Oxidative modification of low-density lipoproteins and the outcome of renal allografts at 1 1/2 years

Background. Previous studies reported a significant association between hyp erlipidemia of the recipient and chronic allograft nephropathy (CAN). Howev er, the nature and the patho genic mechanism of circulating lipid abnormali ties in CAN remain unclear. Methods. In a prospective study of 50 consecutive adult recipients of a cad averic renal allograft, we investigated the impact of lipid abnormalities o n the outcome of the graft at 1 1/2, years. Besides morphometric analysis o f implantation and protocol biopsies, clinical and biochemical variables we re studied at three-month intervals. Plasma concentrations of oxidized low- density lipoprotein (OxLDL) were determined by means of enzyme-linked immun osorbent assay. Immunohistochemical staining for OxLDL and macrophages was performed on paired renal biopsies. Study end points were the fractional in terstitial volume and the 24-hour creatinine clearance at 1 1/2 years. Results. High-density lipoprotein (HDL) cholesterol of the recipient less t han or equal to 47 mg/dL was a risk factor for the functional (RR = 1.56; 9 5% CI, 0.978 to 2.497) and the morphological (RR = 2.75; 95% CI, 1.075 to 7 .037) outcome of the graft, mainly in patients without acute rejection (RR = 2.03; 95% CI, 1.13 to 3.65, and RR = 4.67; 95% CI, 1.172 to 18.582, respe ctively). Interstitial accumulation of OxLDL was inversely associated with HDL cholesterol (R = -0.476, P = 0.019), and was associated with a higher d ensity of tubulointerstitial macrophages (R = 0.656, P = 0.001) and a highe r fractional interstitial volume at 1 1/2 years (P = 0.049). Conclusion. Decreased HDL cholesterol levels of the recipient adversely aff ect the outcome of renal allografts through the accumulation of OxLDL in th e renal interstitium of the graft. Interstitial accumulation of OxLDL was a ssociated with the presence of macrophages and the development of interstit ial fibrosis.