Doxycycline: a pilot study to reduce diabetic proteinuria

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.

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.

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.

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.