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1.
Arch Pathol Lab Med ; 144(10): 1199-1203, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33002152

RESUMO

CONTEXT.­: The burden of chronic kidney disease in Indigenous Australians is 7.3 times higher than that of non-Indigenous Australians. If chronic kidney disease is detected early and managed, deterioration in kidney function can be reduced. Urine albumin to creatinine ratio is a key marker of early renal damage. OBJECTIVE.­: To report on 16 years of analytic quality of urine albumin to creatinine ratio testing on Siemens DCA devices enrolled in the national Quality Assurance for Aboriginal and Torres Strait Islander Medical Services point-of-care testing program. DESIGN.­: Quality Assurance for Aboriginal and Torres Strait Islander Medical Services participants are required to test 2 quality assurance samples each month across two 6-monthly testing cycles per year. Participants also test 2 quality control samples monthly. RESULTS.­: The percentage of urine albumin, creatinine, and albumin to creatinine ratio results for quality assurance point-of-care testing that were within assigned allowable limits of performance averaged 96.9%, 95.9%, and 97.5%, respectively. The percentage acceptable quality control results for urine albumin and creatinine averaged 93.5% and 86.8%. The median imprecision for urine albumin, creatinine, and albumin to creatinine ratio quality assurance testing averaged 5.5%, 4.1%, and 3.3%, respectively, and the median within-site imprecision for quality control testing averaged 5.4%, 4.3%, and 5.7%, respectively, for the low sample and 4.0%, 4.1%, and 4.5%, respectively, for the high sample. CONCLUSIONS.­: For 16 years the DCA system has proven to be reliable and robust and operators at Aboriginal medical services have demonstrated they are able to conduct point-of-care testing for urine albumin to creatinine ratio that consistently meets analytic performance standards.


Assuntos
Albuminúria/urina , Creatinina/urina , Testes Imediatos , Insuficiência Renal Crônica/diagnóstico , Austrália , Humanos , Grupo com Ancestrais Oceânicos , Garantia da Qualidade dos Cuidados de Saúde , Controle de Qualidade , Insuficiência Renal Crônica/urina , Urinálise
2.
N Engl J Med ; 383(12): 1117-1128, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32937045

RESUMO

BACKGROUND: In adults with active lupus nephritis, the efficacy and safety of intravenous belimumab as compared with placebo, when added to standard therapy (mycophenolate mofetil or cyclophosphamide-azathioprine), are unknown. METHODS: In a phase 3, multinational, multicenter, randomized, double-blind, placebo-controlled, 104-week trial conducted at 107 sites in 21 countries, we assigned adults with biopsy-proven, active lupus nephritis in a 1:1 ratio to receive intravenous belimumab (at a dose of 10 mg per kilogram of body weight) or matching placebo, in addition to standard therapy. The primary end point at week 104 was a primary efficacy renal response (a ratio of urinary protein to creatinine of ≤0.7, an estimated glomerular filtration rate [eGFR] that was no worse than 20% below the value before the renal flare (pre-flare value) or ≥60 ml per minute per 1.73 m2 of body-surface area, and no use of rescue therapy), and the major secondary end point was a complete renal response (a ratio of urinary protein to creatinine of <0.5, an eGFR that was no worse than 10% below the pre-flare value or ≥90 ml per minute per 1.73 m2, and no use of rescue therapy). The time to a renal-related event or death was assessed. RESULTS: A total of 448 patients underwent randomization (224 to the belimumab group and 224 to the placebo group). At week 104, significantly more patients in the belimumab group than in the placebo group had a primary efficacy renal response (43% vs. 32%; odds ratio, 1.6; 95% confidence interval [CI], 1.0 to 2.3; P = 0.03) and a complete renal response (30% vs. 20%; odds ratio, 1.7; 95% CI, 1.1 to 2.7; P = 0.02). The risk of a renal-related event or death was lower among patients who received belimumab than among those who received placebo (hazard ratio, 0.51; 95% CI, 0.34 to 0.77; P = 0.001). The safety profile of belimumab was consistent with that in previous trials. CONCLUSIONS: In this trial involving patients with active lupus nephritis, more patients who received belimumab plus standard therapy had a primary efficacy renal response than those who received standard therapy alone. (Funded by GlaxoSmithKline; BLISS-LN ClinicalTrials.gov number, NCT01639339.).


