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1.
Int J Mol Sci ; 20(15)2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31366007

RESUMO

Acute kidney injury (AKI) is a serious complication of acute pancreatitis (AP), which occurs in up to 70% of patients with severe AP and significantly increases the risk of mortality. At present, AKI is diagnosed based on dynamic increase in serum creatinine and decreased urine output; however, there is a need for earlier and more accurate biomarkers. The aim of the study was to review current evidence on the laboratory tests that were studied as the potential biomarkers of AKI in AP. We also briefly summarized the knowledge coming from the studies including sepsis or ICU patients since severe acute pancreatitis is associated with systemic inflammation and organ failure. Serum cystatin C and serum or urine NGAL have been shown to predict or diagnose AKI in AP; however, this evidence come from the single center studies of low number of patients. Other markers, such as urinary kidney injury molecule-1, cell cycle arrest biomarkers (tissue inhibitor metalloproteinase-2 and urine insulin-like growth factor-binding protein 7), interleukin-18, liver-type fatty acid-binding protein, or calprotectin have been studied in other populations suffering from systemic inflammatory states. In AP, the potential markers of AKI may be significantly influenced by either dehydration or inflammation, and the impact of these factors may be difficult to distinguish from kidney injury. The subject of AKI complicating AP is understudied. More studies are needed, for both exploratory (to choose the best markers) and clinical (to evaluate the diagnostic accuracy of the chosen markers in real clinical settings).


Assuntos
Lesão Renal Aguda/sangue , Pancreatite/sangue , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Biomarcadores/sangue , Biomarcadores/urina , Cistatina C/sangue , Humanos , Complexo Antígeno L1 Leucocitário/sangue , Lipocalina-2/sangue , Lipocalina-2/urina , Pancreatite/complicações , Pancreatite/urina , Inibidor Tecidual de Metaloproteinase-2/sangue
2.
Curr Drug Metab ; 20(8): 656-664, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31296157

RESUMO

BACKGROUND: Drug-induced Acute Kidney Injury (AKI) develops in 10-15% of patients who receive nephrotoxic medications. Urinary biomarkers of renal tubular dysfunction may detect nephrotoxicity early and predict AKI. METHODS: We prospectively studied patients who received aminoglycosides, vancomycin, amphotericin, or calcineurin inhibitors, and collected their serial urine while on therapy. Patients who developed drug-induced AKI (fulfilling KDIGO criteria) were matched with non-AKI controls in a 1:2 ratio. Their urine samples were batch-analyzed at time-intervals leading up to AKI onset; the latter benchmarked against the final day of nephrotoxic therapy in non- AKI controls. Biomarkers examined include clusterin, beta-2-microglobulin, KIM1, MCP1, cystatin-C, trefoil-factor- 3, NGAL, interleukin-18, GST-Pi, calbindin, and osteopontin; biomarkers were normalized with corresponding urine creatinine. RESULTS: Nine of 84 (11%) patients developed drug-induced AKI. Biomarkers from 7 AKI cases with pre-AKI samples were compared with those from 14 non-AKI controls. Corresponding mean ages were 55(±17) and 52(±16) years; baseline eGFR were 99(±21) and 101(±24) mL/min/1.73m2 (all p=NS). Most biomarker levels peaked before the onset of AKI. Median levels of 5 biomarkers were significantly higher in AKI cases than controls at 1-3 days before AKI onset (all µg/mmol): clusterin [58(8-411) versus 7(3-17)], beta-2-microglobulin [1632(913-3823) versus 253(61-791)], KIM1 [0.16(0.13-0.76) versus 0.07(0.05-0.15)], MCP1 [0.40(0.16-1.90) versus 0.07(0.04-0.17)], and cystatin-C [33(27-2990) versus 11(7-19)], all p<0.05; their AUROC for AKI prediction were >0.80 (confidence intervals >0.50), with average accuracy highest for clusterin (86%), followed by beta-2-microglobulin, cystatin-C, MCP1, and KIM1 (57%) after cross-validation. CONCLUSION: Serial surveillance of these biomarkers could improve the lead time for nephrotoxicity detection by days.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/urina , Adulto , Idoso , Aminoglicosídeos/efeitos adversos , Anfotericina B/efeitos adversos , Biomarcadores/urina , Inibidores de Calcineurina/efeitos adversos , Quimiocina CCL2/urina , Clusterina/urina , Ciclosporina/efeitos adversos , Cistatina C/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A/análise , Humanos , Masculino , Pessoa de Meia-Idade , Tacrolimo/efeitos adversos , Vancomicina/efeitos adversos , Microglobulina beta-2/urina
3.
Toxicol Lett ; 313: 169-177, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31284021

