ORCID Profile
0000-0002-6362-1221
Current Organisations
Centenary Institute
,
University of Sydney
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Publisher: Elsevier BV
Date: 02-2009
Publisher: Oxford University Press (OUP)
Date: 28-09-2023
Abstract: Alcohol is a commonly co-ingested compound during self-poisoning with pesticides. Clinical experiences suggest alcohol co-ingestion (or withdrawal) makes patient management more difficult after self-poisoning and may contribute to poor clinical outcomes. We aimed to systematically review the world literature to explore the relationship between alcohol co-ingestion and outcome in pesticide self-poisoning. We searched 13 electronic databases and Google scholar, conducted citation searching and a review of reference lists to find studies which investigated the relationship of alcohol with clinical outcome of pesticide self-poisoning in different countries. Thirteen studies, including 11 case series/reports and two cohort studies were considered for inclusion. Meta-analysis showed that alcohol co-ingestion in pesticide self-poisoning was associated with increased risk of death [odds ratio (OR) 4.9, 95% confidence interval (CI) 2.9–8.2 P& .0001] and that alcohol co-ingested group required intubation eight times more often than non-co-ingested group in organophosphorus insecticide self-poisoning (OR 8.0, 95% CI 4.9–13.0 P& .0001). Cases who co-ingested alcohol were older than non-alcohol group in two studies. One cohort study demonstrated that alcohol co-ingestion was associated with larger pesticide ingestions but did not itself affect the outcome. This systematic review indicates that alcohol co-ingestion may worsen clinical outcome in pesticide self-poisoning.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.TOXLET.2018.10.002
Abstract: Deliberate self-poisoning with a combination washing powder containing oxalic acid (H We investigated the performance of three serum biomarkers and nine urinary biomarkers in 85 patients in an ongoing multicenter prospective cohort study in Sri Lanka exploring AKI following poisoning. Sixty two (62/85, 73%) patients developed AKI (acute kidney injury network, AKIN, criteria). Early and rapid increases in serum creatinine (sCr) peaking on day 3 were observed in AKIN stage 2 and 3 patients. In these patients, serum cystatin C (sCysC) rose more gradually but also peaked on day 3. Biomarker concentrations (normalized to urinary creatinine) of urinary albumin (uAlbumin), clusterin (uClusterin), beta-2-microglobulin (uB2M), osteopontin (uOPN), neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury molecule-1 (uKIM-1) in the AKIN2/3 group increased above the 95th centile concentration of the healthy population. Within 8 h of ingestion, the normalized uAlbumin and sCysC predicted AKIN2/3 with respective area under receiver operating characteristic curve, AUC-ROC values, of 0.94 (95% CI 0.86-1.00) and 0.85 (95% CI 0.76-0.95). Urinary albumin was the best performing AKI biomarker following ingestion of H
Publisher: MDPI AG
Date: 08-10-2023
Publisher: MDPI AG
Date: 15-09-2023
Publisher: WHO Press
Date: 14-06-2016
Publisher: Wiley
Date: 2011
DOI: 10.1002/JCLA.20487
Publisher: Informa UK Limited
Date: 06-12-2016
Publisher: Informa UK Limited
Date: 23-08-2016
DOI: 10.1080/15563650.2016.1217421
Abstract: In Asia methemoglobinemia (MetHb) is commonly caused through self-poisoning with the pesticide propranil. MetHb can cause hypoxia, coma and death, but usually responds to methylene blue. It is therefore vital to have accurate methods to measure blood MetHb to guide appropriate treatments. The gold standard to measure MetHb utilizes a spectrophotometer, but recent bedside tests have been developed e.g., pulse co-oximeter probe and blood color chart. Nine propanil poisoned patients had data collected from hospitals in Sri Lanka during 2008. Several MetHb readings were taken from each patient from admission up to 50 hours using spectrophotometry (Unico UV-Vis model no. 2800), pulse co-oximetry (Radical-7, Masimo, CA), and color chart. The co-oximeter underestimated the MetHb percentage when compared with spectrophotometry and the color chart, especially when the average MetHb was greater than 20%. The color chart demonstrated acceptable accuracy compared with formal spectrophotometry with the majority of values showing no more than 10% difference. This small cohort highlights the potential for extreme inaccuracy of the Radical-7 co-oximeter, especially with a MetHb greater than 20%. Pulse co-oximeters should be required to be validated for the complete range of MetHb prior to regulatory approval.
