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1.
Medicine (Baltimore) ; 99(42): e22509, 2020 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-33080685

RESUMO

INTRODUCTION: Proton pump inhibitors (PPIs) are widely prescribed and generally well tolerated but can rarely cause severe allergic reactions, such as drug rash with eosinophilia and systemic symptoms (DRESS). We report a case of DRESS and renal injury induced by PPIs, and describe the therapeutic process. PATIENT CONCERNS: The patient was a 66-year-old female who complained of fever, pruritus, desquamation, erythema multiforme, and anuria caused by omeprazole taken for 2 weeks to treat abdominal distention. DIAGNOSIS: The clinical history revealed a similar episode of PPI-induced fever, eosinophilia, and acute kidney injury more than 1 year ago. The present laboratory tests revealed eosinophilia and oliguric renal failure. The renal biopsy was performed subsequently and proved the diagnosis of PPI-induced DRESS. INTERVENTIONS: After the suspected diagnosis of PPI-induced DRESS, omeprazole was discontinued and methylprednisolone infusion (40 mg qd) was initiated. Because of oliguric renal failure, the patient received intermittent hemodialysis. OUTCOMES: The patient initially responded to omeprazole discontinuation, hemodialysis, and glucocorticoids but later died from severe infection during the tapering of glucocorticoid therapy. CONCLUSION: Clinicians should remain on high alert for potential life-threatening complications when prescribing PPIs. If unexplained renal injury develops in a patient taking a PPI, renal biopsy may help in identifying the pathogenesis and might facilitate timely intervention.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Síndrome de Hipersensibilidade a Medicamentos/etiologia , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Idoso , Evolução Fatal , Feminino , Humanos
2.
J Pharmacol Sci ; 144(4): 229-236, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33070842

RESUMO

The kidneys are the major organs for erythropoietin (EPO) production in adults, and thus, kidney damage results in reduced EPO levels and anemia. Inhibitors of Hypoxia-inducible factor-prolyl hydroxylase domain-containing protein (HIF-PHD) are awaited as new therapeutic options for renal anemia. It can be predicted that most patients who receive HIF-PHD inhibitors have renal dysfunction as a cause of anemia. Therefore, in the present study, we investigated the effects of the HIF-PHD inhibitor molidustat on anemia and renal dysfunction when initiated after the onset of renal anemia. Male C57BL/6J mice received adenine orally to induce nephropathy. After the onset of nephropathy, the mice were treated with either vehicle or molidustat. After 4 weeks of administration, vehicle-treated mice displayed significant anemia, and molidustat ameliorated this anemia. Vehicle-treated mice exhibited reduced creatinine clearance and body weight, increased blood urea nitrogen levels, histopathological changes, immune cell infiltration, and dehydration. Molidustat reversed immune cell infiltration, dehydration, and renal fibrosis without improving renal functional parameters. In conclusion, molidustat treatment initiated after the onset of nephropathy and renal anemia reversed anemia in mice. Molidustat improved some parameters of renal abnormality, but it did not restore renal function.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/complicações , Adenina/efeitos adversos , Anemia/tratamento farmacológico , Anemia/etiologia , Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Inibidores de Prolil-Hidrolase , Pirazóis/uso terapêutico , Triazóis/uso terapêutico , Lesão Renal Aguda/metabolismo , Animais , Modelos Animais de Doenças , Eritropoetina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Pirazóis/administração & dosagem , Pirazóis/farmacologia , Triazóis/administração & dosagem , Triazóis/farmacologia
3.
J Oleo Sci ; 69(9): 1107-1115, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32879198

RESUMO

Medicinal plants and their secondary metabolites have long been a rich source of biologically active compounds that can prevent many diseases. In this context, we investigated the antioxidant activities of the essential oil of Lavandula officinalis and tested its potency against hepatic and renal toxicity induced by hydrogen peroxide in adult male mice based on measurements of biochemical parameters, oxidative stress, and tissue damage in both organs. We proved a remarkable antioxidant power of this plant (in vitro) by correcting the harmful effects of the prooxidant (in vivo). It can be concluded that lavender is an aromatic plant capable of reducing the stress caused by reactive oxygen species.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/tratamento farmacológico , Antioxidantes , Doença Hepática Induzida por Substâncias e Drogas/tratamento farmacológico , Peróxido de Hidrogênio/toxicidade , Lavandula/química , Óleos Voláteis/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fitoterapia , Folhas de Planta/química , Animais , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Feminino , Técnicas In Vitro , Masculino , Camundongos , Óleos Voláteis/isolamento & purificação , Óleos Voláteis/uso terapêutico , Espécies Reativas de Oxigênio/metabolismo
4.
Toxicol Lett ; 334: 21-26, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32910981