RESUMO

Acute kidney injury (AKI) is a heterogeneous clinical syndrome with diverse outcomes. The recovery from AKI has prognostic importance. Little research has been done in order to find biomarkers that can predict recovery from AKI. Cav-2 is one of the main constituents of caveolae and is expressed in kidney. This study analyzed the time course of Cav-2 urinary excretion and renal expression in rats treated with cisplatin. Male Wistar rats were injected with cisplatin (5 mg/kg b.w., i.p.), and the studies were performed after 2, 4 and 14 days. Cav-2 abundance was evaluated in urine, in renal homogenates and in apical membranes by Western blotting. Cav-2 in urine was increased only 14 days after treatment, in the recovery phase of cisplatin-induced AKI. These results show that Cav-2 in urine could be useful as a biomarker of renal recovery, but not as an early biomarker of cisplatin-induced AKI. Cav-2 expression in total renal homogenates was not modified with treatment, but a down-regulation of Cav-2 in apical membranes was observed in treated animals. We hypothesize that Cav-2 internalizes into renal cells from their apical membrane in response to cisplatin, and regulates in this manner different signaling proteins involved in the physiopathology of renal damage.


Assuntos
Lesão Renal Aguda/urina , Caveolina 2/urina , Cisplatino , Rim/metabolismo , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/fisiopatologia , Animais , Biomarcadores/urina , Modelos Animais de Doenças , Rim/fisiopatologia , Masculino , Ratos Wistar , Recuperação de Função Fisiológica , Eliminação Renal , Fatores de Tempo
4.
PLoS Negl Trop Dis ; 13(7): e0007486, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31260445

RESUMO

BACKGROUND: Acute kidney injury (AKI) is a major complication of snake envenoming, but early diagnosis remains problematic. We aimed to investigate the time course of novel renal biomarkers in AKI following Russell's viper (Daboia russelii) bites. METHODOLOGY/PRINCIPAL FINDINGS: We recruited a cohort of patients with definite Russell's viper envenoming and collected serial blood and urine samples on admission (<4h post-bite), 4-8h, 8-16h, 16-24h, 1 month and 3 months post-bite. AKI stage (1-3) was defined using the Acute Kidney Injury Network criteria. AKI stages (1-3) were defined by the Acute Kidney Injury Network (AKIN) criteria. There were 65 Russell's viper envenomings and 49 developed AKI: 24 AKIN stage 1, 13 stage 2 and 12 stage 3. There was a significant correlation between venom concentrations and AKI stage (p = 0.007), and between AKI stage and six peak biomarker concentrations. Although most biomarker concentrations were elevated within 8h, no biomarker performed well in diagnosing AKI <4h post-bite. Three biomarkers were superior to serum creatinine (sCr) in predicting AKI (stage 2/3) 4-8h post-bite: serum cystatin C (sCysC) with an area under the receiver operating curve (AUC-ROC), 0.78 (95%CI:0.64-0.93), urine neutrophil gelatinase-associated lipocalin (uNGAL), 0.74 (95%CI:0.59-0.87) and urine clusterin (uClu), 0.81 (95%CI:0.69-0.93). No biomarker was better than sCr after 8h. Six other urine biomarkers urine albumin, urine beta2-microglobulin, urine kidney injury molecule-1, urine cystatin C, urine trefoil factor-3 and urine osteopontin either had minimal elevation, and/or minimal prediction for AKI stage 2/3 (AUC-ROC<0.7). CONCLUSIONS/SIGNIFICANCE: AKI was common and sometimes severe following Russell's viper bites. Three biomarkers uClu, uNGAL and sCysC, appeared to become abnormal in AKI earlier than sCr, and may be useful in early identification of envenoming.


