Advanced glycation end products and oxidative stress are increased in chronic allograft nephropathy.
BACKGROUND
The histologic picture of chronic allograft nephropathy (CAN) resembles early arteriosclerotic lesion. Oxidative stress and advanced glycation end products (AGES) have been implicated in the pathogenesis of atherosclerosis and progression of renal disease.


METHODS
The authors serially measured the plasma malonyldialdehyde (MDA), carbonyl protein (CP), pentosidine, and argpyramidine levels in 11 postrenal transplant patients with normal renal function (KPT) and 10 patients with biopsy proven CAN at 1, 3, 6, 9 through 12, and 18 through 24 months posttransplant. Data were also obtained in 16 controls and 13 patients with chronic renal failure (CRF).


RESULTS
Although serum creatinine, MDA, CP, pentosidine, and argpyrimidine levels decreased during follow-up in KPT, it progressively increased in patients with CAN. The mean serum creatinine level was higher in patients with CRF (3.3 +/- 0.8 mg/dL [291.7 +/- 70.7 micromol/L]) and CAN (2.4 +/- 1.1 mg/dL [212.1 +/- 96.6 micromol/L]) than in controls (1.2 +/- 0.3 mg/dL [105.8 +/- 26.7 micromol/L]) and KPT patients (1.2 +/- 0.2 mg/dL [109.7 +/- 17.7 micromol/L]; P < 0.001). Markers of oxidative stress and AGEs measured at 18 to 24 months posttransplant in patients with CAN were higher than in KPT, controls, and CRF patients. MDA (nmol/mL) was significantly higher in patients with CAN (1.30 +/- 0.30) compared with controls (0.53 +/- 0.12), KPT (0.52 +/- 0.15), and CRF (0.74 +/- 0.27) groups (P < 0.001). Plasma CP (nmol/mg protein) in patients with CAN (4.3 +/- 1.00) was higher than in controls (1.90 +/- 0.69) and KPT (2.62 +/- 1.00) groups at the same time-point (P < 0.001), but comparable with CRF (2.69 +/- 1.20). Plasma pentosidine (pmol/micromol protein) level in patients with CAN (19.69 +/- 5.05) was higher compared with controls (2.49 +/- 0.86), CRF (13.10 +/- 3.68), and KPT (14.32 +/- 6.28) groups (P < 0.001). Plasma argpyrimidine (pmol/10 micromol protein) was higher in patients with CAN (123.8 +/- 17.9) compared with controls (4.81 +/- 1.91), CRF (56.92 +/- 29.67), and KPT (31.1 +/- 11.1; P < 0.001) groups.


CONCLUSIONS
Oxidative stress and AGEs are increased in patients with CAN, which cannot be explained by the decline in renal function alone. Oxidative stress and AGEs may be one among the nonimmune mediators of CAN.
Raj
Dominic S C
DS
Division of Nephrology, University of New Mexico, Albuquerque, NM, USA. draj@salud.unm.edu
Lim
Gideon
G
Levi
Moshe
M
Qualls
Clifford
C
Jain
Sushil K
SK
D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D005260:Female; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D016030:Kidney Transplantation / Q000502:physiology*; D008239:Lysine / Q000031:analogs & derivatives* / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D009952:Ornithine / Q000031:analogs & derivatives* / Q000097:blood*; D018384:Oxidative Stress; D011743:Pyrimidines / Q000097:blood*; D014184:Transplantation, Homologous
D017127:Glycation End Products, Advanced; D007166:Immunosuppressive Agents; D011743:Pyrimidines; C107313:argpyrimidine; D008315:Malondialdehyde; D001120:Arginine; D003404:Creatinine; C062187:pentosidine; D009952:Ornithine; D008239:Lysine