Doxycycline: a pilot study to reduce diabetic proteinuria.

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.
MATERIAL AND 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.
CONCLUSION: 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. 2007 S. Karger AG, Basel