RESUMO

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.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , MicroRNAs , Ácido Oxálico/envenenamento , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/genética , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Coortes , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , MicroRNAs/sangue , MicroRNAs/urina
5.
Medicine (Baltimore) ; 99(37): e21386, 2020 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-32925711

RESUMO

Serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) are standard biomarkers of contrast-induced nephropathy (CIN). However, recent studies suggest that serum neutrophil gelatinase-associated lipocalin (sNGAL) and urine neutrophil gelatinase-associated lipocalin (uNGAL) may be better predictors, particularly within 24 hours of contrast medium exposure.We conducted a prospective, observational cohort study of 107 consecutive patients diagnosed with arteriosclerosis obliterans between February 2016 and October 2018. We divided the patients into 2 groups: CIN (n = 22) and non-CIN (n = 85). We assessed the correlation between sNGAL and uNGAL concentrations and standard renal markers at baseline, 6, 24, and 48 hours post-procedure. We constructed conventional receiver operating characteristic (ROC) curves and calculated the area under the curve to assess the performance of SCr, eGFR, sNGAL, and uNGAL. We derived biomarker cutoff levels from ROC analysis to maximize sensitivity and specificity.The incidence of CIN within our cohort was 20.6%. sNGAL levels correlated significantly with SCr and eGFR at baseline, 6, 24, and 48 hours post-contrast medium exposure. Similarly, uNGAL levels correlated with SCr and eGFR at baseline, 24, and 48 hours post-exposure. sNGAL and uNGAL were significantly elevated as early as 6 hours post-catheterization in the CIN group, whereas only minor changes were observed in the non-CIN group. SCr was also significantly elevated in the CIN group, but not until 24 hours post-catheterization.Both sNGAL and uNGAL may be superior to SCr and eGFR as early biomarkers of CIN in patients with peripheral vascular disease undergoing endovascular therapy.


Assuntos
Lesão Renal Aguda/diagnóstico , Meios de Contraste/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Lipocalina-2/análise , Complicações Pós-Operatórias/diagnóstico , Lesão Renal Aguda/induzido quimicamente , Idoso , Área Sob a Curva , Arteriosclerose Obliterante/cirurgia , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Masculino , Complicações Pós-Operatórias/induzido quimicamente , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade
6.
Chem Biol Interact ; 331: 109233, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32991863

RESUMO

Cisplatin (cis-Dichlorodiammine platinum, CP), as the first-line chemotherapy drug of choice for many cancers such as urogenital system tumors and digestive tract tumors, also causes toxicity and side effects to the kidney. Previous studies have shown that Pulsatilla chinensis has significant anti-inflammatory and antioxidant activities, but the mechanism of cisplatin induced acute kidney injury (AKI) in vivo has not been thoroughly studied. The purpose of this study is to investigate the protective effect of pulchinenoside B4 (PB4), a representative and major component with a content of up to 10% in root of P. chinensis, on AKI induced by CP in mice. Our results indicated the significant protective effect of PB4 by evaluating renal function indicators, inflammatory factor levels and renal histopathological changes. In addition, PB4 may mainly act on NF-κB signaling pathway to reduce the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in the kidney after CP exposure, thus exerting anti-inflammatory activity. Furthermore, PB4 regulated MAPK signaling pathway and its downstream apoptotic factors to inhibit the occurrence of apoptosis, such as Bax, Bcl-2, caspase 3 and caspase 9. Notably, the activations of caspase 3 induced by cisplatin were strikingly reduced in PB4-treated mice. Therefore, the above evidence suggested that PB4 is a potential renal protectant with significant anti-inflammatory and anti-apoptotic effects.