Publisher: Wiley
Date: 31-08-2023
DOI: 10.1111/LIV.15716
Abstract: Accumulation of lipid in the liver is the first hallmark of both alcohol‐related liver disease (ALD) and non‐alcohol‐related fatty liver disease (NAFLD). Recent studies indicate that specific mutations in lipid genes confer risk and might influence disease progression to irreversible liver cirrhosis. This study aimed to understand the function/s of lipid risk genes driving disease development in zebrafish genetic models of alcohol‐related and non‐alcohol‐related fatty liver. We used zebrafish larvae to investigate the effect of alcohol and high fat to model fatty liver and tested the utility of this model to study lipid risk gene functions. CRISPR/Cas9 gene editing was used to create knockdowns in 5 days post‐fertilisation zebrafish larvae for the available orthologs of human cirrhosis risk genes ( pnpla3 , faf2 , tm6sf2 ). To establish fatty liver models, larvae were exposed to ethanol and a high‐fat diet (HFD) consisting of chicken egg yolk. Changes in morphology (imaging), survival, liver injury (biochemical tests, histopathology), gene expression (qPCR) and lipid accumulation (dye‐specific live imaging) were analysed across treatment groups to test the functions of these genes. Exposure of 5‐day post‐fertilisation (dpf) WT larvae to 2% ethanol or HFD for 48 h developed measurable hepatic steatosis. CRISPR‐Cas9 genome editing depleted pnpla3 , faf2 and tm6sf2 gene expression in these CRISPR knockdown larvae (crispants). Depletion significantly increased the effects of ethanol and HFD toxicity by increasing hepatic steatosis and hepatic neutrophil recruitment ≥2‐fold in all three crispants. Furthermore, ethanol or HFD exposure significantly altered the expression of genes associated with ethanol metabolism ( cyp2y3 ) and lipid metabolism‐related gene expression, including atgl (triglyceride hydrolysis), axox1 , echs1 (fatty acid β‐oxidation), fabp10a (transport), hmgcra (metabolism), notch1 (signalling) and srebp1 (lipid synthesis), in all three pnpla3 , faf2 and tm6sf2 crispants. Nile Red staining in all three crispants revealed significantly increased lipid droplet size and triglyceride accumulation in the livers following exposure to ethanol or HFD. We identified roles for pnpla3 , faf2 and tm6sf2 genes in triglyceride accumulation and fatty acid oxidation pathways in a zebrafish larvae model of fatty liver.
Publisher: Cold Spring Harbor Laboratory
Date: 14-04-2023
DOI: 10.1101/2023.04.14.536511
Abstract: Accumulation of lipid in the liver is the first hallmark of both alcohol-related liver disease (ALD) and non-alcohol-related fatty liver disease (NAFLD). Recent studies indicate that specific mutations in lipid genes confer risk and might influence disease progression to irreversible liver cirrhosis. This study aimed to understand the function/s of lipid risk genes driving disease development in zebrafish genetic models of alcohol- and non-alcohol related fatty liver. We used zebrafish larvae to investigate the effect of alcohol and high fat to model fatty liver and tested the utility of this model to study lipid risk gene functions. CRISPR/Cas9 gene editing was used to create knockdowns in 5 days post-fertilization zebrafish larvae for the available orthologs of human cirrhosis risk genes ( pnpla3, faf2, tm6sf2 ). To establish fatty liver models, larvae were exposed to ethanol and a high fat diet (HFD) consisting of chicken egg yolk. Changes in morphology (imaging), survival, liver injury (biochemical tests, histopathology), gene expression (qPCR) and lipid accumulation (dye specific live imaging) were analysed across treatment groups to test the functions of these genes. Exposure of 5-day post-fertilization (dpf) WT larvae to 2% ethanol or HFD for 48 hours developed measurable hepatic steatosis. CRISPR-Cas9 genome editing depleted pnpla3, faf2 and tm6sf2 gene expression in these CRISPR knockdown larvae (crispants). Knockdown significantly increased effects of ethanol and HFD toxicity by increasing hepatic steatosis and hepatic neutrophil recruitment ≥2-fold in all three crispants. Furthermore, ethanol or HFD exposure significantly altered the expression of genes associated with ethanol metabolism ( cyp2y3 ) and lipid metabolism-related gene expression, including atgl (triglyceride hydrolysis), axox1, echs1 (fatty acid β-oxidation), fabp10a (transport), hmgcra (metabolism), notch1 (signaling) and srebp1 (lipid synthesis), in all three pnpla3, faf2 and tm6sf2 crispants. Nile Red staining in all three crispants revealed significantly increased lipid droplet size and triglyceride accumulation in the livers following exposure to ethanol or HFD. We identified roles for pnpla3, faf2 and tm6sf2 genes in triglyceride accumulation and fatty acid oxidation pathways in a zebrafish larvae model of fatty liver.
