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2.
Nutrients ; 13(8)2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34444907

RESUMO

Background-Some data suggest favorable effects of a high potassium intake on kidney function. The present population-based study investigated cross-sectional and longitudinal relations of urinary potassium with kidney function. Methods-Study cohort included 2027 Gubbio Study examinees (56.9% women) with age ≥ 18 years at exam-1 and with complete data on selected variables at exam-1 (1983-1985), exam-2 (1989-1992), and exam-3 (2001-2007). Urinary potassium as urinary potassium/creatinine ratio was measured in daytime spot samples at exam-1 and in overnight timed collections at exam-2. Estimated glomerular filtration rate (eGFR) was measured at all exams. Covariates in analyses included demographics, anthropometry, blood pressure, drug treatments, diabetes, smoking, alcohol intake, and urinary markers of dietary sodium and protein. Results-In multivariable regression, urinary potassium/creatinine ratio cross-sectionally related to eGFR neither at exam-1 (standardized coefficient and 95%CI = 0.020 and -0.059/0.019) nor at exam-2 (0.024 and -0.013/0.056). Exam-1 urinary potassium/creatinine ratio related to eGFR change from exam-1 to exam-2 (0.051 and 0.018/0.084). Exam-2 urinary potassium/creatinine ratio related to eGFR change from exam-2 to exam-3 (0.048 and 0.005/0.091). Mean of urinary potassium/creatinine ratio at exam-1 and exam-2 related to eGFR change from exam-1 to exam-3 (0.056 and 0.027/0.087) and to incidence of eGFR < 60 mL/min per 1.73 m2 from exam-1 to exam-3 (odds ratio and 95%CI = 0.78 and 0.61/0.98). Conclusion-In the population, urinary potassium did not relate cross-sectionally to eGFR but related to eGFR decline over time. Data support the existence of favorable effects of potassium intake on ageing-associated decline in kidney function.


Assuntos
Envelhecimento/urina , Saúde da População/estatística & dados numéricos , Potássio/urina , Adolescente , Adulto , Idoso , Creatinina/urina , Estudos Transversais , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Adulto Jovem
4.
Cytokine ; 146: 155589, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34161857

RESUMO

BACKGROUND: Acute kidney injury is common in COVID-19 patients admitted to the ICU. Urinary biomarkers are a non-invasive way of assaying renal damage, and so far, urinary cytokines are not fully investigated. The current study aimed to assess urinary cytokine levels in COVID-19 patients. METHODS: Urine was collected from COVID-19 patients (n = 29) in intensive care and compared to a preoperative group of patients (n = 9) with no critical illness. 92 urinary cytokines were analyzed in multiplex using the Olink Target 96 inflammation panel and compared to clinical characteristics, and urinary markers of kidney injury. RESULTS: There were strong correlations between proinflammatory cytokines and between urinary cytokines and urinary kidney injury markers in 29 COVID-19 patients. Several cytokines were correlated to kidney injury, 31 cytokines to AKI stage and 19 cytokines correlated to maximal creatinine. CONCLUSIONS: Urinary inflammatory cytokines from a wide range of immune cell lineages were significantly upregulated during COVID-19 and the upregulation correlated with acute kidney injury as well as urinary markers of kidney tissue damage.


Assuntos
Injúria Renal Aguda/urina , Biomarcadores/urina , COVID-19/urina , Estado Terminal , Citocinas/urina , Idoso , Albuminúria/urina , COVID-19/diagnóstico , COVID-19/virologia , Creatinina/sangue , Creatinina/urina , Cuidados Críticos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/fisiologia
5.
Molecules ; 26(9)2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-34066554

RESUMO

Catecholamines and steroids are well-known neurotransmitters and hormones that rapidly change the excitability of neurons. Alopecia areata is a disease for which the exact cause is unknown, but it is considered to be associated with stress, and so the simultaneous analysis of catecholamines and steroids is required for the diagnosis of alopecia areata. Thus, we herein report the simultaneous analysis of catecholamines and steroids bearing different functional groups for the first time, during which it was necessary to carry out a serial hydrolysis procedure. Following hydrolysis of the urine samples to produce the free forms from the urinary conjugates, ethyl acetate extractions were carried out, and chemical derivatization was performed using dansyl chloride to increase the sensitivity of the liquid chromatography-tandem mass spectrometry method. The matrix effects and recoveries of this analytical method were validated, giving values of 85.4-122.9% and 88.8-123.0%, respectively. In addition, the method accuracy and precision were assessed, giving values of 0.4-21.5% and 2.0-21.6% for the intra-day and inter-day precisions, respectively. This validated method was then applied to identify differences between patients with and without alopecia areata, wherein the metanephrine content was found to be significantly higher in the alopecia areata patient group. This quantitative profiling method can also be applied to steroid-dependent diseases, as well as catecholamine-related diseases.


