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Angostura trifoliata (Willd) T.S. Elías (Rutaceae) es una planta, cuya corteza es empleada en Venezuela para el tratamiento de la diabetes mellitus, la malaria y la disminución de peso. Sin embargo, se ha demostrado que altas dosis de su extracto administrados en forma aguda producen hiperglicemia y alteraciones neurológicas. El objetivo de este estudio fue correlacionar los efectos histológicos a nivel hepático y renal en ratones sanos con la hiperglicemia aguda producida por el extracto de la corteza de esta planta. Métodos: Se realizó un estudio experimental in vivo utilizando el extracto diluido en agua y administrado vía ip a dosis de 452 y 700 mg/kg; se determinó la glicemia utilizando un glucómetro comercial; los efectos histológicos con hematoxilina eosina previa fijación de los órganos con formaldehído al 10%. En todos los casos, se comparó con el grupo control. Resultados: el extracto produjo hiperglicemia significativamente P<0,05. En el tejido hepático causó: pérdida parcial de su arquitectura, binucleación, vasos congestivos con elementos inflamatorios, núcleos hipercromáticos, espacios de Disse dilatados con hematíes y áreas de necrosis. En el riñón originó congestión vascular en los tubos contorneados proximales y distales, concomitante con ruptura y necrosis de la membrana basal. Conclusión: el extracto produce toxicidad hepática y renal que se correlacionan con hiperglicemia, por lo que podría ser considerado como un agente hepatotóxico y nefrotóxico. (AU)

Angostura trifoliata (Willd) T.S. Elías (Rutaceae) is a plant, whose bark is used in Venezuela for the treatment of diabetes mellitus, malaria and weight loss. However, it has been shown that high doses of its extract administered acutely produce hyperglycemia and neurological alterations. The objective of this study was to correlate the histological effects at the liver and kidney level in healthy mice with the acute hyperglycemia produced by the bark extract of this plant. Methods: An in vivo experimental study was carried out using the extract diluted in water and administered ip at doses of 452 and 700 mg/kg; blood glucose was determined using a commercial glucometer; the histological effects with hematoxylin eosin after fixation of the organs with 10% formaldehyde. In all cases, it was compared with the control group. Results: the extract produced hyperglycemia significantly P<0.05. In the liver tissue it caused: partial loss of its architecture, binucleation, congested vessels with inflammatory elements, hyperchromatic nuclei, dilated spaces of Disse with red blood cells and areas of necrosis. In the kidney, it caused vascular congestion in the proximal and distal convoluted tubes, concomitant with rupture and necrosis of the basement membrane. Conclusion: the extract produces liver and kidney toxicity that correlates with hyperglycemia, so it could be considered a hepatotoxic and nephrotoxic agent. (AU)

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Background: Critically ill children are vulnerable to acute kidney injury (AKI) and are often exposed to nephrotoxic medications. Objectives: We aimed to investigate the association between nephrotoxic medications and the risk of AKI in critically ill children admitted to our paediatric intensive care unit (PICU). Methods: Patients aged > 1 month to ≤18 years old were prospectively recruited from 6/2020 to 6/2021. The medication records from 14 days prior to PICU admission to PICU discharge were reviewed. Medication-exposure intensity was defined as the number of concomitant nephrotoxic medications. The relative risk (RR) of nephrotoxic medication exposure indices and other potential predictors for AKI development were determined. Results: Altogether 253 episodes of admissions (median [IQR] age of 4.9 [9.6] years) were enrolled. The AKI incidence was 41.9% and 69.2% of the patients were exposed to ≥1 of the 47 nephrotoxic medications. The total nephrotoxic medication dose (RR: 1.01 [1.00, 1.02]) and medication-exposure intensity (RR: 1.381 [1.101, 1.732]) were significantly associated with AKI development. The risk of AKI increased when the medication-exposure intensity was ≥4 (RR: 3.687 (1.320, 10.301)). During their PICU stay, children with AKI received a higher number (P < .01), total dose (P < .01) and medication exposure intensity (P < .01) of nephrotoxic medications. Children with AKI who received nephrotoxic medications were more likely to have a persistently higher peak-to-baseline ratio (P = .046). Conclusion: Nephrotoxic medication exposure significantly increased the risk of AKI development among critically ill children. The use of nephrotoxic medications among critically ill children at risk for AKI should be monitored frequently.

