ABSTRACT
Prerenal azotemia (PRA) is a major cause of acute kidney injury and uncommonly studied in preclinical models. We sought to develop and characterize a novel model of PRA that meets the clinical definition: acute loss of glomerular filtration rate (GFR) that returns to baseline with resuscitation. Adult male C57BL/6J wild-type (WT) and IL-6-/- mice were studied. Intraperitoneal furosemide (4 mg) or vehicle was administered at time = 0 and 3 h to induce PRA from volume loss. Resuscitation began at 6 h with 1 mL intraperitoneal saline for four times for 36 h. Six hours after furosemide administration, measured glomerular filtration rate was 25% of baseline and returned to baseline after saline resuscitation at 48 h. After 6 h of PRA, plasma interleukin (IL)-6 was significantly increased, kidney and liver histology were normal, kidney and liver lactate were normal, and kidney injury molecule-1 immunofluorescence was negative. There were 327 differentially regulated genes upregulated in the liver, and the acute phase response was the most significantly upregulated pathway; 84 of the upregulated genes (25%) were suppressed in IL-6-/- mice, and the acute phase response was the most significantly suppressed pathway. Significantly upregulated genes and their proteins were also investigated and included serum amyloid A2, serum amyloid A1, lipocalin 2, chemokine (C-X-C motif) ligand 1, and haptoglobin; hepatic gene expression and plasma protein levels were all increased in wild-type PRA and were all reduced in IL-6-/- PRA. This work demonstrates previously unknown systemic effects of PRA that includes IL-6-mediated upregulation of the hepatic acute phase response.NEW & NOTEWORTHY Prerenal azotemia (PRA) accounts for a third of acute kidney injury (AKI) cases yet is rarely studied in preclinical models. We developed a clinically defined murine model of prerenal azotemia characterized by a 75% decrease in measured glomerular filtration rate (GFR), return of measured glomerular filtration rate to baseline with resuscitation, and absent tubular injury. Numerous systemic effects were observed, such as increased plasma interleukin-6 (IL-6) and upregulation of the hepatic acute phase response.
Subject(s)
Acute Kidney Injury , Azotemia , Animals , Male , Mice , Acute Kidney Injury/metabolism , Acute-Phase Reaction/complications , Azotemia/complications , Biomarkers , Disease Models, Animal , Furosemide , Glomerular Filtration Rate/physiology , Interleukin-6/genetics , Interleukin-6/metabolism , Lipocalin-2/genetics , Liver/metabolism , Mice, Inbred C57BLABSTRACT
BACKGROUND: Acute kidney injury (AKI) is common in sick neonates and associated with poor pulmonary outcomes, however, the mechanisms responsible remain unknown. We present two novel neonatal rodent models of AKI to investigate the pulmonary effects of AKI. METHODS: In rat pups, AKI was induced surgically via bilateral ischemia-reperfusion injury (bIRI) or pharmacologically using aristolochic acid (AA). AKI was confirmed with plasma blood urea nitrogen and creatinine measurements and kidney injury molecule-1 staining on renal immunohistochemistry. Lung morphometrics were quantified with radial alveolar count and mean linear intercept, and angiogenesis investigated by pulmonary vessel density (PVD) and vascular endothelial growth factor (VEGF) protein expression. For the surgical model, bIRI, sham, and non-surgical pups were compared. For the pharmacologic model, AA pups were compared to vehicle controls. RESULTS: AKI occurred in bIRI and AA pups, and they demonstrated decreased alveolarization, PVD, and VEGF protein expression compared controls. Sham pups did not experience AKI, however, demonstrated decreased alveolarization, PVD, and VEGF protein expression compared to controls. CONCLUSION: Pharmacologic AKI and surgery in neonatal rat pups, with or without AKI, decreased alveolarization and angiogenesis, producing a bronchopulmonary dysplasia phenotype. These models provide a framework for elucidating the relationship between AKI and adverse pulmonary outcomes. IMPACT: There are no published neonatal rodent models investigating the pulmonary effects after neonatal acute kidney injury, despite known clinical associations. We present two novel neonatal rodent models of acute kidney injury to study the impact of acute kidney injury on the developing lung. We demonstrate the pulmonary effects of both ischemia-reperfusion injury and nephrotoxin-induced AKI on the developing lung, with decreased alveolarization and angiogenesis, mimicking the lung phenotype of bronchopulmonary dysplasia. Neonatal rodent models of acute kidney injury provide opportunities to study mechanisms of kidney-lung crosstalk and novel therapeutics in the context of acute kidney injury in a premature infant.
