109THE IMMUNOGENICITY AND SAFETY OF A NOVEL STAPHYLOCOCCUS AUREUS VACCINE (V710) IN ADULTS WITH END-STAGE RENAL DISEASE RECEIVING HEMODIALYSIS -A PHASE IIA STUDY Moustafa Moustafa, John Buerkert, Tarek Sobeih, Claude Galphin, Gaspar Barreto-Torrella, George Aronoff, Jonathan Hartzel, Elizabeth Brown, Steven Smugar, Nicholas Kartsonis, Dalya Guris South Carolina Nephrology & Hypertension Center, Orangeburg, SC; Columbia Nephrology Associates, PA, Columbia, SC; Nephrology Associates, Chattanooga, TN; Nephrology Associates of South Miami PA, Miami, FL; University of Louisville, Louisville, KY; Merck Sharp & Dohme Corp., Whitehouse Station, NJ Patients with ESRD on hemodialysis are at increased risk for severe S.aureus infections, including septicemia. In Phase I studies, V710, a vaccine containing a surface protein (IsdB) was immunogenic after a single dose in healthy adults. This Phase II study was a randomized, double-blind, placebo-controlled study in adults aged 18-80 years with ESRD on hemodialysis (N=206 randomized, 201 vaccinated). Patients were randomized to receive V710 as a 60-μg dose (with or without adjuvant) or a 90-μg dose (with adjuvant) or placebo. Patients received two doses 28 days apart (V710/V710; V710/placebo; placebo/placebo), and a third dose at Day 180. Blood samples were collected at different intervals through Day 360. The primary hypothesis was that at least 1 of the 3 groups receiving 2 doses of V710 would have a ≥2.5-fold rise in anti-IsdB IgG titers 28 days after the second dose (i.e., Day 56) compared to baseline. All 3 grou ps receiving 2 doses of V710 had significant increases of anti-IsdB titers (15.1-18.9-fold) from baseline (p<0.001) and also had titers at Da y 180 significantly higher (5.7-8.5-fold) than baseline (p<0.001). A single dose of all three V710 formulations resulted in significant increases (11.9-12.9-fold) in anti-IsdB titers 28 days after vaccination (p<0.001). No vaccine-related serious adverse experiences (AE) were reported. The most common AE was injection site pain (<48% after any dose in any V710 group vs. 11% in placebo group), the majority w ith mild or moderate intensity. In conclusion, V710 was immunogenic and generally well tolerated among ESRD patients receiving hemodialysis.

110CIPROFLOXOCIN-ASSOCOATED SEIZURES A PREVENTABLE ADVERSE DRUG REACTION Daniel Gutteridge1, Kavitha Kesari1, Hilana Hatoum1, Aileen Arguelles1, Kalyan Uppaluri1, Fadi Rzouq2. 1Michigan State University/MRMC, Flint, MI. 2Michigan State University/Covenant HealthCare, Saginaw, MI. Background: Ciprofloxacin-associated seizures (CAS) is an uncommon drug complication which occurs frequently in patients with special risk factors that may cause accumulation of drug such as renal insufficiency or that may decrease the threshold of epileptogenic activity like electrolyte abnormalities. Aim: To report a case of ciprofloxacin-associated seizures in an elderly gentleman with CKD. Clinical Vignette: An 86-year-old male admitted to the hospital for a first episode of a generalized tonic-clonic seizure. His CKD was secondary to essential HTN and he has been in good health till few days prior to his presentation where he had urinary tract infection treated with ciprofloxacin. Systemic workup for seizure was done and ruled out the possibility of infection, metabolic disorder, cerebral vascular accident, and malignancy. Upon discharge it was determined seizure activity was likely due to improper dosing of ciprofloxacin in chronic kidney disease, antibiotics were changed and adjusted to his renal function. One month later, his follow-up was totally unremarkable. Discussion: Ciprofloxacin is eliminated primarily by renal excretion; it interferes with neuronal inhibitory activity by blocking the binding of GABA, a major inhibitory neurotransmitter with GABA-A receptor. Advanced age, seizure history, electrolyte imbalances, drug interaction and unadjusted dose for renal insufficiency increase the risk for CAS. Conclusion: Although ciprofloxacin is a safe drug we still need to check the renal function and adjust the dose to prevent serious complications.

