Markers Of Nephrotoxicity Research Articles

Role of δ-Aminolevulinic Acid Dehydratase (ALAD) gene polymorphism in lead induced nephrotoxicity

Background Lead is an important environmental and occupational pollutant and it can cause nephrotoxicity even at low doses. Early detection of renal disease from occupational and environmental exposure to nephrotoxic chemicals is currently limited by the lack of sensitive or chemical specific tests. There are growing body of evidence that supports Kidney injury molecule-1 (KIM-1) as a specific marker for nephrotoxicity, specificallyischemic renal injury. δaminolevulinic acid dehydratase (ALAD) gene polymorphism is known as an important factor affecting workers susceptibility to lead toxicity, further role of ALAD-1-1 and ALAD2-2 genotype is not clear yet. Correlation among the blood lead level, ALAD genotype present, urinary KIM-1 level of workers can provide better understanding about lead intoxication pattern and the role of genetic factor in susceptibility towards lead intoxication among workers.

Oxidative stress, hematological and biochemical alterations in farmers exposed to pesticides

In this study, a cohort of farmers from the Mateur region in the North of Tunisia, were interviewed and examined for the biochemical effects of pesticides. We studied their haematological profile, lipid parameters, serum markers of nephrotoxicity and hepatotoxicity. We also evaluated the activities of Butyrylcholinesterase (BChE), Acetylcholinesterase (AChE) and thiolactonase-paroxonase (PON). Moreover, lipid peroxidation and activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were determined. The duration of pesticide use and the farmers’ age were considered in the analysis. Our results revealed significant differences in some haematological parameters, in liver and kidney functions, in the lipidic status of the pesticide-exposed group. We also reported an increase in the index of incidence of cardiovascular risk in farmer populations. A significant decrease in AChE, BChE and PON levels was found among farmers. Lipid peroxidation, however, increased. The activities of SOD and CAT were remarkably elevated in farmer populations. There was a significant relation between changes in biological markers, the duration of pesticide use and the farmers’ age. This study indicates that a long-term exposure to pesticides may play an important role in the development of vascular diseases via metabolic disorders of lipoproteins, lipid peroxidation and oxidative stress, inhibition of BChE and decrease in thiolactonase-PON levels.

Effect of Ethanol Extract of Calotropis procera Root Bark on Carbon Tetrachloride-Induced Hepatonephrotoxicity in Female Rats

Calotropis procera root is used in traditional medical practice for the treatment of various ailments. The possible hepatoprotective and nephroprotective activities of the ethanolic extract of C. procera root in female rats were investigated. Carbon tetrachloride (CCl 4) was used to induce hepatotoxicity and nephrotoxicity with significant (P < 0.05) increase in the level of serum enzyme markers of hepatotoxicity and nonenzyme markers of nephrotoxicity. Administration of 150 and 300 mg/kg body weight (bw) of the ethanolic extract of C. procera root did not protect the liver and kidney from CCl4induced toxicity. Pretreatment with the extract rather potentiated the toxicity induced by CCl4. This research result did not support the reported hepatoprotective activity of the extract. It is advised strongly that caution should be taken when ingesting alcoholic preparations of C. procera root.

Influence of aminoglycoside antibiotics on chicken cystatin binding to renal brush-border membranes

Drug-induced kidney injury is a serious adverse event which needs to be monitored during aminoglycoside therapy. Urine cystatin C is considered an early and sensitive marker of nephrotoxicity. Cystatin C, a low-molecular-weight serum protein, and basic drugs have a common transport system expressed in the apical membrane of renal proximal tubular cells. The aim of this study was to investigate whether aminoglycoside antibiotics influenced cystatin C binding to the renal brush-border membrane. The binding study was performed using a rapid filtration technique and affinity column displacement method. Concentration-dependent inhibition of chicken cystatin binding to brush-border membranes by gentamicin was observed. The gentamicin interaction with brush-border membranes was of relatively low affinity (Ki = 32 μm) in comparison with the chicken cystatin affinity to the binding sites (Kd = 3.6 μm). Amikacin and gentamicin were only able to displace chicken cystatin from the chromatographic affinity column in concentrations several times higher than normally found in the tubular fluid during standard aminoglycoside therapy. Cystatin reabsorption in the proximal tubule cannot be significantly affected by aminoglycoside antibiotics because of their relatively low affinity to common binding sites on the brush-border membrane.

