Nephrotoxicity biomarkers following propanil (3,4-dichloropropionanilide) self-poisoning
Date
2025
Authors
Shihana, F.
Wijerathna, T.M.
Gawarammana, I.B.
Shahmy, S.
Chathuranga, U.
Palangasinghe, C.
Mostafa, A.
Mackenzie, L.
Roberts, M.S.
Buckley, N.A.
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Journal article
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Clinical Toxicology, 2025; 63(4):236-245
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Abstract
Background: Propanil toxicity is characterised by severe prolonged methaemoglobinaemia, cyanosis, acidosis, and progressive end-organ dysfunction. In vitro studies report propanil-induced kidney toxicity, which has not been studied clinically. This study determined the incidence of acute kidney injury and of methaemoglobinaemia after propanil self-poisoning and reported the diagnostic performance of novel and traditional biomarkers of acute kidney injury.
Methods: Sixty-seven previously healthy patients were recruited following acute propanil self-poisoning, between October 2010 and October 2014. Concentrations of serum biomarkers and urine biomarkers normalised for urine creatinine excretion were measured. Plasma and urine concentrations of propanil, its main metabolite 3,4-dichloroaniline, the antidote methylthioninium chloride (methylene blue), and methaemoglobin levels were measured.
Results: Kidney biomarkers were measured in 52 of the 67 patients, with 40% developing acute kidney injury (stage 1 [32%] and stage 2 [8%]). Blood methaemoglobin levels were recorded in 23 patients. Normalised urine biomarker concentrations of kidney injury molecule-1, trefoil factor 3, neutrophil gelatinase-associated lipocalin and beta2 microglobulin increased in patients who developed acute kidney injury, but only trefoil factor 3 and cystatin C showed a significantly predicted acute kidney injury at 16-24 h and 8-16 h post-ingestion, respectively. In contrast, serum creatinine concentrations had a very good diagnostic performance throughout the 24 h post-ingestion period, with area under the receiver operating characteristic curve values of 0.79-0.96. Blood methaemoglobin levels were higher in patients with acute kidney injury and correlated with plasma propanil and 3,4-dichloroaniline concentrations. Concentrations of serum creatinine, urine beta2 microglobulin, and trefoil factor-3 significantly correlated with plasma and urine concentrations of propanil, 3,4-dichloroaniline, and methylthioninium chloride.
Discussion: Severe methaemoglobinaemia can impair oxygen delivery and may cause acute ischaemic kidney injury. The poor diagnostic performance of novel biomarkers may be attributed to non-renal factors influencing creatinine concentration or an unusual site or mechanism of nephrotoxicity after propanil poisoning.
Conclusions: Patients with propanil self-poisoning exhibited reversible kidney injury diagnosable using serum creatinine concentrations within 4 h. Although other biomarkers were increased, they were not effective for early diagnosis.
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Copyright 2025 The author(s). This is an open access article distributed under the terms of the Creative Commons attribution license. (http://creativecommons.org/licenses/by/4.0/)