Chronic Pain Treatment With Cannabidiol in Kidney Transplant Patients in Uruguay.

BACKGROUND: Chronic pain is a major therapeutic problem in kidney transplant patients owing to nephrotoxicity associated with nonsteroidal antiiflammatory drugs. Benefits in chronic pain treatment with cannabidiol (CBD) have been reported. This study assesses the effect, safety, and possible drug interactions in kidney transplant patients treated with CBD for chronic pain. METHODS: We assessed patients who asked to receive CBD for pain treatment. Doses were increased from 50 to 150 mg twice a day for 3 weeks. Creatinine, blood count, liver function, liver enzymes, and drug levels were determined every 48 hours the first week and then once a week thereafter. RESULTS: We assessed 7 patients with a mean age of 64.5 years (range, 58-75 years). CBD initial dose was 100 mg/d, CBD dose reduction to 50 mg/d has been done on day 4 to patient 1 for persistent nausea. Tacrolimus dose reduction in patient 3 was undertaken on days 4, 7, and 21 owing to persisting elevated levels (even before CBD) and itching, and on day 21 in patient 5. Tacrolimus levels decreased in patient 2 but were normal in the control 1 week later. Patients on cyclosporine were stable. Adverse effects were nausea, dry mouth, dizziness, drowsiness, and intermittent episodes of heat. CBD dose decrease was required in 2 patients. Two patients had total pain improvement, 4 had a partial response in the first 15 days, and in 1 there was no change. CONCLUSIONS: During this follow-up, CBD was well-tolerated, and there were no severe adverse effects. Plasma levels of tacrolimus were variable. Therefore, longer follow-up is required.

Intragraft regulatory T cells in protocol biopsies retain foxp3 demethylation and are protective biomarkers for kidney graft outcome.

Presence of subclinical rejection (SCR) with IF/TA in protocol biopsies of renal allografts has been shown to be an independent predictor factor of graft loss. Also, intragraft Foxp3+ T(reg) cells in patients with SCR has been suggested to differentiate harmful from potentially protective infiltrates. Nonetheless, whether presence of Foxp3 T(reg) cells in patients with SCR and IF/TA may potentially protect from a deleterious graft outcome has not yet been evaluated. This is a case-control study in which 37 patients with the diagnosis of SCR and 68 control patients with no cellular infiltrates at 6-month protocol biopsies matched for age and time of transplantation were evaluated. We first confirmed that numbers of intragraft Foxp3-expressing T cells in patients with SCR positively correlates with Foxp3 demethylation at the T(reg) -specific demethylation region. Patients with SCR without Foxp3+ T(reg) cells within graft infiltrates showed significantly worse 5-year graft function evolution than patients with SCR and Foxp3+ T(reg) cells and those without SCR. When presence of SCR and IF/TA were assessed together, presence of Foxp3+ T(reg) could discriminate a subgroup of patients showing the same graft outcome as patients with a normal biopsy. Thus, presence of Foxp3+ T(reg) cells in patients with SCR even with IF/TA is associated with a favorable long-term allograft outcome.