Zoltan Endre

• BScMed MBBS PhD FRACP FASN
• Head, Department of Nephrology, Prince of Wales Clinical School and Hospital at UNSW Sydney

Background: Although arteriovenous fistulas (AVF) are widely accepted as the gold standard form of dialysis access for hemodialysis patients, high AVF flow may impose significant hemodynamic stress, potentially contributing to adverse cardiovascular events, including heart failure (HF). Understanding this relationship is crucial for improving patie...

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

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 si...

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 ch...

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 membe...

Background: Sparsentan is a novel, non-immunosuppressive, single-molecule, dual endothelin and angiotensin receptor antagonist being examined in an ongoing phase 3 trial in adults with IgA nephropathy. We report the prespecified interim analysis of the primary proteinuria efficacy endpoint, and safety. Methods: PROTECT is an international, rando...

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 chrom...

The current definition of Acute Kidney Injury (AKI) is generic and based only on markers of function, being unsuitable for guiding individualised 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 recognized, based on causati...

Background and aims: Medications remain an important contributor to the development of acute kidney injury (AKI). This study aimed to examine associations between (i) administration of medications known to reduce glomerular filtration rate (GFR), that is, GFR modifiers and subsequent hospital-acquired AKI; and (ii) potentially medication-related A...

Introduction Understanding normative patterns of change in kidney function over the life course may allow targeting of early interventions to slow or prevent the onset of kidney disease, but knowledge about kidney functional change prior to middle age is limited. This study used prospective longitudinal data from a representative birth cohort to ex...

ABSTRACT Cytomegalovirus infection during antiviral prophylaxis occurs in transplant recipients despite individualized regimens based on renal function. Fifty kidney transplant recipients were assessed between 2016 and 2019 for valganciclovir dosing, ganciclovir exposure, cytomegalovirus infection, and genotypic resistance markers during the first...

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 catego...

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 & H3 –controls) served by a single laboratory. The intervention bundle (an interruptive aAlert showing AKI stage and baseline creatinine in the...

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...

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. We aimed to identify the value of functional and injury biomarkers in predicting the development of AKI early following HNV bites. Method...

Background: Urine tissue inhibitor of metalloproteinases-2/insulin-like growth factor-binding protein 7 (TIMP-2/IGFBP7) (NephroCheck, Ortho Clinical Diagnostics, Raritan, NJ, USA) is a US Food and Drug Administration-approved biomarker for risk assessment of acute kidney injury (AKI) in critically ill adult patients in intensive care units; however...

Introduction Kinetic estimated Glomerular Filtration Rate (KeGFR) approximates GFR under non-steady-state conditions. We investigated whether the ratio of KeGFR difference to baseline eGFR could predict Acute Kidney Injury (AKI) earlier than a creatinine-based algorithm that triggered an AKI electronic Alert (eAlert). Methods This retrospective, s...

Background Kidney Functional Reserve (KFR), the only clinical kidney stress test, is not routinely measured because complexity of measurement has limited clinical application. We investigated the utility of plasma cystatin C (CysC) after oral protein loading to determine KFR in stage 3 and 4 CKD. Methods Following a 24 hour low protein diet, KFR w...

Background: Impaired physical function drives adverse outcomes in chronic kidney disease (CKD). Peripheral neuropathy is highly prevalent in CKD, though its contribution to physical function in CKD patients is unknown. This study examined the relationships between neuropathy, walking speed and quality of life (QoL) in CKD. Methods: This was a pr...

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 of cognitive impairment in this at‐risk population. This has implications on service...

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.

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

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 ischa...

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. In Apr...

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. We report the use of haemodialysis in a 20‐year‐old man with chronic meth...

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...

Objective Depression in dialysis patients is often undetected despite associations with poor outcomes. The aim was to determine the prevalence and associations of depressive symptoms and physician recognition of depression within a typical Australian dialysis population. Method A cross-sectional study examined haemodialysis and peritoneal dialysis...

Background Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell’s viper (Daboia russelii) bites. Methodology/Principal findings We recruited a cohort of patients with definite Russell’s viper envenom...

Early detection of graft injury after kidney transplantation is key to maintaining long-term good graft function. Graft injury could be due to a multitude of factors including ischaemia reperfusion injury, cell or antibody-mediated rejection, progressive interstitial fibrosis and tubular atrophy, infections and toxicity from the immunosuppressive d...