Assuntos
Lesão Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/veterinária , Animais , Cisplatino/toxicidade , Modelos Animais de Doenças , Interleucina-1beta/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Fosforilação , Substâncias Protetoras/química , Fator de Necrose Tumoral alfa/metabolismo
7.
Am J Case Rep ; 21: e926464, 2020 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-32799217

RESUMO

BACKGROUND Although coronavirus disease 2019 (COVID-19) manifests primarily as a lung infection, its involvement in acute kidney injury (AKI) is gaining recognition and is associated with increased morbidity and mortality. Concurrent infection, which may require administration of a potentially nephrotoxic agent, can worsen AKI and lead to poor outcomes. Stenotrophomonas maltophilia is a multidrug-resistant gram-negative bacillus associated with nosocomial infections, especially in severely immunocompromised and debilitated patients. Trimethoprim/sulfamethoxazole combination (TMP/SMX) is considered the treatment of choice but can itself lead to AKI, posing a significant challenge in the management of patients with concomitant COVID-19 and S. maltophilia pneumonia. CASE REPORT A 64-year-old male with end-stage renal disease and post renal transplant presented with severe respiratory symptoms of COVID-19 and was intubated upon admission. His renal functions were normal at the time of admission. The patient subsequently developed superimposed bacterial pneumonia with S. maltophilia requiring administration of TMP/SMX. However, TMP/SMX led to the development of AKI, which continued to worsen despite appropriate management including hemodialysis. This coincided with and most likely resulted in the patient's clinical deterioration and ultimate death. CONCLUSIONS The etiology of kidney disease involvement in patients with COVID-19 is still evolving and appears to be multifactorial. The condition can significantly worsen especially when nephrotoxic agents are given, probably due to a cumulative or synergistic effect. Great caution should be taken when administering nephrotoxic agents in the setting of COVID-19 as it can lead to adverse patient outcomes.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Infecções por Coronavirus/complicações , Infecções por Bactérias Gram-Negativas/complicações , Pneumonia Bacteriana/microbiologia , Pneumonia Viral/complicações , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Betacoronavirus , Deterioração Clínica , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Evolução Fatal , Humanos , Hospedeiro Imunocomprometido , Transplante de Rim , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Bacteriana/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Stenotrophomonas maltophilia , Transplantados , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem
8.
N Z Med J ; 133(1519): 12-23, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32777791

RESUMO

AIM: The objective of this research is to determine community dwelling patients' awareness of temporarily discontinuing medicines during acute illness, and the actions they would undertake when acutely unwell. METHOD: Adults taking long-term oral medicines for chronic health conditions completed a four-question self-completion paper-based questionnaire collecting data requiring quantitative analysis. Recruitment occurred in six participating Hawke's Bay community pharmacies during 2017 and 2018. RESULTS: One hundred and thirty people completed the survey. Seventeen (13%) recalled receiving guidance from a health professional on which medicines to stop during excessive vomiting or diarrhoea. Only three people, however, would stop their medicines. Eighteen percent (17/95) of participants aged 65 years and older were prescribed both a NSAID and either an angiotensin-converting-enzyme inhibitor (ACEi) or angiotensin-II receptor blocker (ARB); five reported receiving advice to withhold medicines. Three participants were prescribed a Triple Whammy combination; none reported being advised to withhold medicines. CONCLUSION: A small proportion of the participants recalled receiving guidance to temporarily withhold medicines during acute illness; many indicated the advice would not be followed. The results indicate a degree of acute kidney injury prior (AKI) at-risk prescribing. There are opportunities to empower people to self-manage at-risk medicines during periods of acute illness.


Assuntos
Doença Aguda , Lesão Renal Aguda/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Educação de Pacientes como Assunto/estatística & dados numéricos , Medicamentos sob Prescrição/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Fatores de Risco
9.
J Gastrointestin Liver Dis ; 29(3): 470, 2020 09 09.
Artigo em Inglês | MEDLINE | ID: mdl-32830825
10.
Life Sci ; 259: 118284, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32798557