Assuntos
Alopecia em Áreas/urina , Catecolaminas/urina , Esteroides/urina , Calibragem , Cromatografia Líquida , Creatinina/urina , Compostos de Dansil/química , Humanos , Hidrólise , Metanefrina/análise , Reprodutibilidade dos Testes , Esteroides/química , Espectrometria de Massas em Tandem
6.
Res Vet Sci ; 138: 11-18, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34090202

RESUMO

Proteinuria is a recognized risk factor for progression of canine chronic kidney disease (CKD). However, the prognosis of non-azotemic proteinuric CKD in dogs has been studied only to a limited extent. Moreover, the degree to which proteinuria should be decreased to delay CKD progression remains unknown. The purposes of this study were (1) to identify factors associated with disease progression and (2) to investigate the degree of proteinuria, albuminuria, and blood pressure during the course of treatment associated with the progression using time-averaged urine protein:creatinine ratio (UPC) and urine albumin:creatinine ratio (UAC) in canine non-azotemic proteinuric CKD. Twenty-one dogs with non-azotemic proteinuric CKD were included in the study. High UPC and UAC were associated with CKD progression (P < .05). Time-averaged high UPC and UAC were significantly related to progression (P < .05). The cutoff values of these time-averaged parameters for predicting the progression were 4.1 and 2.0, respectively. In dogs with non-azotemic proteinuric CKD, more severe proteinuria and albuminuria were associated with progression. The present study suggests that because UPC ≥ 4.1 and UAC ≥ 2.0 during treatment were associated with a faster progression of non-azotemic proteinuric CKD, therapeutic intervention is warranted.


Assuntos
Albuminúria/veterinária , Azotemia/veterinária , Pressão Sanguínea , Creatinina/urina , Doenças do Cão/etiologia , Proteinúria/veterinária , Insuficiência Renal Crônica/veterinária , Albuminúria/tratamento farmacológico , Albuminúria/etiologia , Animais , Azotemia/tratamento farmacológico , Azotemia/etiologia , Progressão da Doença , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Masculino , Proteinúria/tratamento farmacológico , Proteinúria/etiologia , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/etiologia
7.
Molecules ; 26(11)2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34071971

RESUMO

In consideration of its relatively constant urinary excretion rate, creatinine (2-amino-1-methyl-5H-imidazol-4-one, MW 113.1) in urine is a useful endogenous biochemical parameter to correct the urinary excretion rate of numerous endogenous and exogenous substances. Reliable measurement of creatinine by gas chromatography (GC)-based methods requires derivatization of its amine and keto groups. Creatinine exists in equilibrium with its open form creatine (methylguanidoacetic acid, MW 131.1), which has a guanidine and a carboxylic group. Trimethylsilylation and trifluoroacetylation of creatinine and creatine are the oldest reported derivatization methods for their GC-mass spectrometry (MS) analysis in human serum using flame- or electron-ionization. We performed GC-MS studies on the derivatization of creatinine (d0-creatinine), [methylo-2H3]creatinine (d3-creatinine, internal standard) and creatine (d0-creatine) with N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) using standard derivatization conditions (60 min, 60 °C), yet in the absence of any base. Reaction products were characterized both in the negative-ion chemical ionization (NICI) and in the positive-ion chemical ionization (PICI) mode. Creatinine and creatine reacted with BSTFA to form several derivatives. Their early eluting N,N,O-tris(trimethylsilyl) derivatives (8.9 min) were found to be useful for the precise and accurate measurement of the sum of creatinine and creatine in human urine (10 µL, up to 20 mM) by selected-ion monitoring (SIM) of m/z 271 (d0-creatinine/d0-creatine) and m/z 274 (d3-creatinine) in the NICI mode. In the PICI mode, SIM of m/z 256, m/z 259, m/z 272 and m/z 275 was performed. BSTFA derivatization of d0-creatine from a freshly prepared solution in distilled water resulted in formation of two lMate-eluting derivatives (14.08 min, 14.72 min), presumably creatinyl-creatinine, with the creatininyl residue existing in its enol form (14.08 min) and keto form (14.72 min). Our results suggest that BSTFA derivatization does not allow specific analysis of creatine and creatinine by GC-MS. Preliminary analyses suggest that pentafluoropropionic anhydride (PFPA) is also not useful for the measurement of creatinine in the presence of creatine. Both BSTFA and PFPA facilitate the conversion of creatine to creatinine. Specific measurement of creatinine in urine is possible by using pentafluorobenzyl bromide in aqueous acetone.


