title: Proteomic analysis of urine in medication-overuse headache patients: possible relation with renal damages.
abstract: Medication-overuse headache (MOH) is a chronic disorder associated with overuse of analgesic drugs, triptans, non-steroidal anti-inflammatory drugs (NSAIDs) or other acute headache compounds. Various epidemiologic investigations proved that different drug types could cause nephrotoxicity, particularly in chronic patients. The aim of the present work was to analyze, by a proteomic approach, the urinary protein profiles of MOH patients focusing on daily use of NSAIDs, mixtures and triptans that could reasonably be related to potential renal damage. We selected 43 MOH patients overusing triptans (n = 18), NSAIDs (n = 11), and mixtures (n = 14), for 2-30 years with a mean daily analgesic intake of 1.5 ± 0.9 doses, and a control group composed of 16 healthy volunteers. Urine proteins were analyzed by mono-dimensional gel electrophoresis and identified by mass spectrometry analysis. Comparing the proteomic profiles of patients and controls, we found a significantly different protein expression, especially in the NSAIDs group, in which seven proteins resulted over-secreted from kidney (OR = 49, 95% CI 2.53-948.67 vs. controls; OR = 11.6, 95% CI 0.92-147.57 vs. triptans and mixtures groups). Six of these proteins (uromodulin, α-1-microglobulin, zinc-α-2-glycoprotein, cystatin C, Ig-kappa-chain, and inter-α-trypsin heavy chain H4) were strongly correlated with various forms of kidney disorders. Otherwise, in mixtures and in triptans abusers, only three proteins were potentially associated to pathological conditions (OR = 4.2, 95% CI 0.33-53.12, vs. controls). In conclusion, this preliminary proteomic study allowed us to define the urinary protein pattern of MOH patients that is related to the abused drug. According with the obtained results, we believe that the risk of nephrotoxicity should be considered particularly in MOH patients who abuse of NSAIDs.
authors: Medical Faculty, Department of Laboratory, Pathological Anatomy and Forensic Medicine, University Hospital of Modena and Reggio Emilia, Via del Pozzo 71, 41100, Modena, Italy. elisa.bellei@unimore.it
authors: Elisa
authors: E
authors: Bellei
authors: Aurora
authors: A
authors: Cuoghi
authors: Emanuela
authors: E
authors: Monari
authors: Stefania
authors: S
authors: Bergamini
authors: Luca Isaia
authors: LI
authors: Fantoni
authors: Maurizio
authors: M
authors: Zappaterra
authors: Simona
authors: S
authors: Guerzoni
authors: Annalisa
authors: A
authors: Bazzocchi
authors: Aldo
authors: A
authors: Tomasi
authors: Luigi Alberto
authors: LA
authors: Pini
mesh_terms: D000328:Adult; D000368:Aged; D000700:Analgesics / Q000009:adverse effects*; D020552:Comet Assay; D005260:Female; D006261:Headache / Q000139:chemically induced* / Q000652:urine; D006801:Humans; D007674:Kidney Diseases / Q000139:chemically induced* / Q000652:urine*; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D040901:Proteomics
chemical_list: D000700:Analgesics