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Azatioprina/uso terapêutico , Creatinina/urina , Ciclofosfamida/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Inibidores Enzimáticos/uso terapêutico , Feminino , Taxa de Filtração Glomerular , Humanos , Imunossupressores/efeitos adversos , Infusões Intravenosas , Análise de Intenção de Tratamento , Nefrite Lúpica/mortalidade , Masculino , Ácido Micofenólico/uso terapêutico , Indução de Remissão
3.
N Engl J Med ; 383(12): 1149-1155, 2020 09 17.
Artigo em Inglês | MEDLINE | ID: mdl-32937047

RESUMO

Daratumumab, a human monoclonal antibody that targets CD38, depletes plasma cells and is approved for the treatment of multiple myeloma. Long-lived plasma cells are implicated in the pathogenesis of systemic lupus erythematosus because they secrete autoantibodies, but they are unresponsive to standard immunosuppression. We describe the use of daratumumab that induced substantial clinical responses in two patients with life-threatening lupus, with the clinical responses sustained by maintenance therapy with belimumab, an antibody to B-cell activating factor. Significant depletion of long-lived plasma cells, reduction of interferon type I activity, and down-regulation of T-cell transcripts associated with chronic inflammation were documented. (Supported by the Deutsche Forschungsgemeinschaft and others.).


Assuntos
ADP-Ribosil Ciclase 1/antagonistas & inibidores , Anticorpos Monoclonais/uso terapêutico , Imunossupressores/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Glicoproteínas de Membrana/antagonistas & inibidores , Plasmócitos/efeitos dos fármacos , ADP-Ribosil Ciclase 1/metabolismo , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Creatinina/sangue , Creatinina/urina , Regulação para Baixo , Feminino , Humanos , Interferon Tipo I/antagonistas & inibidores , Quimioterapia de Manutenção , Glicoproteínas de Membrana/metabolismo , Pessoa de Meia-Idade , Proteinúria , Linfócitos T/efeitos dos fármacos , Linfócitos T/metabolismo
5.
Nutr. hosp ; 37(3): 436-442, mayo-jun. 2020. tab, graf
Artigo em Inglês | IBECS | ID: ibc-193849

RESUMO

Aim and background: the incidence of obesity has increased among children, and obesity has been considered an independent risk factor for chronic kidney disease. We aimed to determine the degree of kidney function impairment by evaluating urine neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) levels. MATERIALS AND METHODS: in total, 15 obese, 26 overweight, and 26 control adolescents aged 10 to 16 years were enrolled into the study. Urine samples were evaluated for NGAL and KIM-1 levels using enzyme-linked immunosorbent assay kits. We investigated the association between obesity and related comorbidities with urinary NGAL and KIM-1 excretion. RESULTS: no significant differences were noted between the obese, overweight, and control groups in urinary NGAL and KIM-1 excretion (p = 0.327 and p = 0.917, respectively). In the obese and overweight groups urinary NGAL levels were 50.39 [30.88-74.22] in females and 26.67 [23.24-45.59] in males (p = 0.013). Also, urinary NGAL levels were increased in obese and overweight adolescents with LDL dyslipidemia at 64.12 [30.98-114.32] as compared to those without LDL dyslipidemia: 39.51 [25.59.56.37] (p = 0.024). Furthermore, a correlation was observed between insulin and homeostasis model assessment of insulin resistance levels with the NGAL/creatinine ratio in the overweight group (r = 0.515; p = 0.008, and r = 0.483; p = 0.014, respectively). Such correlation was not found in the obese group. CONCLUSION: the effect of obesity on renal function could not be determined in children. A longer exposure may be required for obesity-induced disruption of renal function in children. Renal function may be disrupted by dyslipidemia in obese adolescents. Furthermore, obesity impaired renal function in female adolescents. The normalization of these urinary markers as related to urine creatinine should be discussed


