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Survival Following Intentional Glyphosate/Surfactant Ingestion Despite the Development of Acute Renal Failure
... GPSH mediated toxicity may also be due to lipid peroxidation (Mensah et al., 2012), oxidative stress (Guilherme et al., 2012) and DNA damage (Navarro and Martinez, 2014). Although most patients remain asymptomatic following mild poisoning (Bradberry et al., 2004;Chen et al., 2009;Roberts et al., 2010), acute kidney injury (AKI) is a salient clinical feature of moderate to severe poisoning (Bradberry et al., 2004;Lee et al., 2008;Moon and Chun, 2010;Moon et al., 2006;Nelsen J et al., 2009;Roberts et al., 2010;Seok et al., 2011) and an important predictor of poor outcome (Bradberry et al., 2004;Lee and Guo, 2011;Lee et al., 2000;Moon and Chun, 2010). ...
... However, novel structural injury biomarkers of AKI appear earlier than serum creatinine (sCr) and may be specific to site of kidney injury (Bonventre et al., 2010). Serum Cr is the most commonly studied biomarker in GPSH-induced clinical nephrotoxicity (Lee et al., 2008;Lee and Guo, 2011;Moon and Chun, 2010;Moon et al., 2006;Nelsen J et al., 2009;Seok et al., 2011). The utility of structural kidney injury biomarkers has not been investigated following GPSH toxicity in humans. ...
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 samples 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 16 hours 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 8 hours in patients who developed AKIN ≥ 2. Maximum 8 and 16 hour 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 24 hours 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.
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