RETROSPECTIVE EVALUATION OF VECTRA GRAFTS VS. PTFE GRAFTS FOR HEMODIALYSIS PATIENTS. Janice Weatherspoon, Ivan Maya, Carlton Young, Michael Allon. University of Alabama at Birmingham. Divisions of Nephrology and Transplant Surgery. Birmingham. AL Conventional PTFE dialysis grafts cannot be cannulated for 2-3 weeks following their creation. In contrast, the Vectra graft, made of a self-sealing polyurethane material, can be cannulated within 24 hours of implantation, representing a potential advantage in patients with limited catheter options. Since FDA approval of the Vectra graft in December 2000, little has been published on the relative outcomes of Vectra and PTFE grafts. Using a prospective, computerized vascular access database we identified 31 patients with a Vectra graft placed between 7/1/01 and 6/30/06, and compared them to 56 date-matched controls with a standard PTFE graft. The Vectra and PTFE groups were comparable in terms of age (55 vs 58), sex (39 vs 35% females), race (95 vs 98% blacks), diabetes (48 vs 42%), HTN (96 vs 90%), CAD (23 vs 29%), PVD (13 vs 6%), and proportion of thigh grafts (55 vs 55%). The median thrombosis-free graft survival (from creation to first thrombosis or failure) was similar for Vectra and PTFE grafts (median, 189 vs 216 days; 1-year survival, 29 vs 37%, P=0.52). The cumulative graft survival (from creation to permanent failure) was also similar (median, 987 vs 1098 days; 1-year survival 60 vs 60%, P=0.93). Finally, the cumulative risk of graft infection was 37.5% for thigh Vectras, 23% for upper arm Vectras, 21% for thigh PTFE, and 5% for upper arm PTFE (P=0.015 for the trend). In conclusion, the likelihood of thrombosis and failure is similar for Vectra and PTFE grafts. However, Vectra grafts have a higher risk of infection, particularly when they are placed in the thigh. Implantation of a Vectra graft represents a tradeoff between earlier cannulation and higher risk of infection.

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PERMANENT EXPOSURE OF A CRYPTIC ACTIN BINDING SITE IN FSGS-CAUSING MUTANT ALPHA-ACTININ-4Astrid Weins1, Johannes S. Schlondorff1, Fumihiko Nakamura2,Martin R. Pollak1

1Renal Division and 2Hematology Division, Brigham and Women’s Hospital, Boston We have identified 5 mutations in the head domain of the actin crosslinking protein -actinin-4 which cause an autosomal-dominant and slowly progressive form of focal segmental glomerulosclerosis (FSGS). All mutations lead to increased actin binding and form large cytoplasmic aggregates in cultured cells. These aggregates occur in podocytes in vivo, are highly insoluble and contain large amounts of actin, suggesting that glomerular damage in this disease is caused by a direct effect on the podocyte actin cytoskeleton. By means of in vitro studies, we further defined the effect of one disease-causing mutation (K255E) on actin crosslinking. Using recombinant proteins, mutant -actinin-4 shows dramatically increased actin binding affinity, resulting in the formation of a greatly altered actin filament network structure with different viscoelastic properties. Furthermore, the stochiometry of -actinin-4/actin molecules was increased. Supported by recent data on the crystal structure of -actinin-1, we postulated that an otherwise buried actin binding site is exposed or activated by the mutation. In further experiments, inactivation of this buried actin binding site by site-directed mutagenesis returned the actin binding affinity of the mutant to that of the wild type protein but showed no effect on wild type -actinin-4. We propose that the mutation locks the head domain of -actinin-4 in one conformation, thereby exposing a high-affinity actin binding site which leads to dysregulation of the actin binding properties of -actinin-4. Over time, this results in direct structural damage of the actin cytoskeleton in the podocyte foot process and ultimately foot process effacement with destruction of the glomerular filter.

