No abstract

No abstract

We studied the immunohistochemical localization of advanced glycosylation end products (AGEs) in the progression of diabetic nephropathy. Fourteen NIDDM patients with diabetic nephropathy were evaluated: 2 patients with normoalbuminuria, 4 with microalbuminuria (MA) and 8 with overt proteinuria (OP). Three patients with minor glomerular abnormalities were used as nondiabetic controls. Immunoreactivity to a monoclonal anti-AGE antibody (6D12) was recognized on the internal elastic membranes of arterial walls in every diabetic group. Hyaline lesions of arterioles of the MA and OP groups demonstrated strong reactions with 6D12. A portion of the nodular and exudative lesions in glomeruli of OP group patients also revealed immunoreactivity to 6D12. No immunoreactivity to 6D12 was observed in nondiabetic control specimens. We confirm that the accumulation of AGEs began in arterial walls of the early stage and presented in glomerular lesions of the late stage of the progression of diabetic nephropathy.

Background/Aims: Pregnancy in hemodialysis (HD) patients tends to be diagnosed late because of its infrequency and the lack of validity of urine pregnancy tests, and because these patients tend to have menstrual irregularities. The outcome is influenced by pregnancy-related anemia. We investigated the characteristics of pregnancy-related anemia and whether it is a useful diagnostic clue to pregnancy in HD patients. Methods: We retrospectively investigated six pregnancies of 5 HD patients (mean age 30 years), including 4 patients treated with recombinant human erythropoietin (rHuEpo) and a transfusion-dependent patient with two pregnancies in the pre-rHuEpo era. Results: The mean duration of HD was 6 years, the mean duration of the patients’ marriages at the time of pregnancy was 6 years, and the mean gestational age at diagnosis was 11 weeks and 4 days. The progression of anemia (an 8% decrease in the hematocrit) was detected by 8 weeks of gestation in all patients. The prepregnancy hematocrit was stable in 5 pregnancies, facilitating the detection of changes, but during one of the pregnancies of the transfusion-dependent patient the hematocrit was low and was influenced by the transfusions. The amount of rHuEpo required to attain a target hematocrit of 30% increased gradually or rapidly until delivery. Conclusions: The progression of anemia or hyporesponsiveness to rHuEpo was a useful early diagnostic clue to pregnancy in HD patients. However, the prepregnancy hematocrit should be stabilized with rHuEpo, so that decreases can be easily detected. The precise mechanisms of hyporesponsiveness to rHuEpo, which progressed during pregnancy and subsided after delivery, remain to be clarified.

Background. Hemodialysis (HD) patients are in a highly oxidative state, which may contribute to accelerated atherosclerosis. Methylguanidine (MG) and lipid peroxides may be used as markers of the oxidative status in HD patients. A recent study demonstrated the non-enzymatic generation of nitric oxide (NO) via a reaction between hydrogen peroxide and arginine. We determined the relationships between serum concentrations of the oxidation products of NO (NOx) and oxidative status markers, and the relationships between these markers and the prevalence of atherosclerotic disease in HD patients. Methods. We measured serum concentrations of MG, creatinine (Cr), NOx, and thiobarbituric acid reactive substances (TBARS), and determined the presence of apparent vascular disease in 324 nondiabetic HD patients. Results. The MG concentration, but not the NOx concentration, was correlated with the Cr concentration (r ϭ 0.64; P Ͻ 0.001). Based on simple linear regression analysis, the NOx concentration (r ϭ 0.13; P Ͻ 0.05) correlated with the MG/Cr ratio, but did not correlate with the TBARS concentration. Multiple linear regression analysis revealed that the serum NOx concentration (r ϭ 0.13; P Ͻ 0.01) and the duration of dialysis (r ϭ 0.13; P ϭ 0.05) correlated with the MG/Cr ratio. There were no significant differences in the concentrations of NOx, TBARS, or the MG/Cr ratio between HD patients with and without vascular disease. Multivariate logistic regression analysis showed that only age and hypertension were independent risk factors for prevalent vascular disease. Conclusions. These results suggest that non-enzymatic synthesis of NO via oxidative stress may occur in HD patients. However, the serum markers of oxidation status at any one single moment may not correlate with the prevalence of apparent vascular disease in HD patients.