Urinary metabolomic markers of aminoglycoside nephrotoxicity in newborn rats

BackgroundAminoglycoside exposure is a common cause of acute kidney injury (AKI). Delay in the diagnosis of AKI using conventional biomarkers has been one of the important obstacles in applying early effective interventions. We tested the hypothesis that urinary metabolomics could identify novel early biomarkers for toxic renal injury.Methods3 days old rats were divided into 3 groups; they received a single daily injection of vehicle (0.9% NaCl solution) or gentamicin at a dose of 10 or 20 mg/kg/day for 7 days. Urine and blood were collected after 3 and 7days of injections. Urinary metabolites were evaluated using High-performance liquid chromatography and gas chromatography/ mass spectrometry.ResultsA distinct urinary metabolic profile characterized by glucosuria, phosphaturia and aminoaciduria was identified preceding changes in serum creatinine. At both gentamicin doses, urinary tryptophan was significantly (p<0.05) increased; fold change (1.91 and 2.31 after 3d, 1.81and 1.93 after 7d). Similarly, kynurenic acid, a tryptophan metabolite, showed a significant (p<0.05) decrease, fold change (0.26 and 0.24 after 3d, 0.21 and 0.52 after 7d), suggesting interruption of the normal tryptophan metabolism pathway.ConclusionWe conclude that urinary metabolomic profiling provides a robust approach for identifying early and novel markers of gentamicin induced AKI.

Interleukin 18 as a Marker of Chronic Nephropathy in Children after Anticancer Treatment

Novel markers of nephrotoxicity, including kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), and beta-2 microglobulin, were used in the detection of acute renal injury. The aim of the study was to establish the frequency of postchemotherapy chronic kidney dysfunction in children and to assess the efficacy of IL-18, KIM-1, and beta-2 microglobulin in the detection of chronic nephropathy. We examined eighty-five patients after chemotherapy (median age of twelve years). The median age at the point of diagnosis was 4.2 years, and the median follow-up time was 4.6 years. We performed classic laboratory tests assessing kidney function and compared the results with novel markers (KIM-1, beta-2 microglobulin, and IL-18). Features of subclinical renal injury were identified in forty-eight children (56.3% of the examined group). Nephropathy, especially tubulopathy, appeared more frequently in patients treated with ifosfamide, cisplatin, and/or carboplatin, following nephrectomy or abdominal radiotherapy (P = 0.14, P = 0.11, and P = 0.08, resp.). Concentrations of IL-18 and beta-2 microglobulin were comparable with classic signs of tubulopathy (P = 0.0001 and P = 0.05). Concentrations of IL-18 were also significantly higher in children treated with highly nephrotoxic drugs (P = 0.0004) following nephrectomy (P = 0.0007) and abdominal radiotherapy (P = 0.01). Concentrations of beta-2 microglobulin were higher after highly toxic chemotherapy (P = 0.004) and after radiotherapy (P = 0.02). ROC curves created utilizing IL-18 data allowed us to distinguish between children with nephropathy (value 28.8 pg/mL) and tubulopathy (37.1 pg/mL). Beta-2 microglobulin and IL-18 seem to be promising markers of chronic renal injury in children after chemotherapy.

