Epidemiology, toxicokinetics and biomarkers after self-poisoning with Gloriosa superba.

Introduction: Gloriosa superba is a flowering plant that contains colchicine. Deliberate self-poisoning with this plant in Sri Lanka is common and potentially fatal. The objective of this study was to describe the epidemiology, toxicokinetics and selected biomarkers in these patients. Materials and methods: The study consisted of three parts; epidemiologic and outcome data (n = 297), concentrations and toxicokinetics (n = 72), evaluation of urinary and serum biomarkers (n = 45). Plasma colchicine levels were measured by high-performance liquid chromatography (HPLC). We also measured serum biomarkers: creatinine (sCr), cystatin C (sCysC) and creatine kinase (CK), and urinary biomarkers: creatinine, kidney injury molecule-1 (KIM - 1), clusterin, albumin, beta-2-microglobulin (ß2M), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN) and trefoil factor 3 (TFF3). Results: The case fatality was 10% (29/297), and death was much more common in older patients. Median concentrations of colchicine were higher in those over 65 [median 4.7 ng/mL (IQR: 1.7-6.6) vs. 1.2 (IQR: 0.2-2.7) for those <35]. Admission colchicine concentrations were highly correlated with a fatal outcome [median 7.8 ng/ml (IQR: 5.8-18.7) vs 1.2 (0-2.3) in survivors]. The area under the receiver operating characteristic curve (AUC-ROC) for uncorrected admission colchicine level was highly predictive of a fatal outcome, and this improved even further with two methods we developed to correct for the expected change with time. The best method had an AUC-ROC of 0.98 (95%CI 0.94-1.00) in predicting death, with 100% sensitivity and 96% specificity at the best cut-point. Discussion: Fatal outcomes and high concentrations were both much more common in the elderly following poisoning with Gloriosa superba. Our findings are consistent with kinetic data after medicinal colchicine ingestion. Conclusions: Gloriosa superba self-poisoning causes significant mortality. High concentration of colchicine is highly predictive of a fatal outcome. Ingestion of Gloriosa superba caused only mild acute kidney injury (AKI) and rhabdomyolysis.

Albuminuria and other renal damage biomarkers detect acute kidney injury soon after acute ingestion of oxalic acid and potassium permanganate.

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 therapies. METHODS: 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. RESULTS: 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). CONCLUSIONS: Urinary albumin was the best performing AKI biomarker following ingestion of H2C2O4/KMnO4. This may reflect glomerular injury and/or proximal tubular injury. The urinary albumin concentrations observed in this study could generally be detected using albumin specific dipstick methods, easily available even in resource poor settings.

Serum creatinine and cystatin C provide conflicting evidence of acute kidney injury following acute ingestion of potassium permanganate and oxalic acid.

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 multicenter prospective cohort study in Sri Lanka exploring AKI following poisoning. METHODS: Multiple measures of change in kidney function were evaluated in 48 consenting patients who had serial sCr and serum cystatin C (sCysC) data available. RESULTS: 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. CONCLUSIONS: 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 H2C2O4 and KMnO4. Increased early creatinine excretion supports the latter explanation, since creatinine excretion usually decreases transiently in AKIN2/3 from other causes.