Assuntos
Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Mordeduras de Serpentes/complicações , Venenos de Víboras/sangue , Venenos de Víboras/urina , Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , Adolescente , Adulto , Idoso , Animais , Biomarcadores/sangue , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Víbora de Russell , Fatores de Tempo , Adulto Jovem
5.
Medicine (Baltimore) ; 98(26): e16232, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31261582

RESUMO

BACKGROUND: Tissue inhibitor of metalloproteinase-2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7) are recently identified urinary biomarkers of acute kidney injury (AKI) in critically ill patients. Because their predictive accuracies vary widely, a meta-analysis was performed to evaluate the accuracy of previously reported urinary TIMP-2 and IGFBP7 cut-offs for predicting AKI. METHODS: This meta-analysis was reported following the guideline of PRISMA. Four databases, PubMed, the Cochrane Library, the ISI Web of Knowledge, and Embase, were systematically searched from inception to June 2018 by 2 investigators, who independently selected studies, extracted relevant data, and evaluated study quality. A bivariate model was used to calculate the pooled estimates. RESULTS: The search identified 5 studies with 1619 critically ill patients. Urinary TIMP-2 and IGFBP7 cut-off points of 0.3 (ng/ml)/1000 had a sensitivity of 0.89 [95% confidence interval (CI) 0.85-0.93], a specificity of 0.48 (95% CI 0.45-0.51) and a diagnostic odds ratio (DOR) of 8.33 (95% CI 5.55-12.52). The area under the curve (AUC) estimated by the summary receiver operating characteristic (SROC) curve was 0.748. Based on 891 critically ill patients from 4 studies, urinary TIMP-2 and IGFBP7 cut-off points of 2.0 (ng/ml)/1000 had a sensitivity of 0.45 (95% CI 0.37-0.53), a specificity of 0.93 (95% CI 0.91-0.95) and a DOR of 11.43 (95% CI 7.43-17.57). The AUC estimated by SROC was 0.844. CONCLUSION: Cut-off values around 0.3 (ng/ml)/1000 (high sensitivity) and 2.0 (ng/ml)/1000 (high specificity) could be accurate surrogate biomarkers predicting AKI in critically ill patients. The urinary TIMP-2 and IGFBP7 cut-off point of 2.0 (ng/mL)/1000 appears to have the highest overall accuracy. TRIAL REGISTRATION: PROSPERO registration number 2018: CRD42018084457 Registered on 11 February 2018.


Assuntos
Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/urina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Inibidor Tecidual de Metaloproteinase-2/urina , Estado Terminal , Humanos , Valor Preditivo dos Testes
6.
J Vet Diagn Invest ; 31(5): 688-695, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31347464

RESUMO

Detection of equine acute kidney injury (AKI) is hindered by limited markers of early renal damage in horses. N-acetyl-ß-D-glucosaminidase (NAG), a lysosomal enzyme in renal tubular epithelium released into urine during tubular insult, has shown promise for early identification of AKI in humans and other species. We validated an assay for NAG in equine urine and measured urinary NAG in 7 azotemic and 7 non-azotemic client-owned adult horses. The enzymatic NAG assay was validated using within- and between-run coefficients of variation (CVs), recovery following standard addition, and linearity of dilution. Intra- and inter-run CVs (21% and 3.2%, respectively), average recovery following standard addition (99-109%), and linearity under serial dilution (R2 = 0.997) were satisfactory. Urine NAG index was significantly correlated with urinary fractional excretion of sodium (FENa; ρ = 0.76, p < 0.001) and plasma creatinine (ρ = 0.74, p = 0.001). Median urine NAG indices were higher in azotemic horses (p = 0.006), in horses with increased urinary FENa (p = 0.006), and in horses with increased urine gamma-glutamyl transferase index (p = 0.032). Urine NAG can be measured in horses and shows positive correlation with 2 current renal biomarkers. Additional work is needed to establish normal equine reference intervals and characterize the increase of urine NAG index in horses in relation to tubular injury.