INTRODUCCIÓN: la incidencia de la obesidad en la edad infantil ha aumentado. Se considera la obesidad como un factor de riesgo independiente para el desarrollo de la enfermedad renal crónica. El objetivo de este estudio fue valorar el grado de alteración de la función renal evaluando los niveles urinarios de NGAL y KIM-1. MATERIAL Y MÉTODOS: el estudio incluyó a 15 adolescentes con obesidad, 26 con sobrepeso y 26 controles sanos. Las edades de los participantes estaban entre los 10 y los 16 años. Los niveles de NGAL y KIM-1 en orina se determinaron mediante un kit ELISA. Se investigó la asociación entre la obesidad y su comorbilidad con la excreción urinaria de NGAL y KIM-1. RESULTADOS: no se encontraron diferencias significativas en la excreción urinaria de NGAL y KIM-1 entre los sujetos con obesidad, los sujetos con sobrepeso y los controles sanos (p = 0,327 y 0,917, respectivamente). En el grupo con sobrepeso y obesidad, los niveles de NGAL en las niñas fueron de 50,39 (30,88-74,22), mientras que en los niños fueron de 26,67 (23,24-45,59) (p = 0,013). Para los sujetos con dislipemia de LDL, el nivel de NGAL fue de 64,12 (30,98-114,32) frente a 39,5 (25,59-56,37) entre los que no la tenían (p = 0,024). Se encontró correlación entre los nivles de insulina, el HOMA-IR y la ratio NGAL/creatinina en el grupo con sobrepeso (r = 0,515; p = 0,008, y r = 0,483; p = 0,014, respectivamente). En el grupo con obesidad no se encontró dicha correlación. CONCLUSIONES: se precisa una duración más prolongada para encontrar alterada la función renal en los niños con exceso de peso. La función renal puede alterase por la dislipemia en el caso de los adolescentes con obesidad. La función renal se afecta más en las adolescentes femeninas. En el artículo se discute la normalización de estos marcadores urinarios con la creatinina en orina


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Lipocalina-2/análise , Obesidade/epidemiologia , Sobrepeso/epidemiologia , Lipocalina-2/urina , Creatinina/urina , Sobrepeso/diagnóstico , Obesidade/diagnóstico , Ensaio de Imunoadsorção Enzimática/métodos
6.
Artigo em Inglês | MEDLINE | ID: mdl-32545523

RESUMO

Preeclampsia affects 2-5% of pregnant women and is one of the leading causes of maternal and perinatal morbidity and mortality. We aimed to extensively evaluate proteinuria in women with preeclampsia and to determine the analytical sensitivity and specificity of and the cutoff values for urine protein-to-creatinine ratio (UPCR) and total protein in 24 h urine samples. This study included 88 women. We used the urine dipstick test, UPCR, and total protein measurement in a 24 h urine sample. The patients were divided in gestational hypertension (GH, n = 44) and preeclampsia (PE, n = 44) groups. In the GH group, 25% (11/44) of the patients presented incidentally positive results. UPCR and total protein in 24 h urine specimens were increased in the GH group compared to the PE group. Receiver operating characteristic analysis showed a UPCR cutoff of 30 mg/mmol as significant for preeclampsia, while the sensitivity and specificity were 89% (95% CI, 75-97) and 100% (95% CI, 87-100), respectively. In the 24 h urine protein test, sensitivity and specificity were 80% (95% CI, 61-92) and 100% (95% CI, 88-100), respectively, for the cutoff value of 0.26 g/24 h. In comparison to the other commonly used tests here considered, UPCR determination is a reliable, relatively faster, and equally accurate method for the quantitation of proteinuria, correlates well with 24 h urine protein estimations, and could be used as an alternative to the 24 h proteinuria test for the diagnosis of preeclampsia.


Assuntos
Pré-Eclâmpsia , Proteinúria , Adulto , Creatina/urina , Creatinina/urina , Feminino , Humanos , Pré-Eclâmpsia/diagnóstico , Gravidez , Estudos Prospectivos , Proteínas , Sensibilidade e Especificidade , Urinálise , Adulto Jovem
7.
Diabetes Res Clin Pract ; 165: 108272, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32561454

RESUMO

BACKGROUND: Several studies have indicated that high albuminuria is associated with renal function decline. However, the relationship between the urinary albumin-to-creatinine ratio (ACR) and risk of developing tubular injury remains unclear. Our aim was to investigate the association of ACR with the risk of developing tubular impairment in patients with type 2 diabetes. METHODS: This longitudinal observational study compared baseline with follow-up data in 183 patients with type 2 diabetes. ACR, urinary alpha-1-microglobulin-to-creatinine ratio (A1MCR) and estimated glomerular filtration rate (eGFR) were used to evaluate albuminuira, tubular injury and glomerular filtration function, respectively. RESULTS: Levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and A1MCR were significantly different at the two-year follow-up compared with baseline levels. Among patients both with baseline ACR above and below 30 mg/g, the percentage with A1MCR > 15 mg/g clearly increased after follow-up (P < 0.05). The risk of A1MCR rising from normal ranges to >15 mg/g over the follow-up increased with increasing baseline ACR values lower baseline eGFR. Among the patients with baseline ACR > 63.10 mg/g, all showed increased A1MCR values at follow-up compared with baseline. In the multivariate regression analysis, the patients with baseline ACR > 63.10 mg/g had a strong risk of A1MCR rising from normal to >15 mg/g (odds ratio (OR) = 11.12, P = 0.001) over the follow-up, while the males had a 2.89-fold risk of A1MCR increasing from normal to >15 mg/g compared with females. CONCLUSION: Baseline ACR level is related to increased risk of developing renal tubular injury; in particular, this association is much stronger in patients with type 2 diabetes and baseline ACR > 63.10 mg/g.


