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Background: Many lines of evidence highlight the genetic contribution on the development of diabetic nephropathy (DN). One of the studied genes is SERPINE1 whose the role in the risk of developing DN remains questionable. In order to elucidate the contribution of SERPINE1 in DN progression in the context of type 2 diabetes mellitus (T2DM), we conducted an association study and meta-analysis of SERPINE1 genetic variants. Materials and Methods: A total of 190 patients with DN, 150 T2DM (type 2 diabetes mellitus) patients without DN and 238 healthy controls were recruited. We selected five tag single-nucleotide polymorphisms (SNPs) from the HapMap. The generalized odds ratio (ORG) was calculated to estimate the risk on DN development. Subgroup analyses based on ethnicity and type of diabetes were also performed. Results: Both the present association study regarding SERPINE1 SNPs (rs2227667, rs2070682, rs1050813, rs2227690, rs2227692) did not found any significant association between SERPINE1 variants and DN and the meta-analysis of variant 4G>5G (rs1799889) did not also reveal a significant association between 4G>5G variant and DN in main and subgroup analyses. Discussion: In conclusion, the present association study and meta-analysis provides strong evidence that SERPINE1 genetic variant 4G>5G is not implicated in the risk or development of DN in Caucasians. Further studies in other populations remain to further investigate the role of this variant in the course of DN.

Ischemia-reperfusion injury is the commonest form of acute kidney injury (AKI). Tubular epithelial cell senescence contributes to incomplete recovery from AKI and predisposes to subsequent chronic kidney disease. In cultures of primary proximal renal tubular epithelial cells (RPTECs) subjected to anoxia or reoxygenation, we evaluated the role of indoleamine 2,3-dioxygenase 1 (IDO) in cellular senescence. Proteins of interest were assessed with Western blotting or enzyme-linked immunosorbent assay or histochemically. Under anoxia or reoxygenation, IDO expression and activity were increased. Moreover, the two IDO-derived pathways, the general control nonderepressible 2 kinase (GCN2K) pathway and the aryl-hydrocarbon receptor (AhR) pathway, were also activated. A DNA damage response (DDR) took place and led to increased levels of the cell-cycle inhibitors p21 and p16, and senescence-associated β-galactosidase (SA-β-Gal) activity. Cell proliferation was inhibited, and more IL-6 was produced. The IDO inhibitor 1-DL-methyl-tryptophan ameliorated the DDR, decreased p21, p16, and SA-β-Gal activity, restored cell proliferation, and decreased IL-6 production. The AhR inhibitor CH223191 did not affect the above parameters. In conclusion, anoxia and the subsequent reoxygenation upregulate IDO. IDO depletes tryptophan and activates GCN2K. The latter enhances the anoxia- or reoxygenation-induced DDR, resulting in increased p21 and p16 expression and eventually leading to RPTEC senescence. Since cellular senescence affects AKI outcome, the role of IDO in cellular senescence and the possible therapeutic role of IDO inhibitors deserve further investigation.

Disturbed iron homeostasis contributes to resistance to recombinant human erythropoietin (rHuEpo) in hemodialysis (HD) patients. Although increased hepcidin, which downregulates the iron exporter ferroportin, had been incriminated, such an association has not been confirmed. Albeit not universally accepted, it has been supported that in case of copper deficiency, decreased activity of multicopper oxidases induces endocytosis and degradation of ferroportin. Ferroportin in monocytes, serum copper, ceruloplasmin and markers of iron status were measured, and associations with rHuEpo resistance index (ERI) were evaluated. After a 4-week washout period from iron treatment, 34 HD patients and 20 healthy volunteers enrolled in the study. Ferroportin was assessed by means of Western blotting, copper colorimetrically, whereas ceruloplasmin with enzyme-linked immunosorbent assay. Hemoglobin, serum iron, ferritin and transferrin saturation (TSAT) were also measured. Ferroportin in monocytes of HD patients was decreased. Serum copper, ceruloplasmin, iron and TSAT were decreased. No correlation between copper or ceruloplasmin and ferroportin was detected. ERI was negatively correlated with ferroportin and all the markers of iron adequacy, but not with copper or ceruloplasmin. Although copper deficiency and decreased ferroportin are common in HD patients, copper might not play role in ferroportin level in monocytes and in iron metabolism in this population.

Psoas abscess is an infrequent clinical entity which poses diagnostic and therapeutic challenges. Few cases have been reported in chronic hemodialysis patients. We describe a case of psoas abscess in a dialysis patient with dialysis-related amyloidosis, successfully treated with percutaneous drainage and parenteral antibiotics.