Acute and Subchronic Toxicity Evaluation of Poly(ɛ-Caprolactone) Lipid-Core Nanocapsules in Rats

Owing to concerns over the effects of the physicochemical properties of nanoparticles and their interaction with biological systems, further investigation is required. We investigated, for the first time, the toxicity of lipid-core nanocapsules (LNCs) containing a polymeric wall of poly(ε-caprolactone) and a coating of polysorbate 80 used as drug delivery devices (~245nm) in Wistar rats after single- and repeated-dose treatments. The suspensions were prepared by interfacial deposition of the polymer and were physicochemically characterized. Toxicological effects were determined after single doses of 18.03, 36.06, and 72.12 × 10(12) LNC/kg and repeated doses of 6.01, 12.02, and 18.03 × 10(12) LNC/kg for 28 days by ip administration. The results for both the treatments showed no mortality or permanent body weight changes during the experiments. A granulomatous foreign body reaction was observed in the liver and spleen of higher dose groups in acute and subchronic treatments. Most of the hepatotoxicity and nephrotoxicity markers were within the reference values and/or were similar to the control group. However, a slight alteration in the hematologic parameters was observed in both the studies. Thus, to verify a possible methodological influence, we performed an in vitro test to confirm such influence. These findings are in agreement with earlier reports regarding no appreciable toxicity of biodegradable polymeric nanoparticles, indicating that LNC might be a safe candidate for drug delivery system. Furthermore, the results presented in this study are important for health risk assessment and to implement strategies for testing biodegradable polymeric nanoparticles.

Metabolomics evaluation of hydroxyproline as a potential marker of melamine and cyanuric acid nephrotoxicity in male and female Fischer F344 rats

Following kidney failure in domesticated pets in the US and kidney issues requiring hospitalization with some deaths in children in China, investigators determined the cause was adulteration of pet foods and baby formula with melamine. It has since been noted that exposure of rats to melamine and cyanuric acid forms melamine cyanurate crystals in the kidney leading to acute nephrotoxicity. This metabolomics study aimed to identify biomarkers of melamine and cyanuric acid-induced renal injury. Male and female Fischer 344 rats were fed a diet fortified with varying doses of melamine and cyanuric acid for 28days. Analysis of urinary amino acids showed hydroxyproline was increased in both sexes in a manner consistent with the clinical chemistry and histopathology data; most prominent when total urine output was taken into account. Furthermore, rats with the highest levels of urinary hydroxyproline were the only rats that exhibited fibrosis within the kidney. Clinical chemistry and histopathology indicated male rats were slightly more affected than female rats following dosing with the 120 and 180ppm formulations; hydroxyproline excretion also supports this finding. Hydroxyproline may be a noninvasive urinary biomarker for detection of acute kidney injury potentially associated with kidney fibrosis.

Elevated urinary levels of kidney injury molecule-1 among Chinese factory workers exposed to trichloroethylene

Epidemiological studies suggest that trichloroethylene (TCE) exposure may be associated with renal cancer. The biological mechanisms involved are not exactly known although nephrotoxicity is believed to play a role. Studies on TCE nephrotoxicity among humans, however, have been largely inconsistent. We studied kidney toxicity in Chinese factory workers exposed to TCE using novel sensitive nephrotoxicity markers. Eighty healthy workers exposed to TCE and 45 comparable unexposed controls were included in the present analyses. Personal TCE exposure measurements were taken over a 2-week period before urine collection. Ninety-six percent of workers were exposed to TCE below the current US Occupational Safety and Health Administration permissible exposure limit (100 ppm 8h TWA), with a mean (SD) of 22.2 (35.9) ppm. Kidney injury molecule-1 (KIM-1) and Pi-glutathione S transferase (GST) alpha were elevated among the exposed subjects as compared with the unexposed controls with a strong exposure-response association between individual estimates of TCE exposure and KIM-1 (P < 0.0001). This is the first report to use a set of sensitive nephrotoxicity markers to study the possible effects of TCE on the kidneys. The findings suggest that at relatively low occupational exposure levels a toxic effect on the kidneys can be observed. This finding supports the biological plausibility of linking TCE exposure and renal cancer.