Publisher: Elsevier BV
Date: 11-2020
Publisher: Wiley
Date: 18-02-2021
DOI: 10.1002/PRP2.695
Abstract: Acute kidney injury induced by nephrotoxic agents is common, increasing in incidence and associated with considerable morbidity and mortality in developing countries. MicroRNAs are stable biomarkers that can be detected in extracellular fluids. This systematic scoping review aims to describe published research on urinary and circulating microRNAs in toxic acute kidney injury in both animal and human studies. We conducted a literature search, using EMBASE and Medline, for articles on urinary and circulating microRNA in nephrotoxic injuries to February 2020. A total of 21 publications studied acute kidney injury from 12 different toxic agents. Cisplatin was the most common nephrotoxic agent (n = 10), followed by antibiotics (n = 4). There were no randomized controlled trials. An increase in urinary miR‐218 predicted acute kidney injury in six different studies, suggesting it is a promising biomarker for nephrotoxin‐induced acute kidney injury. There were many factors that prevented a more comprehensive synthesis of microRNA performance including highly variable models, no consistent protocols for RNA isolation, cDNA synthesis and PCR lification, and variability in normalization methods using reference controls. In conclusion, while microRNAs are promising biomarkers to study nephrotoxic acute kidney injury, the replication of most positive findings is not assessable due to deficient reporting of negative outcomes. A very narrow range of poisons have been studied, and more human data are required. In particular, further studies are needed on the most important causes of nephrotoxic injury, such as pesticides, chemicals, snake envenoming, and medicines other than aminoglycosides and cisplatin.
Publisher: Informa UK Limited
Date: 17-11-2018
DOI: 10.1080/15563650.2018.1530778
Abstract: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are used in clinical management to confirm the diagnosis and indicate the severity of organophosphorus and carbamate poisoning. ChE check mobile is a new portable cholinesterase testing system developed in Germany. The study aims to evaluate the accuracy of ChE check mobile compared to the standard reference method and Test-mate ChE system. Patients with organophosphorus and carbamate poisoning were recruited from two general hospitals in Sri Lanka between September 2013 and November 2014. The AChE was measured using the three methods. Blood s les were collected from 185 self-poisoned patients (170 organophosphorus and 15 carbamate) and 20 normal in iduals. ChE check mobile correlated well with spectrophotometer readings (Pearson's correlation coefficient 0.87) but gave higher values (Mean bias for AChE: +6.55 (95% CI: -11 to 24) U/g Hb). A similar positive bias from Test-mate results was also observed. Applying a correction factor derived from the volunteer s les ( iding by 1.353) greatly improved agreement in pesticide poisoned patients. ChE check mobile system allowed for rapid determination of AChE activity but gave somewhat higher AChE compared to other methods. Applying a correction factor of 1.353 provide a good agreement to both reference and Test-mate ChE machine in this setting.