Assuntos
Química Farmacêutica/métodos , Creatina/urina , Creatinina/urina , Cromatografia Gasosa-Espectrometria de Massas/métodos , Compostos de Trimetilsilil/química , Urinálise/métodos , Acetona , Cromatografia Líquida de Alta Pressão , Humanos , Íons , Modelos Lineares , Reprodutibilidade dos Testes , Temperatura
8.
Nutrients ; 13(5)2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-34064372

RESUMO

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) are associated with chronic kidney disease (CKD). Diet could play a predisposing role in the development of increased albuminuria in patients with NAFLD and MetS; however, published evidence is still limited. The aim of this cross-sectional analysis was to assess whether dietary fats are associated with changes in urinary albumin-to-creatinine ratio (UACR) in 146 patients aged 40-60-years with NAFLD and MetS. Dietary data were collected by food frequency questionnaire; UACR was measured in a single first morning void. Sources and types of dietary fats used in the analysis were total fat, fats from animal and vegetable sources, saturated, monounsaturated, polyunsaturated, and trans fats. One-way analysis of variance was performed to assess differences in dietary fats intakes across stages of UACR. The association between dietary fats and UACR was assessed by Pearson's correlation coefficient and multivariable linear regression. Patients with increased UACR showed a worse cardiometabolic profile and higher intakes of animal fat, as compared to patients with normal levels of albuminuria. Animal fat intake was associated with mean UACR, independent of potential covariates.


Assuntos
Albuminúria/etiologia , Dieta/efeitos adversos , Gorduras na Dieta/efeitos adversos , Síndrome Metabólica/urina , Hepatopatia Gordurosa não Alcoólica/urina , Adulto , Animais , Fatores de Risco Cardiometabólico , Creatinina/urina , Estudos Transversais , Dieta/métodos , Inquéritos sobre Dietas , Gorduras na Dieta/análise , Ingestão de Alimentos/fisiologia , Feminino , Humanos , Modelos Lineares , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações
9.
J Occup Health ; 63(1): e12222, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33973692

RESUMO

OBJECTIVES: To assess pesticide exposure and understand the resultant health effects of agricultural workers in Northern Thailand. METHODS: This was a cross-sectional study. We quantified exposure to pesticides, including chlorpyrifos, methomyl, and metalaxyl, by air sampling and liquid chromatography/mass spectrometry. We estimated differences in self-reported health outcomes, complete blood counts, cholinesterase activity, and serum/urine calcium and creatinine concentrations at baseline between farmworkers and comparison workers, and after pesticide spraying in farmworkers only. RESULTS: This study included 97 men between the ages of 22 and 76 years; 70 were conventional farmworkers; and 27 did not report any prior farmwork or pesticide spraying. None of the farmworkers wore standardized personal protective equipment (PPE) for the concentrated chemicals they were working with. Methomyl (8.4-13 481.9 ng/m3 ), ethyl chlorpyrifos (11.6-67 759 ng/m3 ), and metalaxyl (13.9-41 191.3 ng/m3 ) were detected via personal air sampling. When it came to reporting confidence in the ability to handle personal problems, only 43% of farmworkers reported feeling confident, which reflects higher stress levels in comparison to 78% of comparison workers (P = .028). Farmworkers also had significantly lower monocyte counts (P = .01), serum calcium (P = .01), red blood count (P = .01), white blood cell count (P = .04), and butyrylcholinesterase activity (P < .0001), relative to comparison workers. After adjusting for body mass index (BMI), age, and smoking, methomyl air concentrations were associated with a decrease in farmworker acetylcholinesterase activity (beta = -0.327, P = .016). CONCLUSIONS: This population of farmworkers had significant alterations in stress measures and clinical biomarkers, including decreased blood cell counts and cholinesterase activity, relative to matched controls. These changes are potentially linked to occupational pesticide exposures. Improving PPE use presents a likely route for preventive intervention in this population.


