title: Effects of Minocycline on Urine Albumin, Interleukin-6, and Osteoprotegerin in Patients with Diabetic Nephropathy: A Randomized Controlled Pilot Trial.
abstract: BACKGROUND
  We tested minocycline as an anti-proteinuric adjunct to renin-angiotensin-aldosterone system inhibitors (RAASi) in diabetic nephropathy (DN) and measured urinary biomarkers to evaluate minocycline's biological effects.
  
  
  METHODS
  
  
  
  METHODS
  Prospective, single center, randomized, placebo-controlled, intention-to-treat pilot trial. Inclusion. Type 2 diabetes/DN; Baseline creatinine clearance >30 mL/min; proteinuria ≥1.0 g/day; Age ≥30 years; BP <150/95 mm Hg; intolerant of/at maximum RAASi dose. Protocol. 3-wk screening; Baseline randomization; Urine and blood measures at months 1, 2, 4, and Month 6 study completion. Urine interleukin-6 (IL-6) and osteoprotegerin were measured in a subset. Primary outcome. Natural log of urine protein/creatinine (ln U P:Cr) ratio at Month 6 vs Baseline.
  
  
  RESULTS
  30 patients completed the study. The 15% decline in U P: Cr in minocycline patients (6 month P:Cr ÷ Baseline P:Cr, 0.85 vs. 0.92) was not significant (p = 0.27). Creatinine clearance did not differ in the 2 groups. Urine IL-6:Cr (p = 0.03) and osteoprotegerin/Cr (p = 0.046) decrements were significant. Minocycline modified the relationship between urine IL-6 and proteinuria, suggesting a protective biological effect.
  
  
  CONCLUSIONS
  Although the decline in U P:Cr in minocycline patients was not statistically significant, the significant differences in urine IL-6 and osteoprotegerin suggest that minocycline may confer cytoprotection in patients with DN, providing a rationale for further study.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT01779089.
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90509, United States of America.
authors.forename: Anuja P
authors.initials: AP
authors.lastname: Shah
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90509, United States of America.
authors.forename: Jenny I
authors.initials: JI
authors.lastname: Shen
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90509, United States of America.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90509, United States of America.
authors.forename: Lili
authors.initials: L
authors.lastname: Tong
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90509, United States of America.
authors.forename: Youngju
authors.initials: Y
authors.lastname: Pak
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90509, United States of America.
authors.forename: Ali
authors.initials: A
authors.lastname: Andalibi
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90509, United States of America.
authors.forename: Janine A
authors.initials: JA
authors.lastname: LaPage
authors.affiliation: Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, Torrance, CA, 90509, United States of America.
authors.forename: Sharon G
authors.initials: SG
authors.lastname: Adler
mesh_terms: D000328:Adult; D000418:Albumins / Q000032:analysis*; D003404:Creatinine / Q000097:blood / Q000652:urine; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000652:urine; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000032:analysis* / Q000097:blood / Q000652:urine; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000627:therapeutic use*; D053244:Osteoprotegerin / Q000032:analysis* / Q000097:blood / Q000652:urine; D010865:Pilot Projects; D015990:Placebo Effect; D011446:Prospective Studies; D011506:Proteins / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D015850:Interleukin-6; D053244:Osteoprotegerin; D011506:Proteins; D003404:Creatinine; D008911:Minocycline