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, place...

Background Acute kidney injury (AKI) is a rapid deterioration of renal function, often caused by a variety of co‐existing morbidities complicating its recognition and treatment, leading to short‐ and long‐term adverse clinical outcomes. There are limited data on the incidence of AKI in Australia using the Kidney Disease Improving Global Outcomes (K...

Background: Deliberate self-poisoning with a combination washing powder containing oxalic acid (H2C2O4) and potassium permanganate (KMnO4) is a significant medical problem in the Southern Province of Sri Lanka. Acute kidney injury (AKI) is a frequent consequence. Biomarkers for early diagnosis of nephrotoxicity could guide appropriate supportive th...

Mortality and morbidity associated with acute kidney injury (AKI) are high. Depending on the definition used, AKI has been estimated to occur in 3–30% of hospitalised patients and up to 60% of critically ill patients, with severe AKI that requires dialysis complicating the care of more than 5% of patients in intensive care. It is an increasingly im...

While there are no clear definitions of recovery, it is clear that the goals of recovery depend on the severity of acute kidney injury and the clinical context. The degree of renal recovery affects both renal and clinical prognosis. There are presently few guidelines on recovery targets, which range in extent from dialysis independence via normaliz...

Objective: To demonstrate construct validity of the Total Neuropathy Score (TNS) in assessing peripheral neuropathy in subjects with chronic kidney disease (CKD). Methods: 113 subjects with CKD and 40 matched controls were assessed for peripheral neuropathy using the TNS. An exploratory factor analysis was conducted and internal consistency of t...

In critically ill patients, the use of recombinant human erythropoietin, rHuEPO, and other erythropoiesis-stimulating agents (ESAs) has been advocated for the management of anemia and for tissue protection. Early enthusiasm has been tempered by the overall lack of positive outcomes except in selected groups. Here we review the use of ESAs in both t...

Acute kidney injury is common in critically ill patients and portends a significant impact on mortality, progressive chronic kidney disease, and cardiovascular disease and mortality. Though most physicians alter therapy depending on changes in serum creatinine, this often represents delayed intervention. Various AKI biomarkers have been discovered...

Aim: Acute kidney injury (AKI) is common following deliberate self-poisoning with a combination washing powder containing oxalic acid (H2C2O4) and potassium permanganate (KMnO4). Early and rapid increases in serum creatinine (sCr) follow severe poisoning. We investigated the relationship of these increases with direct nephrotoxicity in an ongoing...

Extensive structural damage within the kidney must be present before serum creatinine increases. However, a subclinical phase of chronic kidney disease (CKD) usually goes undetected. Here we tested whether experimental subclinical CKD would modify functional and damage biomarker profiles of acute kidney injury (AKI). Subclinical CKD was induced in...

Background Paraquat ingestion is frequently fatal. While biomarkers of kidney damage increase during paraquat-induced acute kidney injury (AKI), significant concurrent proteinuria may alter diagnostic thresholds for diagnosis and prognosis to an unknown extent. This study evaluated the effect of albuminuria on biomarker cutoffs for diagnosis and ou...

Background Plasma cystatin C (pCysC) may be superior to serum creatinine (sCr) as a surrogate of GFR. However, the performance of pCysC for diagnosing acute kidney injury (AKI) after cisplatin-based chemotherapy is potentially affected by accompanying corticosteroid anti-emetic therapy and hydration. Methods In a prospective observational study...

Consensus definitions have been reached for both acute kidney injury (AKI) and chronic kidney disease (CKD) and these definitions are now routinely used in research and clinical practice. The KDIGO guideline defines AKI as an abrupt decrease in kidney function occurring over 7 days or less, whereas CKD is defined by the persistence of kidney diseas...

Background Erythropoiesis stimulating agents (ESAs) were proposed to enhance survival of renal tissues through direct effects via activation of EPO receptors on renal cells resulting in reduced cell apoptosis, or indirect effects via increased oxygen delivery due to increased numbers of Hb containing red blood cells. Thus through several mechanisms...

Background Damage biomarkers may identify mechanisms and sites of acute kidney injury (AKI). However, the utility of novel AKI biomarkers differs by context, and their utility for monitoring treatment of AKI is unknown. We hypothesized that selected AKI biomarkers would facilitate monitoring of mechanism-specific treatment. We examined this using a...

