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. MATERIAL AND 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.
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. MATERIAL AND 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: William P Martin; Chloe Conroy; Serika D Naicker; Sarah Cormican; Tomás P Griffin; Md Nahidul Islam; Eibhlin M McCole; Ivan McConnell; John Lamont; Peter FitzGerald; John P Ferguson; Ciarán Richardson; Susan E Logue; Matthew D Griffin Journal: Kidney360 Date: 2021-05-21