Assuntos
Agricultura , Fazendeiros/estatística & dados numéricos , Exposição Ocupacional/efeitos adversos , Praguicidas/toxicidade , Adulto , Idoso , Monitoramento Biológico , Biomarcadores/sangue , Biomarcadores/urina , Contagem de Células Sanguíneas , Cálcio/sangue , Cálcio/urina , Colinesterases/sangue , Creatinina/sangue , Creatinina/urina , Estudos Transversais , Monitoramento Ambiental , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Exposição Ocupacional/prevenção & controle , Equipamento de Proteção Individual/estatística & dados numéricos , Tailândia , Adulto Jovem
10.
J Am Soc Nephrol ; 32(8): 1961-1973, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34045313

RESUMO

BACKGROUND: Mutations in COL4A5 are responsible for 80% of cases of X-linked Alport Syndrome (XLAS). Although genes that cause AS are well characterized, people with AS who have similar genetic mutations present with a wide variation in the extent of kidney impairment and age of onset, suggesting the activities of modifier genes. METHODS: We created a cohort of genetically diverse XLAS male and female mice using the Diversity Outbred mouse resource and measured albuminuria, GFR, and gene expression. Using a quantitative trait locus approach, we mapped modifier genes that can best explain the underlying phenotypic variation measured in our diverse population. RESULTS: Genetic analysis identified several loci associated with the variation in albuminuria and GFR, including a locus on the X chromosome associated with X inactivation and a locus on chromosome 2 containing Fmn1. Subsequent analysis of genetically reduced Fmn1 expression in Col4a5 knockout mice showed a decrease in albuminuria, podocyte effacement, and podocyte protrusions in the glomerular basement membrane, which support the candidacy of Fmn1 as a modifier gene for AS. CONCLUSION: With this novel approach, we emulated the variability in the severity of kidney phenotypes found in human patients with Alport Syndrome through albuminuria and GFR measurements. This approach can identify modifier genes in kidney disease that can be used as novel therapeutic targets.


Assuntos
Albuminúria/urina , Colágeno Tipo IV/genética , Creatinina/urina , Forminas/genética , Nefrite Hereditária/genética , Albuminúria/etiologia , Animais , Mapeamento Cromossômico , Modelos Animais de Doenças , Feminino , Forminas/ultraestrutura , Expressão Gênica , Taxa de Filtração Glomerular , Masculino , Camundongos , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Mutação , Nefrite Hereditária/complicações , Nefrite Hereditária/fisiopatologia , Fenótipo , Podócitos/patologia , Estudo de Prova de Conceito , Locos de Características Quantitativas , RNA-Seq , Fatores Sexuais , Sequenciamento Completo do Genoma
11.
J Chromatogr A ; 1648: 462190, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33979756

RESUMO

A two-dimensional capillary isotachophoresis-capillary zone electrophoresis method hyphenated with tandem mass spectrometry was developed and validated for ultrasensitive quantification of serotonin in real human urine samples. Under optimal conditions, the separation was achieved within 12 min (including on-line sample preparation) with the limit of detection of 34 pg mL-1 (due to a large volume sample injection, here 10 µL, and isotachophoretic preconcentration). This concentration limit represents the lowest value for serotonin in comparison to other previously published separation methods employing mass spectrometry detection and applied to urine matrices. Thanks to high orthogonality, on-line concentration and clean-up effects of this approach, other excellent validation parameters such as linearity (coefficient of determination > 0.99), inter-day and intra-day precision (relative standard deviations 3.5-12.2%), accuracy (relative errors within 99-109.4%), and recovery (96-102%) could be easily obtained too. To demonstrate applicability of the method, we monitored serotonin levels in various real samples (from a healthy volunteer and clinical ones). The determined levels, normalized on the creatinine concentrations, were in the range of 6.81-12.86 ng mmol-1 creatinine This advanced method is suggested for an effective, reliable, high sample throughput, and low cost routine clinical screening or targeted metabolomic studies of serotonin in urine samples.


Assuntos
Eletroforese Capilar/métodos , Isotacoforese/métodos , Serotonina/urina , Espectrometria de Massas em Tandem/métodos , Creatinina/urina , Humanos , Limite de Detecção
12.
Medicine (Baltimore) ; 100(20): e26009, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011099

