title: Does Immunosuppressive Therapy Affect Markers of Kidney Damage?
abstract: BACKGROUND
  Markers currently used to detect kidney damage are effective in both early (KIM-1, NGAL) and late (MCP-1, MMP, TIMP) stages of renal tubular damage, indicating the progression of chronic kidney disease. Immunosuppressive drugs may damage the transplanted organ through their direct toxic effects and by contributing to the development of chronic fibrosis and tubular atrophy. The aim of this study was to determine if immunosuppressive drugs per se affect the concentration of kidney damage markers, by using concentrations and doses of immunosuppressive within therapeutic, not toxic, levels in rat blood.
  
  
  METHODS
  The study involved 36 rats grouped according to the immunosuppressive regimen used (tacrolimus, mycophenolate mofetil, cyclosporin A, rapamycin, and prednisone). The rats were treated with a 3-drug protocol for 6 months. No drugs were administered to the control group. The blood samples were collected to determine the concentration of kidney damage markers by using enzyme-linked immunosorbent assay (ELISA).
  
  
  RESULTS
  1. In the groups receiving regimens based on cyclosporin A (CyA), significantly higher concentrations of KIM-1 in plasma was observed compared to cases not treated with drugs. 2. The use of tacrolimus was associated with increased concentrations of MCP-1 in plasma and rapamycin was associated with decreased concentrations of MCP-1 in plasma. 3. Rapamycin induces an unfavorable, profibrotic imbalance between metalloproteinase-9 and its inhibitor, TIMP-1.
  
  
  CONCLUSIONS
  Commonly used immunosuppressive drugs influence the concentration of blood markers of kidney damage. This fact should be taken into account when analyzing the association between the concentration of these markers and pathological processes occurring in the transplanted kidney.
authors.affiliation: Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Karolina
authors.initials: K
authors.lastname: Kędzierska
authors.affiliation: Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sindrewicz
authors.affiliation: Department of Maxillofacial Surgery, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Sporniak-Tutak
authors.affiliation: Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Gołembiewska
authors.affiliation: Department of General Surgery and Transplantology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Labib
authors.initials: L
authors.lastname: Zair
authors.affiliation: Department of General Surgery and Transplantology, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Sieńko
authors.affiliation: Department of Medical Chemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Stańczyk-Dunaj
authors.affiliation: Department of Biochemistry, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Irena
authors.initials: I
authors.lastname: Baranowska-Bosiacka
authors.affiliation: Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, Szczecin, Poland.
authors.forename: Kazimierz
authors.initials: K
authors.lastname: Ciechanowski
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood*; D004334:Drug Administration Schedule; D004797:Enzyme-Linked Immunosorbent Assay; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007677:Kidney Function Tests; D016030:Kidney Transplantation; D008297:Male; D011183:Postoperative Complications / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis; D051381:Rats; D017208:Rats, Wistar; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000139:chemically induced* / Q000175:diagnosis / Q000209:etiology
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents