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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; 5g/24h on ACEi/ARB for >4 mo + SBP 500 micromol/l). 23 MEPEX patients with AH received high dose IV methylprednisolone and 17 plasma exchange. 12 of the 24 (50%) MEPEX AH patients who died were treated with plasma exchange and 12 with methylprednisolone. Causes of death were sepsis in16/30 (53.3%) and respiratory failure in 8/30 (26.7%). Conclusions: Alveolar haemorrhage was present in 24% of AAV patients at presentation and subsequently developed in a further 4%. The frequency of AH was not influenced by ANCA subtype. AH was associated with the presence but not the severity of renal vasculitis, consistent with the two manifestations having a common pathogenesis. In contrast to previous reports, AH was not associated with a higher mortality, which may be a reflection of the exclusion of those with severe AH.

Diabetes – basic research OSu006

RESTORING cGMP LEVELS IN DIABETIC RATS ATTENUATES PODOCYTE DAMAGE

Lilla Fang 1 , Tamas Radovits 2 , Gabor Szabo 2 , Miklos M. Mozes 1 , Laszlo Rosivall 1 , Gabor Kokeny 1 . 1 Institute of Pathophysiology, Semmelweis University, Budapest, Hungary; 2 Experimental Laboratory of Cardiac Surgery, Department of Cardiac Surgery, University of Heidelberg, Germany Introduction and Aims: Diabetic nephropathy leads to glomerulosclerosis (GS). In animal models, the progression of GS is associated with increased cyclic 3’,5’-nucleotide phosphodiesterase (PDE) isoenzyme activity (PDE3, 4, 5) leading to cGMP depletion. We hypothesized that restoring cGMP levels may attenuate podocyte damage in diabetic nephropathy. Therefore, selective inhibition of PDE5 with vardenafil may ameliorate the progression of GS in the rat model of streptozotocin (STZ) diabetes. Methods: Male Sprague-Dawley rats (250-300g) were divided into 2 groups after induction of diabetes with 60 mg/kg STZ: 1) STZ control (non treated, STZ, n=6) and 2) STZ + vardenafil treatment (10 mg/kg/day, STZ-vard, n=8). Non diabetic rats of the same age served as negative control (Co, n=8). Rats were treated for eight weeks, when kidney function was determined (urine protein/creatinine ratio, PC) and kidneys were removed for histology

Downloaded from http://ckj.oxfordjournals.org/ at University of Manitoba on June 18, 2015

Narayan Prasad 1 , Tabrej Jafar 2 , Vikas Agarwal 3 , Raj K. Sharma 1 , Suraksha Agarwal 2 , Amit Gupta 1 . 1 Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India; 2 Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India; 3 Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, UP, India

Sunday, June 27, 2010

Sunday, June 27, 2010

OSu007 DUAL INHIBITION OF CLASSICAL PKC-α AND PKC-β-ISOFORMS IN A PHARMACOLOGICAL AND DOUBLE KNOCK-OUT MOUSE APPROACH LEADS TO PROTECTION AGAINST EXPERIMENTAL MURINE DIABETIC NEPHROPATHY

Jan Menne, Joon-Keun Park, Nelli Shushakova, Hermann Haller, Matthias Meier. Medical School Hannover, Germany Introduction and Aims: Both classical PKC isoforms, PKC-α and -β, have been implicated in the pathogenesis of diabetic microvascular diseases. We previously elucidated the specific role of these individual isoforms and revealed that activation of the PKC-β-isoform contributes to high-glucoseinduced renal fibrosis whereas perlecan as well as nephrin and VEGF expression are regulated by a PKC-α-isoform-dependent signaling pathway leading to diabetic albuminuria. Methods: We now tested the hypothesis if deletion of both classical PKC isoforms is able to completely abolish the development of diabetic nephropathy in the streptozotocin-induced diabetic mouse model. We therefore studied distinct pharmacological approaches while inhibiting both classical PKC isoforms and validated the phenotype of nondiabetic and streptozotocin-induced diabetic homozygeous PKC-α/β double knock-out mice (PKC-α/β-/- ) compared to appropriate 129/SV wild type mice. Results: After 8 weeks of diabetes mellitus the high-glucose-induced renal and glomerular hypertrophy as well as the increased expression of extracellular matrix proteins such as collagen and fibronectin was abolished in the PKC-α/β-/- mice compared to WT controls. Furthermore, the high-glucose-induced expression of the profibrotic cytokine TGF-β1 was significantly diminished in the PKC-α/β-/- mice in comparison to diabetic WT mice. The loss of the basal membrane proteoglycan perlecan and the podocyte protein nephrin is prevented in the diabetic state in the PKC-α/β-/mice. Furthermore, we were able to demonstrate, that a PKC-α/β inhibitor had a similar effect. Conclusions: In summary, blockade of the two prominent PKC isoforms α and β are able to prevent early diabetic nephropathy while inhibiting prosclerotic glomerular and tubulo-interstitial changes as well as the development of albuminuria. These results demonstrate that downregulation of the dual PKC-isoform activation in the diabetic state in vivo is a suitable therapeutic target in the prevention of diabetic microvascular complications such as diabetic nephropathy.

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OSu008 REGULATION OF TRPC6 CHANNELS IN PODOCYTES BY VEGF

Florian Thilo, Ying Liu, Martin Tepel. Charite CBF, Nephrology, Berlin, Germany Introduction and Aims: Increased plasma concentrations of vascular endothelial growth factor (VEGF) and increased expression of transient receptor potential canonical type 6 (TRPC6) channels in podocytes have been associated with kidney diseases. Now, we investigated whether VEGF regulates TRPC6 in podocytes. Methods: The expression of TRPC6-mRNA and TRPC6 protein were analyzed in cultured podocytes after administration of VEGF165 using quantitative real-time RT-PCR and immunoblotting. Processing of YFPtagged TRPC6 in podocytes was analyzed using confocal laser scanning microscopy. TRPC6-associated calcium influx was measured fluorometrically. Results: Administration of 10ng/mL VEGF165 to podocytes significantly increased TRPC6-mRNA by 3.03fold and TRPC6 protein by 6.72fold (n=10; p

Sunday, june 27, 2010: free communications.

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