RESUMO

ABSTRACT: Increased water intake correlated to lower vasopressin level and may benefit kidney function. However, results of previous studies were conflicted and inconclusive. We aimed to investigate the association between water intake and risk of chronic kidney disease (CKD) and albuminuria.In this cross-sectional study, the study population were adult participants of 2011-2012 National Health and Nutrition Examination Survey (NHANES) whose estimated glomerular filtration rate (eGFR) were ≥30 ml/min/1.73 m2. Data of water intake were obtained from the NHANES 24-h dietary recall questionnaire. Participants were divided into three groups based on volume of water intake: <500 (low, n = 1589), ≥500 to <1200 (moderate, n = 1359), and ≥1200 ml/day (high, n = 1685). CKD was defined as eGFR <60 ml/min/1.73 m2, and albuminuria as albumin-to-creatinine ratio (ACR) ≥30 mg/g.Our results showed that 377 out of 4633 participants had CKD; the prevalence inversely correlated to volume of water intake: 10.7% in low, 8.2% in moderate, and 5.6% in high intake groups (P < .001). Prevalence of albuminuria was also lower in high (9.5%) compared with moderate (12.8%) and low intake groups (14.1%), P < .001. Additionally, water intake positively correlated to eGFR and negatively correlated to urinary ACR, as well as plasma and urine osmolality. Multivariable logistic regression showed that low water intake group had higher risk of CKD (OR 1.35, 95% CI 1.01-1.82) and albuminuria when compared to high water intake group (OR 1.42, 95% CI 1.13-1.79).In conclusion, increased water intake was associated lower risk of CKD and albuminuria. Meticulous studies are needed to elucidate the underlying mechanisms.


Assuntos
Albuminúria/epidemiologia , Ingestão de Líquidos/fisiologia , Insuficiência Renal Crônica/epidemiologia , Adulto , Idoso , Albuminúria/fisiopatologia , Albuminúria/urina , Creatinina/urina , Estudos Transversais , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais/estatística & dados numéricos , Prevalência , Fatores de Proteção , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina
13.
J Forensic Sci ; 66(5): 1855-1861, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33904587

RESUMO

Many illicit drug users attempt to manipulate urine drug testing; dilution is one of the methods. In screening tests, false-negative results below the cut-off values can create positive results after creatinine normalization. This study aimed to evaluate the impact of a creatinine reference value on the normalization of the drug concentration in diluted urine. The study focused on 25 630 cases and the following information: gender, age, urine collection time, drug screening test results, creatinine concentration (CR), and confirmation analysis result. Mean CR value was 143.71 ± 83.68 mg/dl. There was a significant difference between CR and gender (p = 0.03). The mean CR for women was lower than that for men. The correlation between age and CR was not significant (r = -0.08, p = 0.00). However, after grouping the sample into age groups of 10 years, there was a significant difference between age groups and mean CR (p = 0.00). The mean CR was significantly lower in the 0-9 year age group (n = 34) than in the 20-29 year age group (n = 10 943). According to the urine specimen collection time, CR levels during the early hours of the day (06:00-06:59) were lower than those during the remaining hours (p = 0.00). The highest converted drug-negative to drug-positive results were obtained from 153.23 mg/dl CR reference value. Reference CR values were evaluated according to gender, age, and urine collection time. Different rates of positive results were obtained for each reference value. There is no published local creatinine value for spot urine samples in many countries, including Turkey. This will be useful to develop appropriate normalization models when reporting drug test results.


Assuntos
Creatinina/urina , Detecção do Abuso de Substâncias , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores Sexuais , Transtornos Relacionados ao Uso de Substâncias/urina , Adulto Jovem
14.
Am J Kidney Dis ; 78(3): 350-360.e1, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33895181

RESUMO

RATIONALE & OBJECTIVE: Changes in urinary albumin-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) have been used separately as alternative kidney disease outcomes in randomized trials. We tested the hypothesis that combined changes in UACR and eGFR predict advanced kidney disease better than either alone. STUDY DESIGN: Observational cohort study. SETTING & PARTICIPANTS: 91,319 primary care patients assembled from the Clinical Practice Research Datalink in the United Kingdom between 2000 and 2015. EXPOSURES: Changes in UACR and eGFR (categorized as ≥30% increase, stable, or ≥30% decrease), alone and in combination, over a 3-year period. OUTCOMES: The primary outcome was advanced CKD (sustained eGFR <30 mL/min/1.73 m2); secondary outcomes included kidney failure, cardiovascular disease, and all-cause mortality. ANALYTICAL APPROACH: Multivariable Cox regression with bias from missing values assessed using multiple imputation; discrimination statistics compared across exposure groups. RESULTS: 91,319 individuals were studied, with a mean eGFR of 72.6 mL/min/1.73 m2 and median UACR of 9.7 mg/g; 70,957 (77.7%) had diabetes. During a median follow-up of 2.9 years, 2,541 people progressed to advanced CKD. Compared with stable values, hazard ratios for a ≥30% increase in UACR and ≥30% decrease in eGFR were 1.78 (95% CI, 1.59-1.98) and 7.53 (95% CI, 6.70-8.45), respectively, for the outcome of advanced CKD. Compared with stable values of both, the hazard ratio for the combination of an increase in UACR and a decrease in eGFR was 15.15 (95% CI, 12.43-18.46) for the outcome of advanced CKD. The combination of changes in UACR and eGFR predicted kidney outcomes better than either alone. LIMITATIONS: Selection bias, relatively small proportion of individuals without diabetes, and very few kidney failure events. CONCLUSIONS: In a large-scale general population, the combination of an increase in UACR and a decrease in eGFR was strongly associated with the risk of advanced CKD. Further assessment of combined changes in UACR and eGFR as an alternative outcome for kidney failure in trials of CKD progression is warranted.