Assuntos
Albuminúria/urina , Creatinina/urina , Diabetes Mellitus Tipo 2/complicações , Testes de Função Renal/métodos , Insuficiência Renal/diagnóstico , Insuficiência Renal/urina , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco
8.
Eur J Endocrinol ; 183(2): 129-139, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32413848

RESUMO

Background: In patients with phaeochromocytomas or paragangliomas (PPGLs), 24-h urine collections for metanephrines (uMNs) are cumbersome. Objective: To evaluate the diagnostic utility of ratios to creatinine of 'spot' uMNs. Methods: Concentrations of uMNs and plasma metanephrines (pMNs) were measured by HPLC-mass-spectrometry. We retrospectively compared correlations of 24-h-urine output and ratio to creatinine in historical specimens and prospectively assessed 24-h and contemporaneous spot urines and, where possible, pMNs. Using trimmed log-transformed values, we derived reference intervals based on age and sex for spot urines. We used multiples of upper limit of normal (ULNs) to compare areas under curves (AUCs) for receiver-operator characteristic curves of individual, and sum and product of, components. Results: In 3143 24-h-urine specimens on 2416 patients, the correlation coefficients between the ratios and outputs of metanephrine, normetanephrine and 3-methoxytyramine in 24-h urines were 0.983, 0.905 and 0.875, respectively. In 96 patients, the correlations between plasma concentrations, urine output and ratios in spot specimens were similar to those for raw output or ratios in 24-h specimens. Of the 160 patients with PPGLs, the CIs for AUCs for individual metabolites overlapped for all four types of measurement, as did those for the sum of the multiple ULNs although these were slightly higher (AUC for spot urine: 0.838 (0.529-1), plasma: 0.929 (0.874-0.984) and output: 0.858 (0.764-0.952)). Conclusions: Ratios of fractionated metanephrines to creatinine in spot urine samples appear to have a similar diagnostic power to other measurements. The ease of spot urine collection may facilitate diagnosis and follow-up of PPGLs through improved patient compliance.


Assuntos
Neoplasias das Glândulas Suprarrenais/urina , Metanefrina/sangue , Metanefrina/urina , Paraganglioma/urina , Feocromocitoma/urina , Adolescente , Neoplasias das Glândulas Suprarrenais/sangue , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Cromatografia Líquida de Alta Pressão , Creatinina/sangue , Creatinina/urina , Dopamina/análogos & derivados , Dopamina/sangue , Dopamina/urina , Feminino , Humanos , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Normetanefrina/sangue , Normetanefrina/urina , Paraganglioma/sangue , Feocromocitoma/sangue , Curva ROC , Valores de Referência , Estudos Retrospectivos , Fatores Sexuais , Adulto Jovem
9.
Transl Res ; 222: 17-27, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32438071

RESUMO

The mineralocorticoid receptor antagonist spironolactone significantly reduces albuminuria in subjects with diabetic kidney disease, albeit with a large variability between individuals. Identifying novel biomarkers that predict response to therapy may help to tailor spironolactone therapy. We aimed to identify a set of metabolites for prediction of albuminuria response to spironolactone in subjects with type 2 diabetes. Systems biology molecular process analysis was performed a priori to identify metabolites linked to molecular disease processes and drug mechanism of action. Individual subject data and urine samples were used from 2 randomized placebo controlled double blind clinical trials (NCT01062763, NCT00381134). A urinary metabolite score was developed to predict albuminuria response to spironolactone therapy using penalized ridge regression with leave-one-out cross validation. Bioinformatic analysis identified a set of 18 metabolites linked to a diabetic kidney disease molecular model and potentially affected by spironolactone mechanism of action. Spironolactone reduced UACR relative to placebo by median -42% (25th to 75% percentile -65 to 6) and -29% (25th to 75% percentile -37 to -1) in the test and replication cohorts, respectively. In the test cohort, UACR reduction was higher in the lowest tertile of the baseline urinary metabolite score compared with middle and upper tertiles -58% (25th to 75% percentile -78 to 33), -28% (25th to 75% percentile -46 to 8), -40% (25th to 75% percentile -52% to 31), respectively, P = 0.001 for trend). In the replication cohort, UACR reduction was -54% (25th to 75% percentile -65 to -50), -41 (25th to 75% percentile -46% to 30), and -17% (25th to 75% percentile -36 to 5), respectively, P = 0.010 for trend). We identified a set of 18 urinary metabolites through systems biology to predict albuminuria response to spironolactone in type 2 diabetes. These data suggest that urinary metabolites may be used as a tool to tailor optimal therapy and move in the direction of personalized medicine.


