Serum levels of 12 renal function and injury markers in patients with glomerulonephritis.

INTRODUCTION    Glomerulonephritis (GN) is a complex disease that affects the function of the whole nephron. There are few data on the serum levels of the most common biomarkers of kidney function and injury in GN, or the studies provide ambiguous results. OBJECTIVES    The aim of the study was to evaluate the levels of known kidney-specific and nonspecific markers of renal function or injury in the serum of patients with diagnosed primary or secondary GN, with or without the presence of nephrotic syndrome (NS) and arterial hypertension (AH). PATIENTS AND METHODS    The study included 58 patients with diagnosed GN and 6 patients with congenital defects (CD) of the kidney and AH (CD+AH). The serum levels of ß2-microglobulin (ß2M), neutrophil­gelatinase associated lipocalin (NGAL), osteopontin, trefoil factor 3 (TFF-3), calbindin, glutathione-S­transferase- π (GST-π), interleukin 18 (IL-18), kidney injury molecule 1 (KIM-1), and monocyte chemoattractant protein 1 (MCP-1) were measured with Kidney Toxicity Panels 1 and 2 using the Bio-Plex method. Renalase levels were measured using an enzyme-linked immunosorbent assay. RESULTS    In the whole group and in the subgroups (GN, GN+AH, GN+NS, CD+AH), NGAL, KIM-1, TFF-3, IL-18, ß2M, and calbindin levels correlated with estimated glomerular filtration rate (eGFR). In patients with NS, this correlation for calbindin was reversed. Renalase, MCP-1, GST-π, and osteopontin levels were independent of eGFR. Increase in IL-18 levels in the group with GN was assiociated with lower odds of the kidney disease. When this group was divided according to eGFR into subgroups G1-G5, TFF-3, NGAL, and ß2M levels increased with the stage of the disease. CONCLUSIONS In patients with NS, renalase and MCP-1 might regulate each other's levels. Further studies are needed to investigate associations between renalase, MCP-1, and osteopontin as factors unrelated to eGFR in GN. NS may contribute to the loss of calbindin from serum. NGAL, KIM-1, TFF-3, IL-18, ß2M, and calbindin are good indicators of kidney function loss in patients with GN.

Induction of the Estrogenic Marker Calbindn-D9k by Octamethylcyclotetrasiloxane.

Interrupting the hormonal balance of an organism by interfering with hormones and their target receptors gives rise to various problems such as developmental disorders. Collectively, these reagents are known as endocrine disruptors (EDs). Cyclic volatile methyl siloxanes (cVMSs) are a group of silicone polymers that including octamethylcyclotetrasiloxane (D4). In the present study, we examined the estrogenicity of D4 through in vitro and in vivo assays that employed calcium-binding protein 9K (calbindin-D9k; CaBP-9K) as a biomarker. For in vitro investigation, GH3 rat pituitary cells were exposed to vehicle, 17ß-estradiol (E2), or D4 with/without ICI 182 780 (ICI). CaBP-9K and progesterone receptor (PR) both were up-regulated by E2 and D4 which were completely blocked by ICI. Transcription of estrogen receptor α (ER α) was decreased by E2 and D4 but increased by ICI. D4 was also administered to immature female rats for an uterotrophic (UT) assay and detection of CaBP-9K. Ethinyl estradiol (EE) or D4 was administered subcutaneously with or without ICI. Although uterine weight was not significant altered by D4, an effect thought to be due to cytochrome P450 (CYP), it induced CaBP-9K and PR gene expression. Based on these results we reveal that D4 has estrogenic potential proven under in vitro and in vivo experimental conditions.