ABSTRACTS DAY 3

NEPHROLOGY 2012; 17 (Suppl. 2), 76–88

doi:10.1111/j.1440-1797.2012.01633.x

ABSTRACTS DAY 3 187 RELATIVE ENERGY BALANCE, CHRONIC KIDNEY DISEASE AND RISK OF CARDIOVASCULAR AND ALL-CAUSE MORTALITY S IFF1, G WONG1, AC WEBSTER1,2, V FLOOD3, JJ WANG4, P MITCHELL4, J CRAIG1,2 1 Centre for Kidney Research, Kids Research Institute, Children’s Hospital at Westmead, Sydney, Australia; 2Sydney School of Public Health, University of Sydney, Sydney, Australia; 3School of Health Sciences, Faculty of Health and Behavioural Sciences, University of Wollongong, Wollongong, Australia; 4Centre for Vision Research, Department of Ophthalmology and the Westmead Millennium Institute, University of Sydney, Sydney, New South Wales, Australia Aim: To determine the association between the relative energy intake, and the risk of all-cause and cardiovascular mortality in people with early to moderate stage CKD. Background: Obesity and excess energy intake relative to output are risk factors for cardiovascular and all-cause mortality in the general population. However, previous studies have reported an inverse relationship between obesity and mortality risk among those on dialysis. The association between relative energy intake and mortality risk among those with mild-moderately reduced kidney function is unclear. Methods: Analysis included 1245 men and 1490 women aged ≥49 years at baseline from a population-based cohort in the Blue Mountains, Sydney, Australia. We assessed the relationship between relative energy balance and the risk of all-cause and cardiovascular mortality in people with and without reduced kidney function using unadjusted and adjusted Cox proportional regression models. Results: There is an increased risk of all-cause (adjusted HR 1.48, 95% CI 1.05 to 2.09, p = 0.026) and cardiovascular mortality (adjusted HR 1.64, 95% CI 0.94 to 2.84, p = 0.078) among those with higher relative energy intake compared with those with lower relative energy intake in the CKD population. Simple sugar (per 100 g, HR: 1.33, 95% CI: 1.08 to 1.64, p = 0.007) was significantly associated with an increased risk of all-cause mortality. Conclusions: Relative energy intake, but not BMI, is a significant risk factor for all-cause and cardiovascular mortality among elderly people with CKD. Doubling the relative energy intake is associated with a 48% increased risk for all-cause and 63% vascular mortality among those with early to moderate stage CKD, irrespective of their body mass index. Strategies to limit the energy and sugar intake may reduce the burden of premature deaths.

188 URINARY BIOMARKERS MAY HELP PREDICT RENAL DECLINE IN PATIENTS WITH CHRONIC KIDNEY DISEASE D LEE1, MM CAI1, ER SMITH1,2, ML FORD2, LA TOMLINSON3, C RAJKUMAR2, LP MCMAHON1, SG HOLT1,2 1 Department of Renal Medicine, Eastern Health Clinical School, Monash University, Melbourne VIC, Australia; 2Brighton and Sussex University Hospitals NHS Trust, Brighton, United Kingdom; 3Department of Clinical Pharmacology, Addenbrooke’s Hospital, Cambridge, CB2 2QQ, United Kingdom Aim: To determine whether measurements of urinary neutrophil gelatinaseassociated lipocalin (uNGAL) and/or fetuin-A (uFet-A) help predict renal decline in patients with Chronic Kidney Disease (CKD). Background: uNGAL and uFet-A have both been associated with the development of acute kidney injury. However, their role in predicting progression of CKD, either independently or in combination with established risk factors, is unknown. Methods: 200 patients with CKD 3&4 enrolled in a prospective observational study had uNGAL and uFet-A measured at baseline in addition to conventional risk factors for CKD progression. Cox proportional hazard ratios (HR) were calculated to evaluate the association of each predictor to the risk of renal decline, using a composite endpoint of >25% reduction in eGFR or commencement of renal replacement therapy. Net reclassification improvement (NRI) scores were used to assess the contribution of uNGAL or uFet-A to this multivariate model in predicting the 3-year risk of renal decline. Results: 44 patients (22%) reached the primary composite endpoint after a median follow-up of 45 months. uNGAL and uFet-A were both independently associated with CKD progression after adjustment for age, gender, eGFR, SBP, haemoglobin, albumin, triglycerides, PTH and albuminuria (uNGAL, HR 1.3, P = 0.025; uFet-A, HR, 1.5, P = 0.033). On ROC analysis the base model and

