LANTHANUM CARBONATE VS STANDARD PHOSPHATE BINDER THERAPY: EVOLUTION OF RENAL OSTEODYSTROPHY OVER 1 AND 2 YEARS OF TREATMENT Hartmut H. Malluche1 and Raymond D. Pratt2; 1Division of Nephrology, University of Kentucky, Lexington, KY, USA and 2ShirePharmaceuticals, Wayne, PA, USA Lanthanum carbonate (LC, Fosrenol®) and standard phosphate binder (Stx, primarily calcium-based agents) therapies were compared in a prospective, randomized controlled trial, designed to investigate the evolution of renal osteodystrophy over 2 years of treatment. Following tetracycline labelling, bone biopsies were taken from hemodialysis patients before randomization and following 1 and/or 2 years of treatment. Bone turnover, activation frequency, bone volume and mineralization status (mineralization lag time [Mlt] and osteoid thickness [O.th]) were evaluated. Baseline demographics were similar between the treatment groups. Paired biopsies were available from 99 patients: 1-year biopsies from 34 patients receiving Stx and 32 receiving LC, and 2-year biopsies from 24 patients receiving Stx and 32 receiving LC. Mean serum phosphorus levels decreased in both treatment groups; values remained below the 5.9 mg/dl target for the duration of the study. In patients receiving LC, serum calcium levels were lower, and PTH, osteocalcin and bone specific alkaline phosphatase levels were higher, compared with Stx treatment. Group comparisons of histomorphometric bone parameters with Stx and LC showed no statistical differences in mean values after 1 or 2 years of treatment. Analysis of changes in individual patients with respect to normal ranges showed improvements in bone turnover and formation at 2 years with LC, compared with Stx treatment. Two patients in the LC group developed a mineralization defect (Mlt > 100 days and O.th > 20 µm) compared with no patients in the Stx group. In conclusion, LC treatment resulted in similar serum phosphorus control, lower serum calcium levels, and biochemical and histological evidence of increased bone formation, compared with Stx.

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THE CARDIO-RENAL-ANEMIA SYNDROME (CRA) IN HEMODIALYSIS PATIENTS. Jolanta Malyszko1, Jacek S Malyszko1, Piotr Kozminski2,Maria Wanic-Kossowska3 Irena Glowinska, Wlodzimierz Ratajewski3, and Adrian Iaina4. 1Nephrology, Med. Univ., Bialystok, Poland; 2Dialysis Unit, Dzialdowo; 3Nephrology Dept., Med Univ., Poznan and 4Head Nephrology, APC Health-Specialists Clinics, Benei Berak, Israel. Background : The correction of anemia was effective in the amelioration of both cardiac and renal failure. The aim of the present work was to study the relationship between the severity of CRA syndrome in chronic hemodialysis patients and survival probability. Patients : 444 patients on hemodialysis were followed for 5 years. Results: A total number of 153/444, 34% patients died during the study. The median value for the severity score of the whole group of dialysis patients was 1.83. In Kaplan-Meier analysis CRA severity score was strongly associated with the mortality, p<0.001.The severity score was also correlated with : albumin, hsCRP, Kt/V, erythropoietin treatment, triglycerides, Hb and CaxP product (p<0.001 at least).In the Cox regression analysis Hb, albumin, erythropoietin treatment and CaxP product remained significant predictors of death. Conclusions: The severity score of CRA syndrome in HD patients is an independent and very significant predictor of death. The patients with a high severity score had more hypoalbuminemia , higher inflammation markers and probably more severe renal osteodystrophy. CRA severity scoring as defined by us is an easy tool to predict outcome of dialysis patients.

