title: T helper (Th)-cytokines in the urine of patients with primary glomerulonephritis treated with immunosuppressive drugs: Can they predict outcome?
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.
  
  
  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: Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: dkalavrizioti@yahoo.com.
authors: Dimitra
authors: D
authors: Kalavrizioti
authors: Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: mgerolymos@yahoo.com.
authors: Miltiadis
authors: M
authors: Gerolymos
authors: Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece. Electronic address: marodi_biol@yahoo.gr.
authors: Maria
authors: M
authors: Rodi
authors: Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: pkalliak@gmail.com.
authors: Pantelitsa
authors: P
authors: Kalliakmani
authors: Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: simellap@gmail.com.
authors: Simela
authors: S
authors: Provatopoulou
authors: Department of Nephrology, School of Medicine, University of Thessaly, Larissa, Greece. Electronic address: teleftheriadis@yahoo.com.
authors: Theodoros
authors: T
authors: Eleftheriadis
authors: Division of Hematology, Department of Internal Medicine, Medical School, University of Patras, Patras, Greece. Electronic address: mouzaki@upatras.gr.
authors: Athanasia
authors: A
authors: Mouzaki
authors: Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece. Electronic address: dgoumenos@upatras.gr.
authors: Dimitrios S
authors: DS
authors: Goumenos
mesh_terms: D000328:Adult; D000368:Aged; D018932:Chemokine CCL2 / Q000652:urine; D016207:Cytokines / Q000652:urine*; D005260:Female; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology* / Q000503:physiopathology; D005923:Glomerulosclerosis, Focal Segmental / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000652:urine; D016753:Interleukin-10 / Q000652:urine; D020381:Interleukin-17 / Q000652:urine; D007376:Interleukin-2 / Q000652:urine; D015847:Interleukin-4 / Q000652:urine; D015850:Interleukin-6 / Q000652:urine; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011507:Proteinuria
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D016207:Cytokines; C508609:IL10 protein, human; C508717:IL17A protein, human; D007166:Immunosuppressive Agents; D020381:Interleukin-17; D007376:Interleukin-2; D015850:Interleukin-6; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma
keywords: Focal segmental glomerulosclerosis; IgA nephropathy; MCP-1 chemokine; Membranous nephropathy; Minimal change disease; Th-cytokines