Kidney functional reserve and damage biomarkers in subclinical chronic kidney disease and acute kidney injury.

Significant loss of kidney function is not easily identified by serum creatinine (sCr)-based measurements. In the presence of normal sCr, decreased kidney functional reserve (KFR) may identify a significant loss of function. We evaluated KFR in experimental subclinical chronic kidney disease (sCKD) before and after brief ischemia-reperfusion injury (IRI).

Precision management of acute kidney injury in the intensive care unit: current state of the art.

Acute kidney injury (AKI) is a prototypical example of a common syndrome in critical illness defined by consensus. The consensus definition for AKI, traditionally defined using only serum creatinine and urine output, was needed to standardize the description for epidemiology and to harmonize eligibility for clinical trials. However, AKI is not a simple disease, but rather a complex and multi-factorial syndrome characterized by a wide spectrum of pathobiology.

Balanced crystalloid solution versus saline in deceased donor kidney transplantation (BEST-Fluids): a pragmatic, double-blind, randomised, controlled trial.

Background: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content.

Plasma arginine metabolites in health and chronic kidney disease.

Background: Elevated plasma asymmetric and symmetric dimethylarginine (ADMA and SDMA) are risk factors for chronic kidney disease (CKD) and cardiovascular disease. Using plasma cystatin C (pCYSC)-based estimated glomerular filtration rate (eGFR) trajectories, we identified a cohort at high risk of poor kidney-related health outcomes amongst members of the Dunedin Multidisciplinary Health and Development Study (DMHDS). We therefore examined associations between methylarginine metabolites and kidney function in this cohort.

Comparison of SPEED, S-Trap, and In-Solution-Based Sample Preparation Methods for Mass Spectrometry in Kidney Tissue and Plasma.

Mass spectrometry is a powerful technique for investigating renal pathologies and identifying biomarkers, and efficient protein extraction from kidney tissue is essential for bottom-up proteomic analyses. Detergent-based strategies aid cell lysis and protein solubilization but are poorly compatible with downstream protein digestion and liquid chromatography-coupled mass spectrometry, requiring additional purification and buffer-exchange steps. This study compares two well-established detergent-based methods for protein extraction (in-solution sodium deoxycholate (SDC); suspension trapping (S-Trap)) with the recently developed sample preparation by easy extraction and digestion (SPEED) method, which uses strong acid for denaturation.

Baseline Characteristics and Representativeness of Participants in the BEST-Fluids Trial: A Randomized Trial of Balanced Crystalloid Solution Versus Saline in Deceased Donor Kidney Transplantation.

Unlabelled: Delayed graft function (DGF) is a major complication of deceased donor kidney transplantation. Saline (0.9% sodium chloride) is a commonly used intravenous fluid in transplantation but may increase the risk of DGF because of its high chloride content.

Definitions, phenotypes, and subphenotypes in acute kidney injury-Moving towards precision medicine.

The current definition of acute kidney injury (AKI) is generic and, based only on markers of function, is unsuitable for guiding individualized treatment. AKI is a complex syndrome with multiple presentations and causes. Targeted AKI management will only be possible if different phenotypes and subphenotypes of AKI are recognised, based on causation and related pathophysiology.

Biomarkers in Cardiorenal Syndrome and Potential Insights Into Novel Therapeutics.

Heart and kidney failure often co-exist and confer high morbidity and mortality. The complex bi-directional nature of heart and kidney dysfunction is referred to as cardiorenal syndrome, and can be induced by acute or chronic dysfunction of either organ or secondary to systemic diseases. The five clinical subtypes of cardiorenal syndrome are categorized by the perceived primary precipitant of organ injury but lack precision.

Electronic alerts and a care bundle for acute kidney injury-an Australian cohort study.

Background: Early recognition of hospital-acquired acute kidney injury (AKI) may improve patient management and outcomes.

Methods: This multicentre study was conducted at three hospitals (H1-intervention; H2 and H3-controls) served by a single laboratory. The intervention bundle [an interruptive automated alerts (aAlerts) showing AKI stage and baseline creatinine in the eMR, a management guide and junior medical staff education] was implemented only at H1.

Peripheral nerve morphology and intraneural blood flow in chronic kidney disease with and without diabetes.

Introduction/aims: Sonographic alterations of peripheral nerves in pre-dialytic kidney disease are yet to be determined. We aimed to assess peripheral nerve cross-sectional area (CSA) and intraneural blood flow in patients with pre-dialytic chronic kidney disease (CKD) and diabetic kidney disease (DKD).

Methods: Subjects with CKD (n = 20) or DKD (n = 20) underwent ultrasound to assess CSA of the median and tibial nerves as well as intraneural blood flow of the median nerve.

Identifying Candidate Protein Markers of Acute Kidney Injury in Acute Decompensated Heart Failure.

