Predicting mid-life capital formation with pre-school delay of gratification and life-course measures of self-regulation.

How well do pre-school delay of gratification and life-course measures of self-regulation predict mid-life capital formation? We surveyed 113 participants of the 1967-1973 Bing pre-school studies on delay of gratification when they were in their late 40's. They reported 11 mid-life capital formation outcomes, including net worth, permanent income, absence of high-interest debt, forward-looking behaviors, and educational attainment. To address multiple hypothesis testing and our small sample, we pre-registered an analysis plan of well-powered tests.

Cohort effects in children's delay of gratification.

In the 1960s at Stanford University's Bing Preschool, children were given the option of taking an immediate, smaller reward or receiving a delayed, larger reward by waiting until the experimenter returned. Since then, the "Marshmallow Test" has been used in numerous studies to assess delay of gratification. Yet, no prior study has compared the performance of children across the decades.

Evaluation of biomarkers of cell cycle arrest and inflammation in prediction of dialysis or recovery after kidney transplantation.

Early prediction of delayed graft function (DGF) after kidney transplantation would facilitate patient management. Cell cycle arrest and inflammation are implicated in the pathogenesis of DGF. We assessed the utility of two novel acute kidney injury (AKI) biomarkers, urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7), and five inflammatory markers to predict DGF following deceased-donor kidney transplantation.

Kidney damage biomarkers detect acute kidney injury but only functional markers predict mortality after paraquat ingestion.

Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine samples from patients from 5 Sri Lankan hospitals. Functional AKI was diagnosed using serum creatinine (sCr) or serum cystatin C (sCysC).

Kinetic Estimation of GFR Improves Prediction of Dialysis and Recovery after Kidney Transplantation.

Background: The early prediction of delayed graft function (DGF) would facilitate patient management after kidney transplantation.

Methods: In a single-centre retrospective analysis, we investigated kinetic estimated GFR under non-steady-state conditions, KeGFR, in prediction of DGF. KeGFR(sCr) was calculated at 4h, 8h and 12h in 56 recipients of deceased donor kidneys from initial serum creatinine (sCr) concentrations, estimated creatinine production rate, volume of distribution, and the difference between consecutive sCr values.

Fab fragments of ovine antibody to colchicine enhance its clearance in the rat.

Context: Colchicine is an anti-inflammatory alkaloid used for the treatment of acute gout, but has a narrow therapeutic index. Colchicine overdoses are relatively rare, but have high mortality requiring rapid treatment.

Objective: To evaluate the ability of a newly available ovine fragment antigen-binding (Fab) antibody to colchicine (ColchiFab(™)) to protect rats against renal and other injury 24 h after colchicine ingestion.

Mechanisms underlying early rapid increases in creatinine in paraquat poisoning.

Background: Acute kidney injury (AKI) is common after severe paraquat poisoning and usually heralds a fatal outcome. The rapid large increases in serum creatinine (Cr) exceed that which can be explained by creatinine kinetics based on loss of glomerular filtration rate (GFR).

Methods And Findings: This prospective multi-centre study compared the kinetics of two surrogate markers of GFR, serum creatinine and serum cystatin C (CysC), following paraquat poisoning to understand and assess renal functional loss after paraquat poisoning.

Biomarkers of calcineurin inhibitor nephrotoxicity in transplantation.

Over 35 years of use has demonstrated the revolutionary therapeutic benefits of calcineurin inhibitors (CNI) in not only preventing transplant rejection, but also the renal and nonrenal toxicity of CNI. Acute reversible and insidious irreversible forms of CNI nephrotoxicity have been identified, with ischemia from an imbalance between vasoconstrictors and vasodilators playing an important role. The ongoing search to define toxicity pathways has been enriched by 'Omics' studies.

Clusterin in kidney transplantation: novel biomarkers versus serum creatinine for early prediction of delayed graft function.

Background And Objectives: Current methods for rapid detection of delayed graft function (DGF) after kidney transplantation are unreliable. Urinary clusterin is a biomarker of kidney injury but its utility for prediction of graft dysfunction is unknown.

Methods: In a single-center, prospective cohort study of renal transplant recipients (N=81), urinary clusterin was measured serially between 4 hr and 7 days after transplantation.

A comparison of the ability of levels of urinary biomarker proteins and exosomal mRNA to predict outcomes after renal transplantation.

Background: mRNA for biomarkers of kidney injury extracted from urinary exosomes may reflect or predict levels of the corresponding protein after transplantation and clinical outcomes.

Methods: Urinary exosomes were isolated from patients following renal transplantation, from healthy controls, and patients with CKD. Expression of exosomal mRNA for the injury biomarkers neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and cystatin C was compared with the concentrations of corresponding urinary proteins, 18S RNA and serum creatinine.

Kidney biomarkers in MCPA-induced acute kidney injury in rats: reduced clearance enhances early biomarker performance.

For improved early detection and assessment of severe acute kidney damage following accidental or intentional ingestion of the herbicide MCPA, we compared a panel of 14 novel kidney injury biomarkers with plasma creatinine. Male Wistar rats received four different oral doses of MCPA and plasma and urine biomarker levels were measured at 8, 24 and 48 h after MCPA exposure. Diagnostic performances using absolute levels, urine levels normalized to urine creatinine or urinary excretion rate were determined by ROC analysis.

Use of a glyphosate-based herbicide-induced nephrotoxicity model to investigate a panel of kidney injury biomarkers.