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Acute kidney injury (AKI) is associated with long-term consequences and poor outcomes in the neonatal intensive care unit. Its precocious diagnosis represents one of the hardest challenges in clinical practice due to the lack of sensitive and specific biomarkers. Currently, neonatal AKI is defined with urinary markers and serum creatinine (sCr), with limitations in early detection and individual treatment. Biomarkers and risk factor scores were studied to predict neonatal AKI, to early identify the stage of injury and not the damage and to anticipate late increases in sCr levels, which occurred when the renal function already began to decline. Sepsis is the leading cause of AKI, and sepsis-related AKI is one of the main causes of high mortality. Moreover, preterm neonates, as well as patients with post-neonatal asphyxia or after cardiac surgery, are at a high risk for AKI. Critical patients are frequently exposed to nephrotoxic medications, representing a potentially preventable cause of AKI. This review highlights the definition of neonatal AKI, its diagnosis and new biomarkers available in clinical practice and in the near future. We analyze the risk factors involving patients with AKI, their outcomes and the risk for the transition from acute damage to chronic kidney disease.

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Systemic lupus erythematosus is an autoimmune disease that results in immune-mediated damage to kidneys and other organs. We investigated the role of response gene to complement-32 (RGC-32), a proinflammatory and profibrotic mediator induced by TGFß and C5b-9, in nephrotoxic nephritis (NTN), an experimental model that mimics human lupus nephritis. Proteinuria, loss of renal function and kidney histopathology were attenuated in RGC-32 KO NTN mice. RGC-32 KO NTN mice displayed downregulation of the CCL20/CCR6 and CXCL9/CXCR3 ligand/receptor pairs resulting in decreased renal recruitment of IL-17+ and IFNγ+ cells and subsequent decrease in the influx of innate immune cells. RGC-32 deficiency attenuated renal fibrosis as demonstrated by decreased deposition of collagen I, III and fibronectin. Thus, RGC-32 is a unique mediator shared by the Th17 and Th1 dependent proinflammatory and profibrotic pathways and a potential novel therapeutic target in the treatment of immune complex mediated glomerulonephritis such as lupus nephritis.

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PURPOSE: Polymyxin B, with its unique structure and mechanism of action, has emerged as a key therapeutic agent against Gram-negative bacteria. The study aims to explore potential factors to influence its effectiveness and safety. METHODS: A model-based meta-analysis of 96 articles was conducted, focusing on factors like dosage, bacterial species, and combined antibiotic therapy. The analysis evaluated mortality rates and incidence rate of renal dysfunction, also employing parametric survival models to assess 30-d survival rates. RESULTS: In the study involving 96 articles and 9716 patients, polymyxin B's daily dose showed minimal effect on overall mortality, with high-dose group mortality at 33.57% (95% confidence intervals [CI]: 29.15-38.00) compared to the low-dose group at 35.44% (95% CI: 28.99-41.88), P = 0.64. Mortality significantly varied by bacterial species, with Pseudomonas aeruginosa infections at 58.50% (95% CI: 55.42-63.58). Monotherapy exhibited the highest mortality at 40.25% (95% CI: 34.75-45.76), P < 0.01. Renal dysfunction was more common in high-dose patients at 29.75% (95% CI: 28.52-30.98), with no significant difference across antibiotic regimens, P = 0.54. The 30-d overall survival rate for monotherapy therapy was 63.6% (95% CI: 59.3-67.5) and 70.2% (95% CI: 64.4-76.2) for association therapy with ß-lactam drugs. CONCLUSIONS: The dosage of polymyxin B does not significantly change death rates, but its effectiveness varies based on the bacterial infection. Certain bacteria like P. aeruginosa are associated with higher mortality. Combining polymyxin B with other antibiotics, especially ß-lactam drugs, improves survival rates. Side effects depend on the dose, with lower doses being safer. These findings emphasize the importance of customizing treatment to balance effectiveness and safety.

