Sunday, June 27, 2010: Free Communications

iii277 Nephrology Dialysis Transplantation Plus 2010 3(Supplement 3): iii275–iii547 Free Communications Glomerular diseases 2 OSu001 REMOVAL OF ELEVATED CIRCULATING ANGIOPOIETIN-2 BY PLASMA EXCHANGE – A PILOT STUDY IN CRITICALLY ILL PATIENTS WITH THROMBOTIC MICROANGIOPATHY OR ANTI-GBM DISEASE Svjetlana Lovric 1 , Alexander Lukasz 1 , Carsten Hafer 1 , Jan T. Kielstein 1 , Marion Haubitz 1 , Hermann Haller 1 , Philipp Kümpers 1,2 . 1 Nephrology & Hypertension, Hannover Medical School, Hannover, Germany; 2 Nephrology and Rheumatology, University Hospital Münster, Germany OSu002 RITUXIMAB (RTX) THERAPY IN IDIOPATHIC MEMBRANOUS NEPHROPATHY (IMN): RESULTS AT 2 YEARS Fernando Fervenza 1 , Stephen Erickson 1 , Patrick Nachman 2 , John Dillon 1 , Nelson Leung 1 , Marie Hogan 1 , LaTonya Hickson 1 , Maria Irazabal 1 , Alfonso Eirin 1 , Qamaruddin Qazi 3 , Daniel Cattran 4 . 1 Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA; 2 Division of Nephrology, University of North Carolina, Chapel Hill, NC, USA; 3 Division of Nephrology, Aurora Medical Group, Green Bay, WI, USA; 4 Division of Nephrology, University of Toronto, ON, Canada Introduction and Aims: In IMN i.v. RTX 1g on days 1-15 leads to complete (CR; <0.3g/24h) or partial (PR; ≤3.5g/24h) remission of proteinuria (P) in 60% of cases at 12 mo (Kidney Int 73, 117–125, 2008). Pharmacokinetic analysis showed RTX levels at 1/2 of those in non-proteinuric patients and may result in undertreatment. We postulate that 4 weekly doses of RTX, with re dosing at 6 mo, would result in a more effective and prolonged B cell depletion, a higher remission rate while maintaining a similar safety profile. Methods: Twenty patients (17M/3F), median age 48 (range 29-80) and P >5g/24h on ACEi/ARB for >4 mo + SBP <130mmHg prospectively OSu003 LATE ONSET FSGS IN 13% OF PATIENTS WITH FAMILIAL MICROSCOPIC HEMATURIA AND THIN GLOMERULAR BASEMENT MEMBRANES DUE TO HETEROZYGOUS MUTATIONS OF COL4A3/COL4A4 AT A MEAN AGE OF 60, IS THE EXPLANATION FOR “AUTOSOMAL DOMINANT ALPORT” FINDINGS IN 172 PATIENTS WITH 4 DIFFERENT MUTATIONS IN 19 LARGE CYPRIOT FAMILY PEDIGREES Alkis Pierides 1 , Maria Arsali 2 , Yiannis Athanasiou 2 , Ioanna Zouvani 3 , Konstantinos Voskarides 4 , Charalampos Patsias 2 , Constantinos Deltas 4 . 1 Department of Nephrology, Hippocrateon Hospital, Nicosia, Cyprus; 2 Department of Nephrology, Nicosia General Hospital, Nicosia, Cyprus; 3 Department of Histopathology, Nicosia General Hospital, Nicosia, Cyprus; 4 Department of Biological Sciences, University of Cyprus, Nicosia, Cyprus Introduction and Aims: Clinical studies since 1984 and molecular genetics studies since 2004 have enabled a long term study on an increasing number of patients with familial microscopic hematuria (FMH) due to heterozygous COL4A3/COL4A4 mutations. A number of these patients, for reasons currently under investigation, develop after their 30’s, 40’s, and 50’s, additional proteinuria, hypertension, CRF and 13.0% reach ESRD. Here, we report on 19 large family pedigrees with four such mutations. Methods: A total of 309 at-risk family members, were genetically studied through PCR-RFLPs methods. 