Subject(s)
Acute Kidney Injury , Bronchopulmonary Dysplasia , Reperfusion Injury , Humans , Infant, Newborn , Animals , Rats , Animals, Newborn , Bronchopulmonary Dysplasia/metabolism , Vascular Endothelial Growth Factor A/metabolism , Lung , Reperfusion Injury/complications , Reperfusion Injury/metabolismABSTRACT
15-Lipoxygenase (15-LO) is a nonheme iron-containing dioxygenase that has both pro- and anti-inflammatory roles in many tissues and disease states. 15-LO is thought to influence macrophage phenotype, and silencing 15-LO reduces fibrosis after acute inflammatory triggers. The goal of the present study was to determine whether altering 15-LO expression influences inflammation and fibrogenesis in a murine model of unilateral ureteral obstruction (UUO). C57BL/6J mice, 15-LO knockout (Alox15-/-) mice, and 15-LO transgenic overexpressing (15LOTG) mice were subjected UUO, and kidneys were analyzed at 3, 10, and 14 days postinjury. Histology for fibrosis, inflammation, cytokine quantification, flow cytometry, and metabolomics were performed on injured tissues and controls. PD146176, a specific 15-LO inhibitor, was used to complement experiments involving knockout animals. Compared with wild-type animals undergoing UUO, Alox15-/- mouse kidneys had less proinflammatory, profibrotic message along with less fibrosis and macrophage infiltration. PD146176 inhibited 15-LO and resulted in reduced fibrosis and macrophage infiltration similar to Alox15-/- mice. Flow cytometry revealed that Alox15-/- UUO-injured kidneys had a dynamic change in macrophage phenotype, with an early blunting of CD11bHiLy6CHi "M1" macrophages and an increase in anti-inflammatory CD11bHiLy6CInt "M2c" macrophages and reduced expression of the fractalkine receptor chemokine (C-X3-C motif) receptor 1. Many of these findings were reversed when UUO was performed on 15LOTG mice. Metabolomics analysis revealed that wild-type kidneys developed a glycolytic shift postinjury, while Alox15-/- kidneys exhibited increased oxidative phosphorylation. In conclusion, 15-LO manipulation by genetic or pharmacological means induces dynamic changes in the inflammatory microenvironment in the UUO model and appears to be critical in the progression of UUO-induced fibrosis.NEW & NOTEWORTHY 15-Lipoxygenase (15-LO) has both pro- and anti-inflammatory functions in leukocytes, and its role in kidney injury and repair is unexplored. Our study showed that 15-LO worsens inflammation and fibrosis in a rodent model of chronic kidney disease using genetic and pharmacological manipulation. Silencing 15-LO promotes an increase in M2c-like wound-healing macrophages in the kidney and alters kidney metabolism globally, protecting against anaerobic glycolysis after injury.
Subject(s)
Arachidonate 12-Lipoxygenase/metabolism , Arachidonate 15-Lipoxygenase/metabolism , Cytokines/metabolism , Energy Metabolism , Inflammation Mediators/metabolism , Kidney/enzymology , Metabolome , Nephritis/etiology , Ureteral Obstruction/complications , Animals , Arachidonate 12-Lipoxygenase/genetics , Arachidonate 15-Lipoxygenase/genetics , Cellular Microenvironment , Cytokines/genetics , Disease Models, Animal , Energy Metabolism/drug effects , Fibrosis , Kidney/drug effects , Kidney/pathology , Leukocytes/enzymology , Lipoxygenase Inhibitors/pharmacology , Macrophages/enzymology , Male , Mice, Inbred C57BL , Mice, Knockout , Nephritis/enzymology , Nephritis/pathology , Nephritis/prevention & control , Phenotype , Ureteral Obstruction/drug therapy , Ureteral Obstruction/enzymology , Ureteral Obstruction/pathologyABSTRACT
Growing epidemiological data demonstrate that acute kidney injury (AKI) is associated with long-term cardiovascular morbidity and mortality. Here, the authors present a 1-year study of cardiorenal outcomes following bilateral ischemia-reperfusion injury in male mice. These data suggest that AKI causes long-term dysfunction in the cardiac metabolome, which is associated with diastolic dysfunction and hypertension. Mice treated with the histone deacetylase inhibitor, ITF2357, had preservation of cardiac function and remained normotensive throughout the study. ITF2357 did not protect against the development of kidney fibrosis after AKI.