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Acute kidney injury (AKI) is a common medication adverse event, particularly in patients with pre-existing medical conditions taking nephrotoxic medications. However, little is known about the differences in the risk of nephrotoxic medication-related complications in children with autism spectrum disorder (ASD) compared to the general pediatric population. A nine-year-old non-verbal boy with ASD was hospitalized for scrotal cellulitis requiring vancomycin and piperacillin/tazobactam due to a lack of clinical response to cephalosporins. His history is significant for being an extremely selective eater, and his appetite decreased over four months prior to presentation. Poorly controlled scrotal pain, despite acetaminophen use, was suspected based on his facial expressions and maternal assessment, especially considering his non-verbal status. Consequently, a non-steroidal anti-inflammatory drug was initiated. The hospital course was complicated by the development of a scrotal abscess, minimal enteral intake, hypoalbuminemia-induced intravascular dehydration, oliguria, and generalized edema. His creatinine increased to 5.11 mg/dL from 0.51 mg/dL despite early discontinuation of nephrotoxic medications and fluid resuscitation, which led to hemodialysis due to worsening AKI. Subsequently, urinary output and edema improved. Creatinine improved to <1 mg/dL with careful creatinine monitoring and concomitant furosemide and albumin infusion in the pediatric intensive care unit. Children with comorbidities, such as malnutrition, who require nephrotoxic medications, need extra attention. Implementing clinical decision support tools or quality improvement programs can promote the prevention of nephrotoxic medication exposure and decrease the incidence of AKI. An alert within an electronic health record system for multiple nephrotoxic drugs and daily multidisciplinary huddles during patient-centered rounds could help reduce and eliminate adverse events. In particular, for non-verbal patients or those with limited communication skills, such as children with ASD, rigorous and close monitoring of vital signs, physical condition, pain, medication intake, and lab results, in addition to a nephrotoxic medication screening and notification system, should be key to optimizing patient care.

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Background: With the development of healthcare services, drug efficacy, and safety have become the focus of drug use, and processing alters drug toxicity and efficacy, exploring the effects of processing on Evodiae fructus (EF) can guide the clinical use of drugs. Methods: Fifty male Kunming mice were randomly divided into the control group (CCN), raw small-flowered EF group (CRSEF), raw medium-flowered EF group (CRMEF), processing small-flowered EF group (CPSEF), and processing medium-flowered EF group (CPMEF). The CRSEF, CRMEF, CPSEF, and CPMEF groups were gavaged with aqueous extracts of raw small-flowered EF dry paste (RSEF), medium-flowered EF dry paste (RMEF), processing small-flowered EF dry paste (PSEF) and processing medium-flowered EF dry paste (PMEF), respectively, for 21 days at 5 times the pharmacopeial dosage. Upon concluding the experiment, histopathological sections of liver and kidney tissues were examined. Additionally, levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), serum creatinine (SCr), and blood urea nitrogen (BUN) were determined. DNA from the intestinal contents of the mice was extracted, and 16S rRNA full-length high-throughput sequencing was performed. Results: After fed EF 21 days, mice exhibited a decreasing trend in body weight. Comparative analysis with the CCN group revealed an upward trend in SCr, BUN, AST, and ALT levels in both CRSEF and CRMEF groups. The CRMEF group displayed notably elevated BUN and AST levels, with an observed increasing trend in Scr and ALT. Kidney sections unveiled cellular edema and considerable inflammatory cell infiltrates, whereas significant liver damage was not evident. Compared with CRSEF, Bun levels were significantly lower while AST levels were significantly higher in the CPMEF group. Additionally, the intestinal microbiota diversity and the relative abundance of Psychrobacter decreased significantly, and the relative abundance of Staphylococcus, Jeotgalicoccus, and Salinicoccus increased significantly in the CPMEF group. AST, ALT, and SCr were positively correlated with Staphylococcus, Jeotgalicoccus, and Salinicoccus. Conclusion: In conclusion, PMEF significantly increased harmful bacteria (Staphylococcus, Jeotgalicoccus, and Salinicoccu) and decreased beneficial bacteria. SEF with 5 times the clinical dose showed nephrotoxicity and SEF nephrotoxicity decreased after processing, but EF hepatotoxicity was not significant, which may be due to insufficient dose concentration and time.