Publisher: Informa UK Limited
Date: 23-05-2017
DOI: 10.1080/15563650.2017.1326607
Abstract: Acute kidney injury (AKI) is common following deliberate self-poisoning with a combination washing powder containing oxalic acid (H Multiple measures of change in kidney function were evaluated in 48 consenting patients who had serial sCr and serum cystatin C (sCysC) data available. Thirty-eight (38/48, 79%) patients developed AKI (AKIN criteria). Twenty-eight (58%) had AKIN stage 2 or 3. Initial increases in urine creatinine (uCr) excretion were followed by a substantial loss of renal function. The AKIN stage 2 and 3 (AKIN2/3) group had very rapid rises in sCr (a median of 118% at 24 h and by 400% at 72 h post ingestion). We excluded the possibility that the rapid rise resulted from the assay used or muscle damage. In contrast, the average sCysC increase was 65% by 72 h. In most AKI, sCysC increases to the same extent but more rapidly than sCr, as sCysC has a shorter half-life. This suggests either a reduction in Cystatin C production or, conversely, that the rapid early rise of sCr results from increased production of creatine and creatinine to meet energy demands following severe oxidative stress mediated by H
Publisher: Informa UK Limited
Date: 2010
Publisher: Informa UK Limited
Date: 31-07-2020
Publisher: Public Library of Science (PLoS)
Date: 27-03-2015
Publisher: Informa UK Limited
Date: 19-05-2016
DOI: 10.1080/15563650.2016.1177651
Abstract: In 2008, self-poisoning with the herbicide propanil had a case-fatality of around 11% in Sri Lanka. A simple quantitative methaemoglobinemia bedside test was developed so that treatment could be titrated according to the methaemoglobin level. To determine whether the new method influenced patient management and changed the case fatality of propanil self-poisoning. The bedside test (using an inexpensive validated colour chart) was introduced in three hospitals (Anuradhapura, Polonnaruwa and Galle) in Sri Lanka from 2008. Junior ward staff were given a brief training on how to use the chart for quantitative estimation of methaemoglobin in patients with propanil poisoning and utilize the results in the context of the national treatment guidelines for propanil poisoning. It was taught that the bedside test should be done repeatedly from admission until it showed consistently low values of methaemoglobin. Treatment with the antidote methylene blue was suggested for patients whose methaemoglobin was greater than 20%. Limited clinical data on poisoning have been prospectively collected from these hospitals from 2003. The case-fatality and management before and after the change were compared with data up to December 2014. The case-fatality decreased from (38/401) 9.5% to (8/262) 3.1% [difference: -6.4%, 95% CI: -10 to -3]. Methylene blue use increased from under 10% of patients before to 55% of patients after the intervention. More patients received repeat doses and infusions, and few received ascorbic acid and exchange transfusion. The simple bedside test for methaemoglobinemia was readily adopted into routine practice and led to large changes in management. A substantial reduction in mortality from propanil poisoning occurred after this intervention.
Publisher: Georg Thieme Verlag KG
Date: 2017
DOI: 10.1160/TH16-10-0769
Abstract: The 20-minute whole blood clotting test (WBCT20) is used as a bed-side diagnostic test for coagulopathic snake envenoming. We aimed to assess the performance of the WBCT20 in diagnosis of venom induced consumption coagulopathy (VICC) in Russell’s viper envenoming. Adult patients admitted with suspected snake bites were recruited from two hospitals. WBCT20 and prothrombin time (PT) test were performed on admission. WBCT20 was done by trained clinical research assistants using 1 ml whole blood in a 5 ml borosilicate glass tube with a 10 mm internal diameter. The PT was measured by a semi-automated coagulation system and international normalised ratio (INR) calculated. VICC was defined as present if the INR was .4. The diagnostic utility of WBCT20 was determined by calculating the sensitivity and specificity of the WBCT20 on admission for detecting VICC. There were 987 snake bites where both WBCT20 and PT were done on admission s les. This included 79 patients (8 %) with VICC. The WBCT20 was positive in 65/79 patients with VICC (sensitivity 82 % 95 % confidence interval [CI]: 72–90 %) and was falsely positive in 13/908 with no coagulopathy. The WBCT20 was negative in 895/908 snake bites with no coagulopathy (specificity: 98 % 95 % CI: 97–99 %) and was falsely negative in 14/79 with VICC. Using trained clinical staff, the WBCT20 test had a relatively good sensitivity for the detection of VICC, but still missed almost one fifth of cases where antivenom was potentially indicated. Supplementary Material to this article is available online at www.thrombosis-online.com.
