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ENERGY ENHANCEMENT TO SEVERE TOXICITY REQUIRING A TRANSPLANT – A CASE OF EPHEDRATOXICITY Monika Gandhi, Muhammad Yaqub. Division of Nephrology, Indiana University, Indianapolis, IN, USA Dietary supplements containing Ephedra alkaloids are commonly found ingredient in weight loss and energy enhancement supplements. In 2004, the FDA banned Ephedra-containing products because of numerous reports of adverse cardiovascular and neurological events. Although it can still be obtained as a traditional Chinese medicine, MaHuang and synthetic ephedrine (Synephrine) have also been created as an over-the-counter medication for asthma and energy-boosting products. We present the case of a previously healthy 34-year-old Caucasian male with a history of Ephedrine ingestion for “energy boost.” He was admitted 2 days after an ingestion of 10 pills of Ephedrine with complains of nausea, vomiting and severe abdominal pain. He was found to have severe acute hepato-renal failure. AST–13,786 units/L, ALT–6,714 units/L with coagulopathy, with INR–6.45 and acute renal failure (ARF) with BUN–16 mg/dL, and Cr–5.19 mg/dL. He had anion-gap metabolic acidosis with acute respiratory alkalosis. His urine was dark on exam, positive for blood, hemoglobin and myoglobulin with mildly elevated CK. He was also found to have hyperkalemia with K-6.6 mmol/L, hypocalcemia with Ca-7.4 mg/dL, and hyperphosphatemia with phosphorus-7.5 mg/dL consistent with acute rhabdomyolysis. Liver biopsy showed 90% necrosis of hepatocytes. He required temporary dialysis with continuous veno-venous replacement therapy. After emergent liver transplant he recovered his renal function and was discharged home without any further need of dialysis. Our patient was thought to have toxic hepatitis with, ARF from rhabdomyolysis and hypoperfusion kidney injury from vasoconstrictive affects of Ephedrine. However, he had no prior history of exercise and yet was showing signs of acute rhabodomyolysis. This point towards the importance of extreme caution in using these supplements, as it is commonly used in the setting of weight loss, energy and performance enhancement, and often by younger generation without any knowledge of the severe toxicity involved, placing them at higher risk.

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IN-VIVO ANAYLYSIS OF GLOMERULAR AND PROXIMAL TUBULE HANDLING OF AGE-MODIFIED ALBUMIN USING TWO-PHOTON MICROSCOPY Monika Gandhi, Mark Wagner, Bruce Molitoris, Ruben Sandoval, George Rhodes. Division of Nephrology, Indiana University, Indianapolis, IN, USA. Advanced glycation end product (AGE) modification of tissue and circulating proteins has been shown as a strong marker of complication in Diabetes. However, AGE compounds derived from the Dicarbonyl α-oxaldehyde Methylglyoxal (MGO) are closely associated with hyperglycemia, poor control of diabetes and increased susceptibility to diabetic nephropathy. Previous studies indicate that proximal tubule cells may be the site of catabolism of AGE proteins. However, little is known about the glomerular and proximal tubule handling of these glycated albumins in live kidney tissue. Therefore, this study explores the hypothesis that there is no difference in glomerular handling of AGE-modified albumin, but proximal tubule cells process AGE-modified albumin differently compared to un-glycated albumin. To directly quantify the in vivo processing of albumin filtration and proximal tubule handling of the AGE-modified albumin, two-photon microscopy of Munich Wistar rat kidney following infusion of Texas red albumins (modified and un-modified) was investigated. Similar glomerular permeability was found between AGE-modified albumin and un-glycated albumin. However, AGE-modified albumin showed a significant reduction in plasma florescence at 2 and 24 hrs compared to un-glycated albumin. These differences indicate that it is not the glomerular handling, but protein handling and trafficking by the renal proximal tubule of the AGE-modified proteins that is affected. This may confirm a link between the pathogenic role of AGEs and early proximal tubule functional changes seen leading to hypertrophy and nephropathy in diabetes.

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ROLE OF COFILIN IN PODOCYTE ACTIN DYNAMICS Puneet Garg1, Rakesh Verma1, Leslie Cook1, Abdul Soofi1 and Lawrence Holzman1,2. 1University of Michigan, Ann Arbor, MI, USA, 2University of Pennsylvania, Philadelphia, PA, USA. We report that slit diaphragm junctional protein Nephrin recruits and regulates the activity of cofilin1 (Cfl), a highly conserved, ubiquitously expressed protein involved in actin filament severing/de-polymerization and recycling of actin monomers. As podocytes are highly polarized cells and develop unique actin rich processes, both during development and injury high turnovers of actin and polarized actin dynamics is required. We speculated a role for Cfl1 and regulation of its activity by the Nephrin. Activation of Nephrin in cell culture studies lead to dephosphorylation of Cfl1 on its serine 3 residue resulting in activation of Cfl1. Using a previously described cultured podocyte model of Nephrin activation (induced clustering of CD16/7-Nephrin chimeric protein and various mutants) We corroborated that nephrin signals to Cfl1 in podocytes by mapping cofilin pathway signaling intermediaries. Cfl1dephosphorylation required pI3 kinase activity as it was attenuated either with pI3K inhibitors or by introducing nephrin mutations at its p85- pI3K interaction sites. We were further able to show dephosphorylation of slingshot (SSH1) a phosphatase described to dephosphorylate Cfl1 is responsible for the Nephrin mediated Cfl1 dephosphorylation. To study this further we also developed a podocyte specific conditional Cfl1 null mouse. Surprisingly we did not observe a podocyte developmental abnormality but mice developed proteinuria by 3 months of age and foot process spreading by 8 months. Overall, these results provide evidence that cofilin is essential for podocyte structure and function. We speculate/propose that nephrin mediated cofilin activation establishes gradients of cofilin activity necessary for polarized actin dynamics required both during podocyte development and injury.

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ACUTE KIDNEY INJURY AFTER ROBOTIC ASSISTED LAPROSCOPIC RADICAL PROSTATECTOMY (RARP), HOW REAL IS IT? Sajid Melvin George, Chidi Okafor, Charles Brooks. University Of Virginia Health System, Charlottesville, VA. The overall incidence of acute kidney injury is 24-30 cases/1000 hospital discharges. We present an interesting case of AKI whose management differed as the raise in creatinine was result of reabsorption of accumulated urinary creatinine. 62 y/o male presented 2 days after having a robotic prostatectomy with abdominal fullness & increased drainage from the JP drains. As urinary out put declined and creatinine increased to 4mg/dl nephrology was consulted. Abdominal girth increased. Urinary leak into peritoneal cavity was suspected. Creatinine sent on the abdominal fluid was 9.6mg/dl confirming spillage of urine into abdominal cavity. Paracentesis removed 10 liters of fluid. An urethro cystoscopy with urethrogram confirmed the leak at the posterior anastamotic site, and foley repositioned. The JP drains out put decreased and serum creatinine normalized. Complications rate for RARP ranges from 2.3% to 21.6%. The elevation of serum creatinine as a result of reabsorption of urinary creatinine from urinary leak into abdominal cavity has not been clearly described in literature. Given the different mechanism contributing to AKI, the management differed. Such mechanism causing spurious AKI should be kept in mind while evaluating post operative urology patients, & testing the ascitic/abdominal fluid for creatinine will aid in confirming the diagnosis.

NKF 2010 Spring Clinical Meetings AbstractsA56