Assuntos
Albuminúria/tratamento farmacológico , Albuminúria/urina , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/urina , Metaboloma , Espironolactona/uso terapêutico , Albuminas/análise , Creatinina/urina , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biologia de Sistemas
10.
J Korean Med Sci ; 35(13): e95, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32242346

RESUMO

BACKGROUND: The 24-hour uric acid excretion measurement is important in assessing disease status and helping to select the appropriate uric acid-lowering agent for patients with gout, however, it is inconvenient. The authors investigated the efficacy of the random urine uric acid-to-creatinine (UA/CR) ratio to screen the patients who under-secreted 24-hour urine uric acid. METHODS: This was a retrospective cross-sectional study. Ninety patients with gout, without undergoing uric acid-lowering treatment were enrolled. Twenty-four-hour urine and random urine samples were obtained on the same day. Six hundred mg of uric acid in the 24-hour urine sample was used as a standard for distinguishing between over and under-excretion groups. RESULTS: The random urinary UA/CR ratio showed positive correlation with 24-hour urine uric acid excretion (γ = 0.398, P < 0.001). All the patients with the random UA/CR less than 0.2 excreted less than 600 mg uric acid in 24-hour urine collection. When the random urine UA/CR ratio < 0.2 was regarded as a positive result, the positive predictive value, negative predictive value, sensitivity, and specificity in the uric acid under-excretion were 100% (8 of 8), 64.6% (53 of 82), 21.6% (8 of 37), and 100% (53 of 53), respectively. CONCLUSION: There is a moderate positive correlation between the random urinary UA/CR ratio and 24-hour urine uric acid excretion, so that UA/CR ratio may not be a good predictor of 24-hour urine uric acid excretion. However, the random urine UA/CR ratio 0.2 can be a useful predictor to screen the gouty patients who need to be treated with uricosuric drugs.


Assuntos
Creatinina , Gota , Ácido Úrico , Uricosúricos , Adulto , Idoso , Creatinina/urina , Estudos Transversais , Feminino , Gota/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Ácido Úrico/urina , Uricosúricos/uso terapêutico
11.
Int J Clin Oncol ; 25(7): 1278-1284, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32347432

RESUMO

BACKGROUND: Proteinuria induced by lenvatinib is a class effect that occurs secondary to VEGFR suppression. Withholding of lenvatinib is required in cases with severe proteinuria. Urine protein-creatinine ratio (UPCR, g/gCre) has recently attracted attention as an alternative to 24-h urine collection for assessing proteinuria. The aim of this study was to examine the correlation between the results of proteinuria assessed by the dipstick test and UPCR, and to investigate the influence of proteinuria grading with UPCR on lenvatinib dose adjustment compared to that with only the dipstick test. METHOD: Three hundred and ten urine samples from 63 patients with advanced thyroid cancer under treatment with lenvatinib, which were tested by both the dipstick test and UPCR were analyzed. Lenvatinib was withheld when there was evidence of CTCAE grade 3 proteinuria, and restarted when it resolved. The frequency of proteinuria, correlation between the results of the dipstick test and UPCR test, and the effect of dose withholding in cases with results of 3 + in the dipstick test were calculated. RESULTS: Proteinuria was seen in 56 (88.9%) patients. Of the 154 dipstick 3 + samples, only 56 (36.4%) were judged as more than 3.5 g/gCre by UPCR (grade 3 proteinuria), although none of the 1 + and only 3.7% of 2 + samples were judged as grade 3 proteinuria. We were able to prevent unnecessary lenvatinib interruption due to proteinuria in 63.6% of dipstick 3 + samples by assessment of UPCR. CONCLUSIONS: Urinalysis by combination of the dipstick test and UPCR assessment might be a better strategy for preventing unnecessary interruption of lenvatinib.