ABSTRACT
Neutrophil gelatinase associated lipocalin (NGAL, Lcn2) is the most widely studied biomarker of acute kidney injury (AKI). Previous studies have demonstrated that NGAL is produced by the kidney and released into the urine and plasma. Consequently, NGAL is currently considered a tubule specific injury marker of AKI. However, the utility of NGAL to predict AKI has been variable suggesting that other mechanisms of production are present. IL-6 is a proinflammatory cytokine increased in plasma by two hours of AKI and mediates distant organ effects. Herein, we investigated the role of IL-6 in renal and extra-renal NGAL production. Wild type mice with ischemic AKI had increased plasma IL-6, increased hepatic NGAL mRNA, increased plasma NGAL, and increased urine NGAL; all reduced in IL-6 knockout mice. Intravenous IL-6 in normal mice increased hepatic NGAL mRNA, plasma NGAL and urine NGAL. In mice with hepatocyte specific NGAL deletion (Lcn2hep-/-) and ischemic AKI, hepatic NGAL mRNA was absent, and plasma and urine NGAL were reduced. Since urine NGAL levels appear to be dependent on plasma levels, the renal handling of circulating NGAL was examined using recombinant human NGAL. After intravenous recombinant human NGAL administration to mice, human NGAL in mouse urine was detected by ELISA during proximal tubular dysfunction, but not in pre-renal azotemia. Thus, during AKI, IL-6 mediates hepatic NGAL production, hepatocytes are the primary source of plasma and urine NGAL, and plasma NGAL appears in the urine during proximal tubule dysfunction. Hence, our data change the paradigm by which NGAL should be interpreted as a biomarker of AKI.
Subject(s)
Acute Kidney Injury , Lipocalins , Acute Kidney Injury/diagnosis , Acute-Phase Proteins/genetics , Animals , Biomarkers , Hepatocytes , Interleukin-6 , Lipocalin-2/genetics , MiceABSTRACT
BACKGROUND: The duration of renal ischemia that is associated with (or leads to) renal injury in patients is uncertain, and a reverse translational research approach has been proposed to improve animal models of AKI to facilitate clinical translatability. We developed a two murine models of unilateral renal ischemia to match a recently published human study that investigated renal injury after unilateral renal ischemia during partial nephrectomy. METHODS: Eight 10-week-old C57BL/6 male mice underwent left UiAKI or sham procedure, with or without intra-operative ice packs. Functional, histological, and biomarker outcomes were followed at 2, 6 and 24 hours, or 14 or 28 days later. The 14 and 28 day cohorts were duplicated such that contralateral nephrectomy could be performed 3 days prior to sacrifice with functional measurements obtained to isolate the glomerular filtration rate of the injured kidney. RESULTS: The short-term outcomes correlated with the human study findings with urine and serum biomarkers of injury peaking around 24 hours and then normalizing, and reassuring immediate histological outcomes. Functional and histological outcomes at the later time-points (14 and 28 days) demonstrate an increase in fibrosis markers, and a reduction in glomerular filtration rate in the injured kidney, corresponding to the duration of ischemia, while serum and urine biomarkers remained reassuring. CONCLUSIONS: Our findings suggest that clinically available biomarkers of renal function are falsely reassuring against long-term injury following UiAKI, and that the duration of ischemia correlates with impaired function and increased fibrosis.