additional urinary biomarkers gave an AUC of 0.92–0.94. Addition of either urinary marker to the base model increased the NRI score (uNGAL, 42.8%; uFet-A, 35.8%, P < 0.001) and improved model fit. Conclusions: uNGAL and uFet-A independently predict progression of CKD. Addition of uNGAL and/or uFet-A improves prediction of renal decline based on conventional risk factors.

189 IT IS A RISKY BUSINESS: NEW METRICS FOR ASSESSING CANDIDATE BIOMARKERS JW PICKERING, ZE ENDRE University of Otago Christchurch, Christchurch, New Zealand Aim: To assess the validity and usefulness of new statistical metrics to quantify the added value of a new biomarker. Background: New biomarkers should improve the diagnostic performance of available tests. Traditionally performance has been assessed by the area under the receiver operator characteristic curve (AUC). Three new metrics, the Net Reclassification Improvement (NRI), the category free NRI (cfNRI) and the Integrated Discrimination Improvement (IDI) have been rapidly adopted since 2008. Methods: We compared the application of these metrics in ascertaining the added value of the novel biomarker urinary Cystatin C in 528 critically ill patients with risk models for three events, namely sepsis, acute kidney injury (AKI), and 30-day mortality. We also devised a risk assessment plot for visualising these metrics analogous to the receiver operator characteristic curve. Results: All three new metrics identified that addition of urinary Cystatin C improved the model for sepsis (NRI 25 [95% CI 14 to 40]; cfNRI 86 [60 to 105]; IDI 0.16 [0.095 to 0.25]). The NRI was sensitive to the choice of risk threshold. The risk assessment plot identified that the addition of urinary Cystatin C to the model decreased risk for some who did not have sepsis but increased it for others. The cfNRI was also high in those without the event for AKI and death models (44% and 37% respectively), however this was driven by very small changes in risk. The IDI reflected those small changes (0.016 and 0.019). Conclusions: The IDI, reported separately for those with and without the event of interest, best represented the added value of the new test. The risk assessment plot identified differences in the models not apparent in any of the metrics.

190 ANGIOTENSIN CONVERTING ENZYME 2 IN CHRONIC KIDNEY DISEASE MA ROBERTS1,2, E VELKOSKA2, FL IERINO1,2, LM BURRELL2 1 Austin Health, Melbourne, Australia; 2University of Melbourne, Melbourne, Australia Aim: To determine plasma angiotensin-converting enzyme 2 (ACE2) activity in patients with kidney disease and associated clinical parameters. Background: ACE2 is a novel regulator of the renin-angiotensin system that counteracts the adverse effects of angiotensin II. Plasma ACE2 is an independent predictor of adverse events and elevated levels are associated with greater severity of myocardial dysfunction in patients with heart failure. To date there have been no studies examining plasma ACE2 activity in patients with kidney disease, who have a substantial risk of cardiovascular disease (CVD). Methods: Patients groups included (a) chronic kidney disease Stage III/IV (CKD), (b) patients treated with haemodialysis (HD), and (c) kidney transplant recipients (KTR). Plasma ACE2 enzyme activity was measured (serum stored at −80°C) using a fluorescent substrate assay. Linear regression was performed in males and females separately to determine covariates associated with log-transformed ACE2. Results: The median (inter-quartile range) plasma ACE2 activity in pmol/ minute/mL was 15.9 (8.4–24.2) in CKD (n = 57), 9.2 (3.9–18.2) in HD (n = 100) and 13.1 (5.7–21.9) in KTR (n = 80; p < 0.01). Males on HD had levels of 12.1 (6.8–19.6) compared to 4.4 (2.5–10.3) in females undergoing HD (p < 0.01). Log-transformed ACE2 plasma activity was most strongly associated with the post-HD systolic blood pressure (SBP) in females (β-coefficient 0.04, 95% confidence interval 0.01–0.06, p < 0.01), and with B-type Natriuretic Peptide (BNP) in males (0.39, 0.19–0.60, p < 0.01). Conclusions: Plasma ACE2 activity is reduced in HD patients compared to CKD patients, and in female HD patients compared to male. In HD patients, the

