title: Doxycycline: a pilot study to reduce diabetic proteinuria.
abstract: BACKGROUND
  Activity of matrix metalloproteinases (MMPs), the enzymes primarily responsible for the deposition of extracellular matrix proteins, contributes to the pathogenesis of diabetic proteinuria. We evaluated the effect of doxycycline, a potent nonselective MMPs inhibitor, on reduction of proteinuria in diabetic patients.
  
  
  METHODS
  In a self-control clinical trial, 35 patients with overt diabetic nephropathy (proteinuria >300 mg/24 h) received oral doxycycline 100 mg/day for 2 months. Twenty-four-hour urine volume, Cr and protein excretion were measured at baseline, after 1 and 2 months of treatment, and after 4 months of its discontinuation. Treatment-related side effects were closely monitored and documented.
  
  
  RESULTS
  Mean (+/-SD) 24-hour urine protein was 888 +/- 419 mg at baseline, 884 +/- 368 mg after 1 month, and 643 +/- 386 mg after the 2 months of doxycycline treatment. There was statistically significant reduction in proteinuria at 2 months of treatment vs. at the baseline (p < 0.001). Mean 24-hour urine protein excretion increased to 1,021 +/- 422 mg 4 months after doxycycline was discontinued. The changes in serum sodium, potassium, BUN and Cr concentrations, and blood pressure measurements during the 2 months of treatment and follow-up period were not statistically significant.
  
  
  CONCLUSIONS
  Proteinuria in patients with diabetic nephropathy can be reduced with low dose doxycycline therapy over a 2-month period of drug administration. Further studies are necessary to determine the long-term effect, the optimal dose, and the optimal duration of this potentially novel therapy.
authors.affiliation: Division of Nephrology, Isfahan University of Medical Sciences and Health Services, Isfahan, Iran.
authors.forename: Afsoon Emami
authors.initials: AE
authors.lastname: Naini
authors.forename: Ali Amini
authors.initials: AA
authors.lastname: Harandi
authors.forename: Javad
authors.initials: J
authors.lastname: Moghtaderi
authors.forename: Bahar
authors.initials: B
authors.lastname: Bastani
authors.forename: Ali
authors.initials: A
authors.lastname: Amiran
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003928:Diabetic Nephropathies / Q000188:drug therapy*; D004318:Doxycycline / Q000494:pharmacology / Q000627:therapeutic use*; D005109:Extracellular Matrix / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D008875:Middle Aged; D010865:Pilot Projects; D011507:Proteinuria / Q000188:drug therapy*
chemical_list: D000900:Anti-Bacterial Agents; D061965:Matrix Metalloproteinase Inhibitors; D004318:Doxycycline