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RECURRENT ATYPICAL HEMOLYTIC UREMIC SYNDROME ASSOCIATED WITH FACTOR I MUTATION IN A LIVING RELATED RENAL TRANSPLANT RECIPIENT Micah R. Chan, Christie P. Thomas, Richard J. Smith, Jose Torrealba, Millie Samaniego, University of Wisconsin Hospitals and Clinics, Madison, WI; University of Iowa Hospitals and Clinics, Iowa City, IA Hemolytic uremic syndrome (HUS) is described by the clinical triad of acute renal failure, microangiopathic hemolytic anemia and thrombocytopenia. Approximately 90% of HUS is triggered by infectious agents such as Stx-E. coli; the remaining 10% of cases can be genetic, acquired or idiopathic and are collectively known as atypical HUS (aHUS). Approximately 50% of patients with aHUS have a mutation in one of three complement regulatory proteins - complement factor H (CFH), membrane cofactor protein (MCP) or factor I (FI) - that inhibit activation of the alternative complement pathway thereby limiting complement-mediated tissue injury. Identifying these genetic cases is of clinical relevance in patients with aHUS who progress to end-stage renal failure, as most patients with CFH and FI mutations develop recurrent disease that leads to graft loss. A previously healthy 26-year-old white female presented with fevers, vomiting, abdominal cramping, and dense renal failure. A renal biopsy showed diffuse capillary fibrin deposition and segmental staining for fibrin and IgM along the glomerular basement membrane, consistent with thrombotic microangiopathy (TMA). Six months later, the patient underwent a haploidentical living-related renal transplant from her father. She had excellent graft function initially but within one month was hospitalized with renal failure and biopsy-proven recurrent TMA with negative C4d and donor-specific antibodies. Because of the rapid recurrence of aHUS in the transplanted kidney with evidence of complement activation, we considered the possibility that she may have a defect in complement regulation. Direct sequencing of three complement control genes revealed a heterozygous missense mutation, Y369S, within a functional domain of FI. This report emphasizes the importance of genetic testing in patients with aHUS prior to renal transplantation, and demonstrates the challenges in the management of these patients.

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HO-1 OVEREXPRESSION REDUCES PROTEINURIA IN EARLY GLOMERULAR IMMUNE INJURY. alan chu, pu duann, elias lianos, robert wood johnson university hospital, new brunswick, NJ

HO-1, the rate-limiting heme degradation enzyme, has emerged as a renoprotective protein in various models of kidney injury. However, we demonstrated that, compared to tubules, glomeruli are refractory to HO-1 upregulation in response to injury. We , therefore, generated transgenic mice with overexpression of HO-1 targeted to glomerular epithelial cells (GEC) using a nephrin (Neph) promoter to drive expression of FLAG-tagged human (h)HO-1. In these mice we explored: 1) whether integrity of glomerular permeability to protein is altered, and 2) whether this overexpression reduces proteinuria following onset of glomerulonephritis induced by antibody against the GBM (anti-GBM GN). In transgenic mice, there was a 16-fold higher transgene expression in kidney compared to other organs (liver). Dual immunostaining for (FLAG-tagged HO-1) transprotein and the GEC marker WT-1 overlaid on GEC. The transgenic mice were no different from wild-type littermates with respect to motility, fur color, body weight, breeding capability and urinary protein excretion rate, indicating that GEC-targeted HO-1 overexpression had no effect on glomerular protein permeability. There was a significant reduction in urine protein excretion (Up/Uc) in transgenic compared to wild-type mice following onset of anti-GBM GN. Specifically, Up/Uc in transgenic mice (n=8) was 0.97 ± 0.43 on day - 4, 2.62 ± 0.43 on day 3, and 3.43 ± 1.94 on day 6. Up/Uc in wild type mice (n=7) was 1.03 ± 0.51 on day -4, 5.48 ± 2.56 on day 3, and 8.34 ± 4.76 on day 6. This salutary effect was abolished by day 9 at which point Up/Uc in transgenic mice (n=8) was 41.5 ± 68.7 while Up/Uc in wild type (n=7) was 41.6 ± 58.2. These observations indicate that GEC-targeted HO-1 expression reduces proteinuria at early stages of anti-GBM GN. The transient nature of this effect could be due to the pronounced increase in synthesis/release of potent HO-1 inducers, including reactive oxygen and nitrogen species and cytokines, known to occur in glomeruli at these stages. Increased HO-1 activity promotes degradation of heme, resulting in the generation of bilirubin, ferritin and CO, offering powerful local antioxidant and cytoprotective functions to the kidney.