Publisher: Elsevier BV
Date: 11-2020
Publisher: MDPI AG
Date: 05-03-2019
Abstract: Acute kidney injury (AKI) following snakebite is common in developing countries and Bothrops genus is the main group of snakes in Latin America. To evaluate the pathogenic mechanisms associated with Bothrops venom nephrotoxicity, we assessed urinary and blood s les of patients after hospital admission resulting from Bothrops snakebite in a prospective cohort study in Northeast Brazil. Urinary and blood s les were evaluated during hospital stay in 63 consenting patients, ided into AKI and No-AKI groups according to the KDIGO criteria. The AKI group showed higher levels of urinary MCP-1 (Urinary monocyte chemotactic protein-1) (median 547.5 vs. 274.1 pg/mgCr p = 0.02) and urinary NGAL (Neutrophil gelatinase-associated lipocalin) (median 21.28 vs. 12.73 ng/mgCr p = 0.03). Risk factors for AKI included lower serum sodium and hemoglobin levels, proteinuria and aPTT (Activated Partial Thromboplastin Time) on admission and disclosed lower serum sodium (p = 0.01, OR = 0.73, 95% CI: 0.57–0.94) and aPTT (p = 0.031, OR = 26.27, 95% CI: 1.34–512.11) levels as independent factors associated with AKI. Proteinuria showed a positive correlation with uMCP-1 (r = 0.70, p 0.0001) and uNGAL (r = 0.47, p = 0.001). FENa (Fractional Excretion of sodium) correlated with uMCP-1 (r = 0.47, P = 0.001) and uNGAL (r = 0.56, p 0.0001). sCr (serum Creatinine) showed a better performance to predict AKI (AUC = 0.85) in comparison with new biomarkers. FEK showed fair accuracy in predicting AKI (AUC = 0.92). Coagulation abnormality was strongly associated with Bothrops venom-related AKI. Urinary NGAL and MCP-1 were good biomarkers in predicting AKI however, sCr remained the best biomarker. FEK (Fractional Excretion of potassium) emerged as another diagnostic tool to predict early AKI. Positive correlations between uNGAL and uMCP-1 with proteinuria and FENa may signal glomerular and tubular injury. Defects in urinary concentrations highlighted asymptomatic abnormalities, which deserve further study.
Publisher: Springer Science and Business Media LLC
Date: 28-04-2021
DOI: 10.1038/S41598-021-87918-0
Abstract: MicroRNAs in biofluids are potential biomarkers for detecting kidney and other organ injuries. We profiled microRNAs in urine s les from patients with Russell’s viper envenoming or acute self-poisoning following paraquat, glyphosate, or oxalic acid [with and without acute kidney injury (AKI)] and on healthy controls. Discovery analysis profiled for 754 microRNAs using TaqMan OpenArray qPCR with three patients per group (12 s les in each toxic agent). From these, 53 microRNAs were selected and validated in a larger cohort of patients (Russell’s viper envenoming = 53, paraquat = 51, glyphosate = 51, oxalic acid = 40) and 27 healthy controls. Urinary microRNAs had significantly higher expression in patients poisoned/envenomed by different nephrotoxic agents in both discovery and validation cohorts. Seven microRNAs discriminated severe AKI patients from no AKI for all four nephrotoxic agents. Four microRNAs (miR-30a-3p, miR-30a-5p, miR-92a, and miR-204) had 17 fold change ( p 0.0001) and receiver operator characteristics area-under-curve (ROC-AUC) 0.72. Pathway analysis of target mRNAs of these differentially expressed microRNAs showed association with the regulation of different nephrotoxic signaling pathways. In conclusion, human urinary microRNAs could identify toxic AKI early after acute injury. These urinary microRNAs have potential clinical application as early non-invasive diagnostic AKI biomarkers.
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.TOXLET.2015.06.008
Abstract: Acute kidney injury (AKI) is common following paraquat ingestion. The diagnostic performance of injury biomarkers was investigated in serial blood and urine s les 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 urinary biomarker cutoffs for diagnosing structural AKI. 50 poisoned patients provided 2 or more specimens, 76% developed functional AKI [AKIN stage 1 (n=12), 2 (n=7) or 3 (n=19)] 19/26 patients with AKIN stage 2/3 also had functional AKI by sCysC criteria (≥50% increase). Urinary cystatin C (uCysC), clusterin (uClu) and NGAL (uNGAL) increased within 24h of ingestion compared with NoAKI patients and healthy controls. Each biomarker demonstrated moderate diagnostic utility [AUC-ROC: uCysC 0.79, uNGAL 0.79, uClu 0.68] for diagnosis of functional AKI at 16h. Death occurred only in subjects with functional AKI. Structural biomarker-based definitions detected more AKI than did sCr or sCysC, but did not independently predict death. Renal injury biomarkers did not add clinical value to patients who died rapidly due to multi-organ failure. Use of injury biomarkers within 16-24h may guide early intervention for reno-protection in less severe paraquat poisoning.
