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MICROALBUMINURIA AND LACTATE DEHYDROGENASE (LDH) AS PREDICTORS OF KIDNEY INVOLVEMENT IN A PEDIATRIC SICKLE CELL DISEASE (SCD) POPULATION Kyla J Scarponi1, Hilary Hotchkiss2, Beth Savage1, Richard Drachtman1,and Sevgi Gurkan1. 1Pediatrics, University of Medicine and Dentistry of New Jersey(UMDNJ)-Robert Wood Johnson Medical School(RWJMS), New Brunswick, NJ, United States and 2Pediatrics, Mount Sinai School of Medicine, New York, NY, United States. Renal failure due to sickle cell nephropathy is seen in 4-20% of adult SCD patients. Duration of disease, severity of anemia and genetic factors are believed to influence the risk of development of renal disease among patients with SCD. The purpose of this project is to determine the prevalence of renal involvement in a SCD population and identify potential risk factors for renal involvement. Forty patients with SCD between the ages of 5-19 years that were seen within the past year are identified from UMDNJ-RWJMS Pediatric Hematology and Oncology Clinic. Following IRB approval, a retrospective chart review was performed for age, sex, height, body mass index (BMI), serum creatinine and estimated GFR (eGFR) by Schwartz and MDRD formulas, type of SCD, Hb level (total Hb and % HbF), LDH level, reticulocyte count, blood pressure, history of splenectomy, history of hydroxyurea use and history of transfusions to determine clinical correlates for microalbuminuria and proteinuria. All variables are correlated with microalbuminuria and proteinuria by univariate and multivariate regression analysis. The mean age of the study population was 12 +/- 4.5 years. The prevalence of microalbuminuria and proteinuria was 32 % and 10 % respectively. Univariate analyses revealed a significant correlation between LDH level and microalbuminuria (Pearson r=0.47, p=0.04) and proteinuria (Pearson r=0.48, p=0.035). Multivariate analysis revealed a significant correlation between microalbuminuria and LDH level (p=0.04) and microalbuminuria and history of splenectomy (p= 0.05) when controlled for other variables. In this pediatric SCD population, LDH is found to strongly correlate with microalbuminuria and proteinuria. Further studies are needed to confirm LDH as an early marker for risk of kidney involvement among SCD patients.

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LONG-TERM CLINICAL EXPERIENCE WITH HEMATIDE™ Brigitte Schiller1,2; E Martin2; P Pergola2; S Zeig2; F Whittier2; R Leong3; C Francisco3; AM Duliege3 1Satellite Healthcare Inc., Mountain View, CA, USA; 2AFX01-03/09 Hematide Study Groups; 3Affymax, Inc., Palo Alto, CA, USA Hematide™ is the first synthetic, peptidic ESA that is in phase 3 development for the treatment of anemia associated with CKD. Results from 2 initial phase 2 (completed) studies and 2 ongoing long-term extension studies with once-monthly Hematide are reported herein. This unplanned analysis included 100 HD patients who had stable Hb levels on epoetin (baseline) before entry into the initial studies. Each patient received ≥24 weeks of Hematide treatment in 1 of 2 initial studies and continued to receive Hematide in 1 of 2 open-label extension studies; the Hematide dose was adjusted as necessary to maintain a Hb level of 10 to 12 g/dL (updated from the original 2006 protocol target of 11 to 13 g/dL). Mean Hb levels were maintained within 1 g/dL from baseline (Figure). AEs were reported for 93 patients (93%). Of these patients, 7 (7%) had AEs possibly related to Hematide; each type of AE occurred only once. Serious AEs were reported in 67 patients (67%). A single patient experienced a serious AE that was considered possibly Hematide related (fatal pulmonary embolism).

These results indicate that long-term once-monthly Hematide treatment was generally well tolerated and maintained mean Hb levels within 1 g/dL from baseline over a long duration of treatment.