172 (55.7%) were heterozygous for one of four mutations. Mutation G1334E (COL4A3) was found in 11 pedigrees, mutation G871C (COL4A3) in five, mutation 3854delG (COL4A4) in two pedigrees and mutation 3533delC (COL4A3) in one. Clinico-pathological correlations were available in all of these patients. Renal biopsies in 24 patients showed various stages of FSGS. Fifteen biopsies were also studied with EM and showed additional thin glomerular basement membranes (TGBM). Results: In patients under age 30, microscopic hematuria was the only urinary finding (100%). “Microscopic hematuria alone” fell to 72% between ages 31-50, to 39% between ages 51-70 and to only 18.5% over age 71. Proteinuria with CRF developed on top of microscopic hematuria in 6% between ages 31-50, in 20% between ages 51-70 and in 44.5% over 71. Altogether 23 of these 170 MC (13.0%) developed ESRD, at a mean age of 60 years. Six patients also developed late onset sensorineural deafness (3.5%). There were no specific ocular findings. Two pairs of MC married together, (one couple with the same 3533delC mutation and the other Introduction and Aims: Microvascular endothelial-cell injury coupled to progression of platelet microthrombi is the hallmark of thrombotic microangiopathy (TMA). Angiopoietin (Ang)-2, a circulating antagonistic ligand of the endothelial specific Tie2 receptor facilitates endothelial activation, whereas its antagonist Angiopoietin (Ang)-1 protects the vasculature from inflammation in a non-redundant manner. So far neither the Ang-Tie2 system nor its possible modulation by plasma exchange has been evaluated in patients with TMA. Methods: Plasma Ang-1 and Ang-2 was measured by in-house immunoluminometric assays (ILMA) in nine critically ill TMA patients with renal involvement and four patients with anti-glomerular basement membrane (anti-GBM) disease before and after up to four sessions of plasma exchange (PE). Twenty apparently healthy volunteers served as controls. Results: Median (IQR) plasma levels of Ang-2 were markedly increased in TMA patients (7.3 (2.4-21.1) ng/mL) and anti-GBM nephritis (5.8 (3.4-7.0) ng/mL) compared to healthy controls (1.0 (0.9-1.4) ng/mL, P <0.001). Moreover, Ang-1 plasma levels were decreased in both, TMA (1.02 (0.621.62) ng/mL) and anti-GBM disease patients (0.74 (0.59-3.62) ng/mL) compared to healthy controls (2.5 (1.93-3.47) ng/mL, P <0.005). During a total of 32 treatments, PE effectively lowered elevated mean (SD) Ang-2 plasma levels by 36.7±19.6% per treatment (P <0.0001). In contrast, low Ang-1 plasma levels remained unchanged (-0.3±58.5%;P =0.147). During the early clinical course, a significant rebound of circulating Ang-2 occurred after the first PE treatment. However, Ang-2 levels declined to almost normal values during ≤ 4 PE treatments (Friedman’s test p <0.0001). Conclusions: Ang-2 is a potential facilitator of endothelial activation and microvascular endothelial-cell injury in TMA and anti-GBM disease. For the first time we could show an effective strategy to restore the balance between Ang-1 and Ang-2 as PE effectively lowered excess systemic Ang-2 levels. It remains to be elucidated if the removal of Ang-2 is crucial to ameliorate endothelial damage in critically ill patients with severely altered endothelial integrity. received RTX (375mg/m2 ) on days 1, 8, 15 and 22 and no other immunosuppressant. RTX was repeated at 6 mo regardless of P. Follow up (FU) was at 3, 6, 9, 12, 18 and 24 mo. Results: All patients tolerated RTX well and achieved B cell depletion [Baseline mean CD19+ B cells = 193.36 cells/μl (range 60-524); Day 28 = 1.05/μl (range 0-5)]. Mean ± SD baseline creatinine = 1.5±0.5 mg/dl. Baseline P = 11.9±4.9g/24h (range 5.7-26.5) decreased to 7.3±4.1g, 6.6±5.3g, 4.1±3.4g, 4.2±3.8 g/24h, 2.7±2.8 g/24h and 2.1±2.2 g/24h (0.2-8 (...truncated)