Assuntos
Acetilglucosaminidase/urina , Lesão Renal Aguda/veterinária , Doenças dos Cavalos/diagnóstico , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/urina , Animais , Biomarcadores/urina , Creatinina/sangue , Feminino , Doenças dos Cavalos/urina , Cavalos , Humanos , Masculino , Sódio/urina , gama-Glutamiltransferase/urina
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(2): 224-229, 2019 Apr 25.
Artigo em Chinês | MEDLINE | ID: mdl-31309763

RESUMO

Cardiac surgery-related acute kidney injury (CSA-AKI) is a common and serious complication after cardiac surgery in adults. Currently, there is no specific examination method, and the diagnosis relying on serum creatinine and urine volume changes is of hysteresis. Biomarkers with the potential to predict CSA-AKI have become the focus in recent years. Clinical studies have shown that neutrophil gelatinase related lipid transporters and cell cycle inhibitors are of high diagnostic value; liver fatty acid binding protein can be used to assist in the diagnosis of CSA-AKI; microRNAs help to assess the poor prognosis of patients; the combined application of biomarkers may be used to predict the occurrence of CSA-AKI. CSA-AKI biomarkers provide the possibility for early clinical diagnosis and timely intervention, and are expected to become a new breakthrough in the diagnosis and treatment of CSA-AKI.


Assuntos
Lesão Renal Aguda , Biomarcadores , Procedimentos Cirúrgicos Cardíacos , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Adulto , Biomarcadores/análise , Biomarcadores/sangue , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Creatinina/sangue , Humanos
8.
PLoS One ; 14(6): e0217424, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31220087

RESUMO

AKI is associated with increased risk of death, prolonged length of stay and development of de-novo chronic kidney disease. The aim of our study is the development and validation of prediction models to identify the risk of AKI in ICU patients up to 7 days. We retrospectively recruited 692 consecutive patients admitted to the ICU at San Bortolo Hospital (Vicenza, Italy) from 1 June 2016 to 31 March 2017: 455 patients were treated as the derivation group and 237 as the validation group. Candidate variables were selected based on a literature review and expert opinion. Admission eGFR< 90 ml/min /1.73 mq (OR 2.78; 95% CI 1.78-4.35; p<0.001); SOFAcv ≥ 2 (OR 2.23; 95% CI 1.48-3.37; p<0.001); lactate ≥ 2 mmol/L (OR 1.81; 95% CI 1.19-2.74; p = 0.005) and (TIMP-2)•(IGFBP7) ≥ 0.3 (OR 1.65; 95% CI 1.08-2.52; p = 0.019) were significantly associated with AKI. For the q-AKI score, we stratified patients into different AKI Risk score levels: 0-2; 3-4; 5-6; 7-8 and 9-10. In both cohorts, we observed that the proportion of AKI patients was higher in the higher score levels.


Assuntos
Lesão Renal Aguda , Cuidados Críticos , Taxa de Filtração Glomerular , Unidades de Terapia Intensiva , Sistema de Registros , Lesão Renal Aguda/diagnóstico , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/urina , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
9.
Anal Chim Acta ; 1076: 82-90, 2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31203967

RESUMO

We present a method to preserve and process urine proteins for proteomic analysis in a filter aided sample preparation (FASP) format. The method combines concentration of urine proteins in ultrafiltration devices, their thermal stabilization, allowing long term storage of the samples, and filter aided sample preparation. Proteomes of four different urines were preserved during 48 h and 6 months using (i) the classic freeze preservation at -20 °C, (ii) snap-heated freeze-free preservation at laboratory temperature (20 °C) and (iii) snap-heated preservation at -60 °C. The three storage methods can effetely preserve the urine proteome for at least 6 months without significant alterations. Abundances of more than 500 proteins and specially 24 selected -cleared or -approved protein assayed in serum or plasma were found similar within the three preservation methods assessed. The new method here proposed dramatically simplifies the conditions for preserving the urine proteome for biobanks in terms of space and storage, including lowering the risks of sample degradation caused by misfunction of the freezer. Furthermore, the shipping of large number of samples can be made without the need of freezing. The application of the FASP format to isolate and preserve the proteins facilitates long-term storage and processing of proteome of urine samples.


Assuntos
Proteoma/química , Manejo de Espécimes/métodos , Urina/química , Lesão Renal Aguda/urina , Adulto , Biomarcadores/análise , Análise por Conglomerados , Calefação , Humanos , Biópsia Líquida , Masculino , Estudo de Prova de Conceito , Proteoma/análise , Proteoma/isolamento & purificação , Adulto Jovem
11.
Lancet ; 394(10197): 488-496, 2019 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-31202596