Assuntos
Creatinina/urina , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Biomarcadores/urina , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/urina , Fatores de Risco , Urinálise
15.
Int J Mol Sci ; 22(6)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33801801

RESUMO

BACKGROUND: Vancomycin is commonly used as a first line therapy for gram positive organisms such as methicillin resistant Staphylococcusaureus. Vancomycin-induced acute kidney injury (V-AKI) has been reported in up to 43% of patients, especially in those with higher targeted trough concentrations. The precise mechanism of injury in humans remains elusive, with recent evidence directed towards proximal tubule cell apoptosis. In this study, we investigated the protein contents of urinary exosomes in patients with V-AKI to further elucidate biomarkers of mechanisms of injury and potential responses. METHODS: Urine samples from patients with V-AKI who were enrolled in the DIRECT study and matched healthy controls from the UAB-UCSD O'Brien Center Biorepository were included in the analysis. Exosomes were extracted using solvent exclusion principle and polyethylene glycol induced precipitation. Protein identity and quantification was determined by label-free liquid chromatography mass spectrometry (LC/MS). The mean peak serum creatinine was 3.7 ± 1.4 mg/dL and time to kidney injury was 4.0 ± 3.0 days. At discharge, 90% of patients demonstrated partial recovery; 33% experienced full recovery by day 28. Proteomic analyses on five V-AKI and 7 control samples revealed 2009 proteins in all samples and 251 proteins significantly associated with V-AKI (Pi-score > 1). The top discriminatory proteins were complement C3, complement C4, galectin-3-binding protein, fibrinogen, alpha-2 macroglobulin, immunoglobulin heavy constant mu and serotransferrin. CONCLUSION: Urinary exosomes reveal up-regulation of inflammatory proteins after nephrotoxic injury in V-AKI. Further studies are necessary in a large patient sample to confirm these findings for elucidation of pathophysiologic mechanisms and validation of potential injury biomarkers.


Assuntos
Injúria Renal Aguda/metabolismo , Biomarcadores/metabolismo , Exossomos/metabolismo , Inflamação/metabolismo , Proteômica/métodos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/urina , Adulto , Biomarcadores/urina , Cromatografia Líquida/métodos , Creatinina/urina , Humanos , Inflamação/urina , Masculino , Pessoa de Meia-Idade , Espectrometria de Massas em Tandem/métodos , Vancomicina/efeitos adversos , Adulto Jovem
16.
Nutrients ; 13(4)2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33920400

RESUMO

Sodium effects on proteinuria are debated. This observational, cross-sectional, population-based study investigated relationships to proteinuria and albuminuria of sodium intake assessed as urinary sodium/creatinine ratio (NaCR). In 482 men and 454 women aged 35-94 years from the Moli-sani study, data were collected for the following: urinary NaCR (independent variable); urinary total proteins/creatinine ratio (PCR, mg/g), urinary albumin/creatinine ratio (ACR, mg/g), and urinary non-albumin-proteins/creatinine ratio (calculated as PCR minus ACR) (dependent variables). High values were defined as PCR ≥ 150 mg/g, ACR ≥ 30 mg/g, and urinary non-albumin-proteins/creatinine ratio ≥ 120 mg/g. Urinary variables were measured in first-void morning urine. Skewed variables were log-transformed in analyses. The covariates list included sex, age, energy intake, body mass index, waist/hip ratio, estimated urinary creatinine excretion, smoking, systolic pressure, diastolic pressure, diabetes, history of cardiovascular disease, reported treatment with antihypertensive drug, inhibitor or blocker of the renin-angiotensin system, diuretic, and log-transformed data of total physical activity, leisure physical activity, alcohol intake, and urinary ratios of urea nitrogen, potassium, and phosphorus to creatinine. In multivariable linear regression, standardized beta coefficients of urinary NaCR were positive with PCR (women and men = 0.280 and 0.242, 95% confidence interval = 0.17/0.39 and 0.13/0.35, p < 0.001), ACR (0.310 and 0.265, 0.20/0.42 and 0.16/0.38, p < 0.001), and urinary non-albumin-proteins/creatinine ratio (0.247 and 0.209, 0.14/0.36 and 0.09/0.33, p < 0.001). In multivariable logistic regression, higher quintile of urinary NaCR associated with odds ratio of 1.81 for high PCR (1.55/2.12, p < 0.001), 0.51 of 1.62 for high ACR (1.35/1.95, p < 0.001), and of 1.84 for high urinary non-albumin proteins/creatinine ratio (1.58/2.16, p < 0.001). Findings were consistent in subgroups. Data indicate independent positive associations of an index of sodium intake with proteinuria and albuminuria in the population.