© 2012 The Authors Nephrology © 2012 Asian Pacific Society of Nephrology, 17 (Suppl. 2), 77–88

ANZSN 48th Annual Scientific Meeting

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association of plasma ACE2 activity with BNP in males and SBP in females indicates that the role of ACE2 in CVD may differ by gender.

191 SERUM FETUIN-A AND BONE MINERAL MARKERS AMONG PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 AND 4 R KRISHNASAMY1, G ELDER2, C HAWLEY1, N ISBEL1 1 Department of Renal Medicine, University of Queensland, Princess Alexandra Hospital, QLD; 2Department of Renal Medicine, University of Sydney, Westmead Hospital, NSW Aim: This study aimed to determine the relationship between fetuin-A and markers of bone mineral metabolism in patients with moderate kidney disease. Background: Fetuin-A, a liver derived glycoprotein is a potent calcification inhibitor especially in patients with advanced kidney disease. Fetuin-A has been shown to regulate osteogenesis through neutralizing transforming growth factorbeta (TGF-β) superfamily. Hence, fetuin-A may indirectly inhibit calcification through its influence on bone mineralization and remodelling. Methods: Demographic and laboratory data were collected on 148 patients with chronic kidney disease stages 3–4. Assays were performed for serum Fetuin-A, corrected calcium, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25OHD), 1,25 hydroxyvitamin D (1,25(OH)2D), bone formation marker; bone specific alkaline phosphatase (b-ALP) and bone resorption marker; tartrate resistant acid phosphatase (TRAcP-5b). A multivariate regression model was used to assess associations between serum fetuin-A and factors important to bone metabolism and turnover. Values are mean ± SD. Results: The age of subjects was 60 ± 9.4 years and estimated GFR was 40 ± 9.2 ml/min/1.73 m2. Serum fetuin-A correlated positively to serum calcium (r = 0.2, p = 0.018) and negatively to TRAcP-5b (r = −0.16, p = 0.049). In a multivariate regression analysis with adjustment for demographic and bone mineral parameters, serum calcium (p = 0.009), PTH (p = 0.018) and TRAcP-5b (p = 0.027) were all independent predictors of fetuin-A (R2 = 0.18, p = 0.036). Conclusions: Levels of fetuin-A vary with parameters of bone mineral metabolism in patients with chronic kidney disease stages 3–4. The positive association to calcium and PTH suggest a linkage between abnormal bone mineral metabolism and regulation of fetuin-A. The negative relationship to TRAcP-5b suggests that fetuin-A may inhibit bone resorption. Further studies are needed to ascertain the regulation and direct interaction of fetuin-A and bone mineral metabolism.

192 ASSOCIATIONS OF 25-OH VITAMIN D AND PARATHYROID HORMONE LEVELS IN SUBJECTS WITH MILD TO MODERATE CHRONIC KIDNEY DISEASE MJ DAMASIEWICZ1,2, ZX LU2,3, KA SIKARIS3, PG KERR1,2, KR POLKINGHORNE1,2 1 Department of Nephrology, Monash Medical Centre, Clayton, VIC; 2Department of Medicine, Monash University, Clayton, VIC 3Melbourne Pathology, Collingwood, VIC Aim: To assess the relationship between 25-OH vitamin D (25OHD) and parathyroid hormone (PTH) levels in patients with mild to moderate CKD. Background: The associaiton between 25OHD deficiency and an elevated PTH level in the general population is well described, however this associaiton is less defined in people with mild to moderate CKD. Methods: 16629 subjects underwent blood tests at Melbourne Pathology and had a complete dataset for creatinine, phosphate, 25OHD and PTH. 25OHD deficency and severe deficiency were defined as serum levels of