RESUMO

AIMS: To study how to effectively prevent or reduce renal injury caused by contrast agents in diabetic patients. MAIN METHODS: Sprague Dawley (SD) rats were bred with a high-fat diet for eight weeks, then intraperitoneally injected with Streptozotocin (STZ) to prepare the diabetes model. Rats were treated with Iodixanol to prepare a contrast-induced acute kidney injury (CIAKI) model. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, was administrated to diabetic rats with or without Rapamycin treatment. Serum creatinine (SCr) and blood urea nitrogen (BUN) were examined using Biochemical detector. Kidney injury molecule-1 (KIM-1), N-acetyl-ß-D-amino glycosidase (NAG) in urine, inflammatory and oxidative stress factors in serum were determined by ELISA. The expression level of ROS was quantified by immunofluorescence (IF). The protein expressions of Bax, BCl-2, LC3, Beclin1, mTOR and p70S6K in renal tissue were detected by Western blot. KEY FINDINGS: Rapamycin was demonstrated to improve renal injury induced by Iodixanol diabetic rats, decrease the levels of SCr, BUN, KIM-1, NAG, improve renal functions, reduce inflammatory response and oxidative stress injury, down-regulate Bax, while up-regulate BCl-2 and inhibit apoptosis. Moreover, Rapamycin could inhibit the phosphorylation of mTOR/p70S6K pathway-associated proteins, activate autophagy and increase the levels of LC3 and Beclin1. After treatment with 3MA, an inhibitor of mTOR/p70S6K signaling pathway, the protective effects of Rapamycin on CIAKI were weakened. SIGNIFICANCE: Rapamycin can alleviate renal injury induced by Iodixanol diabetic rats, and its regulatory mechanisms may be related to the regulation of mTOR/p70S6K signaling pathway and the activating autophagy.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Sirolimo/metabolismo , Sirolimo/farmacologia , Lesão Renal Aguda/induzido quimicamente , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Diabetes Mellitus Experimental/metabolismo , Rim/metabolismo , Masculino , Fosforilação , Ratos , Ratos Sprague-Dawley , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estreptozocina/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Ácidos Tri-Iodobenzoicos/farmacologia
11.
Lancet ; 396(10246): 277-287, 2020 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-32711803

RESUMO

Acute and chronic kidney disease encompasses a complex set of diseases that can both lead to, and result from, cancer. In particular, kidney disease can arise from the use of chemotherapeutic agents. Many of the current and newly developed cancer chemotherapeutic agents are nephrotoxic and can promote kidney dysfunction, which frequently manifests during the terminal stages of cancer. Given the link between kidney disease and cancer development and treatment, the aim of this Review is to highlight the importance of multidisciplinary collaboration between oncologists and nephrologists to predict and prevent chemotherapeutic-induced nephrotoxicity. As new therapies are introduced to treat cancer, new renal toxicities require proper diagnosis and management. We anticipate that multidisciplinary collaborations will lead to the development and implementation of guidelines for clinicians to improve the therapeutic management of patients with both cancer and renal impairment.


Assuntos
Antineoplásicos/efeitos adversos , Nefropatias/induzido quimicamente , Neoplasias/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Lesão Renal Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Humanos , Comunicação Interdisciplinar , Nefropatias/patologia , Nefrologistas , Oncologistas , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia
12.
PLoS One ; 15(7): e0235849, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32649695

RESUMO

Nephrotoxicity severely limits the chemotherapeutic efficacy of cisplatin (CDDP). Oxidative stress is associated with CDDP-induced acute kidney injury (AKI). Methylglyoxal (MG) forms advanced glycation end products that elevate oxidative stress. We aimed to explore the role of MG and its metabolite D-lactate and identify the proteins involved in CDDP-induced AKI. Six-week-old female BALB/c mice were intraperitoneally administered CDDP (5 mg/kg/day) for 3 or 5 days. Blood urea nitrogen (42.6 ± 7.4 vs. 18.3 ± 2.5; p < 0.05) and urinary N-acetyl-ß-D-glucosaminide (NAG; 4.89 ± 0.61 vs. 2.43 ± 0.31 U/L; p < 0.05) were significantly elevated in the CDDP 5-day group compared to control mice. Histological analysis confirmed AKI was successfully induced. Confocal microscopy revealed TNF-α was significantly increased in the CDDP 5-day group. Fluorogenic derivatized liquid chromatography-tandem mass spectrometry (FD-LC-MS/MS) showed the kidney MG (36.25 ± 1.68 vs. 18.95 ± 2.24 mg/g protein, p < 0.05) and D-lactate (1.78 ± 0.29 vs. 1.12 ± 0.06 mol/g protein, p < 0.05) contents were significantly higher in the CDDP 5-day group than control group. FD-LC-MS/MS proteomics identified 33 and nine altered peaks in the CDDP 3-day group and CDDP 5-day group (vs. control group); of the 35 proteins identified using the MOSCOT database, 11 were antioxidant-related. Western blotting confirmed that superoxide dismutase 1 (SOD-1) and parkinson disease protein 7 (DJ-1) are upregulated and may participate with MG in CDDP-induced AKI. This study demonstrates TNF-α, MG, SOD-1 and DJ-1 play crucial roles in CDDP-induced AKI.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Cisplatino/efeitos adversos , Ácido Láctico/análise , Aldeído Pirúvico/análise , Lesão Renal Aguda/metabolismo , Lesão Renal Aguda/patologia , Animais , Cromatografia Líquida , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Ácido Láctico/metabolismo , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Aldeído Pirúvico/metabolismo , Espectrometria de Massas em Tandem
13.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 32(6): 716-720, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-32684219