Assuntos
Antineoplásicos/efeitos adversos , Compostos de Fenilureia/efeitos adversos , Proteinúria/induzido quimicamente , Quinolinas/efeitos adversos , Neoplasias da Glândula Tireoide/tratamento farmacológico , Urinálise/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Creatinina/urina , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/uso terapêutico , Proteinúria/diagnóstico , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Neoplasias da Glândula Tireoide/mortalidade , Neoplasias da Glândula Tireoide/urina
12.
Pregnancy Hypertens ; 20: 92-95, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32203727

RESUMO

The diagnosis of preeclampsia superimposed on underlying kidney disease is complicated by physiological changes in renal function, blood pressure and proteinuria during pregnancy. Previous studies have demonstrated a significant increase in proteinuria during pregnancy in women with diabetic nephropathy in the absence of superimposed preeclampsia. There is a paucity of studies addressing changes in proteinuria during pregnancy in other conditions causing chronic kidney disease. A retrospective audit of changes in urine protein:creatinine ratios in 68 pregnancies to women with preconception proteinuria was performed, to determine whether changes in proteinuria may be useful in diagnosing preeclampsia. A 100% or greater increase in proteinuria from baseline increase was regarded as a significant change. In 51 pregnancies (75%) the peak urine protein:creatinine ratio did not rise significantly from values at the start of pregnancy. Where a greater than doubling of urine protein:creatinine ratio was seen, 12 of 17 pregnancies (70%) were judged clinically to have superimposed preeclampsia A significant increase in proteinuria also occurred in 3 women with lupus nephritis, and 2 with diabetic nephropathy, in the absence of preeclampsia. Larger studies of women with chronic kidney disease would be important to determine whether changes in proteinuria during pregnancy may be of diagnostic value for superimposed preeclampsia.


Assuntos
Pressão Sanguínea , Rim/fisiopatologia , Pré-Eclâmpsia/diagnóstico , Proteinúria/diagnóstico , Insuficiência Renal Crônica/diagnóstico , Adulto , Biomarcadores/urina , Creatinina/urina , Feminino , Humanos , Pré-Eclâmpsia/fisiopatologia , Valor Preditivo dos Testes , Gravidez , Proteinúria/etiologia , Proteinúria/fisiopatologia , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Adulto Jovem
13.
Ecotoxicol Environ Saf ; 195: 110467, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32182532

RESUMO

Heavy metals and pesticides can be easily enriched in food chains and accumulated in organisms, thus pose significant threat to human health. However, their combined effects for long-term exposure at low dose has not been thoroughly investigated; especially there was no biofluid biomarker available to noninvasively diagnose the toxicosis of the combined exposure of the two chemicals at their low levels. In this study, we investigated the change of urine metabolites of rats with 90-day exposure to heavy metal cadmium (Cd) and/or organophosphorus pesticide chlorpyrifos (CPF) using gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach. Our results showed that the interaction of Cd and CPF mainly displayed an antagonistic effect. We identified the panels of metabolite biomarkers in urine: benzoic acid and mannose were unique biomarkers for Cd exposure; creatinine and N-phenylacetyl glycine were unique biomarkers for CPF exposure; anthranilic acid, ribitol, and glucose were unique biomarkers for Cd plus CPF exposure. Our results suggest that 90-day exposure to Cd and/or CPF could cause a disturbance in energy and amino acid metabolism. And urine metabolomics analysis can help understand the toxicity of low dose exposure to mixed environmental chemicals.


Assuntos
Cádmio/toxicidade , Clorpirifos/toxicidade , Inseticidas/toxicidade , Animais , Ácido Benzoico/urina , Biomarcadores/urina , Creatinina/urina , Interações Medicamentosas , Cromatografia Gasosa-Espectrometria de Massas , Glicina/análogos & derivados , Glicina/urina , Masculino , Manose/urina , Metabolômica , Ratos
15.
Am J Epidemiol ; 189(9): 942-950, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32219380

RESUMO

Few studies have comprehensively investigated the association of 2 key kidney disease measures, estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (ACR), with cancer incidence. In 8,935 participants at the baseline (1996-1998) from the Atherosclerosis Risk in Communities study, we quantified the associations of eGFR (based on creatinine and cystatin C) and ACR with cancer risk using Cox regression models adjusted for potential confounders. Due to changing guidelines for prostate cancer screening during the follow-up period, we investigated overall cancer, overall nonprostate cancer, and site-specific cancer. During a median follow-up of 14.7 years, 2,030 incident cancer cases occurred. In demographically adjusted models, low eGFR and high ACR were associated with cancer incidence (both overall and overall nonprostate cancer). These associations were attenuated after adjusting for other shared risk factors, with a significant association remaining only for ACR (≥103 compared with 5 mg/g) and overall nonprostate cancer. For site-specific cancer, only high ACR showed a significant association with lung and urinary tract cancers. Of these, the association between ACR and lung cancer appeared most robust in several sensitivity analyses. Kidney disease measures, particularly high ACR, were independently associated with cancer risk. The association between ACR and lung cancer was uniquely robust, warranting future studies to explore potential mechanisms.


