209

GRANULOMATOUS INTERSTITIAL NEPHRITIS SECONDARY TO CARBAMAZEPINE CAUSING ACUTE RENAL FAILURE Prashanth Podaralla1, Nagaraju Sarabu2, Marcos Rothstein1, 1 Barnes Jewish Hospital, Washington University, St. Louis, MO. 2 St. Luke’s Hospital, Chesterfield, MO. Granulomatous interstitial nephritis (GIN) is a specific subtype of interstitial nephritis that is present in 0.5% to 0.9% of native kidney biopsies. Thus, GIN is a rare histologic finding and has been associated with medications, infections, sarcoidosis and Wegener’s granulomatosis. Common medications causing GIN include antibiotics, non-steroidal anti-inflammatory drugs, allopurinol, diuretics and anticonvulsants. We present the case of a 77-year-old male with past medical history of hypertension, hypothyroidism and seizure disorder, who came with one week history of nausea, vomiting and decreased urine output. About two months prior to presentation, he was started on carbamazepine for his seizures. Physical examination was remarkable only for bilateral basilar crackles. Laboratory data showed normal white cell count with slightly increased eosinophil count, normal hemoglobin, blood urea nitrogen 132 mg/dl, and creatinine 9.4 mg/dl (baseline 1.1, 3 weeks ago). Urine analysis showed 3+ protein and spot urine protein to creatinine ratio was 2.43. He required dialysis soon after presentation. Percutaneous biopsy of the kidney showed extensive interstitial non-caseating granulomatous inflammation with eosinophils. Patient also developed a maculopapular rash all over his trunk during hospital stay. CT scan of the chest failed to show any hilar lymphadenopathy or pulmonary infiltrates. Based on the clinical presentation, temporal association with carbamazepine, and biopsy findings, the diagnosis of carbamazepine induced GIN was made. Carbamazepine was stopped and he was switched to Zonisamide for seizure control. Patient was started on prednisone, which dramatically reversed his acute renal failure, and he came off of dialysis within 4 weeks. After one year of presentation he retains his normal kidney function.

In conclusion, we present a case of GIN due to carbamazepine requiring renal replacement therapy, which is rare, but a recognized severe complication of carbamazepine.

210

CLINICAL UTILITY OF RENAL ULTRASOUND IN ACUTE KIDNEY INJURY Amber S. Podoll , Kevin W. Finkel, University of Texas Health Science Center, Houston Texas Acute kidney injury(AKI) occurs in hospitalized patients especially the critically ill with an incidence of 16% to 23%. A small incremental rise in serum creatinine has been shown to portend a higher mortality. A renal ultrasound(RUS) is commonly obtained in AKI to exclude obstruction. Conversely, the cause of AKI in the hospitalized patient most commonly occurs from acute tubular necrosis, acute interstitial nephropathy or contrast-induced nephropathy. Therefore, in a patient with previously stable renal function, the likelihood of an acute obstruction leading to AKI is low. We have conducted a systematic review of RUS studies performed during the period of 2003-2005 at a tertiary referral center. Data collected included age, sex, cause of AKI, history of chronic kidney disease, history of abdominal malignancy, benign prostatic hypertrophy or GU malformation. A total of 4443 inpatient RUS were performed over the three year period, of which 2854 studies were selected after exclusion of patients if they were transplant recipients, institutionalized, pregnant or pediatric. Forty-seven cases of the 2854 (1.6%) were identified to have an obstructive etiology of AKI. A higher predictive risk of obstructive uropathy was found in men over 65, history of BPH or history of prior nephrolithiasis. No difference was seen in patients with prior cancers in this population. 28% of patients had a previous RUS performed and 17% had >2 prior RUS ordered. 65% of RUS were done with Doppler measurements of arterial blood flow. The use of RUS as a standard diagnostic test in all cases of AKI does not change the clinical impression or therapeutic treatment plan in most of the patients in a general medical population. Additionally, most RUS were ordered with Doppler readings of the renal arteries. While the utility of Doppler studies is important in the diagnosis of renal artery stenosis, it provides little diagnostic information in the setting of AKI and increases cost per ultrasound examination. We propose the selective use of RUS in the evaluation of AKI to be limited to cases of high pre-test probability or when clinically indicated in an attempt to reduce unnecessary testing and clinical costs.