Subject(s)
Acute Kidney Injury/pathology , Ischemia/pathology , Nephrectomy/methods , Reperfusion Injury/pathology , Animals , Biopsy, Needle , Creatinine/blood , Disease Models, Animal , Disease Progression , Glomerular Filtration Rate , Humans , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Random Allocation , Recovery of Function , Reperfusion Injury/physiopathology , Time FactorsABSTRACT
In inflammatory diseases, the 5-lipoxygenase (5-LO) pathway contributes to epithelial damage and fibrosis by catalyzing the production of leukotrienes (LTs). Antagonists of the 5-LO pathway are currently approved for use in patients and are well tolerated. We found that expression of 5-LO is strongly induced in three models of chronic kidney disease: unilateral ureteral obstruction (UUO), folate nephropathy, and an orthologous mouse model of polycystic kidney disease. Immunohistochemistry showed that macrophages are the dominant source of 5-LO. Zileuton, a US Food and Drug Administration-approved antagonist of 5-LO, significantly reduced fibrosis at 7 and 14 days after UUO; these findings were confirmed using a genetically modified [5-LO-associated protein-knockout ( Alox5ap-/-)] mouse strain. Inhibition of 5-LO did not appear to change infiltration of leukocytes after UUO as measured by flow cytometry. However, fluorescence-lifetime imaging microscopy showed that 5-LO inhibitors reversed the glycolytic switch in renal tubular epithelial cells after UUO. Two downstream enzymes of 5-LO, LTA4 hydrolase (LTA4H) and LTC4 synthase (LTC4S), are responsible for the synthesis of LTB4 and cysteinyl LTs, respectively. Fibrosis was reduced after UUO in Ltc4s-/-, but not Lta4h-/-, mice. In contrast, using the folate nephropathy model, we found reduced fibrosis and improved renal function in both Ltc4s-/- and Lta4h-/- mice. In summary, our studies suggest that manipulation of the 5-LO pathway may represent a novel treatment approach for chronic kidney disease.
Subject(s)
Kidney/pathology , Lipoxygenase Inhibitors/therapeutic use , Renal Insufficiency, Chronic/drug therapy , Renal Insufficiency, Chronic/pathology , Animals , Arachidonate 5-Lipoxygenase/genetics , Fibrosis , Kidney Tubules/pathology , Mice, Inbred C57BL , Mice, Knockout , Polycystic Kidney Diseases/drug therapy , Receptors, Leukotriene/genetics , Receptors, Leukotriene/metabolism , Renal Insufficiency, Chronic/chemically induced , Signal Transduction/drug effects , Ureteral Obstruction/drug therapy , Ureteral Obstruction/etiologyABSTRACT
The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme directs a complex "eicosanoid storm" that accompanies the tissue response to injury. cPLA2α and its downstream eicosanoid mediators are also implicated in the pathogenesis of fibrosis in many organs, including the kidney. We aimed to determine the role of cPLA2α in bone marrow-derived cells in a murine model of renal fibrosis, unilateral ureteral obstruction (UUO). WT C57BL/6J mice were irradiated and engrafted with donor bone marrow from either WT mice [WT-bone marrow transplant (BMT)] or mice deficient in cPLA2α (KO-BMT). After full engraftment, mice underwent UUO and kidneys were collected 3, 7, and 14 days after injury. Using picrosirius red, collagen-3, and smooth muscle α actin staining, we determined that renal fibrosis was significantly attenuated in KO-BMT animals as compared with WT-BMT animals. Lipidomic analysis of homogenized kidneys demonstrated a time-dependent upregulation of pro-inflammatory eicosanoids after UUO; KO-BMT animals had lower levels of many of these eicosanoids. KO-BMT animals also had fewer infiltrating pro-inflammatory CD45+CD11b+Ly6Chi macrophages and reduced message levels of pro-inflammatory cytokines. Our results indicate that cPLA2α and/or its downstream mediators, produced by bone marrow-derived cells, play a major role in eicosanoid production after renal injury and in renal fibrinogenesis.
Subject(s)
Bone Marrow/metabolism , Group IV Phospholipases A2/metabolism , Kidney Diseases/metabolism , Ureteral Obstruction/metabolism , Animals , Fibrosis/metabolism , Fibrosis/pathology , Group IV Phospholipases A2/deficiency , Group IV Phospholipases A2/genetics , Kidney Diseases/pathology , Mice , Mice, Inbred C57BL , Ureteral Obstruction/pathologyABSTRACT
Lymphangiogenesis appears to accompany renal fibrosis, but signals that regulate the lymphangiogenic growth factor vascular endothelial growth factor C are not well understood. Kinashi et al. have shown that conditionally deleting connective tissue growth factor reduces renal fibrosis, vascular endothelial growth factor C, and lymphangiogenesis. Connective tissue growth factor has pleiotropic effects in the setting of renal fibrosis; this study adds a potentially new mechanism for the profibrotic effects of connective tissue growth factor.