RESUMO

BACKGROUND: Cardiac surgery is associated with a high risk of postoperative acute kidney injury (AKI) and subsequent loss of kidney function. We explored the clinical utility of urinary dickkopf-3 (DKK3), a renal tubular stress marker, for preoperative identification of patients at risk for AKI and subsequent kidney function loss. METHODS: This observational cohort study included patients who had cardiac surgery in a derivation cohort and those who had cardiac surgery in a validation cohort (RenalRIP trial). The study comprised consecutive patients who had elective cardiac surgery at the Saarland University Medical Centre (Homburg, Germany; derivation cohort) and those undergoing elective cardiac surgery (selected on the basis of a Cleveland Clinical Foundation score of 6 or higher) who were enrolled in the prospective RenalRIP multicentre trial (validation cohort) and who were randomly assigned to remote ischaemic preconditioning or a sham procedure. The association between the ratio of preoperative urinary concentrations of DKK3 to creatinine (DKK3:creatinine) and postoperative AKI, defined according to the Kidney Disease Improving Global Outcomes criteria, and subsequent kidney function loss, as determined by estimated glomerular filtration rate, was assessed. FINDINGS: In the 733 patient in the derivation cohort, urinary concentrations of DKK3 to creatinine that were higher than 471 pg/mg were associated with significantly increased risk for AKI (odds ratio [OR] 1·65, 95% CI 1·10-2·47, p=0·015), independent of baseline kidney function. Compared with clinical and other laboratory measurements, urinary concentrations of DKK3:creatinine significantly improved AKI prediction (net reclassification improvement 0·32, 95% CI 0·23-0·42, p<0·0001). High urinary DKK3:creatinine concentrations were independently associated with significantly lower kidney function at hospital discharge and after a median follow-up of 820 days (IQR 733-910). In the RenalRIP trial, preoperative urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with a significantly higher risk for AKI (OR 1·94, 95% CI 1·08-3·47, p=0·026), persistent renal dysfunction (OR 6·67, 1·67-26·61, p=0·0072), and dialysis dependency (OR 13·57, 1·50-122·77, p=0·020) after 90 days compared with DKK3:creatinine concentrations of 471 pg/mg or less. Urinary DKK3:creatinine concentrations higher than 471 pg/mg were associated with significantly higher risk for AKI (OR 2·79, 95% CI 1·45-5·37) and persistent renal dysfunction (OR 3·82, 1·32-11·05) only in patients having a sham procedure, but not remote ischaemic preconditioning (AKI OR 1·35, 0·76-2·39 and persistent renal dysfunction OR 1·05, 0·12-9·45). INTERPRETATION: Preoperative urinary DKK3 is an independent predictor for postoperative AKI and for subsequent loss of kidney function. Urinary DKK3 might aid in the identification of patients in whom preventive treatment strategies are effective. FUNDING: No study funding.


Assuntos
Lesão Renal Aguda/fisiopatologia , Biomarcadores/urina , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Peptídeos e Proteínas de Sinalização Intercelular/urina , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Idoso , Idoso de 80 Anos ou mais , Quimiocinas , Creatinina/urina , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/urina , Estudos Prospectivos
12.
Clin Nephrol ; 92(3): 141-150, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31198169

RESUMO

AIMS: Acute and chronic kidney dysfunction is common in patients with end-stage liver disease. Differentiation between acute kidney injury (AKI) due to hepatorenal syndrome (HRS) or acute tubular necrosis (ATN) remains difficult, however urine cast scoring systems using renal tubular epithelial cells (RTECs) and granular casts (GCs) can help to identify intrinsic kidney diseases. The objective of this study was to evaluate the urine sediment profile of patients with liver disease and hyperbilirubinemia/hyperbilirubinuria and the use of a urine sediment scoring system to identify the most common score in AKI patients and high urine bilirubin concentrations. MATERIALS AND METHODS: A retrospective study in the database of a large laboratory that assists a hospital-complex in Brazil was performed. RESULTS: Urinary casts, in particular GCs, as well as RTECs were observed more frequently in patients with hyperbilirubinemia/hyperbilirubinuria, while hyaline casts were observed in patients without hyperbilirubinemia/hyperbilirubinuria. Regardless of the AKI or non-AKI condition, the relative risk for scores 2 or 3 (sediment consistent with tubular damage, with GCs and/or RTECs in different quantities) in group 4 was 3.61 times higher compared to patients in group 1. CONCLUSION: In patients with higher urinary bilirubin levels, the urine sediment had greater numbers of GCs and RTECs and higher urine sediment scores (scores 2 or 3). The presence of a larger number of urine particles (RTECs and GCs) originating in the kidneys in the groups with higher levels of urinary bilirubin suggests an association between hyperbilirubinemia/hyperbilirubinuria and tubular injury independent of AKI or non-AKI.