Assuntos
Creatinina/urina , Proteinúria/epidemiologia , Sódio na Dieta/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Proteinúria/diagnóstico , Proteinúria/etiologia , Proteinúria/urina , Sódio na Dieta/urina
17.
Nutrients ; 13(3)2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33802012

RESUMO

The effects of beta-hydroxy-beta-methylbutyrate (HMB) complex administration and the significance of titin, a biomarker of muscle injury, in elderly minor trauma patients in acute phase has not been established. In this single-center, randomized controlled study, trauma patients aged ≥ 70 years with an injury severity score < 16 were included. Titin values on days 1 and 3 were measured and the intervention group received HMB complex (2.4 g of HMB + 14 g of glutamine + 14 g of arginine) and the control group received glutamine complex (7.2 g of protein including 6 g of glutamine). The cross-sectional area of the rectus femoris (RFCSA) on ultrasound, grip strength, and the Barthel Index were assessed on the first day of rehabilitation and after 2 weeks. We analyzed 24 HMB and 25 control participants. Titin values on day 3 correlated with grip strength (r = -0.34, p = 0.03) and the Barthel Index (r = -0.39, p = 0.01) at follow-up. HMB complex supplementation had no effect on the RFCSA (2.41 vs. 2.45 cm2, p = 0.887), grip strength (13.3 vs. 13.1 kg, p = 0.946), or the Barthel Index (20.0 vs. 50.0, p = 0.404) at follow-up. Titin values might associate with subsequent physical function. Short-term HMB complex supplementation from acute phase did not ameliorate muscle injury.


Assuntos
Conectina/urina , Músculo Esquelético/lesões , Fragmentos de Peptídeos/urina , Valeratos/administração & dosagem , Ferimentos e Lesões/terapia , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Creatinina/urina , Suplementos Nutricionais , Feminino , Força da Mão , Humanos , Masculino , Músculo Esquelético/patologia
18.
N Engl J Med ; 384(13): 1216-1226, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33789010

RESUMO

BACKGROUND: Primary hyperoxaluria type 1 (PH1) is a rare genetic disease caused by hepatic overproduction of oxalate that leads to kidney stones, nephrocalcinosis, kidney failure, and systemic oxalosis. Lumasiran, an investigational RNA interference (RNAi) therapeutic agent, reduces hepatic oxalate production by targeting glycolate oxidase. METHODS: In this double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with PH1 who were 6 years of age or older to receive subcutaneous lumasiran or placebo for 6 months (with doses given at baseline and at months 1, 2, 3, and 6). The primary end point was the percent change in 24-hour urinary oxalate excretion from baseline to month 6 (mean percent change across months 3 through 6). Secondary end points included the percent change in the plasma oxalate level from baseline to month 6 (mean percent change across months 3 through 6) and the percentage of patients with 24-hour urinary oxalate excretion no higher than 1.5 times the upper limit of the normal range at month 6. RESULTS: A total of 39 patients underwent randomization; 26 were assigned to the lumasiran group and 13 to the placebo group. The least-squares mean difference in the change in 24-hour urinary oxalate excretion (lumasiran minus placebo) was -53.5 percentage points (P<0.001), with a reduction in the lumasiran group of 65.4% and an effect seen as early as month 1. The between-group differences for all hierarchically tested secondary end points were significant. The difference in the percent change in the plasma oxalate level (lumasiran minus placebo) was -39.5 percentage points (P<0.001). In the lumasiran group, 84% of patients had 24-hour urinary oxalate excretion no higher than 1.5 times the upper limit of the normal range at month 6, as compared with 0% in the placebo group (P<0.001). Mild, transient injection-site reactions were reported in 38% of lumasiran-treated patients. CONCLUSIONS: Lumasiran reduced urinary oxalate excretion, the cause of progressive kidney failure in PH1. The majority of patients who received lumasiran had normal or near-normal levels after 6 months of treatment. (Funded by Alnylam Pharmaceuticals; ILLUMINATE-A ClinicalTrials.gov number, NCT03681184.).


