. The overall prevalence and rate of progression of CKD in the region have not been described.
© 2014 The Authors Nephrology © 2014 Asian Pacific Society of Nephrology, 19 (Supp. 4), 17–57
NEPHROLOGY 2014; 19 (SUPP. 4)
Methods: Using a retrospective de-identified extraction of all records with a serum creatinine or urinary albumin-to-creatinine ratio from the single largest ambulatory pathology provider to the Top End of the NT between 1st February 2002 and 31st December 2011, we calculated the yearly total and age-specific prevalence of measured microalbuminuria, overt albuminuria and estimated glomerular filtration rate (eGFR) less than 60 mL/min/1.73 m2, and the prevalence of progressive CKD. Results: Over almost ten years 495,672 tests were done for 127,526 individuals, covering at most 26.3% of the adult estimated resident population. There was a steady increase in the proportion tested across all health districts in the region, more prominent in non-urban districts. In 2009, the overall regional prevalence of measured microalbuminuria and overt albuminuria was 1.5%, overt albuminuria alone 0.7% and eGFR