Subject(s)
Connective Tissue Growth Factor , Vascular Endothelial Growth Factor C , Fibrosis , Humans , Intercellular Signaling Peptides and Proteins , Kidney Diseases , LymphangiogenesisABSTRACT
Hyperkalemia is a potentially life-threatening electrolyte disorder appreciated with greater frequency in patients with renal disease, heart failure, and with use of certain medications such as renin angiotensin aldosterone inhibitors. The traditional views that hyperkalemia can be reliably diagnosed by electrocardiogram and that particular levels of hyperkalemia confer cardiotoxic risk have been challenged by several reports of patients with atypic presentations. Epidemiologic data demonstrate strong associations of morbidity and mortality in patients with hyperkalemia but these associations appear disconnected in certain patient populations and in differing clinical presentations. Physiologic adaptation, structural cardiac disease, medication use, and degree of concurrent illness might predispose certain patients presenting with hyperkalemia to a lower or higher threshold for toxicity. These factors are often overlooked; yet data suggest that the clinical context in which hyperkalemia develops is at least as important as the degree of hyperkalemia is in determining patient outcome. This review summarizes the clinical data linking hyperkalemia with poor outcomes and discusses how the efficacy of certain treatments might depend on the clinical presentation.
Subject(s)
Hyperkalemia , Critical Illness , Humans , Hyperkalemia/complications , Hyperkalemia/mortality , Hyperkalemia/therapy , Practice Guidelines as Topic , Prognosis , Renal Insufficiency, Chronic/complicationsABSTRACT
The group IVA calcium-dependent cytosolic phospholipase A2 (cPLA2α) enzyme controls the release of arachidonic acid from membrane bound phospholipids and is the rate-limiting step in production of eicosanoids. A variety of different kidney injuries activate cPLA2α, therefore we hypothesized that cPLA2α activity would regulate pathologic processes in HK-2 cells, a human renal tubular epithelial cell line, by regulating cell phenotype and proliferation. In two lentiviral cPLA2α-silenced knockdowns, we observed decreased proliferation and increased apoptosis compared to control HK-2 cells. cPLA2α-silenced cells also demonstrated an altered morphology, had increased expression E-cadherin, and decreased expression of Ncadherin. Increased levels of E-cadherin were associated with increased promoter activity and decreased levels of SNAIL1, SNAIL2, and ZEB1, transcriptional repressors of E-cadherin expression. Addition of exogenous arachidonic acid, but not PGE2, reversed the phenotypic changes in cPLA2α-silenced cells. These data suggest that cPLA2α may play a key role in renal repair after injury through a PGE2-independent mechanism.
Subject(s)
Cell Dedifferentiation , Epithelial Cells/cytology , Group IV Phospholipases A2/metabolism , Kidney Tubules/cytology , Arachidonic Acid/pharmacology , Cadherins/genetics , Cell Dedifferentiation/drug effects , Cell Line , Cell Proliferation/drug effects , Dinoprostone/metabolism , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Gene Silencing , Group IV Phospholipases A2/deficiency , Group IV Phospholipases A2/genetics , Humans , Phenotype , Promoter Regions, Genetic/geneticsABSTRACT
The retinoid X receptor (RXR) partners with numerous nuclear receptors, such as the peroxisome proliferator activated receptor (PPAR) family, liver X receptors (LXRs), and farnesoid X receptor (FXR). Although each heterodimer can be activated by specific ligands, a subset of these receptors, defined as permissive nuclear receptors, can also be activated by RXR agonists known as rexinoids. Many individual RXR heterodimers have beneficial effects in vascular smooth muscle cells (SMCs). Because rexinoids can potently activate multiple RXR pathways, we hypothesized that treating SMCs with rexinoids would more effectively reverse the pathophysiologic effects of angiotensin II than an individual heterodimer agonist. Cultured rat aortic SMCs were pretreated with either an RXR agonist (bexarotene or 9-cis retinoic acid) or vehicle (dimethylsulfoxide) for 24 hours before stimulation with angiotensin II. Compared with dimethylsulfoxide, bexarotene blocked angiotensin II-induced SM contractile gene induction (calponin and smooth muscle-α-actin) and protein synthesis ([(3)H]leucine incorporation). Bexarotene also decreased angiotensin II-mediated inflammation, as measured by decreased expression of monocyte chemoattractant protein-1 (MCP-1). Activation of p38 mitogen-activated protein (MAP) kinase but not extracellular signal-related kinase (ERK) or protein kinase B (Akt) was also blunted by bexarotene. We compared bexarotene to five agonists of nuclear receptors (PPARα, PPARγ, PPARδ, LXR, and FXR). Bexarotene had a greater effect on calponin reduction, MCP-1 inhibition, and p38 MAP kinase inhibition than any individual agonist. PPARγ knockout cells demonstrated blunted responses to bexarotene, indicating that PPARγ is necessary for the effects of bexarotene. These data demonstrate that RXR is a potent modulator of angiotensin II-mediated responses in the vasculature, partially through inhibition of p38.