Participation by nephrologists is needed in most intensive care units, even when such units are ‘closed'. This participation should assist with diagnosis and management of intrinsic and complex renal diseases such as vasculitis, complex metabolic and electrolyte disorders including hyponatremia, and acute kidney injury (AKI) with and without underl...

Chronic kidney disease (CKD) is an established independent risk factor for cardiovascular disease. Likewise cardiovascular disease is the major cause of morbidity and mortality in patients with CKD. With the progression of CKD, there is a change from the traditional atherosclerotic related cardiovascular events, such as stroke and myocardial infarc...

Background: Management of vascular access for haemodialysis is a leading cause of morbidity and hospitalization in patients with end-stage renal disease. We sought to evaluate the change in admission and procedural outcomes before and after the establishment of a vascular surgeon-led comprehensive renal vascular access clinic (RVAC). Method: A r...

Objective: To determine whether a low perioperative minimum urine output target is safe and fluid sparing when compared with the standard target. Background: A minimum hourly urine output of 0.5 mL/kg is a key target guiding perioperative fluid therapy. Few data support this standard practice, which may contribute to perioperative fluid overload...

Selected ion flow tube-mass spectrometry (SIFT-MS) provides rapid, non-invasive measurements of a full-mass scan of volatile compounds in exhaled breath. Although various studies have suggested that breath metabolites may be indicators of human disease status, many of these studies have included few breath samples and large numbers of compounds, li...

Aim: To provide a first year progress report on the NHMRC CKD.CRE. Background/Methods: The Centre is dedicated to improving knowledge of CKD and its management across the health care spectrum. Although based at The University of Queensland, the Centre includes collaborators in almost every Australian state/territory. Its core research streams are C...

No new biomarker of Acute Kidney Injury (AKI) has entered routine clinical practice after a decade of promise, although L-FABP, NGAL, and the combination of TIMP2 and IGFBY-7 are approved for use in some jurisdictions. Acceptance of creatinine as a surrogate of not just GFR but also renal injury, changes in nephrologist work loads, failure to estab...

Diagnosis of transplant dysfunction usually requires kidney biopsy. Sidgel et al. compared urinary proteomics with matched kidney biopsies to develop a biomarker panel to differentiate acute rejection, BK viral nephropathy, and chronic allograft nephropathy. The results suggest that monitoring a panel of urinary peptides may ultimately facilitate n...

Acute kidney injury (AKI) is common following glyphosate surfactant herbicide (GPSH) self-poisoning. Serum creatinine (sCr) is the most widely used renal biomarker for diagnosis of AKI although a recent study in rats suggested that urinary kidney injury molecule-1 predicted AKI earlier and better after GPSH-induced nephrotoxicity. We explored the u...

Post transplant repeated measurements of urine volume and serum creatinine (sCr) are used to assess kidney function. Under non-steady state conditions, repeated measurement of sCr allows calculation of the kinetic estimated GFR (KeGFR). Additional measurement of urinary creatinine allows the calculation of the creatinine excretion to (estimated) pr...

Introduction: This article addresses general biomarkers of drug-induced acute kidney injury (AKI) and their application in development and progression of AKI in the adult. It also highlights some clinical benefits, but also uncertainties, of biomarker use. Areas covered: Drug-induced AKI is traditionally diagnosed by monitoring serum creatinine (SC...

Aim: To describe the newly established NHMRC Chronic Kidney Disease Centre of Research Excellence (CKD.CRE). Background: Globally, CKD is a significant health problem. It is associated with a greatly increased risk of non-renal death and is the pathway to development of end stage kidney failure (ESKF). In Australia, the costs of renal replacement t...

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...

OBJECTIVES Acute kidney injury is common following cardiac surgery. Experimental models of acute kidney injury suggest that successful therapy should be implemented within 24–48 h of renal injury. However, it is difficult to detect acute kidney injury shortly after cardiac surgery, because creatinine concentration is diluted by cardiopulmonary bypa...

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). The 95th centile in healthy subjects defined the urinar...

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 o...

We compared estimated glomerular filtration rate (eGFR) according to the Chronic Kidney Disease Epidemiology Collaboration equation, with (CKD-EPI, mL/min/1.73m(2) ) and without body surface area (BSA)-normalisation (CKD-EPI_noBSA, mL/min), against measured Tc-DTPA GFR (mL/min) in 222 individuals, including 80 with malignancy. BSA was calculated fo...