Protective effect of Moringa oleifera leaves against gentamicin-induced nephrotoxicity in rabbits

Oxidative stress due to abnormal production of reactive oxygen species has been implicated in the nephrotoxicity induced by gentamicin. The nephroprotective effect of aqueous-ethanolic extract of Moringa oleifera leaves (150 and 300 mg/kg) was evaluated against gentamicin-induced (80 mg/kg) renal injury in rabbits. Serum urea and creatinine levels were evaluated as the markers of renal nephrotoxicity. At the end of the experiment, the kidneys of rabbits were excised for histological examinations and determination of lipid peroxidation levels. Serum urea and creatinine levels were reduced in the M. oleifera (150 and 300 mg/kg) plus gentamicin treated groups. On histological examinations, kidney of intoxicated rabbits groups which received M. oleifera extract showed reparative tendencies. A highly significant (p < 0.01) elevation was observed in lipid peroxidation (LPO) level in the kidneys of gentamicin-intoxicated rabbits whereas combined treatment of M. oleifera and gentamicin group showed a highly significant (p < 0.01) depletion in LPO. The present study indicates that aqueous-ethanolic extract of M. oleifera leaves attenuates renal injury in rabbits treated with gentamicin, possibly by inhibiting lipid peroxidation.

Specificity of Histological Markers of Long-Term CNI Nephrotoxicity in Kidney-Transplant Recipients Under Low-Dose Cyclosporine Therapy

The specificity of chronic histological lesions induced by calcineurin inhibitors (CNI) is often questioned, but few studies have directly compared long-term lesions in renal-transplant patients who received this treatment and those who did not. We therefore conducted a retrospective study of 141 kidney-transplant recipients treated with (n = 48) or without (n = 93) cyclosporine (CsA) to compare the histological lesions observed at 3-month, 24-month and 10-year protocol biopsies. All of the chronic elementary lesions (glomerulosclerosis, interstitial fibrosis, tubular atrophy, arteriolar hyalinosis, fibrointimal thickening) progressed in frequency and severity in both groups, although significantly more in the CsA group. Ten-year biopsy results showed that 92% of patients in the CsA-treated group and 65% in the control group had arteriolar hyalinosis lesions. When we focused on muscular arteriolar hyaline deposits more specific to CsA arteriolopathy, we observed these lesions in 68% of CsA patients and 28% of patients who had never received CsA. CsA was not the sole factor involved in the development of arteriolar hyalinosis and was independently associated with an increased risk of graft loss. In summary, we observed that histological lesions commonly attributed to CsA nephrotoxicity were not sufficiently specific to definitively diagnose CNI nephrotoxicity.

Evaluation of cholesterol depletion as a marker of nephrotoxicity in vitro for novel β-cyclodextrin derivatives

Cyclodextrins (CDs) have been shown to improve physicochemical and biopharmaceutical properties of drugs when low solubility and low safety limit their use in the pharmaceutical field. Recently, we have developed new multi-substituted-β-CDs, hydroxypropyl-sulfobutyl ether-β-cyclodextrin (HPn-SBEm-β-CD). HPn-SBEm-β-CD exhibit low hemolysis, good solubility, strong inclusion ability, and an appropriate average molecular weight. In this study, we chose two products of HPn-SBEm-β-CD (HP3-SBE2-β-CD and HP2-SBE3-β-CD) and compared their effects to sulfobutyl ether-β-cyclodextrin (SBE7-β-CD), methyl-β-cyclodextrin (M-β-CD) and 2,6-di-O-methyl-β-cyclodextrin (DM-β-CD). We evaluated viability, membrane damage, induction of apoptosis and necrosis, cholesterol depletion, and morphological changes in human embryonic kidney 293A cells (HEK293A) in vitro. CDs caused a reduction of cell viability and increased LDH levels in a concentration-dependent manner. The effect of HP3-SBE2-β-CD or HP2-SBE3-β-CD on cell viability, membrane damage, and the induction of apoptosis and necrosis resembled that of SBE7-β-CD, whereas the effects were significantly lower for M-β-CD or DM-β-CD. HP3-SBE2-β-CD and HP2-SBE3-β-CD exhibited morphological changes at high concentrations. In conclusion, the results showed that cholesterol depletion may be as a marker for evaluating the cytotoxicity of novel β-CD derivatives. These results will provide useful information for HPn-SBEm-β-CD as a promising safe adjuvant for intravenous administration in the future.

