Yasar Caliskan1,2, Erol Demir3, Ecem Karatay4, Yasemin Ozluk4, Safak Mirioglu3,5, Ahmet Burak Dirim3, Ayse Serra Artan3, Sebahat Usta Akgul6, Ozgur Akin Oto3, Fatma Savran Oguz6, Aydin Turkmen3, Krista L Lentine7, Halil Yazici3. 1. Division of Nephrology, Saint Louis University School of Medicine, 3660 Vista Ave, Saint Louis, MO, USA. yasar.caliskan@health.slu.edu. 2. Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. yasar.caliskan@health.slu.edu. 3. Division of Nephrology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 4. Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 5. Division of Nephrology, Bezmialem Vakif University School of Medicine, Istanbul, Turkey. 6. Department of Medical Biology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey. 7. Division of Nephrology, Saint Louis University School of Medicine, 3660 Vista Ave, Saint Louis, MO, USA.
Abstract
BACKGROUND: The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). METHODS: A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining. RESULTS: Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. CONCLUSIONS: An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.
BACKGROUND: The aim of this study was to evaluate the interactions among serum levels of galactose-deficient IgA1 (Gd-IgA1), oxidative stress and macrophage infiltration and their clinical correlates in patients with IgA Nephropathy (IgAN). METHODS: A total of 47 patients with biopsy-proven primary IgAN, aged between 16 and 79 years, with a follow-up period ≥ 1 year or who showed progression to end stage kidney disease (ESKD) regardless the duration of follow-up were included. Study endpoint was the progression to ESKD. Serum Gd-IgA1 and advanced oxidation protein product (AOPP) levels were measured using ELISA assays. Kidney biopsies were evaluated according to the Oxford MEST-C scoring, with C4d and CD68 staining. RESULTS: Seventeen patients (36%) experienced ESKD during a median follow-up time of 6 years (IQR 3.7-7.5). Serum AOPP levels were correlated with the intensity of glomerular C3 deposition (r = 0.325, p = 0.026), glomerular (r = 0.423, p = 0.003) and interstitial CD68 + cell count (r = 0.298, p = 0.042) and Gd-IgA1 levels (r = 0.289, p = 0.049). Serum Gd-IgA1 levels were correlated with the intensity of C3 deposition (r = 0.447, p = 0.002). eGFR at biopsy (adjusted HR (aHR) 0.979 p = 0.011), and E score (aHR, 8.305, p = 0.001) were associated with progression to ESKD in multivariate analysis. 5-year ESKD-free survival rate was significantly lower in patients with higher E score compared to patients with E score 0 [p = 0.021]. CONCLUSIONS: An increased number of macrophages in the glomerular and tubulointerstitial area may play a role in oxidative stress and complement system activation. Endocapillary hypercellularity is a predictive factor for poor prognosis in IgAN.
Authors: Ali G Gharavi; Zina Moldoveanu; Robert J Wyatt; Catherine V Barker; Susan Y Woodford; Richard P Lifton; Jiri Mestecky; Jan Novak; Bruce A Julian Journal: J Am Soc Nephrol Date: 2008-02-13 Impact factor: 10.121
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Authors: Krzysztof Kiryluk; Yifu Li; Francesco Scolari; Simone Sanna-Cherchi; Murim Choi; Miguel Verbitsky; David Fasel; Sneh Lata; Sindhuri Prakash; Samantha Shapiro; Clara Fischman; Holly J Snyder; Gerald Appel; Claudia Izzi; Battista Fabio Viola; Nadia Dallera; Lucia Del Vecchio; Cristina Barlassina; Erika Salvi; Francesca Eleonora Bertinetto; Antonio Amoroso; Silvana Savoldi; Marcella Rocchietti; Alessandro Amore; Licia Peruzzi; Rosanna Coppo; Maurizio Salvadori; Pietro Ravani; Riccardo Magistroni; Gian Marco Ghiggeri; Gianluca Caridi; Monica Bodria; Francesca Lugani; Landino Allegri; Marco Delsante; Mariarosa Maiorana; Andrea Magnano; Giovanni Frasca; Emanuela Boer; Giuliano Boscutti; Claudio Ponticelli; Renzo Mignani; Carmelita Marcantoni; Domenico Di Landro; Domenico Santoro; Antonello Pani; Rosaria Polci; Sandro Feriozzi; Silvana Chicca; Marco Galliani; Maddalena Gigante; Loreto Gesualdo; Pasquale Zamboli; Giovanni Giorgio Battaglia; Maurizio Garozzo; Dita Maixnerová; Vladimir Tesar; Frank Eitner; Thomas Rauen; Jürgen Floege; Tibor Kovacs; Judit Nagy; Krzysztof Mucha; Leszek Pączek; Marcin Zaniew; Małgorzata Mizerska-Wasiak; Maria Roszkowska-Blaim; Krzysztof Pawlaczyk; Daniel Gale; Jonathan Barratt; Lise Thibaudin; Francois Berthoux; Guillaume Canaud; Anne Boland; Marie Metzger; Ulf Panzer; Hitoshi Suzuki; Shin Goto; Ichiei Narita; Yasar Caliskan; Jingyuan Xie; Ping Hou; Nan Chen; Hong Zhang; Robert J Wyatt; Jan Novak; Bruce A Julian; John Feehally; Benedicte Stengel; Daniele Cusi; Richard P Lifton; Ali G Gharavi Journal: Nat Genet Date: 2014-10-12 Impact factor: 38.330