Assuntos
Albuminúria/epidemiologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/urina , Taxa de Filtração Glomerular , Falência Renal Crônica/epidemiologia , Neoplasias/epidemiologia , Creatinina/sangue , Creatinina/urina , Cistatina C/sangue , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Fatores de Risco , Estados Unidos/epidemiologia
16.
J Urol ; 204(2): 231-238, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32125227

RESUMO

PURPOSE: Patients with kidney cancer are at risk for chronic kidney disease after radical and partial nephrectomy. We determined if the urine albumin-to-creatinine ratio is independently associated with progressive chronic kidney disease after nephrectomy. MATERIALS AND METHODS: We performed a cohort study based within a large, integrated health care system. We identified patients who underwent radical or partial nephrectomy from 2004 to 2014 with urine albumin-to-creatinine ratio measured in the 12 months before surgery. We fit multivariable models to determine if the urine albumin-to-creatinine ratio was associated with the time to chronic kidney disease progression (defined as reaching stage 4 or 5 chronic kidney disease, estimated glomerular filtration rate less than 30 ml/minute/1.73 m2). We performed a parallel analysis measuring the time to stage 3b, 4 or 5 chronic kidney disease (estimated glomerular filtration rate less than 45 ml/minute/1.73 m2) among patients with normal or near normal preoperative kidney function (estimated glomerular filtration rate 60 ml/minute/1.73 m2 or greater). We also examined the association between urine albumin-to-creatinine ratio and survival. RESULTS: A total of 1,930 patients underwent radical or partial nephrectomy and had preoperative urine albumin-to-creatinine ratio and preoperative and postoperative estimated glomerular filtration rate. Of these patients 658 (34%) and 157 (8%) had moderate (urine albumin-to-creatinine ratio 30 to 300 mg/gm) or severe albuminuria (urine albumin-to-creatinine ratio greater than 300 mg/gm), respectively. Albuminuria severity was independently associated with progressive chronic kidney disease after radical (moderate albuminuria HR 1.7, 95% CI 1.4-2.2; severe albuminuria HR 2.3, 95% CI 1.7-3.1) and partial nephrectomy (moderate albuminuria HR 1.8, 95% CI 1.2-2.7; severe albuminuria HR 4.3, 95% CI 2.7-7.0). Albuminuria was also associated with survival following radical and partial nephrectomy. CONCLUSIONS: In patients undergoing radical or partial nephrectomy the severity of albuminuria can stratify risk of progressive chronic kidney disease.


Assuntos
Albuminúria/urina , Creatinina/urina , Rim/fisiopatologia , Nefrectomia , Complicações Pós-Operatórias/urina , Insuficiência Renal Crônica/urina , Idoso , Estudos de Coortes , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Período Pós-Operatório , Período Pré-Operatório
17.
J Agric Food Chem ; 68(9): 2765-2772, 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32045244

RESUMO

Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD esters) are processing-induced food toxicants, with the kidney as their major target organ. For the first time, this study treated Sprague Dawley (SD) rats with 3-MCPD 1-monooleate at 10 and 100 mg/kg BW/day and 1-monostearate at 15 and 150 mg/kg BW/day for 90 days and examined for their potential semi-long-term nephrotoxicity and the associated molecular mechanisms. No bodyweight difference was observed between groups during the study. Both 3-MCPD 1-monooleate and 1-monostearate resulted in a dose-dependent increase of serum urea creatinine, uric acid and urea nitrogen levels, and histological renal impairment. The proteomic analysis of the kidney samples showed that the 3-MCPD esters deregulated proteins involved in the pathways for ion transportation, apoptosis, the metabolism of xenobiotics, and enzymes related to endogenous biological metabolisms of carbohydrates, amino acids, nitrogen, lipids, fatty acids, and the tricarboxylic acid (TCA) cycle, providing partial explanation for the nephrotoxicity of 3-MCPD esters.