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Background: Nephrotoxic drugs may hasten the decline in kidney function and worsen the progression of renal impairment as a result; these drugs should be avoided or used with caution in patients with pre-existing renal insufficiency. The purpose of this study was to assess the burden of nephrotoxic medication use and its predictors among patients with underlying renal impairment. Methods: A multicenter, institution-based, cross-sectional study was conducted from May 30, 2021 to July 30, 2021, at medical wards. Renal impaired patients admitted during the data collection period who took at least one medication were enrolled in the study. A simple random sampling technique was used to select the study participants. Data was collected through an interview and a medical card review. Both bivariable and multivariable binary logistic regression analyses were fitted to identify factors associated with nephrotoxic drug use. Results: Among the 422 participants, more than half of them (53.6 %) were male. The mean patient's age was 47.5 (±16.7) years. A total of 1310 drugs were prescribed for 422 patients with renal impairment, of which 80.15 % were nephrotoxic. Nephrotoxic drugs were prescribed for 66.4 % of patients. The burden of nephrotoxic medication prescription was significantly associated with variables like the presence of comorbidity (AOR = 6.31, 95 % CI: 2.01-19.79), the number of medications prescribed (AOR = 1.43, 95 % CI: 1.05-1.93), and the age of participants (AOR = 1.12, 95 % CI: 1.07-1.17). Conclusion: The present study demonstrated that two-third of the patients with renal impairment were exposed to nephrotoxic medications. Furosemide, Enalapril, and vancomycin were the most frequently prescribed nephrotoxic medications. The study suggests that prescribers need to give special attention to older patients who have underlying renal insufficiency, a comorbid condition, and polypharmacy regarding exposure to contraindicated nephrotoxic medication.

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BACKGROUND: We assessed the incidence of and risk factors for acute kidney injury (AKI) in very low birthweight infants (VLBW) in a center with a specific neonatal management protocol focusing on avoidance of early mechanical ventilation (MV). METHODS: This retrospective single center analysis includes 128 infants born in 2020 with a gestational age ≥ 22 weeks who were screened for AKI using the nKDIGO criteria. RESULTS: AKI was identified in 25/128 patients (19.5%) with eight of them (6.3%) presenting with severe AKI. Low gestational age, birthweight and 10-minute Apgar score as well as high CRIB-1 score were all associated with incidence of AKI. Forty-five percent of the infants with MV developed AKI vs. 8.9% of those without MV (p < 0.001). Early onset of MV and administration of more than 3 dosages of NSAIDs for patent duct were identified as independent risk factors for AKI in a logistic regression analysis. CONCLUSIONS: We report a substantially lower frequency of AKI in VLBW infants as compared to previous studies, along with a very low rate of MV. A neonatal protocol focusing on avoidance of MV within the first days of life may be a key factor to decrease the risk of AKI in immature infants.

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Amaranthus spp. is a nephrotoxic plant with unknown toxic principle, affecting production animals worldwide, mainly in South America. The aim of this paper is to describe 5 spontaneous outbreaks of A. hybridus intoxication in beef cattle, where 7 autopsies were performed. Main gross findings were pale diffuse and enlarged kidneys. Microscopically, kidneys were characterized by severe tubular acute to subacute nephrosis, with dilatated tubules showing different degrees of epithelial degeneration and necrosis, and containing intraluminal eosinophilic hyaline casts. Intratubular birefringent crystals, compatible with oxalate, were observed under polarized light in kidneys from 3 autopsies. Positive von Kossa and red alizarin S staining confirmed the intratubular crystals as calcium deposits. This intoxication occurs mainly in stubble paddocks during summer and early autumn. The data from the present study suggests that oxalates were related to nephrotoxicity due to Amaranthus consumption.