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IMPACT OF A SOCIAL SUPPORT GROUP INTERVENTION IN ESRD PATIENTS Scott D. Cohen*, Brenna Clougherty**, Prashant Khetpal*, Sholey Argani***, Gloria Wiggs***, Rolf A. Peterson****, Paul L. Kimmel* *Division of Renal Diseases and Hypertension, Department of Medicine, George Washington University,**George Washington University School of Medicine,***Washington DC VA Medical Center, Renal Section,****George Washington University, Psychology No study has examined the impact of social support interventions in ESRD patients. The purpose of this study was to determine whether a randomized controlled trial of a social support group intervention designed for ESRD patients would lead to improvements in perception of social support, depressive affect, and quality of life (QOL). All patients with ESRD at the K Street and Southeast Dialysis Units were eligible to participate. Informed consent was obtained. Patients were asked to complete questionnaires before and after the social support group intervention including the Beck Depression Inventory (BDI) to measure depressive affect, the Multidimensional Scale for Perceived Social Support (MSP) to measure perception of social support, the Illness Effects Questionnaire (IEQ) to measure perception of burden of illness, and the satisfaction with life scale (SWLS). Baseline demographic data was obtained. The social support group interventions consisted of 5 weekly sessions. A total of 35 patients were randomized to the intervention and control groups. The patients in both groups were well matched for all variables at baseline. 19 patients were randomized to the intervention and 16 patients were randomized to the control group. In the intervention group, there was a trend towards improvement in perception of QOL and decreased perception of burden of illness. However, these did not reach statistical significance when compared to the results of the control group. There was also a trend towards a decrease in depressive affect in the intervention group compared to the control group. There was no significant change over time in the MSP in either group. A social support group intervention for dialysis patients is possible to implement. Additional patients will need to participate in trials to determine whether these trends reach statistical significance.

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A RETROSPECTIVE REVIEW OF PERIOPERATIVE MANAGEMENT OF SERUM POTASSIUM MEASUREMENTS IN CHRONIC HEMODIALYSIS PATIENTS clenton coleman , harminder sandhu maria devita Lenox Hill Hospital Department of Nephrology New York NY Potassium balance plays a significant role in the management of end-stage renal disease patients on hemodialysis (HD). In addition, data has shown that when these patients undergo surgical procedures they experience an increased frequency of perioperative complications with hyperkalemia being the most common. There is limited data on specific recommendations for the perioperative management of HD patients in regards to potassium management. To determine the perioperative management of potassium balance in HD patients at our institution, we retrospectively reviewed the medical records of patients undergoing arteriovenous (AV) access surgery during a 4 month period. Data regarding the date of the last preoperative HD, perioperative potassium concentrations, and the need for unscheduled or emergent HD was recorded. Fifty-eight patient charts were available for review. Of the 58 patients, 48 patients had serum potassium measurements recorded prior to the procedure. The preoperative data was obtained between 1 to 30 days prior to the procedure with the average serum potassium being measured 9.2 days before surgery. The average potassium concentration at this measurement was 5.9 mg/dl (range 3.0-7.6mg/dl). Nineteen of the 48 patients had preoperative potassium measurements within 24 hours of surgery with the average serum potassium concentration being 4.9mg/dl (3.5-6.9mg/dl). There were a total of 34 patients who had postoperative potassium measurements with an average serum potassium concentration of 4.7mg/dl (range 3.8-6.4mg/dl). One patient required emergent HD prior to surgery to manage a potassium concentration of 6.9 mg/dl and two patients required HD post procedure for potassium concentrations of 5.3 and 5.8mg/dl. Information regarding the last HD prior to surgery was not recorded for most patients. These data show a significant variability in the perioperative care of HD patients undergoing surgery with regard to potassium management. A broad range of potassium concentrations were evident and urgent HD was needed on several occasions. The surgeries reviewed here were classified as minor procedures therefore the wide variations in potassium concentrations were greater than expected. More prospective analysis should be done to better determine potassium concentration fluctuations in patients undergoing longer and more complicated surgery.

NKF 2008 Spring Clinical Meetings Abstracts A39