Urinary levels of regenerating islet-derived protein III β and gelsolin differentiate gentamicin from cisplatin-induced acute kidney injury in rats

A key aspect for the clinical handling of acute kidney injury is an early diagnosis, for which a new generation of urine biomarkers is currently under development including kidney injury molecule 1 and neutrophil gelatinase-associated lipocalin. A further diagnostic refinement is needed where one specific cause among several potentially nephrotoxic insults can be identified during the administration of multidrug therapies. In this study we identified increases in regenerating islet-derived protein III beta (reg IIIb) and gelsolin as potential differential urinary markers of gentamicin's nephrotoxicity. Indeed, urinary levels of both reg IIIb and gelsolin distinguish between the nephrotoxicity caused by gentamicin from that caused by cisplatin where these markers were not increased by the latter. Reg IIIb was found to be overexpressed in the kidneys of gentamicin-treated rats and excreted into the urine, whereas urinary gelsolin originated from the blood by glomerular filtration. Our results illustrate an etiological diagnosis of acute kidney injury through analysis of urine. Thus, our results raise the possibility of identifying the actual nephrotoxin in critically ill patients who are often treated with several nephrotoxic agents at the same time, thereby providing the potential for tailoring therapy to an individual patient, which is the aim of personalized medicine.

Early Markers of Nephrotoxicity in Patients With Metal-on-metal Hip Arthroplasty

Metal ions released from arthroplasty devices are largely cleared in urine, leading to high exposure in renal tissues. Validated early markers of renal damage are routinely used to monitor workers in heavy metal industries, and renal risk can be quantified in these industries. It is unclear if the ion levels in patients with metal-on-metal hips are sufficient to cause renal damage. Does metal-on-metal (MOM) bearing use over a 10-year period lead to elevation of early renal markers compared with the levels expected in subjects with no metal exposure? We retrospectively reviewed 31 patients who underwent MOM hip resurfacings 10 years earlier. Whole blood specimens were collected for metal ion analysis, serum for creatinine estimation, and urine for timed metal ion output and renal markers. The renal marker levels of 30 age- and gender-matched subjects with no metal exposure and no known renal problems or diabetes mellitus were used as controls for renal markers. Median serum creatinine level in the MOM group was 1.1 mg/dL (interquartile range, 1.0-1.2 mg/dL) and median creatinine clearance was 79.2 mL/min. In this cohort, the number of patients with markers of renal damage above the reference range was comparable to the controls. None of the renal markers were associated with metal levels. The absence of elevation of renal markers in this cohort 10 years after MOM bearing implantation is reassuring. However, we believe surveillance through further longer-term, large-scale controlled trials are needed to monitor this arthroplasty-induced low-intensity (but long-term) trace element exposure to rule out potential nephrotoxicity.

DNA damage and cholinesterase activity in occupational workers exposed to pesticides

The present study was designed to evaluate genotoxicity, acetyl cholinesterase (AChE) activity, hepatic and renal toxicity in occupational workers exposed to mixture of pesticides ( n = 70) with same number of healthy subjects as controls. The mean comet tail DNA % (TD %) and tail moment (TM) were used to measure DNA damage, while AChE activity and other biochemical parameters such as markers of nephrotoxicity (urea and creatinine) and hepatotoxicity (AST, ALT and ALP) were measured as biomarkers for toxicity due to exposure of pesticides. The occupational workers were continuously exposed to mixture of pirimiphos methyl, chlorpyrifos, temephos and malathion on a regular interval as per usage and activity. The comet assay using lymphocytes of exposed workers showed significantly higher TD percentage value (60.43% vs. 31.86%, p < 0.001) and TM value (14.48 μm vs. 6.42 μm, p < 0.001) in occupational workers as compared to controls. AChE activity in erythrocytes was found to be decreased (3.45 KAU/L vs. 9.55 KAU/L in controls, p < 0.001) and associated with the duration of exposure to pesticides used by the workers. Enzyme levels for hepatic and renal functions were also found significantly different in occupational workers than healthy controls ( p < 0.001). These results suggest that the exposure to mixture of pirimiphos methyl, chlorpyrifos, temephos and malathion may induce DNA damage, decrease in AChE activity, hepatotoxicity as well as nephrotoxicity. Periodic biomonitoring of these biomarkers along with imparting education and training to occupational workers for safe application of pesticides is recommended for its potential hazards.