Subject(s)
Angiotensin II/metabolism , Gene Expression/genetics , Inflammation/genetics , Muscle, Smooth, Vascular/metabolism , Myocytes, Smooth Muscle/metabolism , Retinoid X Receptors/genetics , Retinoid X Receptors/metabolism , Actins/genetics , Actins/metabolism , Angiotensin II/genetics , Animals , Bexarotene , Calcium-Binding Proteins/genetics , Calcium-Binding Proteins/metabolism , Cells, Cultured , Chemokine CCL2/genetics , Chemokine CCL2/metabolism , Gene Expression/drug effects , Inflammation/metabolism , MAP Kinase Signaling System/drug effects , MAP Kinase Signaling System/genetics , Male , Microfilament Proteins/genetics , Microfilament Proteins/metabolism , Muscle, Smooth, Vascular/drug effects , Myocytes, Smooth Muscle/drug effects , PPAR gamma/genetics , PPAR gamma/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Signal Transduction/genetics , Tetrahydronaphthalenes/pharmacology , p38 Mitogen-Activated Protein Kinases/genetics , p38 Mitogen-Activated Protein Kinases/metabolism , CalponinsABSTRACT
BACKGROUND: Fibroblast growth factor 23 (FGF23) has been associated with death in dialysis patients. Since FGF23 shares structural features with FGF19 subfamily members that exert hormonal control of fat mass, we hypothesized that high circulating FGF23 concentrations would be associated with the development of a uremic lipid profile and lower body mass index (BMI). METHODS: This study was conducted among 654 patients receiving chronic hemodialysis. C-terminal FGF23 concentrations were measured in stored plasma samples. Linear regression was used to examine the cross-sectional associations of plasma FGF23 concentrations with BMI, total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C) and triglycerides. Cox proportional hazard models were used to examine the association between FGF23 concentrations and all-cause mortality. RESULTS: Participants had a mean age of 60 ± 11 years and a median (IQR) FGF23 concentration of 4,212 (1,411-13,816) RU/ml. An increase per SD in log10 FGF23 was associated with lower BMI (ß = -1.11; p = 0.008), TC (ß = -6.46; p = 0.02), LDL-C (ß = -4.73; p = 0.04) and HDL-C (ß = -2.14; p = 0.03); after adjusting for age, gender, race, cardiovascular risk factors, serum albumin, markers of mineral metabolism, and use of lipid-lowering drugs. The association of FGF23 with death was attenuated after adjustment for HDL-C (HR of highest quartile 1.53, 95% CI 1.06-2.20 compared to lowest quartile). CONCLUSION: These results indicate that higher plasma FGF23 levels are associated with lower BMI and dyslipidemia in dialysis patients. The association between FGF23 and death may be mediated through unexplored metabolic risk factors unrelated to mineral metabolism.
Subject(s)
Body Mass Index , Dyslipidemias/blood , Fibroblast Growth Factors/blood , Kidney Failure, Chronic/mortality , Renal Dialysis , Aged , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Cohort Studies , Cross-Sectional Studies , Female , Fibroblast Growth Factor-23 , Humans , Kidney Failure, Chronic/blood , Linear Models , Male , Middle Aged , Proportional Hazards Models , Triglycerides/bloodABSTRACT
Since July 2002, ongoing surveillance efforts have been conducted to determine potential vectors of West Nile virus (WNV) and Saint Louis encephalitis virus (SLEV) in the mosquito population occurring in Lubbock County, Texas. Adult mosquitoes collected in Lubbock County during 2002 and 2003 represented 7 genera, with Culex tarsalis and Ochlerotatus sollicitans being the predominant species collected. Mosquitoes were initially screened for WNV and SLEV by using the VecTest antigen panel assay. Positive VecTest results were confirmed by reverse transcriptase-polymerase chain reaction. West Nile virus-positive pools of mosquitoes were detected in 2002 and 2003, with the majority of the positive pools consisting of Cx. tarsalis. None of the mosquito pools tested positive for SLEV.