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 hyperlipidemia of the recipient and chronic allograft nephropathy (CAN). However, the nature and the pathogenic mechanism of circulating lipid abnormalities in CAN remain unclear.


METHODS
In a prospective study of 50 consecutive adult recipients of a cadaveric renal allograft, we investigated the impact of lipid abnormalities on the outcome of the graft at 1 1/2 years. Besides morphometric analysis of implantation and protocol biopsies, clinical and biochemical variables were studied at three-month intervals. Plasma concentrations of oxidized low-density lipoprotein (OxLDL) were determined by means of enzyme-linked immunosorbent assay. Immunohistochemical staining for OxLDL and macrophages was performed on paired renal biopsies. Study end points were the fractional interstitial volume and the 24-hour creatinine clearance at 11/2 years.


RESULTS
High-density lipoprotein (HDL) cholesterol of the recipient < or =47 mg/dL was a risk factor for the functional (RR = 1.56; 95% 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, respectively). Interstitial accumulation of OxLDL was inversely associated with HDL cholesterol (R = -0.476, P = 0.019), and was associated with a higher density of tubulointerstitial macrophages (R = 0.656, P = 0.001) and a higher fractional interstitial volume at 11/2 years (P = 0.049).


CONCLUSIONS
Decreased HDL cholesterol levels of the recipient adversely affect the outcome of renal allografts through the accumulation of OxLDL in the renal interstitium of the graft. Interstitial accumulation of OxLDL was associated with the presence of macrophages and the development of interstitial fibrosis.
Bosmans
J L
JL
Department of Nephrology, University (Hospital) of Antwerp, Belgium.
Holvoet
P
P
Dauwe
S E
SE
Ysebaert
D K
DK
Chapelle
T
T
Jürgens
A
A
Kovacic
V
V
Van Marck
E A
EA
De Broe
M E
ME
Verpooten
G A
GA
D000328:Adult; D001706:Biopsy; D008076:Cholesterol, HDL / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D007676:Kidney Failure, Chronic / Q000378:metabolism* / Q000401:mortality / Q000601:surgery; D016030:Kidney Transplantation / Q000401:mortality*; D008077:Lipoproteins, LDL / Q000032:analysis / Q000097:blood*; D008264:Macrophages / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D008875:Middle Aged; D015999:Multivariate Analysis; D010084:Oxidation-Reduction; D011446:Prospective Studies; D012307:Risk Factors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
D008076:Cholesterol, HDL; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D008315:Malondialdehyde