Urinary parameters predictive of cisplatin-induced acute renal injury in dogs

A 28-day study was conducted to evaluate changes in urinary cytokine/chemokine expression levels in dogs with renal injury due to administration of cisplatin. Animals ( n = 17) were administered cisplatin at 0.75 mg/kg/day (i.v.) for five consecutive days. Urine/serum were collected at pre-dosing, 4 h post-dosing and on days 2, 3, 4, 8, 10, 14, 16, 18, 21, 23, 25, 28 and unscheduled terminations. Animals were euthanized when serum creatinine (sCr) levels measured at ⩾1.9 mg/dL, indicating significant loss of renal function (decreased glomerular filtration rate). Relevant clinical observations included lethargy and dehydration. Pre-study sCr levels ranged from 0.6 to 0.8 mg/dL; on days 1 through 4, sCr levels ranged from 0.5 and 1.1 mg/dL; and terminal sCr levels ranged from 0.6 and 6.6 mg/dL. Histologically, cisplatin-related renal changes were characterized as proximal tubule dilatation, vacuolization, degeneration, regeneration, and interstitial inflammation. Increased interleukin (IL)-2, IL-8, monocyte chemoattractant protein-1 (MCP-1), granulocyte–macrophage colony-stimulating factor (GMCSF) and keratinocyte-derived chemokine (KC) occurred on days 3 through 4. Increased IL-7 occurred on day 4. This study showed for the first time that inflammatory cytokines/chemokines in urine positively identified acute renal tubular injury in dogs at time points earlier than sCr, a traditional marker of nephrotoxicity.

Nephroprotective activity of Momordica dioica Roxb. in cisplatin-induced nephrotoxicity

In this study, the ethanol extract of Momordica dioica fruit extract (200 mg kg−1) was studied for nephroprotective and curative activities. Chloroform, ethyl acetate, ethanol and aqueous extracts were prepared. In vitro antioxidant activity was made the basis for the selection of the ethanol extract for further studies. In DPPH free radical scavenging activity, the ethanolic extract has shown maximum inhibition (84.2%), followed by aqueous (74.8%), ethyl acetate (69.4%) and chloroform (59.7%) extract. On the other hand, in total antioxidant activity, the ethanol extract has shown 80.1% inhibition, followed by aqueous (71.9%), ethyl acetate (67.2%) and chloroform (53.2%) extracts. A single dose (5 mg kg−1, i.p.) of cisplatin was administrated to induce nephrotoxicity. Blood urea and serum creatinine were analysed as biochemical markers of nephrotoxicity. Reduced glutathione (GSH) and the product of lipid peroxidation (MDA) were also measured in kidney tissues. A single dose of cisplatin resulted in significant reduction in body weight and increased the urea and creatinine levels. Extract administration has shown significant recovery in the levels of these biochemicals in curative (p < 0.001) and protective groups, whereas a single dose of cisplatin caused significant reduction in GSH and an increase in malondialdehyde production. Recovery was observed in treated groups. This study suggested that the nephroprotective and curative activities of M. dioica fruit extract are due to its antioxidant activity. It is further concluded that this antioxidant activity may be attributed to the phenolics, flavonoids and amino acids present in the extract.