Publisher: Springer Science and Business Media LLC
Date: 19-12-2022
DOI: 10.1038/S41598-022-25313-Z
Abstract: 2-Methyl-4-chlorophenoxyacetic acid (MCPA) is a widely used chlorophenoxy herbicide. MCPA poisoning causes mitochondrial dysfunction, which can lead to kidney injury and death. The objective of this study is to describe the epidemiology, case fatality and extent of renal injury in a large cohort of MCPA self-poisonings. The study consists of two parts: (1) A report of epidemiological data and clinical outcomes in MCPA poisoned patients in Sri Lanka between 2002 and 2019 (2) Evaluation of acute kidney injury (AKI) using renal biomarkers in a subset from this cohort. Serum creatinine (sCr) and biomarkers were measured soon after hospitalization (2 [IQR 1–3] h) and at different time intervals. We measured serum biomarkers: sCr, cystatin C (sCysC), creatine kinase (CK), and urinary biomarkers: creatinine, kidney injury molecule-1 (KIM-1), clusterin, albumin, beta-2-microglobulin (β2M), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), trefoil factor 3 (TFF3) and cytochrome C (CytoC). Kidney Disease Improving Global Outcomes (KDIGO) criteria was used to define acute kidney injury (AKI). There were 1653 patients 65% were male. The median time from ingestion to examination was 3:54 (IQR 2:19–6:57) h. The overall case-fatality rate was 5.3%. Patients who died were older (42 [IQR 33.5–54] vs 27 [IQR 20–37] for survivors). The median estimated amount of MCPA ingested by patients who died was also greater (88 [IQR 34–200] vs. 30 [IQR 15–63] ml in survivors). Moderate to severe AKI (AKI2/3) was uncommon (6/59 patients in the biomarker study had KDIGO stage 2 or 3). Most patients in AKI2/3 group with increased sCr were older (median age 35 years [IQR 27–41]) compared to No AKI (23 years (19–29) years) or AKI1 (26 years (21–40) years) group who had no or mild increase in sCr. These patients had no pre-existing kidney diseases. In these patients, serum creatinine (maximum medium concentration 1.12 [IQR 0.93–1.67] mg/dl) and CK (maximum medium concentration 284 [IQR 94–428] U/l) were increased but sCysC (maximum medium concentration 0.79 [IQR 0.68–0.81] mg/l) remained in the normal range within 72 h. All urinary biomarkers performed poorly in diagnosing AKI (area under the receiver operating characteristic curve 0.68). The higher numbers of men with MCPA poisoning likely reflects greater occupational access to pesticides. Fatal outcome and higher ingested dose were more common in the elderly. Significant AKI with tubular injury biomarkers was uncommon. Most people with raised sCr were older and appeared to have no pre-existing kidney disease.
Publisher: Springer Science and Business Media LLC
Date: 21-02-2020
Publisher: BMJ
Date: 28-04-2009
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.TOXLET.2016.06.001
Abstract: 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 utility of a panel of biomarkers to diagnose GPSH-induced nephrotoxicity in humans. In a prospective multi-centre observational study, serial urine and blood s les were collected until discharge and at follow-up. The diagnostic performance of each biomarker at various time points was assessed. AKI was diagnosed using the Acute Kidney Injury Network (AKIN) definitions. The added value of each biomarker to sCr to diagnose AKI was assessed by the integrated discrimination improvement (IDI) metric. Of 90 symptomatic patients, 51% developed AKI and 5 patients who developed AKIN≥2 died. Increased sCr at 8 and 16h predicted moderate to severe AKI and death. None of the 10 urinary biomarkers tested increased above normal range in patients who did not develop AKI or had mild AKI (AKIN1) most of these patients also had only minor clinical toxicity. Absolute concentrations of serum and urinary cystatin C, urinary interleukin-18 (IL-18), Cytochrome C (CytoC) and NGAL increased many fold within 8h in patients who developed AKIN≥2. Maximum 8 and 16h concentrations of these biomarkers showed an excellent diagnostic performance (AUC-ROC ≥0.8) to diagnose AKIN≥2. However, of these biomarkers only uCytoC added value to sCr to diagnose AKI when assessed by IDI metrics. GPSH-induced nephrotoxicity can be diagnosed within 24h by sCr. Increases in uCytoC and uIL-18 confirm GPSH-induces apoptosis and causes mitochondrial toxicity. Use of these biomarkers may help to identify mechanism specific targeted therapies for GPSH nephrotoxicity in clinical trials.
Location: Sri Lanka
Location: Sri Lanka
No related grants have been discovered for Fathima Shihana.