Assuntos
Lesão Renal Aguda/urina , Bilirrubina/urina , Hiperbilirrubinemia/urina , Urinálise/métodos , Adulto , Idoso , Feminino , Humanos , Necrose Tubular Aguda/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Manejo de Espécimes
13.
Clin Chim Acta ; 495: 552-555, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31175848

RESUMO

BACKGROUND: Plasma neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for predicting acute kidney injury (AKI). The purpose of this study was to evaluate the diagnostic performance of urinary NGAL in predicting AKI in sepsis patients in the emergency department. METHODS: A total of 140 patients were enrolled. We compared serum procalcitonin and urinary NGAL concentrations between patients with local infection, sepsis, and septic shock, and between patients who did and did not develop AKI with sepsis. Receiver-operating characteristic curve analysis was used to evaluate the ability to predict AKI in sepsis patients. RESULTS: Both serum procalcitonin and urinary NGAL concentrations were significantly higher in the sepsis and septic shock groups than in the local infection group (both p < 0.001). In sepsis patients, serum procalcitonin and urinary NGAL concentrations were higher in AKI patients than in those without AKI (p = 0.006, p < 0.001, respectively). The area under the curve for predicting of AKI was higher for a urinary NGAL of 0.820 (95% confidence interval (CI) 0.721-0.895) than for a serum procalcitonin concentration of 0.76 (95% CI 0.597-0.800). CONCLUSION: Urinary NGAL concentration may predict AKI in patients with sepsis in the emergency department.


Assuntos
Lesão Renal Aguda/complicações , Lesão Renal Aguda/urina , Serviço Hospitalar de Emergência , Lipocalina-2/urina , Sepse/complicações , Lesão Renal Aguda/sangue , Lesão Renal Aguda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Prognóstico , Curva ROC
14.
Ann Transplant ; 24: 291-297, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31110167

RESUMO

Acute kidney injury (AKI) is a frequent and serious complication of orthotopic liver transplantation (OLT), with a significant impact on mortality, graft survival, and chronic kidney disease. Currently, the diagnosis of AKI is based on changes in serum creatinine, which is a late marker, usually rising when there is already significant damage to the renal parenchyma. During the last 2 decades, various biomarkers have been studied in many clinical situations, mostly after cardiac surgery, in drug-induced AKI, or in sepsis. The present article summarizes the data on those biomarkers that have been evaluated for the prediction of AKI in patients undergoing OLT.


Assuntos
Lesão Renal Aguda/diagnóstico , Proteínas de Ligação a Ácido Graxo/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Interleucina-18/metabolismo , Lipocalina-2/metabolismo , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/diagnóstico , Lesão Renal Aguda/sangue , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/urina , Biomarcadores/sangue , Biomarcadores/urina , Proteínas de Ligação a Ácido Graxo/sangue , Proteínas de Ligação a Ácido Graxo/urina , Humanos , Interleucina-18/sangue , Interleucina-18/urina , Lipocalina-2/sangue , Lipocalina-2/urina , Complicações Pós-Operatórias/sangue , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/urina , Fatores de Risco
16.
Zhonghua Nei Ke Za Zhi ; 58(5): 349-354, 2019 May 01.
Artigo em Chinês | MEDLINE | ID: mdl-31060142