Urinary clusterin, cystatin C, β2-microglobulin and total protein as markers to detect drug-induced kidney injury

Earlier and more reliable detection of drug-induced kidney injury would improve clinical care and help to streamline drug-development. As the current standards to monitor renal function, such as blood urea nitrogen (BUN) or serum creatinine (SCr), are late indicators of kidney injury, we conducted ten nonclinical studies to rigorously assess the potential of four previously described nephrotoxicity markers to detect drug-induced kidney and liver injury. Whereas urinary clusterin outperformed BUN and SCr for detecting proximal tubular injury, urinary total protein, cystatin C and beta2-microglobulin showed a better diagnostic performance than BUN and SCr for detecting glomerular injury. Gene and protein expression analysis, in-situ hybridization and immunohistochemistry provide mechanistic evidence to support the use of these four markers for detecting kidney injury to guide regulatory decision making in drug development. The recognition of the qualification of these biomarkers by the EMEA and FDA will significantly enhance renal safety monitoring.

Assessing the Impact of Vomiting Episodes on Outcome after Acetaminophen Poisoning

Identifying indices of poor prognosis at first presentation after acetaminophen poisoning is the key to both improving clinical care and determining targets for intervention. This study intended to document the prevalence, clinical characteristics and predictors of vomiting and to investigate the relationship between episodes of vomiting at first hospital presentation and outcome in acetaminophen poisoning. This retrospective cohort study included patients who attended the emergency department and were admitted within 24 hr of acetaminophen ingestion. The study was conducted over a period of 5 years from 1 January 2004 to 31 December 2008. Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. SPSS 15 was used for data analysis. Data from 291 patients were included. Vomiting was present in 65.3% of patients with acetaminophen poisoning at the time of first presentation. Multiple logistic regression showed that significant risk factors for vomiting were present among patients who reported an ingested dose of acetaminophen ≥10 g (p < 0.001) and a latency time of more than 8 hr (p = 0.030). Overall, an increasing trend in prothrombin time (p = 0.03), serum bilirubin (p < 0.001), serum creatinine (p = 0.005), serum potassium (p < 0.001), length of hospital stay (p < 0.001) and the prevalence of patients who had a serum acetaminophen level above a 'possible toxicity' treatment line (p = 0.001) were associated with an increased number of episodes of vomiting. In conclusion, vomiting was common among patients with acetaminophen poisoning. This study suggests that an increase in episodes of vomiting at first presentation appears to be an important risk marker of subsequent nephrotoxicity and hepatotoxicity.

Association between gastrointestinal manifestations following acetaminophen poisoning and outcome in 291 acetaminophen poisoning patients

Acetaminophen poisoning is a common clinical problem, and early identification of patients with more severe poisoning is key to improving outcomes. This study intends to document prevalence, clinical characteristics, and predictors of gastrointestinal (GI) manifestations and to assess the impact of these manifestations on outcome in patients with acetaminophen poisoning. This is a retrospective cohort study of hospital admissions for acute acetaminophen poisoning conducted over a period of 5 years from 1 January 2004 to 31 December 2008. Parametric and non-parametric tests were used to test differences between groups depending on the normality of the data. Statistical Package for Social Sciences (SPSS) 15 was used for data analysis. Two hundred and ninety-one patients were studied; their mean age was 23.01 +/- 7.4 years and 76.6% had GI manifestations. Multiple logistic regression showed that significant risk factors for GI manifestations were present among patients who reported acetaminophen dose ingested >or=10 g (p < 0.001), and latency time more than 8 hours (p = 0.030). GI manifestations at first admission predicted poorer outcomes in terms of estimated acetaminophen levels to be a possible toxic (p < 0.001), elevated bilirubin levels (p = 0.002), prolonged prothrombin time (PT; p = 0.002), elevated creatinine level (p = 0.028), declination of potassium level (p < 0.001), and prolonged hospital stay (p < 0.001). GI manifestations were common among patients with acetaminophen poisoning. This study suggests that the presence of GI manifestations at first presentation appears to be an important risk marker of subsequent hepatotoxicity and nephrotoxicity.