49

PARTICIPANT FOLLOW-UP IN THE KIDNEY EARLY EVALUATION PROGRAM (K EEP) AFTER INITIAL DETECTIONAllan J. Collins,1 Suying Li,1 Shu-Cheng Chen1. 1Chronic Disease Research Group, Minneapolis Medical Research Foundation, Minneapolis, Minnesota Chronic kidney disease (CKD) detection in a targeted, at-risk population has been reported in the National Kidney Foundation’s Kidney Early Evaluation Program (KEEP). This study assessed follow-up within three months of detection to determine if participants saw a physician, kinds of care addressed, and potential interventions.

KEEP is a free, community-based health screening program to raise kidney disease awareness and detect CKD for early disease intervention. Participants receive laboratory results and educational materials about kidney disease risks and treatment options. Physicians receive laboratory results for their participating KEEP patients, and clinical practice guidelines for CKD care.

Between August 2000 and December 2006, 72,395 KEEP participants met entry criteria. Follow-up forms were sent to all participants; response rate was 28.4%. Responders were more likely to be older, female, white, living in the western United States, with high school education or higher, and with decreasing kidney function by estimated glomerular filtration rates. Among respondents, 71% reported seeing physicians in follow-up. Those with evidence of CKD were 24% more likely to see physicians than those without CKD. Follow-up with physicians was more likely with decreasing kidney function levels, increasing albuminuria levels, and more advanced CKD stage.

The KEEP detection program, with disease education, appears to motivate the targeted population to seek physician care for findings noted. Longer term follow-up is needed to determine if detection and physician follow-up lead to changes in care and outcomes that may affect the elevated risk of death, ESRD, or cardiovascular events.

50

RITUXIMAB: A NOVEL TREATMENT OPTION FOR FIBRILLARY GLOMERULONEPHRITIS? Michael Collins1, Sankar D Navaneethan2, James Sloand2, Brad Rovin1; 1Ohio State University, Columbus, OH, USA & 2University of Rochester Medical Center, Rochester, NY, USA Fibrillary Glomerulonephritis (FGN) belongs to a group of disorders characterized by the deposition of fibrils in glomeruli. These fibrils are typically homogeneous and are often composed of IgG4 immunoglobulin subtype, suggesting an underlying B-cell dyscrasia. We speculated that use of an anti-B-cell therapy may be effective in the treatment of FGN. We present 2 patients who had nephrotic range proteinuria (6 and 4.5 grams /day), along with biopsy findings consistent with FGN. Other causes of paraproteinemias were excluded. Both patients were treated with rituximab 375 mg/ meter2 weekly for 4 weeks. One patient was treated with concomitant tacrolimus 1mg per day and the other patient with short course of steroids. Standard therapy of proteinuria consisting of renin angiotensin system blockade and strict blood pressure control were employed in both patients. Both patients demonstrated a decline in proteinuria to a level of less than 1.5 grams per day, one at the end of 27 months and the other at the end of 6 month follow-up. Neither patient demonstrated a worsening of their renal function through the course of therapy. These 2 cases demonstrate that rituximab, an anti-CD20 antibody, might prove to be useful in the treatment of fibrillary glomerulonephritis. While originally used to treat resistant non-Hodgkins lymphoma, rituximab has been used increasingly in the treatment of many different renal diseases such as lupus nephritis, cryoglobulinemia, and membranous glomerulonephritis. This is the first report of the use of anti-B-cell therapy to treat fibrillary glomerulonephritis. These results demonstrate a promising approach to a disease that has been considered refractory to therapy.

51

SCREENING PRACTICES FOR CHRONIC KIDNEY DISEASE(CKD)IN SOUTH CAROLINA Keidre J Corbett, B.Egan, J.Chen,Medical University of South Carolina, Charleston, SC, USA The Medicaid Act 124 states that all patients with a diagnosis of diabetes, hypertension or family history of CKD should be evaluated for kidney disease through routine clinical laboratory assessments of kidney function. However, very little is known about screening practices for CKD in South Carolina (SC)This study will evaluate screening practices among South Carolina primary care physicians and if race, geographical location, age, and other co-morbidities play a role.

This is an observational study which includes members of the Hypertension Initiative database. This database includes more than 70 clinical sites in the southeast and tracks over 200,000 patients.

Screening practices for CKD in SC is sub-optimal. Patients are less likely to be screened for CKD by serum creatinine if they are African-American, or from rural or very rural regions in SC. Variable OR 95% CI P Value Age (Years) 1.004 1.002-1.006 <0.0001 Female 1.210 1.153-1.270 <0.0001 African-American 0.793 0.752-0.835 <0.0001 HTN 1.293 1.050-1.592 0.0178 Diabetes 1.213 1.149-1.280 <0.0001 CVD 0.810 0.760-0.862 <0.0001 CHF 0.908 0.812-1.016 0.0934 Hyperlipidemia 1.841 1.741-1.946 <0.0001 Rural 0.387 0.366-0.410 <0.0001 Very Rural 0.673 0.610-0.742 <0.0001

52

GRANULOGENESIS IN SYMPATHOADRENAL CHROMAFFIN CELLS: CONTRIBUTION OF THE NEUROENDOCRINE SECRETORY PROTEIN SECRETOGRANIN II. Maïté Courel1, Daniel T. O'Connor 1,2, Laurent Taupenot 1,2

1Dept of Medicine, University of California at San Diego, La Jolla, CA, 2VASDHS, San Diego, CA, USA.

The biogenesis of dense-core catecholamine storage vesicles (CSVs) in neuro-endocrine cells is poorly understood. The secretory prohormones chromogranins/secretogranins are widely distributed in biogenic amine- and peptide-containing CSVs, and have been proposed to play a key function in the biogenesis of CSVs. In the present study, we investigated the putative CSV-forming role of secretogranin II (SgII). Downregulation of SgII expression by siRNA resulted in significant decrease in the abundance of CSVs in normal sympathoadrenal cells (PC12). Using a combination of fluorescence deconvolution microscopy and secretagogue-stimulated release approaches, we further assessed the granulogenic role of SgII in the sympathoadrenal cell variant (A35C), which lacks regulated secretory organelles. We show that expression of human SgII in the form of fusion proteins with the hemagglutinin epitope HA, GFP, or embryonic alkaline phosphatase (EAP) reporters induces the formation of secretory vesicles and a regulated secretory pathway in A35C cells. We conclude that the secretory prohormone SgII plays also a key role in the biogenesis of CSVs in neuro-endocrine cells.

NKF 2008 Spring Clinical Meetings AbstractsA40