RESUMO

OBJECTIVE: To investigate the incidence and risk factors of polymyxin B-associated acute kidney injury (AKI) in patients with severe infections caused by extensive drug resistance Gram negative bacteria (XDR-GNB) in intensive care unit (ICU). METHODS: A retrospective study of adult patients with severe infection who received polymyxin B for more than 3 days in the department of critical care medicine of Nanjing Drum Tower Hospital Affiliated to Nanjing University Medical School from April 1st 2018 to January 31st 2020 were performed. AKI was diagnosed by Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The baseline data, indicators during treatment period and prognostic factors were compared between AKI group and non-AKI group. Factors with statistically significant difference in univariate analysis and important clinical factors were included in the Logistic regression model to analyze the risk factors of AKI. RESULTS: Seventy-two patients were treated with polymyxin B for more than 3 days. Forty-nine patients were finally enrolled, with 32 patients developing polymyxin B-associated AKI, and the incidence was 44.4%. The baseline data was balanced in AKI group and non-AKI group, and there was no significant difference in the prognosis [death or discharge without medial order (cases): 14 vs. 6, discharged for improvement (cases): 18 vs. 11, χ2 = 0.329, P = 0.566]. Polymyxin B-associated AKI occurred from 1 day to 14 days after treatment, with an average of (6.8±3.8) days. Among the 32 AKI patients, 2 cases were lost to follow up after discharge, while renal function recovered in 18 cases and unrecovered in 12 cases. The prognosis of patients without recovery of renal function was significantly worse than that of patients with renal function recovery [death or discharge without medial order (cases): 12 vs. 2, discharged for improvement (cases): 0 vs. 16, P = 0.000]. Single factor analysis showed that daily dosage of polymyxin B in AKI group was higher than that in non-AKI group (mg: 151.6±23.7 vs. 132.4±30.3), numbers of patients with daily polymyxin B dose ≥ 150 mg, using vasoactive drugs, or severe hypoalbuminemia (albumin ≤ 25 g/L) were higher than those in non-AKI group (cases: 29 vs. 10, 18 vs. 4, 9 vs. 0), with statistically significant differences (all P < 0.05). Multivariate Logistic regression analysis showed that daily dosage of polymyxin B ≥ 150 mg and use of vasoactive drugs were independent risk factors for polymyxin B-associated AKI [odds ratio (OR) = 37.466, 95% confidence interval (95%CI) was 2.676-524.586, P = 0.007; OR = 22.960, 95%CI was 1.710-308.235, P = 0.018]. CONCLUSIONS: Comparing with non-AKI patients, more patients with polymyxin B-associated AKI had severe hypoalbuminemia, and the probability of using vasoactive drugs and the daily dose of polymyxin B were higher than non-AKI patients. Daily dose of polymyxin B ≥ 150 mg and using vasoactive drugs were independent risk factors for polymyxin B-associated AKI.


Assuntos
Lesão Renal Aguda , Infecções , Polimixina B/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , Fatores de Risco
14.
PLoS One ; 15(7): e0234921, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32673348

RESUMO

BACKGROUND: Subjects with chronic kidney disease are at increased risk for contrast-induced acute kidney injury (CI-AKI). Risk stratification is traditionally based on glomerular filtration rate (GFR) and proteinuria. The present trial examines, whether tubular and inflammatory biomarkers are able to identify subjects at increased risk as well. METHODS: We performed a prospective study in 490 patients undergoing coronary angiography. An increase of serum creatinine concentration ≥ 0.3 mg/dl from baseline to day 2-3 was defined as primary endpoint (CI-AKI). Urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and calprotectin were assessed < 24h before coronary angiography. Prognostic accuracy was assessed by receiver operating characteristics (ROC) calculations. RESULTS: 30 (6.1%) patients suffered from CI-AKI (27 AKIN stage I, 3 AKIN stage II, 0 AKIN stage III). Those subjects who developed CI-AKI had 3.1 fold higher baseline urinary NGAL/creatinine ratios than those without CI-AKI (60.8 [IQR 18.7-93.1] µg/mg vs. 19.9 [IQR 12.3-38.9] µg/mg, p = 0.001). In those subjects without clinically overt CKD (eGFR > 60 ml/min, urinary albumin creatinine ratio <30 mg/g), the NGAL/creatinine ratio was 2.6 higher in CI-AKI vs. no CI-AKI (47.8 [IQR 11.8-75.3] vs. 18.6 [IQR 11.7-36.3] µg/mg). No significant differences were obtained for KIM-1 and calprotectin (p>0.05 each). ROC analyses revealed an area under the curve (AUC) of 0.68 (95% CI 0.60-0.81) for NGAL/creatinine. An NGAL/creatinine ratio < 56.4 µg/mg has a negative predictive value of 96.5%. CONCLUSIONS: The present study is the largest investigation on the use of urinary biomarkers for CI-AKI risk stratification so far. It shows that NGAL provides prognostic information beyond the glomerular biomarkers eGFR and proteinuria.