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INTRODUCTION: Nephrotoxic medication (NTM) exposure is commonly associated with acute kidney injury (AKI) in the neonatal intensive care unit (NICU). Baby Nephrotoxic Injury Negated by Just-in-Time Action (NINJA) is a quality improvement program that assesses for AKI in those exposed to NTM with daily serum creatinine (SCr) levels. However, blood draws for SCr are invasive and have clinical disadvantages. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a promising indicator of AKI. We tested the hypothesis that uNGAL could reliably screen for NTM-AKI in the Baby NINJA program. METHODS: This two-center prospective study screened 174 NICU subjects, of whom 148 met screening criteria from January 29, 2019, to September 18, 2020. Daily SCr and urine samples were obtained for up to 7 days of NTM exposure plus 2 days after exposure ended or end of AKI. AKI was defined by a SCr rise of 50% from baseline. The highest uNGAL obtained was evaluated to determine its relationship to the diagnosis of AKI. Logistic regression models were used to determine optimal uNGAL cutoffs. RESULTS: The negative predictive value of a uNGAL value ≥250 ng/mL was 96.8% (95% CI = 93.3-100%). Urine NGAL ≥400 ng/mL demonstrated the highest ROC-AUC value of 0.72 with a positive likelihood risk for AKI of 2.76 (1.39-4.13). DISCUSSION/CONCLUSION: We propose that uNGAL could be used to screen for NTM-AKI and thus replace many blood draws needed in those exposed to NTM. The ideal uNGAL threshold requires further investigation in infants.

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OBJECTIVE: To determine whether greater duration of simultaneous exposure to antimicrobials with high nephrotoxicity risk combined with lower-risk antimicrobials (simultaneous exposure) in the neonatal intensive care unit (NICU) is associated with worse later kidney health in adolescents born preterm with very low birth weight (VLBW). STUDY DESIGN: Prospective cohort study of participants born preterm with VLBW (<1500 g) as singletons between January 1, 1992, and June 30, 1996. We defined simultaneous exposure as a high-risk antimicrobial, such as vancomycin, administered with a lower-risk antimicrobial on the same date in the NICU. Outcomes were serum creatinine, estimated glomerular filtration rate (eGFR), and first-morning urine albumin-creatinine ratio (ACR) at age 14 years. We fit multivariable linear regression models with days of simultaneous exposure and days of nonsimultaneous exposure as main effects, adjusting for gestational age, birth weight, and birth weight z-score. RESULTS: Of the 147 out of 177 participants who had exposure data, 97% received simultaneous antimicrobials for mean duration 7.2 days (SD 5.6). No participant had eGFR <90 ml/min/1.73 m2. The mean ACR was 15.2 mg/g (SD 38.7) and 7% had albuminuria (ACR >30 mg/g). Each day of simultaneous exposure was associated only with a 1.04-mg/g higher ACR (95% CI 1.01 to 1.06). CONCLUSIONS: Despite frequent simultaneous exposure to high-risk combined with lower-risk nephrotoxic antimicrobials in the NICU, there were no clinically relevant associations with worse kidney health identified in adolescence. Although future studies are needed, these findings may provide reassurance in a population thought to be at increased risk of chronic kidney disease.

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OBJECTIVE: This study aims to clarify the risk of nephrotoxicity with intravenous use of acyclovir (ACV) for the treatment of neonates (ages <3 months) and children (ages ≥3 months to <12 years) with herpes simplex virus (HSV) infections and to identify gaps in knowledge that could be further investigated. METHODS: Multiple databases were searched to identify studies on risk of nephrotoxicity with ACV use for treatment of invasive HSV infections, defined as any neonatal infection or HSV encephalitis (HSE) in children. RESULTS: There were 5 and 14 studies that evaluated the risk of ACV-associated nephrotoxicity in neonates and children, respectively. The US Food and Drug Administration (FDA) delayed the approval of high (HD; 60 mg/kg/day) ACV in neonates secondary to risk of toxicity. Based on our review, the risk of ACV-associated nephrotoxicity was lower in the neonatal compared with the pediatric population. Acyclovir dose >1500 mg/m2, older age, and concomitant use of nephrotoxic drugs were identified as variables that increased the risk of ACV nephrotoxicity in children. Although the FDA has approved the use of HD ACV for the treatment of HSE in children, the American Academy of Pediatrics recommends a lower dose to minimize the risk of toxicity. The efficacy and safety of high vs lower doses of ACV for the management of HSE in children has yet to be evaluated. CONCLUSIONS: The risk of ACV-associated nephrotoxicity was lower among neonates compared with older children. Future studies are needed to identify the optimal dosage that minimizes toxicities and maximizes the efficacy of ACV in children with HSE.

