No abstract

Functional iron-deficient erythropoiesis plays a role in rEPO-hyporesponsive anemia in HD patients with hyperferritinemia. IVAA may be an adjuvant therapy for rEPO in these patients, and E-ZPP of more than 105 micromol/mol heme and TS of less than 25% should be used to guide the IVAA treatment.

Vitamin C supplementation in chronic hemodialysis patients can reduce the lymphocyte 8-OHdG levels and intracellular ROS production, as well as up-regulate hOGG1 gene expression for repair. There is no compelling evidence for an in vivo pro-oxidant effect of vitamin C on lymphocyte DNA base oxidation, even in the status of increased iron stores.

A prospective study with 65 maintenance hemodialysis (MHD) patients on recombinant human erythropoietin (rHuEPO) therapy was conducted to assess the effect of iron balance on responsiveness. An attempt to define the predictors of erythropoietin (EPO) response and identify the specific causes of EPO resistance was undertaken in the present study. The treatment protocol consisted of two stages, the first was rHuEPO therapy for 6 months and the second was iron supplementation plus rHuEPO therapy in patients without response to EPO for the next 6 months. According to the hemoglobin (Hb) changes (increment exceeded 30% of baseline or did not exceed 15% of baseline for 3 consecutive months) and whether or not there was an achievement of target Hb level ( > 10.5 g/dl), all patients (n = 65) were divided into EPO-responsive (n = 20) and EPO-resistant (n = 45) groups. The EPO-resistant patients were then further stratified into iron-responsive (n = 29) and iron-irresponsive (n = 16) groups. Iron metabolism and red cell indices were analyzed prior to and following rHuEPO therapy and iron supplementation. We found the following: (1) only serum ferritin (SF) was a reliable discriminator between the EPO-responsive (SF > 300 µg/l) and EPO-resistant (SF < 300µg/l) groups; (2) similarly, transferrin saturation (TFS) 25% was quoted as the best cut-off value between the iron-responsive (TFS < 25%) and iron-irresponsive (TFS > 25%) groups; (3) EPO-resistant patients with TFS < 2 5 % regained proper EPO response (Hb before and 6 months after therapy: 7.8 ± 0.9 vs. 10.6 ± 0.8 g/dl, p < 0.01) and the mean TFS increased significantly (initial TFS and peak level after therapy: 18.9 ± 4.7 vs. 34.5 ± 10.8%, p < 0.01) following iron therapy; (4) the cumulative incidence of TFS < 25% elevated to 44.5% 6 months following initial rHuEPO therapy, and (5) there was a strong inverse relationship between initial TFS and the changes of Hb following iron therapy in EPO-resistant patients (r = -0.75, p < 0.0001). By means of early detection and correction of functional iron deficiency, the goal of increment of therapeutic efficacy and prevention from unnecessarily high doses of rHuEPO can be achieved. In summary, SF > 300 µg/l equates adequate or increased body iron stores and seems to exclude iron deficiency in MHD patients. On the contrary, SF < 300 µg/l appears to be an insufficient diagnostic threshold for iron deficiency. Once resistance occurs during the rHuEPO therapy, in our opinion only patients with TFS < 25% need iron supplementation. However, in patients with TFS > 25% and resistance to EPO, further investigations are necessary before increasing the dose of rHuEPO to explore other possible conditions, such as aluminum overload, severe hyperparathyroidism, occult blood loss or hemolysis, and episodes of infection or inflammatory processes.

Urinary proteins (5 mg/ml) collected from a group of 16 patients including 13 with IgA nephropathy and 3 with Schönlein-Henoch purpura (SHP) and from a control group consisting of 6 patients with diabetic nephropathy, 5 patients with hypertensive nephrosclerosis, and 5 healthy hospital staff members were studied for the contents of interleukins (IL) 1β, 2, 4, 6, and 12 and tumor necrosis factor alpha (TNF-α). Eleven patients with IgA nephropathy or SHP (11/16) but only 1 of the controls (1/16) had TNF-α activity in urinary proteins (p < 0.01). The IL-lβ activity exhibited a similar tendency but to a lesser extent (10 of 16 patients with IgA nephropathy or SHP vs. 2 of 16 with other conditions, p < 0.05). Conversely, the detection rates of IL-2, IL-4, and IL-6 in both groups were not significantly different. IL-12 was not found in any of the samples from both groups. Sera and nonpurified urine samples from the same individuals were also measured for cytokines. IL-lβ, IL-2, IL-4, and IL-12 were absent in all these samples, but TNF-α was found in four of the serum samples from patients with IgA nephropathy. Urinary proteins (2 mg/ml) were analyzed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, whereby peptides of 52, 49, 45, 34, 30, and 11 kD could be demonstrated in the patients with IgA nephropathy or SHP. Urinary proteins (200 μg/ml) from patients with IgA nephropathy or SHP exerted a mitogen-like effect on the normal human mononuclear cells, as demonstrated by ³H-thymidine incorporation. In addition, these urinary proteins (400 μg/ml) enhanced the prolifera-tive activity of the cultured rat glomerular mesangial cells. The exaggerated proliferation of rat glomerular mesangial cells exerted by urine proteins from 2 patients with active disease was markedly suppressed after treatment with glu-cocorticoids/cyclophosphamide. These results suggest that patients with IgA nephropathy or SHP can excrete excessive amounts of TNF-α and IL-1 β in the urine. The inconsistent presence of these two cytokines in urine and serum may indicate that they can be produced locally and that they are implicated in the development of mesangial inflammation and glomerular damage.