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aPatients remained in the initial studies for 5 to 8 months.

n=49 n=43

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CLINICAL EXPERIENCE IN THE THERAPEUTIC CHALLENGE OF COLLAPSING FOCAL SEGMENTAL GLOMERULOSCLEROSIS (FSGS) Andres Serrano, Lakshmi Nadimpalli, Mt. Sinai Hospital, Chicago, IL, USA There is no clear consensus in the management of idiopathic FSGS collapsing variant. We report our experience with 2 patients who were diagnosed with idiopathic FSGS collapsing variant. The 1st

patient is a 33 year old African American woman with massive proteinuria (urine protein/creatinine (UP/Cr) 18.6 mg/mg) and normal Sr Cr (serum creatinine) 0.8 mg/dl. She was treated with prednisone 60 mg/day for 6 months and lisinopril with a positive response (UP/Cr 8 mg/mg) and her Sr Cr remained normal. She was then initiated on Cyclosporine 150 mg twice daily and the prednisone was tapered off. Ten months later her proteinuria improved (UP/Cr 3.3 mg/mg) and Sr Cr remained stable at 1.1 mg/dl. The 2nd patient is a 20 year old Hispanic man with acute kidney injury (Sr Cr 1.5 mg/dl) and massive proteinuria (UP/Cr 28 mg/mg). He was treated with lisinopril and prednisone 60 mg/day for 6 months with a positive response (UP/Cr 12 mg/mg), but his kidney function deteriorated (Sr Cr 1.9 mg/dl). Cyclosporine 100 mg twice daily was initiated and prednisone was discontinued. After 6 months his proteinuria improved remarkably (UP/Cr 3.8 mg/mg) and Sr Cr has stabilized at 3.4 mg/dl. Thus we report 2 cases of collapsing FSGS whom we treated similarly with a trial of steroids for 6 months followed by Cyclosporine and had partial response with stable renal function.

268

A CASE OF PATHOLOGIC POLYARTERITIS NODOSA (PAN) IN THE SETTING OF CLINICAL CALCIPHYLAXIS Aastha Sethi, Marzouq Qubti, Jin Park, Stuart Levine, Paul Segal, Ira Mandell, David Spector, Gary Briefel Johns Hopkins University, Baltimore, MD, USA Calciphylaxis, also known as calcific uremic arteriolopathy is a form of small vessel vasculopathy. It is characterized by deposition of calcium and phosphorus in the subcutaneous arterial vessels. We describe a case of a woman who was diagnosed and treated as calciphylxis though biopsy revealed medium vessel vasculitis. A 52-year- old woman with end stage renal disease (ESRD) on peritoneal dialysis (PD), status post aortic valve replacement, and on chronic anticoagulation was admitted to our Burn Unit for management of diffuse desquamative skin lesions on the lower extremities. She developed painful violaceous skin lesions on her thighs which rapidly progressed to bullae formation and ulcerations over the entire lower extremities. During the hospital stay, she developed ischemic gangrene of her toes. Laboratory studies revealed iPTH levels of 2389 ng/l, positive antinuclear antibodies and an ESR of 139mm/hr. Skin biopsy showed leukocytoclastic vasculitis. Patient was treated with I.V. Sodium thiosulfate with some improvement in her symptoms. Her skin lesions, however, continued to worsen. A repeat biopsy was also consistent with medium- vessel leukocytoclastic vasculitis with no evidence of calcium deposition. She was started on steroids without clinical improvement. Her hospital course was complicated by atrial fibrillation, upper GI bleed, pneumonia and septic shock. Given her overall poor prognosis, the family elected to withdraw care and she died after a 2-month hospitalization. Calciphylaxis is typically seen in ESRD patients with risk factors such as female sex, a high Ca × P product, PD , hypoalbuminemia and warfarin use. Our patient had many of these risk factors. Myriad reports in the literature reveal calciphylaxis as the diagnosis in cases initially misdiagnosed as primary small vessel vasculitides. To our knowledge, this is the first case in the literature with clinical findings of calciphylaxis having occurred concomitantly with histologic findings of medium sized vessels infiltrated by neutrophils and leukocytoclasia; all characteristics of a medium vessel vasculitis.

NKF 2010 Spring Clinical Meetings AbstractsA98