One-quarter of patients with acute decompensated heart failure (ADHF) experience acute kidney injury (AKI)-an abrupt reduction or loss of kidney function associated with increased long-term mortality. There is a critical need to identify early and real-time markers of AKI in ADHF; however, to date, no protein biomarkers have exhibited sufficient diagnostic or prognostic performance for widespread clinical uptake. We aimed to identify novel protein biomarkers of AKI associated with ADHF by quantifying changes in protein abundance in the kidneys that occur during ADHF development and recovery in an ovine model.

Serum and urinary biomarkers for early detection of acute kidney injury following Hypnale spp. envenoming.

Background: Hump-nosed pit viper (HNV; Hypnale spp.) bites account for most venomous snakebites in Sri Lanka. Acute kidney injury (AKI) is the most serious systemic manifestation (1-10%) following HNV envenoming.

Cystatin C kidney functional reserve: a simple method to predict outcome in chronic kidney disease.

Background: Kidney functional reserve (KFR), the only clinical kidney stress test, is not routinely measured because the complexity of measurement has limited clinical application. We investigated the utility of plasma cystatin C (CysC) after oral protein loading (PL) to determine KFR in Stages 3 and 4 chronic kidney disease (CKD).

Methods: Following a 24-h low-protein diet, KFR was measured after oral protein by hourly plasma CysC and compared with simultaneous creatinine clearance (CrCl) and radionuclide 99technetium diethylenetriaminepentaacetatic acid (Tc-99m-DTPA) measured glomerular filtration rate (mGFR) measurement in an observational, single-centre cohort study of adults with CKD Stages 3 and 4.

Identification of acute kidney injury subphenotypes.

Purpose Of Review: AKI is a complex clinical syndrome with many causes and there is a broad range of clinical presentations that vary according to duration, severity and context. Established consensus definitions of AKI are nonspecific and limited to kidney function. This reduces treatment options to generic approaches rather than individualized, cause-based strategies that have limited both understanding and management of AKI.

Controversies in acute kidney injury: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Conference.

In 2012, Kidney Disease: Improving Global Outcomes (KDIGO) published a guideline on the classification and management of acute kidney injury (AKI). The guideline was derived from evidence available through February 2011. Since then, new evidence has emerged that has important implications for clinical practice in diagnosing and managing AKI.

Neutrophil Gelatinase-Associated Lipocalin Measured on Clinical Laboratory Platforms for the Prediction of Acute Kidney Injury and the Associated Need for Dialysis Therapy: A Systematic Review and Meta-analysis.

Rationale & Objective: The usefulness of measures of neutrophil gelatinase-associated lipocalin (NGAL) in urine or plasma obtained on clinical laboratory platforms for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI-D) has not been fully evaluated. We sought to quantitatively summarize published data to evaluate the value of urinary and plasma NGAL for kidney risk prediction.

Study Design: Literature-based meta-analysis and individual-study-data meta-analysis of diagnostic studies following PRISMA-IPD guidelines.

Prevalence, types and recognition of cognitive impairment in dialysis patients in South Eastern Sydney.

Background: In international studies, cognitive impairment is a common but underdetected issue in dialysis patients. Chronic kidney disease (CKD) shares risk factors with and is an independent risk factor for cognitive impairment. There is a lack of Australian data on cognitive impairment in this at-risk population.

Targeted protection of proximal tubular cells by nanoparticle-enhanced delivery of a TLR9-antagonist.

The kidney target site for injury that leads to acute kidney injury (AKI) is the proximal tubule. Nanoparticle-encapsulation enhanced delivery of a selective Toll-like receptor 9 antagonist to mouse proximal tubules and attenuated experimental ischemia-reperfusion injury in a mouse model of AKI.

Selection and validation of reference genes for normalisation of gene expression in ischaemic and toxicological studies in kidney disease.

Normalisation to standard reference gene(s) is essential for quantitative real-time polymerase chain reaction (RT-qPCR) to obtain reproducible and comparable results of a gene of interest (GOI) between subjects and under varying experimental conditions. There is limited evidence to support selection of the commonly used reference genes in rat ischaemic and toxicological kidney models. Employing these models, we determined the most stable reference genes by comparing 4 standard methods (NormFinder, qBase+, BestKeeper and comparative ΔCq) and developed a new 3-way linear mixed-effects model for evaluation of reference gene stability.

Chronic methyl bromide toxicity is ameliorated by haemodialysis.

Methyl bromide is an odourless, colourless, highly volatile gas, primarily used in fumigation. It can cause significant neurotoxicity, especially with chronic exposure. Haemodialysis has been used in acute toxicity, but its utility in chronic exposure has never been reported.

Relative contributions of diabetes and chronic kidney disease to neuropathy development in diabetic nephropathy patients.

Objective: Chronic kidney disease (CKD) caused by diabetes is known as diabetic kidney disease (DKD). The present study aimed to examine the underlying mechanisms of axonal dysfunction and features of neuropathy in DKD compared to CKD and type 2 diabetes (T2DM) alone.

Methods: Patients with DKD (n = 30), CKD (n = 28) or T2DM (n = 40) and healthy controls (n = 41) underwent nerve excitability assessments to examine axonal function.