Assuntos
Lesão Renal Aguda/etiologia , Lesão Renal Aguda/prevenção & controle , Meios de Contraste/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Idoso , Área Sob a Curva , Biomarcadores/sangue , Angiografia Coronária/efeitos adversos , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Complexo Antígeno L1 Leucocitário/urina , Lipocalina-2/urina , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Proteinúria , Curva ROC , Insuficiência Renal Crônica/complicações
15.
PLoS One ; 15(7): e0236864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730359

RESUMO

BACKGROUND: Combination therapy in the treatment of sepsis, especially the value of combining a ß-Lactam antibiotic with an aminoglycoside, has been discussed. This retrospective cohort study including patients with sepsis or septic shock aimed to investigate whether one single dose of gentamicin at admittance (SGA) added to ß-Lactam antibiotic could result in a lower risk of mortality than ß-Lactam monotherapy, without exposing the patient to the risk of nephrotoxicity. METHODS AND FINDINGS: All patients with positive blood cultures were evaluated for participation (n = 1318). After retrospective medical chart review, a group of patients with community-acquired sepsis with positive blood cultures who received ß-Lactam antibiotic with or without the addition of SGA (n = 399) were included for the analysis. Mean age was 74.6 yrs. (range 19-98) with 216 (54%) males. Sequential Organ Failure Assessment score (SOFA score) median was 3 (interquartile range [IQR] 2-5) and the median Charlson Comorbidity Index for the whole group was 2 (IQR 1-3). Sixty-seven (67) patients (17%) had septic shock. The 28-day mortality in the combination therapy group was 10% (20 of 197) and in the monotherapy group 22% (45 of 202), adjusted HR 3.5 (95% CI (1.9-6.2), p = < 0.001. No significant difference in incidence of acute kidney injury (AKI) was detected. CONCLUSION: This retrospective observational study including patients with community-acquired sepsis or septic shock and positive blood cultures, who meet Sepsis-3 criteria, shows that the addition of one single dose of gentamicin to ß-lactam treatment at admittance was associated with a decreased risk of mortality and was not associated with AKI. This antibiotic regime may be an alternative to broad-spectrum antibiotic treatment of community-acquired sepsis. Further prospective studies are warranted to confirm these results.


Assuntos
Antibacterianos/administração & dosagem , Bacteriemia/mortalidade , Bactérias/efeitos dos fármacos , Infecções Comunitárias Adquiridas/mortalidade , Gentamicinas/administração & dosagem , Sepse/mortalidade , beta-Lactamas/administração & dosagem , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/mortalidade , Lesão Renal Aguda/patologia , Idoso , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Bacteriemia/patologia , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/microbiologia , Infecções Comunitárias Adquiridas/patologia , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Masculino , Escores de Disfunção Orgânica , Estudos Retrospectivos , Sepse/tratamento farmacológico , Sepse/microbiologia , Sepse/patologia
16.
Yakugaku Zasshi ; 140(7): 929-936, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32612058

RESUMO

Cisplatin therapy induces kidney injury as a side effect. Thus, replacement fluid must be administered to prevent kidney injury. In our hospital, we use a Gemcitabine and Cisplatin combination chemotherapy (GC) at a total volume of approximately 500 mL for biliary tract cancer. We investigated the safety of GC with a small amount of replacement fluid. As a result, no serious adverse events and renal injury occurred that required discontinuation of treatment. The median overall survival time was 260 d (95% confidence interval, 154-367 d). This study suggests that GC with a small amount of replacement fluid could be performed tolerability. But we need to be careful about choosing patients such as patients who can drink 1 L orally and patients who can be treated as outpatients.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/prevenção & controle , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/análogos & derivados , Hidratação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
J Infect Dis ; 222(8): 1256-1264, 2020 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-32702098

