Cellular injury leading to oxidative stress in acute poisoning with potassium permanganate/oxalic acid, paraquat, and glyphosate surfactant herbicide.

Previous studies on human acute kidney injury (AKI) following poisoning with potassium permanganate/oxalic acid (KMnO4/H2C2O4), paraquat, and glyphosate surfactant herbicide (GPSH) have shown rapid and large increases in serum creatinine (sCr) that cannot be entirely explained by direct nephrotoxicity. One plausible mechanism for a rapid increase in sCr is oxidative stress. Thus, we aimed to explore biomarkers of oxidative stress, cellular injury, and their relationship with sCr, after acute KMnO4/H2C2O4, paraquat, and GPSH poisonings. Serum biomarkers [sCr, creatine (sCn), cystatin C (sCysC)] and urinary biomarkers [cytochrome C (CytoC), 8-isoprostane (8-IsoPs)] were evaluated in 105 patients [H2C2O4/KMnO4 (N = 57), paraquat, (N = 21), GPSH (N = 27)] recruited to a multicenter cohort study. We used area under the receiver operating characteristics curve (AUC-ROC) to quantify the extent of prediction of moderate to severe AKI (acute kidney injury network stage 2/3 (AKIN2/3)). Patients with AKIN2/3 showed increased levels of CytoC. Early high CytoC predicted AKIN2/3 in poisoning with KMnO4/H2C2O4 (AUC-ROC4-8h: 0.81), paraquat (AUC-ROC4-8h: 1.00), and GPSH (AUC-ROC4-8h: 0.91). 8-Isoprostane levels were not significantly elevated. Reduced sCn and increased sCr/sCn ratios were observed for 48 h post KMnO4/H2C2O4 ingestion. Paraquat exhibited a similar pattern (N = 11), however only 3 were included in our study. Increased CytoC suggests there is mitochondrial injury coupled with energy depletion. The increased sCr within 24 h could be due to increased conversion of cellular creatine to creatinine during the process of adenosine triphosphate (ATP) generation and then efflux from cells. Later increases of sCr are more likely to represent a true decrease in kidney function.

Urinary versus serum microRNAs in human oxalic acid poisoning: Contrasting signals and performance.

MicroRNAs are key regulators of the normal kidney function and development, and altered in acute kidney injury (AKI). However, there is a lack of studies comparing serum and urine miRNA expression in toxic AKI in humans. We aimed to compare the global signature of urinary and serum microRNAs, with and without kidney injury, after human oxalic acid poisoning. We profiled urinary microRNAs in patients who ingested oxalic acid and developed no injury (No AKI n = 3), moderate injury (AKIN2 n = 3) or severe injury (AKIN3 n = 3) and healthy controls (n = 3). We validated a signature of 30 urinary microRNAs identified in the discovery profiling, in a second cohort of individuals exposed to oxalic acid (No AKI n = 15, AKIN2 n=11 & AKIN3 n= 18) and healthy controls (n=-27) and we compared the results with previously published serum data. Global profiling in toxic AKI patients showed a higher expression of urinary microRNAs and lower expression of serum microRNAs. Most urine microRNA in the validation cohort were significantly upregulated (25/30, fold change >2.8 and p < 0.05) in AKIN2/3 patients compared to No AKI. Four urinary microRNAs (miR-191, miR-19b, miR-20a and miR-30b) had good diagnostic performance (AUC greater than 0.8) to predict AKIN2/3 between 4-8 hours post ingestion. Poisoning irrespective of AKI led to significantly lower expression of many microRNAs in serum but relatively few changes in urinary miRNA expression. In conclusion, urinary microRNA signature provides a stronger measure of AKI in oxalic acid poisoning compared to serum microRNA. Kidney injury has the greatest impact on urinary microRNA, while poisoning itself was better reflected in serum miRNA. Plasma and urinary microRNAs signatures provide complementary information in toxic kidney injury.

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.

Oral administration of oxalate-enriched spinach extract as an improved methodology for the induction of dietary hyperoxaluric nephrocalcinosis in experimental rats.

Experimental induction of hyperoxaluria by ethylene glycol (EG) administration is disapproved as it causes metabolic acidosis while the oral administration of chemically synthesized potassium oxalate (KOx) diet does not mimic our natural system. Since existing models comprise limitations, this study is aimed to develop an improved model for the induction of dietary hyperoxaluria, and nephrocalcinosis in experimental rats by administration of naturally available oxalate rich diet. Male albino Wistar rats were divided into five groups. Group I, control; group II rats received 0.75% EG, group III rats fed with 5% KOx diet and group IV and V rats were administered with spinach extract of 250 and 500 mg soluble oxalate/day respectively, for 28 d. Urine and serum biochemistry were analyzed. After the experimental period, rats were sacrificed, liver and kidney tissue homogenates were used for antioxidant and lipid peroxidation assay. Relative change in expression of kidney injury molecule-1 (KIM-1) and crystal modulators genes in kidney tissues were evaluated. Tissue damage was assessed by histology studies of liver and kidney. Experimental group rats developed hyperoxaluria and crystalluria. Urine parameters, serum biochemistry, antioxidant profile, lipid peroxidation levels and gene expression analysis of experimental group II and III rats reflected acute kidney damage compared to group V rats. Histopathology results showed moderate hyperplasia in liver and severe interstitial inflammation in kidneys of group II and III than group V rats. Ingestion of naturally available oxalate enriched spinach extract successfully induced dietary hyperoxaluria and nephrocalcinosis in rats with minimal kidney damage.