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Acute kidney injury (AKI) is a common complication among patients admitted to the neonatal intensive care unit. Nephrotoxic medications (NTMs) are known to increase the incidence of AKI, but the use of these -medications is often unavoidable. Baby NINJA (Nephrotoxic Injury Negated by Just-in-Time Action) is a -quality improvement (QI) project that may be implemented at individual institutions and aims to systematically identify AKI in neonates and infants receiving NTMs. The purpose of this review is to describe nephrotoxic AKI in the neonatal population, introduce the Baby NINJA QI project and its potential to reduce neonatal AKI, and outline strategies for effective implementation of Baby NINJA.

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Population declines of Gyps vultures throughout South Asia were caused by unintentional poisoning by the NSAID diclofenac, which was subsequently banned. However, other vulture-toxic NSAIDs are available, including nimesulide, which, in experiments carried out in South Africa, was shown to be toxic to Gyps vultures. We report on safety-testing of nimesulide carried out on Himalayan Griffons G. himalayensis. We gave two vultures a dose of nimesulide by oral gavage at the maximum level of exposure, with two controls dosed with benzyl alcohol. In the two tested birds, plasma nimesulide concentrations peaked after six hours, while serum uric acid concentrations increased steadily up until 24 h post-treatment, after which both birds died, displaying severe visceral gout. The control birds showed no adverse clinical or biochemical signs. We confirm that nimesulide is toxic to Gyps vultures. Veterinary use of nimesulide should be banned in all Gyps vulture range countries in the region.

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OBJECTIVES: Polymyxin is the last line of defense against resistant forms of microorganisms, but it has significant nephrotoxicity. One of the directions in reducing the nephrotoxicity of polymyxin is to modify the charge of the molecule and accordingly, to change the topicity of the polymyxin derivative to the renal megalin. Such modification can lead to a decrease in the accumulation of polymyxin in the kidneys and reduce its toxicity while maintaining its antimicrobial properties. The study aimed to investigate the structural aspects of polymyxin nephrotoxicity at the atomic level to promote the more purposeful development of the polymyxin's derivatives with the lower nephrotoxic action. MATERIALS AND METHODS: The molecular dynamics simulations of the complexes of polymyxin B and its derivative NAB7061 (that carries only three positive charges located within the macrocycle) with megalin were performed in program package YASARA structure with explicit water (TIP3P) and ions (0.9 % NaCl) in NPT ensemble using the AMRER03 force field. After 10 ns equilibration, each system was simulated at 298 K and pH 7.4 for a 25 ns production phase. Simulations were run twice for each molecular system. RESULTS: By molecular dynamics simulations, the possibility was shown for polymyxin to form a stable complex with two neighbor structural domains of megalin in accord with the universal mechanism of binding the cationic ligands by ligand-binding CR repeats of the LDLR-family receptors. It was reported that interactions of megalin with polymyxin were stronger than with its derivative having no positively charged groups outside the macrocycle. The structural prerequisites of these differences were revealed, explaining the less nephrotoxicity of such derivatives compared to polymyxin. CONCLUSION: Comparative molecular dynamics simulations of megalin interactions with polymyxin B and its derivative NAB7061, which carries no positive charges outside the macrocycle, revealed the possible structural prerequisites for the lower nephrotoxic action of such polymyxin derivatives. The weakening of polymyxins binding with megalin may become an effective preventive measure against polymyxin-induced nephrotoxicity.

