Pentoxifylline in Lupus Nephritis

Inclusion criteria: 1. Patients 18 and older, who meet the 1997 update of the1982 criteria for classification of systemic lupus erythematosus and have established lupus nephritis as documented by any of the following: 1. Kidney biopsy documenting class II, III, IV, or V (RPS/ISN 2004) lupus nephritis within 3 years or 2. Abnormal urine protein excretion on 2 occasions, at least 2 weeks apart, characterized by more than 500 mg urine protein, quantitated either by 24-hour urine collection or by urine protein/creatinine ratio (UPCR) more than 0.5 mg/mg, measured on a first void morning specimen, in the absence of other glomerulopathies; or 3. Abnormal urine sediment, containing more than 5 RBC, more than 5 WBC, or cellular casts on 2 occasions, at least 2 weeks apart, in the absence of infection, concurrent menstruation, anatomic genitourinary abnormalities, or pathologic disorders other than lupus nephritis. 2. Absence of changes in immunosuppressive agents or dose of immunosuppressive agents administered during the 2 months before enrollment. Patients with newly-diagnosed lupus nephritis will not be invited to participate until after they have completed 6 months of initial induction therapy. 3. Unless contraindicated, patients will be required to be taking an ACE inhibitor or ARB, with stable dose for at least 1 month prior to enrollment. Patients with intolerance of ACE/ARB therapies will be eligible to participate, but will be analyzed separately, as indicated in the trial synopsis. 4. Urine protein more than 500 mg/24 hours and/or UPCR more than 0.5 mg/mg at time of baseline. 5. Willingness to remain on stable immunosuppressive drugs for the 6-month duration of the study unless safety issues arise. 6. The SELENA-SLEDAI will be measured at screening but no minimal SLEDAI score will be required for inclusion. 7. Although kidney biopsy is not required for enrollment in this clinical trial, the standard of care at all participating institutions is to recommend renal biopsy for all patients with lupus nephritis, and generally at least 75% of such patients at each participating institution will be expected to have had this procedure. Subjects who qualify for this study according to clinical criteria noted in 1b and 1c above must be confirmed to have lupus nephritis, and no other renal disorder, by the site PI, prior to enrollment. Exclusion criteria: 1. History of retinal, cerebral, or peptic ulcer hemorrhage within 3 months prior to enrollment 2. Current use of warfarin, long-acting heparin, or an oral anti-coagulant (other than low dose aspirin) 3. Pregnancy or currently breast-feeding 4. History of theophylline, pentoxifylline, or caffeine allergy 5. Currently taking theophylline-containing medications 6. Malignancy within 2 years, other than basal cell carcinoma 7. Congestive heart failure, class III or IV 8. Abnormal AST/ALT, more than 2 times ULN 9. Obstructive uropathy 10. Acute kidney injury defined as greater than 50% decrease in GFR within 30 days prior to screening. 11. Myocardial infarction, percutaneous coronary intervention, coronary bypass graft surgery, or unstable angina within 6 months prior to screening 12. BP greater than 150/95 on 2 measurements in the sitting position after 5 minutes of rest, using a manual BP cuff 13. Known diagnosis of diabetes mellitus or hemoglobin A1c greater than 8.0 14. Current (within 3 months) GFR less than 30 mL/min 15. Surgery within 3 months prior to enrollment 16. Concurrent diagnosis of antiphospholipid syndrome (APS), or presence of APS antibodies on 2 occasions, more than 12 weeks apart.