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.

Acute renal failure and metabolic acidosis due to oxalic acid intoxication: a case report.

Most of the reports of oxalic acid intoxication are in cases of ethylene glycol intoxication. These symptoms are known to be central nerve system manifestations, cardiopulmonary manifestations and acute renal failure. There have been only a few reports of direct oxalic acid intoxication. However, there have been a few recent reports of oxalic acid intoxication due to the ingestion of star fruit and ascorbic acid. We herein report the case of a patient with acute renal failure and metabolic acidosis caused directly by consumption of oxalic acid. During the initial examination by the physician at our hospital, the patient presented with tachypnea, a precordinal burning sensation, nausea and metabolic acidosis. After admission, the patient developed renal failure and anion gap high metabolic acidosis, but did not develop any CNS or cardio-pulmonary manifestations in the clinical course. The patient benefitted symptomatically from hemodialysis.

Putative Aspergillus niger-induced oxalate nephrosis in sheep.

A sheep farmer provided a maize-based brewer's grain (mieliemaroek) and bales of Eragrostis curvula hay to ewes and their lambs, kept on zero-grazing in pens. The 'mieliemaroek' was visibly mouldy. After 14 days in the feedlot, clinical signs, including generalised weakness, ataxia of the hind limbs, tremors and recumbency, were noticed. Six ewes died within a period of 7 days. A post mortem examination was performed on 1 ewe. The carcass appeared to be cachectic with mild effusions into the body cavities; mild lung congestion and pallor of the kidneys were observed. Microscopical evaluation revealed nephrosis and birefringent oxalate crystals in the renal tubules when viewed under polarised light. A provisional diagnosis of oxalate nephrosis with subsequent kidney failure was made. Amongst other fungi, Aspergillus niger was isolated from 'mieliemaroek' samples submitted for fungal culture and identification. As A. niger is known to synthesise oxalates, a qualitative screen to detect oxalic acid in the mieliemaroek and purified A. niger isolates was performed using high-performance liquid chromatography (HPLC). Oxalic acid was detected, which supported a diagnosis of soluble oxalate-induced nephropathy.

Emerging epidemic of fatal human self-poisoning with a washing powder in Southern Sri Lanka: a prospective observational study.

INTRODUCTION: Self-poisoning is a public health problem in Sri Lanka. A new laundry detergent consisting of a sachet each of 1.2 g of potassium permanganate and 12.5 g of oxalic acid has become a popular agent among the youth for self-poisoning. METHOD: Prospective clinical data and major outcomes were recorded in all patients admitted to a referring and a referral hospital. Serial biochemistry was performed in 20 patients. Postmortem examinations were performed in some patients. RESULTS: There were 115 patients. The majority developed symptoms of the gastrointestinal tract within the first 24 h. There were 18 deaths. Ingestion of oxalic acid was associated with a case fatality ratio of 25.4% (95% CI = 14-39), while ingestion of both potassium permanganate and oxalic acid was associated with a case fatality ratio of 9.8% (95% CI = 3.2-21). Ingestion of more than one sachet was associated with a significantly higher risk of death (risk ratio = 13.26, 95% CI = 3.2-54, p < 0.05). Majority of the deaths occurred within an hour since ingestion. Postmortem examinations revealed mucosal ulceration in the majority of deaths. DISCUSSION: This case series brings to light an emerging epidemic of fatal self-poisoning in Sri Lanka from a compound that is not regulated. As deaths occur soon after ingestion, medical management of these patients is bound to be difficult. CONCLUSION: This case series highlights a fatal mode of self-poisoning that could be controlled through regulation of the manufacture and sale of the product.

Planned complex suicide by self-poisoning and a manipulated blank revolver: remarkable findings due to multiple gunshot wounds and self-made wooden projectiles.

A remarkable case of complex suicide with poisoning and multiple self-inflicted gunshot wounds to the head is reported. After ingestion of a liquid insecticide, the victim shot himself twice in the head, once in each temple. Self-manufactured wooden dowels were used as projectiles in combination with conventional blank cartridges. The dowels had been glued on top of the blank cartridges and expelled by propellant gases. Moreover, the blank revolver used had been extensively manipulated in a rarely observed manner. Several occlusive devices had been removed from the barrel and the cylinder chamber to enable the expulsion of the wooden projectiles. The investigation of the methods used and the circumstances found at the scene pointed towards a planned complex suicide. A remarkable case with unusual projectiles, i.e., wooden dowels, fired by an extensively manipulated blank gun is reported, emphasizing the importance of close collaboration between the police firearm laboratory and forensic pathology in practical casework.

[Hypocalcemia in a four-week-old foal]. / Hypocalcemie bij een vier weken oud veulen.

Intake of Rumex, a plant genus of the Polygonaceae family, probably led through the assimilation of oxalic acid, to hypocalcaemia in a four-week old foal. This foal was presented with muscle rigidity and a stiff gait. Both the total and ionized calcium concentrations were low, 1.38 mmol/l and 0.54 mmol/l respectively. The foal was treated with a total of 150 ml of a 20% calcium solution IV. The foals neuromuscular signs resolved within a few hours after receiving calcium solution.