Assuntos
Hiperoxalúria Primária/tratamento farmacológico , Oxalatos/urina , RNA Interferente Pequeno/uso terapêutico , Terapêutica com RNAi , Adolescente , Adulto , Criança , Creatinina/urina , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Humanos , Hiperoxalúria Primária/sangue , Hiperoxalúria Primária/complicações , Hiperoxalúria Primária/urina , Cálculos Renais/prevenção & controle , Masculino , Pessoa de Meia-Idade , Oxalatos/sangue , Oxalatos/metabolismo , RNA Interferente Pequeno/efeitos adversos , Adulto Jovem
19.
J Am Soc Nephrol ; 32(5): 1210-1226, 2021 05 03.
Artigo em Inglês | MEDLINE | ID: mdl-33782168

RESUMO

BACKGROUND: Urinary extracellular vesicles (uEVs) are a promising source for biomarker discovery, but optimal approaches for normalization, quantification, and characterization in spot urines are unclear. METHODS: Urine samples were analyzed in a water-loading study, from healthy subjects and patients with kidney disease. Urine particles were quantified in whole urine using nanoparticle tracking analysis (NTA), time-resolved fluorescence immunoassay (TR-FIA), and EVQuant, a novel method quantifying particles via gel immobilization. RESULTS: Urine particle and creatinine concentrations were highly correlated in the water-loading study (R 2 0.96) and in random spot urines from healthy subjects (R 2 0.47-0.95) and patients (R 2 0.41-0.81). Water loading reduced aquaporin-2 but increased Tamm-Horsfall protein (THP) and particle detection by NTA. This finding was attributed to hypotonicity increasing uEV size (more EVs reach the NTA size detection limit) and reducing THP polymerization. Adding THP to urine also significantly increased particle count by NTA. In both fluorescence NTA and EVQuant, adding 0.01% SDS maintained uEV integrity and increased aquaporin-2 detection. Comparison of intracellular- and extracellular-epitope antibodies suggested the presence of reverse topology uEVs. The exosome markers CD9 and CD63 colocalized and immunoprecipitated selectively with distal nephron markers. Conclusions uEV concentration is highly correlated with urine creatinine, potentially replacing the need for uEV quantification to normalize spot urines. Additional findings relevant for future uEV studies in whole urine include the interference of THP with NTA, excretion of larger uEVs in dilute urine, the ability to use detergent to increase intracellular-epitope recognition in uEVs, and CD9 or CD63 capture of nephron segment-specific EVs.


Assuntos
Vesículas Extracelulares/metabolismo , Nefropatias/diagnóstico , Nefropatias/urina , Adulto , Biomarcadores/urina , Estudos de Casos e Controles , Creatinina/urina , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Urinálise
20.
Ren Fail ; 43(1): 452-459, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33657976

RESUMO

BACKGROUND: Diabetic kidney diseases (DKD) were the leading cause of End-stage renal diseases worldwide. Albuminuria was a target for treatment in DKD and decreasing albuminuria was particularly important for improving its prognosis. However, there is still a lack of specific treatment for DKD. METHODS: We conducted a prospective, crossover, open-label study to investigate the effect of amiloride in patients with DKD. Safety and efficacy were assessed by monitoring urine protein creatinine ratio(uPCR), urinary albumin creatinine ratio (uACR), blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid, serum soluble urokinase-type plasminogen activator receptor (suPAR) and urinary suPAR. Ten subjects were enrolled in the trial. RESULTS: In this prospective, crossover, open-label design, amiloride could induce a significant decrease of uACR in DKD. The decrease of serum and urinary suPAR in the amiloride/hydrochlorothiazide (HCTZ) group was also significant compared with those patients using HCTZ as the control group. Correlation analysis showed that the levels of urinary suPAR were positively associated with uPCR and uACR. No significant difference in blood pressure, weight, serum sodium, serum potassium, cholesterol, triglyceride, uric acid was seen between the amiloride/HCTZ group and the control group. CONCLUSION: In summary, among patients with DKD, amiloride could decrease albuminuria without severe side effects, which was accompanied by the significant decline of urinary suPAR.


Assuntos
Albuminúria/tratamento farmacológico , Amilorida/uso terapêutico , Nefropatias Diabéticas/tratamento farmacológico , Hidroclorotiazida/uso terapêutico , Receptores de Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Idoso , Albuminúria/urina , Creatinina/urina , Estudos Cross-Over , Nefropatias Diabéticas/urina , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
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