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OBJECTIVE: To describe a population of horses with acute kidney injury (AKI) following administration of bisphosphonates including clinical signs, clinicopathologic data, treatment, and outcome. DESIGN: Retrospective study from August 2013 to July 2020. SETTING: Veterinary university teaching hospital. ANIMALS: Eight adult horses with AKI following administration of nonnitrogenous bisphosphonates. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Five horses received intramuscular clodronate (5/8; 62.5%) and 3 horses received intravenous tiludronate (3/8; 37.5%). Six horses (6/8; 75%) received concurrent nonsteroidal anti-inflammatory drugs. The most common initial presenting complaint was poor appetite (6/8; 75%), followed by abnormal urination (2/8; 25%). At the time of initial evaluation, the mean serum or plasma creatinine was 451.72 ± 190.06 µmol/L (5.11 ± 2.15 mg/dL) and BUN was 18.84 ± 8.85 mmol/L (52.75 ± 24.77 mg/dL). Five horses (5/6; 83.3%) had either an increased number of red blood cells (n = 4) or hemoprotein (n = 1) in the urine. All horses were treated with IV isotonic, balanced crystalloids either as a bolus, continuous rate infusion, or a combination of the 2. Seven horses (7/8; 87.5%) survived the initial episode of AKI and 1 horse (1/8; 12.5%) was euthanized. Of the 7 surviving horses, 2 horses (2/7; 28.5%) went on to develop chronic renal dysfunction. Warmblood breeds were overrepresented in the AKI group (P = 0.008; odds ratio: 11.5, 95% confidence interval: 1.8-72.1), when compared to horses that received bisphosphonates during the study period and did not develop AKI. CONCLUSIONS: Bisphosphonate administration, with or without concurrent nonsteroidal anti-inflammatory drugs, can be associated with AKI in horses. Serum creatinine should be monitored prior to and following bisphosphonate treatment to minimize this risk. Further evaluation of renal function is warranted in horses that develop clinical signs of poor appetite, lethargy, or altered urination in the days following bisphosphonate treatment.

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Adverse reactions to traditional Chinese medicine have hindered the healthy development and internationalization process of the traditional Chinese medicine industry. The critical issue that needs to be solved urgently is to evaluate the safety of traditional Chinese medicine systematically and effectively. Podophyllotoxin (PPT) is a highly active compound extracted from plants of the genus Podophyllum such as Dysosma versipellis (DV). However, its high toxicity and toxicity to multiple target organs affect the clinical application, such as the liver and kidney. Based on the concurrent effects of PPT's medicinal activity and toxicity, it would be a good example to conduct a systematic review of its safety. Therefore, this study revolves around the Toxicological Evidence Chain (TEC) concept. Based on PPT as the main toxic constituent in DV, observe the objective toxicity impairment phenotype of animals. Evaluate the serum biochemical indicators and pathological tissue sections for substantial toxic damage results. Using metabolomics, lipidomics, and network toxicology to evaluate the nephrotoxicity of PPT from multiple perspectives systematically. The results showed that PPT-induced nephrotoxicity manifested as renal tubular damage, mainly affecting metabolic pathways such as glycerophospholipid metabolism and sphingolipid metabolism. PPT inhibits the autophagy process of kidney cells through the PI3K/Akt/mTOR and Nrf2/HO1 pathways and induces the activation of oxidative stress in the body, thereby causing nephrotoxic injury. This study fully verified the feasibility of the TEC concept for the safety and toxicity evaluation of traditional Chinese medicine. Provide a research template for systematically evaluating the safety of traditional Chinese medicine.

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There has been increased use of cefepime due to concerns about the nephrotoxic effects of the combined use of vancomycin and Zosyn. However, cefepime is associated with neurotoxicity. We conducted a systematic review using online data to explore the trend of cefepime-induced neurotoxicity over the last 10 years. Forty-six articles met our inclusion criteria, including 73 cases of cefepime-induced neurotoxicity. We noticed a steady increase in the reports of cefepime-induced neurotoxicity, from one case in 2013 to 11 cases in 2022. Individuals aged 65 and older accounted for most cefepime-induced neurotoxicity cases (52%). The top three indications for cefepime administration included bone and joint infections (25%), urinary tract infections (22.7%), and pneumonia (22.7%). Most patients with renal impairment have never had a renal adjustment of their cefepime dosage (either 2 g 12 hours a day or 2 g eight hours a day). Most cases of cefepime-induced neurotoxicity occurred between days two and five (n=29, 71%), while most resolution occurred between days one and five (n=29, 85%). While cefepime continues to be a popularly used and effective antibiotic against gram-negative bacteria like Pseudomonas aeruginosa, its dosage needs to be adjusted in patients with renal impairment to avoid neurotoxicity.

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Calcineurin inhibitors (CNI) are the mainstay of immunosuppressant medications in both bone marrow transplants and solid organ transplants. Nephrotoxicity is a well-known adverse effect of this group. Type IV renal tubular acidosis is a potentially under-recognized complication. Here we report a case of Omenn syndrome in a patient who underwent a bone marrow transplant and developed type IV renal tubular acidosis while on treatment with cyclosporine.