211

CATASTROPHIC ANTIPHOSPHOLIPID SYNDROME DUE TO INADEQUATE ANTICOAGULATION LEADING TO END STAGE RENAL DISEASE. Christopher R. Provenzano, MD, Anjali Acharya, MD, Jacobi Medical Center, Albert Einstein College, Bronx, New York. A 30 year old African American female with a history of systemic lupus erythematosus (SLE), hypertension, anti-phospholipid syndrome (APS) and autoimmune hemolytic anemia (AIHA) presented with nausea, vomiting and 6 lb weight loss. On admission, serum creatinine was 2.2mg/dL, hemoglobin 7.7g/dL (baseline 0.9 mg/dl and 10.8g/dl respectively) and INR of 2.5. Pt was diagnosed with recurring AIHA and started on steroids. Renal biopsy showed acute glomerular thrombotic microangiopathy (TMA) with ISN-RPS class II lupus nephritis. Serum creatinine improved to 1.7mg/dL. Patient was discharged on warfarin and tapering prednisone dose. INR was 1.1 on discharge. Pt returned 8 days later with chest pain, shortness of breath and hemoptysis. Pt was intubated for respiratory failure. Blood Urea Nitrogen (BUN) was 190mg/dl and serum creatinine 14.5mg/dL. Chest CT showed alveolar hemorrhage. A diagnosis of possible CAPS was made. Anticoagulation and steroid therapy was continued. She received 4 days of plasmapheresis and IVIg therapy. Hemodialysis was initiated. Repeat renal biopsy showed severe, acute TMA involving arterial vessels, with ISN-RPS class III lupus nephritis and lupus vasculopathy, all worse compared to the prior biopsy. Patient was started on mycophenolate mofetil for the immune complex mediated disease. Despite overall improvement, renal function did not recover. CAPS is a rapidly progressive disease, with multi organ involvement, seen in <1% of APS and carries a mortality of 50%. We hypothesize that CAPS was precipitated by lack of adequate anticoagulation on discharge. Inadequate anticoagulation for only a few days seems to be enough to incite CAPS. Our patient demonstrated a good clinical response overall, despite the presence of SLE which is a poor prognostic indicator. There is paucity of data on progression of renal disease in CAPS. The renal disease progressed to end stage in our patient necessitating continuation of renal replacement therapy eight months after presentation.

212

FG2216, A NOVEL ORAL HIF-PHI, STIMULATES ERYTHROPOIESIS AND INCREASES HEMOGLOBIN CONCENTRATION IN PATIENTS WITH NON-DIALYSIS CKD R Provenzano1, G Fadda2, M Bernardo3, C James4, G Kochendoerfer4,T Lee4, S Nakayama4, T Neff4, BA Piper4; 1St. John Hospital & Medical Center, Detroit, MI, 2California Institute of Renal Research, San Diego, CA, 3Southwest Houston Research, Houston, TX, 4FibroGen, Inc., So San Francisco, CA In this phase 2 single blind, placebo-controlled, dose-ranging study, we examined the ability of FG-2216 to correct anemia in ESA-naïve patients with CKD. 142 patients with CKD Stages 3 & 4 and Hb < 10.8 g/dL were randomized and treated for up to 15 wks. Initial doses included 375mg (n=26), 625mg (n=52), or 1250mg (n=50), dosed twice weekly and placebo (n=14). After 4 wks of stable dosing, elective titration was employed to achieve a target Hb response. The proportion of treated subjects with Hb response, defined as 1 g/dL increase, was 13 (50.0%), 31 (59.6%), 38 (76.0%) for the FG-2216 dose groups and none for placebo. Analysis of the ITT completer population (N=96) excluding treatment non-completers due to early study termination by the sponsor reveals responder rates of 58.8%, 60.5%, and 90.6% for the FG-2216 dose arms. Mean baseline Hb levels for the FG-2216 starting doses and placebo were 10.2, 10.1, 9.9 and 10.1 g/dL, respectively; following up to 15 wks of therapy, maximum mean Hb changes from baseline were 1.1, 1.4, 2.4 and 0.2 g/dL, respectively. Assessment of endogenous EPO and VEGF 12 hours after the first dose revealed a mean increase from baseline in EPO of 11.9, 28.9, 141.6 for the FG-2216 groups and 1.1 mIU/mL for placebo; mean change from baseline in VEGF was -7.8, -5.4, -3.9 for the FG-2216 groups and 5.2 pg/mL for placebo. There were 41 SAEs reported in 25 subjects, 2 were assessed as possibly related to FG-2216 including 1 death due to fulminant hepatitis. There were no increases in BP observed with any dose level or correlated with increasing Hb levels; there was no increased use of BP medications over time. Oral administration of FG-2216 in ESA-naïve patients with CKD not on dialysis was well tolerated and may effectively treat CKD anemia as evidenced by increasing erythropoietic effect with modest EPO elevation, no VEGF increase and no adverse BP changes.

NKF 2008 Spring Clinical Meetings AbstractsA80