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KIDNEY FUNCTION, OXIDIZED LDL AND CARDIOVASCULAR DISEASE (CVD) Wissam Mansour1, Paul Holvoet2, Michael G. Shlipak3, Stephen Kritchevsky4, Tamara Harris5, Anne B. Newman1, Linda F. Fried1,6, for the Health, Aging and Body Composition Study. 1Univ.of Pittsburgh, Pittsburgh PA, 2Catholic Univ., Leuven, Belgium, 3San Francisco VA, San Francisco, CA, 4Wake Forest Univ., Winston-Salem, NC, 5National Institute on Aging, Bethesda, MD, 6VAPHCS, Pittsburgh, PA Oxidative stress has been implicated in CVD. The aim of this analysis is to assess whether oxidized low density lipoprotein (oxLDL) mediates the association of kidney function with CVD. Study participants (N=2920) were older adults participating in the Health, Aging, and Body Composition study (Health ABC) recruited in Memphis, TN, and Pittsburgh, PA. Kidney function was assessed using eGFR and cystatin C. The oxLDL/LDL cholesterol ratio (%) was used as a surrogate of oxidative stress and lipoprotein peroxidation. CVD was defined as history of revascularization, myocardial infarction, or angina and taking antianginal medicines. Logistic regression was used to determine the association of oxLDL/LDL and kidney function with prevalent CVD. The mean age of participants was 74, cystatin C 1.0 g/L, eGFR 72.8 (21% with eGFR <60 ml/min/1.73m2), oxLDL/LDL 1.09 (range 0.08-6.0%); 51% were women, 41% black, 15% had diabetes. Linear regression revealed that cystatin C predicts oxLDL/LDL ratio (p< 0.001) after adjusting for age, race, gender, blood pressure, smoking, and diabetes. EGFR <60 was not associated with oxLDL/LDL (p=0.89), but there was trend for GFR <45 (p=0.09). OxLDL/LDL was associated with CVD after adjustment for age, race, gender (OR 1.25, (95% CI 1.04,1.49), p=0.01). After further adjustment for HDL, diabetes, blood pressure and smoking, the relationship was no longer significant (OR 1.14, (0.95,1.37), p=0.16). Both cystatin C (OR 1.23 per standard deviation, (1.12, 1.35) and eGFR <60 (OR 1.48, (1.19, 1.85) were associated with CVD, after adjustment. The addition of oxLDL/LDL did not attenuate the relationship for cystatin C or eGFR. Decreased kidney function is associated with higher levels of oxidized LDL. However, this does not appear to mediate the association of kidney function with prevalent CVD.

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PLASMA REFERENCE STANDARDS FOR PTH ASSAYS IN PATIENTS ON HEMODIALYSIS Kevin J Martin1, Esther A Gonzalez1, Thomas Manley2 and Sharon Moe3. 1Saint Louis University; 2National Kidney Foundation and 3University of Indiana.Measurement of plasma PTH concentration is critical for the evaluation and treatment of Mineral and Bone Disorder in CKD (CKD-MBD). The KDOQI Guidelines suggest PTH target ranges and, in turn, clinical treatment protocols are based on these targets. However, the evidence used to support these target ranges was primarily based on an assay for Intact PTH that is no longer used. In practice, there are up to 15 different Intact PTH assays in use worldwide. These assays may provide disparate results due to varying cross reactivity with PTH fragments that accumulate in CKD patients and other factors. This pilot study is to test the feasibility of developing biologic reference standards for PTH that can be used to estimate the variation between the different PTH assays. This method of ongoing analysis of PTH assays would help interpretation of clinical results to guide treatment and allow for comparison of research studies in CKD-MBD. Plasma was obtained from hemodialysis patients with varying degrees of SHPT. The specimens were acquired using plasmapheresis. The citrated plasma was then aliquoted into vials and lyophilized for distribution. Eight labs in the U.S. were asked to participate in the pilot test and to analyze four samples for PTH using whatever Intact PTH assay they have available. Values obtained, in pg/mL, ranged from 565-1054; 407-686; 565-741; and 376-683 in Samples 1-4, respectively. These data show that, as expected, there is some variation in results for the same sample between different labs and assays. Strict adherence to numerical values for PTH ranges in current practice guidelines is not advisable.

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NKF 2007 Spring Clinical Meetings AbstractsA58