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. To evaluate the ability of a newly available ovine fragment antigen-binding (Fab) antibody to colchicine (ColchiFab(™)) to protect rats aga...

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). This prospective multi-centre study compared the kinetics of two surrogate markers of...

Acute kidney injury (AKI) has diverse causes and is associated with increased mortality and morbidity. In less developed countries (LDC), nephrotoxic AKI (ToxAKI) is common and mainly due to deliberate ingestion of nephrotoxic pesticides, toxic plants or to snake envenomation. ToxAKI shares some pathophysiological pathways with the much more intens...

Aims To compare estimated glomerular filtration rate (eGFR) according to the CKD-EPI equation, with (CKD-EPI, mL/min/1.73m²) and without body surface area (BSA)-normalisation (CKD-EPI_;BSA, mL/min), against measured Tc-DTPA GFR (mL/min). Methods The CKD-EPI and CKD-EPI_;BSA equations were compared in 222 individuals with Tc-DTPA GFR for bias, prop...

Aims To investigate the association between GFR and body composition in healthy young men with differing body mass. Methods Three age-matched groups were recruited: normal BMI (n = 22) < 25 kg/m², muscular (n = 23) with BMI > 30 kg/m² and BIA body fat ≤20%, and obese (n = 22) with BMI ≥30 kg/m² and BIA body fat > 30%. Dietary analyses, GFR by clea...

Aim In cancer patients receiving chemotherapy treatment, accurate assessment of kidney function is required. The aim of our study was to investigate whether the inclusion of cystatin C together with creatinine in prediction equations would improve the prediction of glomerular filtration rate (GFR). Methods Plasma creatinine and cystatin C were ana...

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 vasoconstrict...

This R package generates risk assessment plots, calibration curves (v1), decision curves (v1) and associated metrics including Net Reclassification Improvement (NRI), Integrated Discrimination Improvement (IDI), weighted NRI, category free NRI, Integrated Sensitivity (IS), Integrated 1-Specificity (IP), and Brier scores (v1). Calculated these metri...

IntroductionAcute Kidney Injury (AKI) biomarker utility depends on sample timing after the onset of renal injury. We compared biomarker performance on arrival in the emergency department (ED) with subsequent performance in the intensive care unit (ICU).Methods Urinary and plasma Neutrophil Gelatinase-Associated Lipocalin (NGAL), and urinary Cystati...

This is a "News & Views" article where we consider the science behind, and implications of, the newly FDA-approved acute kidney injury diagnosis tool "NephroCheck."

The first consensus definition of Acute Kidney Injury (AKI) was published a decade ago. In this mini narrative review we look at the history of the changes in the definition of AKI and consider how it may change again in the near future. The epidemiology of small changes in creatinine and the difficulties with determining baseline creatinine have d...

Establishing the prognosis for recovery has enormous clinical implications. The appropriate definition of renal recovery depends on the stage of acute kidney injury (AKI). As definitions of AKI have broadened to encompass small increases in serum creatinine, definitions of recovery have broadened from becoming dialysis independent to full recovery...

The clinical implementation of urinary and plasma renal injury biomarkers has been hampered by the variability associated with nonstandardized commercially available biomarker assays, uncertainty and variations in patient selection criteria, and the absence of context-specific cutoffs for biomarker concentrations. These limitations are increased by...

An update of the rap_function for R. The output includes Risk Assessment Plots (RAP) and the data needed to reproduce them in other plotting programs, Net Reclassification Improvement (NRI) for as many categories as required, category free NRI, Integrated Discrimination Improvement (IDI), Integrated Sensitivity (IS), Integrated 1-Specificity (IP),...

Background Understanding determinants of glomerular filtration rate (GFR) is important in aiding prediction and interpretation of kidney function. Body composition is known to affect GFR, but is not included in current screening of kidney disease. We investigated the association between GFR and body composition in healthy young men with differing b...

Factors which modify the excretion profiles of acute kidney injury biomarkers are difficult to measure. To facilitate biomarker choice and interpretation we modelled key modifying factors: extent of hyperfiltration or reduced glomerular filtration rate, structural damage, and reduced nephron number. The time-courses of pre-formed, induced (upregula...

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), uri...