title: Mycophenolate mofetil ameliorates accelerated progressive nephropathy in rat.
abstract: BACKGROUND
  Renal ischemia and hypertension have been suggested to be involved in the progression of renal diseases. Recently, we developed a model of accelerated major histocompatibility complex-independent renal injury, where high-renin hypertension aggravates functional and morphological changes induced by ischemia/reperfusion (I/R). In this model, we evaluated the effect of immunosuppressant mycophenolate mofetil (MMF) to test its capability to slow the progression of accelerated nephropathy.
  
  
  METHODS
  34 anesthetized uninephrectomized hypertensive transgenic (mREN2)27 rats (TGR) received a clamp on the renal pedicle for 45 min. Animals were treated with MMF 10 mg/kg/day (n = 10), 20 mg/kg/day (n = 10) or placebo (n = 10) orally via gavage for 12 weeks. Four animals were sham operated and not treated. Proteinuria and blood pressure were evaluated throughout the experiment. At the end of the experiment, kidney function was evaluated and kidneys harvested for morphological analysis and immunohistochemistry (CD4+, CD8+ lymphocytes and specific rat monocyte/macrophage marker ED-1+ cells).
  
  
  RESULTS
  At week 12, both MMF-treated groups had lower proteinuria as compared to the placebo group (MMF 10: 22.4 +/- 9.8, MMF 20: 20.9 +/- 5.6 vs. 126.7 +/- 35.8; p < 0.01; sham 28.1 +/- 1.4 mg/day) and reduced glomerulosclerosis (MMF 10: 11.4 +/- 7.8, MMF 20: 5.2 +/- 2.7 vs. 20.9 +/- 10.9; p < 0.05; sham 15.7 +/- 9.2%). There were no differences in systolic blood pressure among groups. MMF-treated rats had lower CD4+ (MMF 10: 61.2 +/- 46.4, MMF 20: 29.3 +/- 18.2 vs. 125.3 +/- 42.8; p < 0.01, sham 84.9 +/- 6.1 cells/field of view) and CD8+ (MMF 10: 13.7 +/- 10.2, MMF 20: 10.0 +/- 8.1 vs. 37.8 +/- 14.3; p < 0.01; sham: 31.8 +/- 7.6 cells/field of view) lymphocytes infiltration and ED-1 macrophages infiltration (MMF 10: 5.5 +/- 6.4, MMF 20: 2.5 +/- 2.8 vs. 16.7 +/- 4.1; p < 0.01; sham 12.2 +/- 4.6 cells/field of view) than placebo-treated rats.
  
  
  CONCLUSIONS
  Our results thus support the hypothesis about the key role of immune mechanisms in progression of chronic nephropathies.
authors.affiliation: Department of Nephrology, Transplant Center, Prague, Czech Republic.
authors.forename: S
authors.initials: S
authors.lastname: Bloudícková
authors.forename: J
authors.initials: J
authors.lastname: Rajnoch
authors.forename: A
authors.initials: A
authors.lastname: Lodererová
authors.forename: E
authors.initials: E
authors.lastname: Honsová
authors.forename: O
authors.initials: O
authors.lastname: Viklický
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D004195:Disease Models, Animal; D018450:Disease Progression; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007677:Kidney Function Tests; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000473:pathology
chemical_list: D007166:Immunosuppressive Agents; D009173:Mycophenolic Acid