Accidental or intentional ingestion of glyphosate surfactant-based herbicides, like Roundup(®), leads to nephrotoxicity as well as death. In this study, a panel of kidney injury biomarkers was evaluated in terms of suitability to detect acute kidney injury and dysfunction. The Roundup(®) intoxication model involved oral administration of glyphosate to rats at dose levels of 250, 500, 1200 and 2500 mg/kg.

Renal biomarkers predict nephrotoxicity after paraquat.

Paraquat is a widely used herbicide which has been involved in many accidental and intentional deaths. Nephrotoxicity is common in severe acute paraquat poisoning. We examined seven renal injury biomarkers, including cystatin-C, kidney injury molecule-1, β2-microglobulin, clusterin, albumin, neutrophil gelatinase-associated lipocalin and osteopontin, to develop a non-invasive method to detect early renal damage and dysfunction and to compare with the conventional endogenous marker creatinine.

Paradoxically Low Levels of Total and HMW Adiponectin in Relation to Metabolic Parameters in a Tongan Population.

Aim. Adiponectin has demonstrated anti-inflammatory and insulin sensitising properties, and low circulating levels may be an important risk factor for diabetes. We examined levels of adiponectin and its insulin-sensitising HMW isoform and their relationship with metabolic parameters in Tongans, a population prone to type II diabetes.

Clinical use of biomarkers for toxicant-induced acute kidney injury.

Toxicant-induced acute kidney injury (ToxAKI) causes substantial morbidity and retards drug development. ToxAKI is relatively underexplored compared with ischemia-reperfusion injury in clinical biomarker studies. We highlight the rationale for novel AKI biomarkers in management of ToxAKI, and review the contemporary evidence supporting their clinical use.

Factor H binds to the N-terminus of adiponectin and modulates complement activation.

The adipokine adiponectin circulates in high concentration, and activates the classical pathway of complement by binding C1q, leading to the activation of C3 and formation of the membrane attack complex. Such behaviour is potentially pathophysiological. However, we showed adiponectin captured the complement inhibitor Factor H both as a pure protein and from human serum.

Review article: Adiponectin: its role in kidney disease.

The multifactorial glycoprotein, adiponectin has demonstrable insulin-sensitizing, anti-atherogenic and anti-inflammatory properties. However, despite the prevalence of both insulin-resistance and vascular disease in patients with end-stage kidney disease, levels of adiponectin are high. Adiponectin circulates in different sizes (the high-molecular-weight (HMW) isoform is thought to be the most insulin-sensitizing type) and binds to two receptors, adiponectin receptors (AdipoR) 1 and 2.

Adiponectin is present in the urine in its native conformation, and specifically reduces the secretion of MCP-1 by proximal tubular cells.

Aim: To determine whether adiponectin detected in urine is present in its native form and if adiponectin receptors (AdipoR) present and functional in proximal tubular (HK-2) cells.

Background: Adiponectin is a protein with anti-inflammatory, anti-atherogenic and insulin-sensitizing properties. It has previously been detected antigenically in the urine in several forms of renal disease.

Adiponectin binds C1q and activates the classical pathway of complement.

The adipose-specific protein adiponectin binds to a number of target molecules, including damaged endothelium and the surface of apoptotic cells. However, the significance of this binding remains unclear. This study demonstrates the binding of purified C1q to recombinant adiponectin under physiological conditions, and the dependence of this upon Ca(++) and Mg(++).

Complement activation contributes to leukocyte recruitment and neuropathic pain following peripheral nerve injury in rats.

Complement activation triggers inflammation and has been implicated in neurological diseases associated with pain. However, the role of complement in neuropathic pain has not been clearly defined. In this study, we tested whether complement is activated by partial ligation of the rat sciatic nerve, a widely used model of neuropathic pain, and whether complement activation or inhibition in peripheral nerve influences leukocyte recruitment and neuropathic pain.

The effect of renal transplantation on adiponectin and its isoforms and receptors.

Insulin resistance (IR) and other proatherogenic risk factors associated with end-stage kidney disease (ESKD) are improved by renal transplantation. Adiponectin is a protein with insulin-sensitizing, anti-inflammatory, and antiatherogenic properties. It exists in several isoforms, but the high molecular weight (HMW) isoform correlates best with insulin sensitivity.

Glycosylation of human adiponectin affects its conformation and stability.

The collagenous region of adiponectin is glycosylated in vitro with glucosylgalactosyl moieties on four conserved lysines. We investigated the glycosylation of human adiponectin in vivo. Sugar vicinyl hydroxides on adiponectin were oxidized with 10 or 1 mM metaperiodate, and the result analyzed by two-dimensional electrophoresis and immunoblotting.

Up-regulation of adiponectin, its isoforms and receptors in end-stage kidney disease.

Background: Despite the favourable effects of adiponectin on the vasculature and insulin resistance (IR), levels are increased in patients with end-stage kidney disease (ESKD), in whom both IR and atherosclerosis are prevalent.

Methods: To investigate this paradox, we examined the distribution of adiponectin isoforms, the expression of adiponectin receptor (AdipoR) mRNA on peripheral blood mononuclear cells (PBMC) in 41 patients with ESKD on haemodialysis and 41 matched controls, and its function by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation of AdipoR on PBMC. We also compared the expression of AdipoR on PBMC with that on muscle and subcutaneous and visceral fat in 10 patients undergoing elective cholecystectomy.