RESUMO

Objective: To explore the value of renal resistance index (RI) and urine oxygen pressure for early prediction of acute kidney injury (AKI) in patients with septic shock. Methods: Patients with septic shock were enrolled from August 2018 to November 2018 in intensive care unit (ICU) at Peking Union Medical College Hospital. Subjects' general information and AKI characteristics were assessed. Area under the receiver operating characteristic (ROC) curve was used to analyze the predictive value of RI, urine oxygen pressure, or combination of RI on the occurrence of AKI. Results: A total of 72 septic shock patients were enrolled including 29 patients with AKI and 43 without. Logistic regression analysis of AKI risk factors found that RI (OR=1.139, 95%CI 1.029-1.261, P=0.012) and urine oxygen pressure (OR=0.957, 95%CI 0.923-0.991, P=0.014) at admission were independent risk factors for AKI in patients with septic shock. The sensitivity and specificity of dual RI and urine oxygen pressure in predicting AKI were 65.5% and 76.7% respectively (AUCROC 0.772, Youden index 0.423). We selected the cut-off value of RI as 0.70,and urine oxygen pressure as 48 mmHg (1 mmHg=0.133 kPa). According to this two cut-off values patients were divided into four groups, those with RI≥0.70 and urine oxygen pressure≤48 mmHg showed the highest incidence of AKI (75%). There was no statistically difference in 28-day survival rate between the four groups (P=0.197). Conclusion: High RI and low urine oxygen pressure are independent risk factors for the development of AKI in patients with septic shock. The predictive cut-off values are 0.70 for RI and 48 mmHg for urine oxygen pressure. Combination of RI and urine oxygen pressure has a practical predictive value for AKI in patients with septic shock.


Assuntos
Lesão Renal Aguda/diagnóstico , Creatinina/sangue , Oxigênio/urina , Choque Séptico/complicações , Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , Biomarcadores/sangue , Humanos , Valor Preditivo dos Testes , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade , Urodinâmica
17.
Dis Markers ; 2019: 3471215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31061681

RESUMO

Background: To examine whether the new urinary biomarkers TIMP2 and IGFBP7 can predict progression within 24 hours and 72 hours from mild and moderate (KDIGO 1 or 2) to severe (KDIGO 3) AKI in patients with septic shock. Methods: A prospective, multicenter observational study performed in three French ICUs. The urinary biomarkers TIMP2∗IGFBP7 were analyzed at the early phase (<6 hours) of patients admitted for septic shock with mild and moderate AKI. Results: Among the 112 patients included, 45 (40%) progressed to the KDIGO 3 level 24 hours after inclusion (KDIGO 3 H24) and 47 (42%) 72 hours after inclusion (KDIGO 3 H72). The median urinary TIMP2∗IGFBP7 at inclusion (baseline) were higher in the KDIGO 3 group than in the KDIGO<3 group at H24 and H72. All covariates with a p value < 0.1 in the univariate analysis were included in stepwise multiple logistic regression models to identify factors independently associated with the risk of KDIGO 3 at H24 and H72. TIMP2∗IGFBP7 remained independently associated with KDIGO 3 at H24 and H72. Baseline posology of norepinephrine, baseline urine output, and baseline serum creatinine remained also significantly associated with progression to KDIGO 3 at H24. Baseline TIMP2∗IGFBP7 and baseline urinary output had the best AUC ROC. A baseline TIMP2∗IGFBP7 > 2.0 (ng/ml)2/1,000 identified the population at high risk of KDIGO 3 H24 (relative risk 4.19 (1.7-10.4)) with a sensitivity of 76% (60-87) and a specificity of 81% (69-89). But the diagnostic performance at H72 of baseline TIMP2∗IGFBP7 was poor (AUC: 0.69 (0.59-0.77)). Conclusion: The urinary TIMP2∗IGFBP7 concentration and the urine output at the early phase of septic shock are independent factors to identify the population at high risk of progression from mild and moderate to severe AKI over the next 24 but not 72 hours. A TIMP2∗IGFBP7 concentration > 2.0 (ng/ml)2/1,000 quadruples the risk of KDIGO 3 AKI within 24 hours. This trial is registered with (NCT03547414).


Assuntos
Lesão Renal Aguda/urina , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/urina , Choque Séptico/urina , Inibidor Tecidual de Metaloproteinase-2/urina , Lesão Renal Aguda/complicações , Idoso , Biomarcadores/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Choque Séptico/etiologia
18.
Circ Res ; 124(10): 1462-1472, 2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-30929579