111MEMBRANOPROLIFERATIVE GLOMERULONEPHRITIS AFTER A PREMATURE DELIVERY FOR HELLP SYNDROME Laura Habelow and Sam Gao, Naval Medical Center Portsmouth, Portsmouth, Virginia, USA We present the case of a 22-year-old G1P1 postpartum female who was diagnosed with HELLP syndrome at 34 weeks EGA, resulting in urgent premature delivery. At delivery she had normal blood pressure and kidney function and no proteinuria. Two weeks postpartum she presented with hypertension, pulmonary edema and peripheral edema. She was treated for presumed preeclampsia and discharged on anti-hypertensive medications. Her HTN was difficult to control and 6 weeks postpartum she also developed AKI, nephrotic-proteinuria, hematuria and a hemolytic anemia and thrombocytopenia concerning for persistent HELLP syndrome, HUS or a rapidly progressive glomerulonephritis. She was empirically started on high-dose steroids and underwent a renal biopsy. Renal biopsy revealed type I membranoproliferative glomerulonephritis (MPGN). She was tested for autoimmune diseases, viral infections, bacterial infections and monoclonal gammopathies to rule out secondary MPGN. All testing was negative. Aspirin and dipyridamole were added to her initial high-dose steroid course as well as an ACEi, statin, and diuretics. She responded well to therapy and her anemia and AKI quickly resolved; her proteinuria remitted six months into her steroid taper. This is the first reported case (in the MEDLINE literature) of a postpartum diagnosis of idiopathic type I MPGN. A prior case report documented MPGN in a patient who prematurely delivered at 28 weeks EGA and required hemodialysis, high-dose steroids and 6 months of cyclophosphamide therapy before proceeding on to complete remission. Another case report documented an MPGN lesion in a patient with HELLP syndrome at 33 weeks EGA and anuric AKI that also recovered completely after delivery. Idiopathic type I MPGN is a rare disease that most commonly occurs in childhood and usually requires prolonged steroid therapy. Given the clinical recoveries of our patient and these case reports, adult idiopathic type I MPGN in the pregnancy setting may represent a different disease process that responds well to early aggressive medical therapy.

112ANG II INDUCES FAK ACTIVATION AND PODOCYTE MIGRATION VIA A TRPC6-DEPENDENT MECHANISM Gentzon Hall, Guanghong Wu, Michelle Winn. Duke University Medical Center, Durham, North Carolina, USA. Focal Adhesion Kinase (FAK) is a key regulator of cell-to-extracellular matrix interactions. In podocytes, dysregulation of FAK activity is linked to foot process effacement/migration and albuminuria. FAK activation is regulated by multiple kinases including Ca2+/Calmodulin KinaseII (CaMKII) and the Extracellularsignal-Regulated Kinase (ERK). Angiotensin II (Ang II), a potent inducer of glomerular injury and albuminuria, is a known activator of CaMKII and ERK via Ca2+-dependent signaling mechanisms. Previously, we established that selective gene “knock-out” of the Ca2+-permeable transient receptor potential cation channel, type 6 (TRPC6) attenuates Ang II-induced glomerular injury and albuminuria, however, the mechanisms of the insult remain unknown. The purpose of this study was to determine if Ang II induces FAK activation and podocyte migration via the TRPC6-mediated activation of CaMKII and ERK. To address this hypothesis, conditionally immortalized podocyte were stimulated with Ang II following preincubation with pharmacologic inhibitors of TRPC6, ERK, and CaMKII vs. vehicle alone. Cell lysates were then analyzed by immunoblotting for FAK phosphorylation by CaMKII at serine residue 843 (S843) and by ERK at serine 910 (S910). Podocyte motility was assessed using scratch wound healing assays in Ang II-stimulated podocyte cultures in the presence or absence of the aforementioned pharmacologic inhibitors. Our studies revealed that Ang II induces the CaMKII and ERK-mediated phosphorylation of FAK at S843 and S910 respectively. These events were attenuated 2-3 fold in the presence of pharmacologic inhibitors of TRPC6, CaMKII, and ERK. Further, Ang II-induced podocyte migration is inhibited with pharmacologic inhibition of TRPC6, CaMKII and ERK. In conclusion, Ang II induces FAK activation and podocyte migration via the TRPC6-mediated activation of CaMKII and ERK. These studies provide novel mechanistic insights into the pathologic intracellular signaling underlying Ang II-induced podocyte dysfunction and highlights the therapeutic potential of TRPC6 and FAK inhibition in the management of proteineuric kidney disease.

NKF 2011 Spring Clinical Meetings Abstracts

Am J Kidney Dis. 2011;57(4):A1-A108A44