Nephrotoxicity biomarkers following propanil (3,4-dichloropropionanilide) self-poisoning

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.

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.

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.

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.

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.