Low-dose carbon monoxide inhalation prevents development of chronic allograft nephropathy

Chronic allograft nephropathy (CAN) is the primary cause for late kidney allograft loss. Carbon monoxide (CO), a product of heme metabolism by heme oxygenases, is known to impart protection against various stresses. We hypothesized that CO could minimize the chronic fibroinflammatory process and protect kidney allografts from CAN. Lewis kidney grafts were orthotopically transplanted into binephrectomized Brown-Norway rats under short-course tacrolimus. Recipients were maintained in room air or exposed to CO at 20 parts/million for 30 days after transplant. Efficacy of inhaled CO was studied at day 30 and day 80. Isografts maintained normal kidney function throughout the experiment with creatinine clearance of ∼1.5 ml/min. Renal allograft function in air controls progressively deteriorated, and creatinine clearance declined to 0.2 ± 0.1 ml/min by day 80 with substantial proteinuria. CO-treated animals had significantly better creatinine clearance (1.3 ± 0.2 ml/min) with minimal proteinuria. Histological ex...