RESUMO

BACKGROUND: This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients. METHODS: Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed. To account for confounders, patients were substratified by whether they developed hypotension and acute kidney injury (AKI) during the index hospitalization. RESULTS: Mortality (22% vs 17%, P > .05) and intensive care unit (ICU) admission (26% vs 12%, P > .05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups. However, patients who continued ACEi/ARBs in the hospital had a markedly lower ICU admission rate (12% vs 26%; P = .001; odds ratio [OR] = 0.347; 95% confidence interval [CI], .187-.643) and mortality rate (6% vs 28%; P = .001; OR = 0.215; 95% CI, .101-.455) compared to patients who discontinued ACEi/ARB. The odds ratio for mortality remained significantly lower after accounting for development of hypotension or AKI. CONCLUSIONS: These findings suggest that continued ACEi/ARB use in hypertensive COVID-19 patients yields better clinical outcomes.


Assuntos
Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Infecções por Coronavirus/mortalidade , Hipertensão/tratamento farmacológico , Hipertensão/virologia , Pneumonia Viral/mortalidade , Lesão Renal Aguda/induzido quimicamente , Idoso , Idoso de 80 Anos ou mais , Antagonistas de Receptores de Angiotensina/efeitos adversos , Inibidores da Enzima Conversora de Angiotensina/efeitos adversos , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/tratamento farmacológico , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos/epidemiologia
19.
PLoS One ; 15(6): e0235076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32584876

RESUMO

Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Anafilaxia/induzido quimicamente , Excipientes/efeitos adversos , Hiperglicemia/induzido quimicamente , Química Farmacêutica , Excipientes/uso terapêutico , Humanos , Manitol/efeitos adversos , Manitol/uso terapêutico , Polissorbatos/efeitos adversos , Polissorbatos/uso terapêutico , Cloreto de Sódio/efeitos adversos , Cloreto de Sódio/uso terapêutico , Sacarose/efeitos adversos , Sacarose/uso terapêutico , Água/efeitos adversos
20.
Pediatr Blood Cancer ; 67(8): e28396, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32495508

RESUMO

BACKGROUND: Nephrotoxic medication exposure and associated acute kidney injury (AKI) occur commonly in hospitalized children. At Cincinnati Children's Hospital Medical Center, there is an initiative to increase awareness of nephrotoxic medication exposure and decrease rates of associated AKI. The oncology service utilized these data in a quality improvement project to drive reductions in AKI rates. METHODS: Three interventions were implemented targeted at decreasing the incidence of nephrotoxic exposure, as well as protecting against the conversion of exposures to AKI episodes. Cefepime replaced piperacillin-tazobactam for febrile neutropenia, vancomycin stewardship limited empiric courses to 72 hours, and nephroprotection for intravenous contrast administration was standardized for defined high-risk patients. RESULTS: The study cohort comprised 42 520 noncritically ill patient days admitted to the oncology service at Cincinnati Children's Hospital Medical Center. A total of 273 unique patients were exposed to combination nephrotoxic medications, leading to 111 AKI episodes. The rate of nephrotoxic medication exposure within the oncology service decreased by 49% from 16.08 to 8.17 per 1000 patient days. Episodes of AKI associated with nephrotoxic medication exposure decreased by 45% from 3.48 to 1.92 per 1000 patient days. CONCLUSION: Interventions to decrease AKI took a three-pronged approach. Collectively, this approach was proven successful with significant reductions in both rates of nephrotoxic medication exposure and associated AKI among hospitalized oncology patients.


Assuntos
Lesão Renal Aguda , Cefepima/efeitos adversos , Bases de Dados Factuais , Neutropenia Febril , Neoplasias , Combinação Piperacilina e Tazobactam/efeitos adversos , Vancomicina/efeitos adversos , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/epidemiologia , Adolescente , Cefepima/administração & dosagem , Criança , Pré-Escolar , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/epidemiologia , Feminino , Humanos , Lactente , Masculino , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Combinação Piperacilina e Tazobactam/administração & dosagem , Estudos Retrospectivos , Vancomicina/administração & dosagem
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