Increased dietary salt accelerates chronic allograft nephropathy in rats

Background. Chronic allograft nephropathy (CAN), a major problem in renal t ransplantation, is related to both alloantigen-dependent and -independent p rocesses. Because dietary salt intake modulated glomerular production of tr ansforming growth factor-beta, which has been shown to play an important ro le in CAN, we hypothesized that dietary salt would directly enhance renal i njury in a rodent model of CAN. Methods. Dietary NaCl was increased from 1.0% (normal) to 8.0% in a group o f Fisher/Lewis rats 25 days following orthotopic renal transplantation and was continued until 16 weeks after transplantation. Results. Blood pressure, which was recorded using radiotelemetry in the fir st eight-weeks post-transplantation, did not differ between the groups, but allograft recipients on the 8.0% NaCl diet rapidly demonstrated increased urinary albumin excretion. Renal function determined by dynamic functional imaging was worse in allograft recipients on the 8.0% NaCl diet by six week s following transplantation. Histologic examination at 16 weeks confirmed a significant increase in allograft damage in the 8.0% NaCl group compared w ith allografts from rats on 1.0% NaCl diet. These findings included glomeru losclerosis and tubulointerstitial injury that consisted of fibrosis, tubul ar atrophy and dilation, intratubular casts, and tubular epithelial cell da mage. Small arteries and arterioles did not show evidence of damage from hy pertension or other abnormality. Conclusions. In this model of CAN, renal allograft dysfunction preceded hyp ertension and was accelerated significantly by an increase in dietary salt.