BACKGROUND: Retinoic acids, derivatives of vitamin A, act through retinoid receptors that are expressed in renal and immunocompetent cells (B and T cells; monocytes and macrophages). In experimental models of glomerulonephritis and renal interstitial disease, retinoids were shown to reduce both glomerular and tubular damage and inflammation. We therefore examined whether retinoids reduce cellular rejection and renal damage in a model of acute renal allograft rejection. METHODS: Kidneys of Fisher rats (F344, RT11v1) were orthotopically grafted to Lewis rats (RT11). Animals were killed 7 or 14 days after transplantation. Rats undergoing transplantation were treated with isotretinoin (13 cis-retinoic acid) at a low dose of 2 mg/kg body weight per day (LD isotretinoin) or at a high dose of 20 mg/kg body weight per day (HD isotretinoin) or with vehicle. RESULTS: At day 14, albuminuria was reduced by approximately 70% (vehicle: 1.1+/-0.2 mg/24 hr vs. LD isotretinoin: 0.32+/-0.1 mg/24 hr; P<0.001). At days 7 and 14 serum creatinine levels were significantly higher in the vehicle-treated group than in the LD and HD isotretinoin-treated rats (P<0.05). Both LD and HD isotretinoin significantly reduced acute vascular injury compared with vehicle-treated rats (score at day 14: LD isotretinoin 20.1+/-5.1 vs. vehicle 57.8+/-9.9, P<0.01), acute glomerular injury (score: LD isotretinoin 6.8+/-1.0 vs. vehicle 10.6+/-0.9 P<0.05), and the number of glomerular monocytes and macrophages and cytotoxic T cells. Isotretinoin also significantly lessened tubulointerstitial damage, tubulointerstitial cell proliferation, and the number of cells infiltrating the tubulointerstitium. CONCLUSIONS: Isotretinoin significantly ameliorated functional, vascular, glomerular, and tubulointerstitial lesions in acute graft rejection. Although the current study did not definitely eliminate the possibility that isotretinoin only delayed the rejection process, retinoic acid derivatives may provide a new approach in the treatment of acute rejection injury.
BACKGROUND:Retinoic acids, derivatives of vitamin A, act through retinoid receptors that are expressed in renal and immunocompetent cells (B and T cells; monocytes and macrophages). In experimental models of glomerulonephritis and renal interstitial disease, retinoids were shown to reduce both glomerular and tubular damage and inflammation. We therefore examined whether retinoids reduce cellular rejection and renal damage in a model of acute renal allograft rejection. METHODS: Kidneys of Fisher rats (F344, RT11v1) were orthotopically grafted to Lewis rats (RT11). Animals were killed 7 or 14 days after transplantation. Rats undergoing transplantation were treated with isotretinoin (13 cis-retinoic acid) at a low dose of 2 mg/kg body weight per day (LD isotretinoin) or at a high dose of 20 mg/kg body weight per day (HDisotretinoin) or with vehicle. RESULTS: At day 14, albuminuria was reduced by approximately 70% (vehicle: 1.1+/-0.2 mg/24 hr vs. LD isotretinoin: 0.32+/-0.1 mg/24 hr; P<0.001). At days 7 and 14 serum creatinine levels were significantly higher in the vehicle-treated group than in the LD and HDisotretinoin-treated rats (P<0.05). Both LD and HDisotretinoin significantly reduced acute vascular injury compared with vehicle-treated rats (score at day 14: LD isotretinoin 20.1+/-5.1 vs. vehicle 57.8+/-9.9, P<0.01), acute glomerular injury (score: LD isotretinoin 6.8+/-1.0 vs. vehicle 10.6+/-0.9 P<0.05), and the number of glomerular monocytes and macrophages and cytotoxic T cells. Isotretinoin also significantly lessened tubulointerstitial damage, tubulointerstitial cell proliferation, and the number of cells infiltrating the tubulointerstitium. CONCLUSIONS:Isotretinoin significantly ameliorated functional, vascular, glomerular, and tubulointerstitial lesions in acute graft rejection. Although the current study did not definitely eliminate the possibility that isotretinoin only delayed the rejection process, retinoic acid derivatives may provide a new approach in the treatment of acute rejection injury.
Authors: Jens Bedke; Eva Kiss; Carl-Ludwig Behnes; Zoran V Popovic; Markus Heuser; Tomislav Stojanovic; Tjeerd Sijmonsma; Peter Huber; Sophie Domhan; Stefan Muschal; Amir Abdollahi; Norbert Gretz; Hermann-Josef Gröne Journal: Am J Pathol Date: 2007-08-16 Impact factor: 4.307
Authors: Judith Adams; Eva Kiss; Ana B V Arroyo; Mahnaz Bonrouhi; Qiang Sun; Zhen Li; Norbert Gretz; Anna Schnitger; Christos C Zouboulis; Manfred Wiesel; Jürgen Wagner; Peter J Nelson; Hermann-Josef Gröne Journal: Am J Pathol Date: 2005-07 Impact factor: 4.307
Authors: Ivica Grgic; Eva Kiss; Brajesh P Kaistha; Christoph Busch; Michael Kloss; Julia Sautter; Anja Müller; Anuradha Kaistha; Claudia Schmidt; Girija Raman; Heike Wulff; Frank Strutz; Hermann-Josef Gröne; Ralf Köhler; Joachim Hoyer Journal: Proc Natl Acad Sci U S A Date: 2009-08-13 Impact factor: 11.205
Authors: Juliane Scholz; Veronika Lukacs-Kornek; Daniel R Engel; Sabine Specht; Eva Kiss; Frank Eitner; Jürgen Floege; Herrmann-Josef Groene; Christian Kurts Journal: J Am Soc Nephrol Date: 2008-01-30 Impact factor: 10.121