RESUMO

RATIONALE: Acute kidney injury (AKI) has a high prevalence and mortality in critically ill patients. It is also a powerful risk factor for heart failure incidence driven by hemodynamic changes and neurohormonal activation. However, no drugs have been approved by the Food and Drug Administration. Endogenous pGC-A (particulate guanylyl cyclase A receptor) activators were reported to preserve renal function and improve mortality in AKI patients, although hypotension accompanied by pGC-A activators have limited their therapeutic potential. OBJECTIVE: We investigated the therapeutic potential of a nonhypotensive pGC-A activator/designer natriuretic peptide, CRRL269, in a short-term, large animal model of ischemia-induced AKI and also investigated the potential of uCNP (urinary C-type natriuretic peptide) as a biomarker for AKI. METHODS AND RESULTS: We first showed that CRRL269 stimulated cGMP generation, suppressed plasma angiotensin II, and reduced cardiac filling pressures without lowering blood pressure in the AKI canine model. We also demonstrated that CRRL269 preserved glomerular filtration rate, increased renal blood flow, and promoted diuresis and natriuresis. Further, CRRL269 reduced kidney injury and apoptosis as evidenced by ex vivo histology and tissue apoptosis analysis. We also showed, compared with native pGC-A activators, that CRRL269 is a more potent inhibitor of apoptosis in renal cells and induced less decreases in intracellular Ca2+ concentration in vascular smooth muscle cells. The renal antiapoptotic effects were at least mediated by cGMP/PKG pathway. Further, CRRL269 inhibited proapoptotic genes expression using a polymerase chain reaction gene array. Additionally, we demonstrated that AKI increased uCNP levels. CONCLUSIONS: Our study supports developing CRRL269 as a novel renocardiac protective agent for AKI treatment.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Lesão Renal Aguda/urina , Peptídeo Natriurético Tipo C/urina , Fármacos Renais/uso terapêutico , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/prevenção & controle , Angiotensina II/sangue , Animais , Apoptose/efeitos dos fármacos , Biomarcadores/urina , Pressão Sanguínea/fisiologia , GMP Cíclico/biossíntese , Diurese/efeitos dos fármacos , Cães , Taxa de Filtração Glomerular/efeitos dos fármacos , Masculino , Natriurese/efeitos dos fármacos , Receptores do Fator Natriurético Atrial/análise , Receptores do Fator Natriurético Atrial/efeitos dos fármacos , Circulação Renal/efeitos dos fármacos
19.
Internist (Berl) ; 60(6): 578-586, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31001671

RESUMO

In addition to the early detection of an acute kidney injury (AKI), several problems or questions have to be addressed. These include the identification of the etiology, the severity (functional or structural), the prognosis (recovery or transition to chronic renal failure), the course of the disease (dialysis or not), and the identification of specific treatment options for AKI. The following article provides an overview of established and new AKI biomarkers as well as an outlook on the potential of future biomarker-associated models of AKI.


Assuntos
Lesão Renal Aguda/sangue , Lesão Renal Aguda/urina , Biomarcadores/sangue , Biomarcadores/urina , Lesão Renal Aguda/terapia , Creatinina , Humanos , Diálise Renal , Insuficiência Renal Crônica/complicações
20.
Turk J Med Sci ; 49(2): 543-550, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-30997790

RESUMO

Background/aim: Lack of early predictors of acute kidney injury is currently delaying timely diagnosis.This study was done to evaluate the relationship between mild to moderate proteinuria and incidence of acute kidney injury (AKI) and 28-day mortality in intensive care unit (ICU) patients. Materials and methods: This observational, retrospective study was conducted in the internal medicine ICU. A total of 796 patients were screened and 525 patients were used for this analysis. Proteinuria was measured by urine dipstick test. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Results: Patients with dipstick urine protein positivity on admission had higher proportion of AKI and 28-day mortality compared to dipstick urine protein negative group [164 (59.6%) vs. 111 (44.4%) and 101 (36.7%) vs. 54 (21.6%), P = 0.01 and P < 0.01, respectively]. Urine dipstick protein positivity was also a significant predictor of 28-day mortality in patients with GFR > 60 mL/min (hazard ratio: 1.988, 95% confidence interval 1.380­2.862). Conclusion: Proteinuria before ICU admission is a risk factor for development of AKI within seven days of ICU stay and also is a risk factor for 28-day mortality, even in patients with GFR > 60 mL/min.


Assuntos
Lesão Renal Aguda/mortalidade , Unidades de Terapia Intensiva , Proteinúria/urina , Lesão Renal Aguda/fisiopatologia , Lesão Renal Aguda/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Cuidados Críticos , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteinúria/complicações , Proteinúria/mortalidade , Estudos Retrospectivos , Fatores de Risco , Turquia , Adulto Jovem
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