Disturbed iron homeostasis contributes to resistance to recombinant human erythropoietin (rHuEpo) in hemodialysis (HD) patients. Increased hepcidin, which downregulates the iron exporter ferroportin, has been incriminated. However, other factors also control ferroportin expression in mononuclear phagocyte system. Ferroportin in monocytes, as well as serum hepcidin, interleukin-6 (IL-6) and common markers of iron status were measured and correlations with rHuEpo resistance index (ERI) were evaluated. After a 4-week washout period from iron treatment, 34 HD patients and 20 healthy volunteers enrolled in the study. Ferroportin was assessed by means of western blotting, whereas hepcidin and IL-6 with enzyme-linked immunosorbent assay. Hemoglobin, serum iron, ferritin and transferrin saturation (TSAT) were also measured. Ferroportin in monocytes of HD patients was decreased. Serum hepcidin and IL-6 were increased, whereas serum iron and TSAT were decreased. ERI was negatively correlated with ferroportin and all the markers of iron adequacy, but not with hepcidin. Decreased ferroportin in monocytes of HD patients accompanies increased hepcidin, inflammation, decreased iron availability and is correlated with resistance to rHuEpo treatment.

Background/Aims: Insulin resistance is a well-known phenomenon in uremia. Resistin, a recently discovered insulin inhibitor secreted by adipocytes, is associated with obesity and insulin resistance in mice. Adiponectin, also secreted by adipocytes, is known to reduce insulin resistance in humans. The aim of the present study was to address the hypothesis that changes in resistin or adiponectin serum levels may relate to body composition and to insulin resistance in patients with end-stage renal disease. Methods: In a cross-sectional study, 33 non-diabetic patients (24 males and 9 females, mean age 61.5 ± 15.8 years) with end-stage renal disease on chronic hemodialysis (treatment duration 41 ± 31 months) that lacked signs of infection were enrolled. The control group consisted of 33, matched for age, sex and body mass index (BMI), healthy volunteers (22 males, 11 females, mean age 62.6 ± 12.1 years). BMI (kg/m2) was calculated from body weight and height. Body fat (%) was measured by means of bioelectrical impedance. Blood samples were taken always in the morning after a 12-hour fasting period before and after the hemodialysis session. Resistin and adiponectin serum concentrations were measured by enzyme immunoassays and insulin by an electrochemiluminescence immunoassay. The post-treatment values were corrected regarding the hemoconcentration. The homeostasis model assessment index (HOMA-R) was calculated as an estimate of insulin resistance from the fasting glucose and insulin serum levels. Results: Pre-treatment resistin serum levels were significantly increased in hemodialysis patients compared to healthy controls (19.2 ± 6.2 vs. 3.9 ± 1.8 ng/ml; p < 0.001). Hemodialysis did not alter resistin levels, as pre- and post-treatment levels were not different when corrected for hemoconcentration (19.2 ± 6.2 vs. 18.7 ± 5.0 ng/ml; p = 0.54). Adiponectin levels were also increased in hemodialysis patients compared to healthy controls (25.4 ± 21.5 vs. 10.5 ± 5.9 µg/ml; p < 0.001). A significant inverse correlation was observed between the serum adiponectin levels before the hemodialysis session on the one hand and the BMI (r = –0.527, p = 0.002), the HOMA-R (r = –0.378, p < 0.05) and the fasting insulin levels (r = –0.397, p < 0.05) on the other. However, no significant correlation was observed between serum resistin levels on the one hand versus HOMA-R index (3.2 ± 3.9 mmol·µIU/ml; r = –0.098, p = 0.59), insulin levels (13.3 ± 14.4 mU/l; r = –0.073, p = 0.69), glucose levels (89 ± 13 mg/dl; r = –0.049, p = 0.78), BMI (25.6 ± 3.7 kg/m2; r = –0.041, p = 0.82) and body fat content (26.4 ± 8.4%; r = –0.018, p = 0.94) on the other hand. Conclusion: Resistin serum levels are significantly elevated in non-diabetic patients with end-stage renal disease that are treated by hemodialysis. The hemodialysis procedure does not affect the resistin levels. Along with previous observations in patients with renal insufficiency in the pre-dialysis stage, our findings implicate an important role of the kidney in resistin elimination. However, increased resistin serum levels in hemodialysis patients are not related to reduced insulin sensitivity encountered in uremia.