A Trial of Doxycycline in Renal Disease

This is a Phase I, placebo-controlled, randomized crossover trial to determine the effects of
4-week treatment with subantimicrobial-dose doxycycline on serum and urine biomarkers of
fibrosis in patients with pre-dialysis chronic kidney disease (eGFR<30ml/min/1.73m2).
Doxycycline is a matrix metalloproteinase inhibitor and is approved for use as an
anti-fibrotic in the setting of gum and skin disease at low doses (20mgBID). At such a dose,
serum levels are too low for antimicrobial effect and chronic usage is not thought to lead to
tetracycline resistance. Investigators hypothesize that doxycycline will ameliorate cardiac
and renal fibrosis and thus investigators will detect a decrease in fibrotic markers during
treatment with doxycycline.

Inclusion Criteria:

- CKD pre-dialysis (eGFR< 30 ml/min/1.73m2 not on dialysis);

- local 415/650/510 area codes;

- primary language English or Spanish

Exclusion Criteria:

- eGFR worsening by greater than 5ml/min/1.73 m2 during the last 6 months;

- Systolic blood pressure less than 100mmHg or greater than 170 mmHg;

- pregnancy;

- ejection fraction less than 45%;

- NYHA class III or IV HF;

- myocardial infarction or hospitalization for HF within 4 months;

- liver disease;

- moderate or severe chronic obstructive pulmonary disease or pulmonary fibrosis;

- current infection;

- chemotherapy;

- major surgery within last month;

- bilateral dialysis access precluding lab draw;

- self-reported use of IV drugs or cocaine within the last 6 months.