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ALBUMINURIA AND AGE AS PREDICOTRS OF ERYTHROPOIETIN RESPONSE IN CHRONIC KIDNEY DISEASE Adam whaley-connell, harbanksh sangha, kunal chaudhary, georges saab. university of missouri-columbia school of medicine, division of nephrology and harry s truman va medical center, columbia, missouri Resistance to epoietin alpha (EPO) in patients with chronic kidney disease (CKD) has been associated with severe secondary hyperparathyroidism, iron deficiency, medications, and chronic inflammation. There is mounting interest in the metabolic dysregulation seen in CKD patients with Metabolic Syndrome with resultant chronic inflammation as another component of EPO resistance. Recent evidence supports hypertension and albuminuria (components of the metabolic syndrome) as possible modulators of EPO resistance. To investigate the metabolic influence on EPO resistance, we retrospectively collected data on 65 predominantly Caucasian male patients with CKD being treated with recombinant EPO. Erythropoietin resistance index (ERI) was defined as the weekly epoietin dose divided by hemoglobin divided by body weight in kg. Non-parametric correlation testing was used to assess significant relationships between ERI and other variables. Significant correlations were found between ERI and age (r=0.281, p<0.0001), urine protein/creatinine ratio (r=0.301, p=0.001), serum transferrin saturation (r=-0.222, p=0.003), serum albumin level (r=-.300, p<.0001) and serum intact PTH (r=0.157, p=0.012). There were no significant correlations between ERI and serum ferritin level, estimated glomerular filtration rate, mean arterial pressure, systolic blood pressure, or diastolic blood pressure. Multivariate analysis revealed that age (beta = .305) and serum albumin level (beta = -.247) were the only independent variables predicting ERI. Serum albumin varied inversely with urine protein/creatinine ratio (r=-.430, p < .0001) and positively with serum hemoglobin level (r=.300, p < .0001). Use of statin, ace inhibitor, or angiotensin II receptor blocker did not affect erythropoietin responsiveness in this group. Age, proteinuria, and hypoalbuminemia are associated with decreased EPO responsiveness.

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THE ASSOCATION BETWEEN GLYCOSYLATED HEMOGLOBIN (HgbA1c) AND THREE-YEAR MORTALITY RISK IN PATIENTS ON MAINTENANCE HEMODIALYSIS. M Williams, Harvard Medical School, Boston, MA, USA; E Lacson Jr., M Teng, JM Lazarus, R Hakim, Fresenius Medical Care, Lexington, MA, USA We reported that HgbA1c was associated with 1-year death risk at high and low extreme values (Williams et al, KI, 2006). This report extends the follow-up of these patients over 3 years. Hemodialysis (HD) patients in the database of a large dialysis organization with a diagnosis of diabetes, HgbA1c results from Oct. 1 to Dec. 31, 2002, and survival into Jan. 1, 2003 formed the study cohort. They were followed from Jan. 1, 2003 to Dec. 31, 2005. Cox models were used to determine unadjusted, case-mix adjusted (age, gender, race, body surface area, and vintage) and fully adjusted (case mix plus vascular access type, eKt/V, albumin, hemoglobin, phosphorus, and WBC) mortality risk profiles. There were 24,875 patients with mean age 63.7 + 12 years, 52% female, 53% white and 36% black, 94% type 2 diabetic, with mean HgbA1c 6.77%, eKt/V 1.41, Hgb 11.7 g/dL, and albumin 3.82 g/L, in the cohort. Mean HgbA1c > 11% is associated with a ~23% higher risk of death over 3 years (p < 0.05), after adjusting for case-mix, access type, and selected laboratory variables. However, the risk profile is flat over the distribution of HgbA1c < 11%. Findings support keeping HgbA1c < 11%. However, more research is needed to further refine the utility of HgbA1c tests and define outcome-based HgbA1c targets in HD patients.

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NKF 2007 Spring Clinical Meetings Abstracts A83