Dimitra Kalavrizioti1, Miltiadis Gerolymos2, Maria Rodi3, Pantelitsa Kalliakmani4, Simela Provatopoulou5, Theodoros Eleftheriadis6, Athanasia Mouzaki7, Dimitrios S Goumenos8. 1. Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: dkalavrizioti@yahoo.com. 2. Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: mgerolymos@yahoo.com. 3. Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece. Electronic address: marodi_biol@yahoo.gr. 4. Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: pkalliak@gmail.com. 5. Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: simellap@gmail.com. 6. Department of Nephrology, School of Medicine, University of Thessaly, Larissa, Greece. Electronic address: teleftheriadis@yahoo.com. 7. Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece. Electronic address: mouzaki@upatras.gr. 8. Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: dgoumenos@upatras.gr.
Abstract
BACKGROUND: Glomerulonephritides (GNs) represent common causes of chronic kidney disease associated with a wide spectrum of clinical and histological features. Various factors that activate the inflammatory cascade are involved in the development of kidney injury. The aim of this study was to estimate the urinary excretion of pro-inflammatory (IL-2, INF-γ, TNF-α, IL-6, IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β1) cytokines, as well as the chemokine MCP-1 in patients with various types of GN treated by immunosuppressive drugs and to identify any prognostic value of excreted cytokines for future renal function. PATIENTS AND METHODS: Ninety-seven patients (62 M/35 F, age 53.1 ± 15.6 years) with primary glomerulonephritis and 32 healthy controls were studied. The original diagnoses were membranous nephropathy (MN, n=36), IgA nephropathy (IgAN, n=31) and minimal changes disease or focal segmental glomerulosclerosis (MCD/FSGS, n=30). All patients had been treated with immunosuppressive drugs and, at the time of measurement of urinary cytokine excretion, were either in clinical remission or still had active disease with persistent proteinuria. RESULTS: GN patients had significantly higher levels of all cytokines and MCP-1 compared to healthy controls. A strong positive correlation between TGF-β1 and MCP-1 concentrations was observed in all GN patients. Increased urinary excretion of all tested cytokines apart from TNF-α and TGF-β1 was observed even in patients with clinical remission. The main difference between patients with proteinuria and those in clinical remission was the level of MCP-1 urinary excretion. The urinary excretion of MCP-1 and TGF-β1 was significantly higher in patients with MN who showed deterioration of renal function over a follow-up period of five years. CONCLUSIONS: Increased levels of cytokines are observed in the urine of patients with different types of glomerulonephritis, even after the achievement of clinical remission with the administration of immunosuppressive drugs. Urinary excretion of MCP-1 and TGF-β1 indicates the ongoing inflammatory and fibrotic processes in the kidney and is probably related to unfavourable outcomes.
BACKGROUND: Glomerulonephritides (GNs) represent common causes of chronic kidney disease associated with a wide spectrum of clinical and histological features. Various factors that activate the inflammatory cascade are involved in the development of kidney injury. The aim of this study was to estimate the urinary excretion of pro-inflammatory (IL-2, INF-γ, TNF-α, IL-6, IL-17) and anti-inflammatory (IL-4, IL-10, TGF-β1) cytokines, as well as the chemokine MCP-1 in patients with various types of GN treated by immunosuppressive drugs and to identify any prognostic value of excreted cytokines for future renal function. PATIENTS AND METHODS: Ninety-seven patients (62 M/35 F, age 53.1 ± 15.6 years) with primary glomerulonephritis and 32 healthy controls were studied. The original diagnoses were membranous nephropathy (MN, n=36), IgA nephropathy (IgAN, n=31) and minimal changes disease or focal segmental glomerulosclerosis (MCD/FSGS, n=30). All patients had been treated with immunosuppressive drugs and, at the time of measurement of urinary cytokine excretion, were either in clinical remission or still had active disease with persistent proteinuria. RESULTS: GN patients had significantly higher levels of all cytokines and MCP-1 compared to healthy controls. A strong positive correlation between TGF-β1 and MCP-1 concentrations was observed in all GN patients. Increased urinary excretion of all tested cytokines apart from TNF-α and TGF-β1 was observed even in patients with clinical remission. The main difference between patients with proteinuria and those in clinical remission was the level of MCP-1 urinary excretion. The urinary excretion of MCP-1 and TGF-β1 was significantly higher in patients with MN who showed deterioration of renal function over a follow-up period of five years. CONCLUSIONS: Increased levels of cytokines are observed in the urine of patients with different types of glomerulonephritis, even after the achievement of clinical remission with the administration of immunosuppressive drugs. Urinary excretion of MCP-1 and TGF-β1 indicates the ongoing inflammatory and fibrotic processes in the kidney and is probably related to unfavourable outcomes.
Authors: Vanessa Marchant; Antonio Tejera-Muñoz; Laura Marquez-Expósito; Sandra Rayego-Mateos; Raul R Rodrigues-Diez; Lucia Tejedor; Laura Santos-Sanchez; Jesús Egido; Alberto Ortiz; Jose M Valdivielso; Donald J Fraser; Manuel López-Cabrera; Rafael Selgas; Marta Ruiz-Ortega Journal: Biomolecules Date: 2020-09-24