Assuntos
Nefropatias/metabolismo , Rim/efeitos dos fármacos , Estearatos/toxicidade , alfa-Cloridrina/toxicidade , Animais , Creatinina/urina , Ésteres/metabolismo , Ésteres/toxicidade , Humanos , Rim/metabolismo , Nefropatias/etiologia , Nefropatias/genética , Nefropatias/urina , Masculino , Proteômica , Ratos , Ratos Sprague-Dawley , Estearatos/química , Estearatos/metabolismo , Ácido Úrico/urina , alfa-Cloridrina/metabolismo
18.
Medicine (Baltimore) ; 99(8): e19278, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080140

RESUMO

To investigate whether the control of morning blood pressure (MBP) reflects the control of blood pressure (BP) in other periods (daytime, nighttime and 24-hour) and to assess whether morning BP displays a closer association with subclinical target organ damage (TOD) than the BP measured in other periods.One thousand one hundred forty patients with primary hypertension who completed subclinical TOD detection and 24-hour ambulatory BP monitoring were included in the analysis. Pearson correlation analysis, Kappa consistency test, multiple linear regression analysis, and area under the receiver operating curve were used to analyze the data.Morning BP and daytime BP displayed good agreement, but not 24-hour BP , particularly the nighttime BP (all P < .001). Approximately 39.4% of the hypertensive patients receiving drug treatment who had achieved control of the morning BP presented masked nocturnal hypertension, which was associated with worse subclinical TOD. The BP measured in all periods correlated with subclinical TOD, and the correlation was more obvious in the treatment subgroup. However, morning BP did not independently affect subclinical TOD. Morning BP appeared to exhibit less discriminatory power than nighttime BP, particularly with respect to the urinary albumin to creatinine ratio.The use of morning BP for monitoring during hypertension management may not be enough. Masked uncontrolled nocturnal hypertension should be screened when morning BP is controlled.


Assuntos
Monitorização Ambulatorial da Pressão Arterial , Ritmo Circadiano/fisiologia , Hipertensão/fisiopatologia , Hipertensão Mascarada/diagnóstico , Albuminúria , Anti-Hipertensivos/uso terapêutico , Espessura Intima-Media Carotídea , Creatinina/urina , Estudos Transversais , Ecocardiografia , Feminino , Ventrículos do Coração/diagnóstico por imagem , Humanos , Hipertensão/tratamento farmacológico , Masculino , Hipertensão Mascarada/fisiopatologia , Pessoa de Meia-Idade
19.
Am J Ophthalmol ; 213: 306-319, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32035831

RESUMO

PURPOSE: We sought to assess a smartphone-based, gold nanoparticle-based colorimetric lateral flow immunoassay paper sensor for quantifying urine 8-hydroxy-2'-deoxyguanosine (8-OHdG) as a biomarker for diabetic retinopathy (DR) screening. METHODS: Paper strips incorporate gold nanoparticle-8-OHdG antibody conjugates that produce color changes that are proportional to urine 8-OHdG and that are discernible on a smartphone camera photograph. Paper strip accuracy, precision, and stability studies were performed with 8-OHdG solutions of varying concentrations. Urine was collected from 97 patients with diabetes who were receiving DR screening examinations, including 7-field fundus photographs. DR was graded by standard methods as either low risk (no or mild DR) or high risk (moderate or severe DR). Paper sensor assays were performed on urine samples from patients and 8-OHdG values were correlated with DR grades. The differences in 8-OHdG values between the low- and high-risk groups were analyzed for outliers to identify the threshold 8-OHdG value that would minimize false-negative results. RESULTS: Lateral flow immunoassay paper strips quantitatively measure 8-OHdG and were found to be accurate, precise, and stable. Average urine 8-OHdG concentrations in study patients were 22 ± 10 ng/mg of creatinine in the low-risk group and 55 ± 11 ng/mg of creatinine in the high-risk group. Screening cutoff values of 8-OHdG >50 ng/mg of creatinine or urine creatinine >1.5 mg minimized screen failures, with 91% sensitivity and 81% specificity. CONCLUSIONS: Urinary 8-OHdG is a useful biomarker to screen DR. Quantitative 8-OHdG detection with the lateral flow immunoassay paper sensor and smartphone camera demonstrates its potential in DR screening. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.


Assuntos
8-Hidroxi-2'-Desoxiguanosina/urina , Biomarcadores/urina , Retinopatia Diabética/urina , Ouro/química , Imunoensaio/instrumentação , Monitorização Ambulatorial , Colorimetria , Creatinina/urina , Retinopatia Diabética/diagnóstico , Reações Falso-Positivas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nanopartículas/química , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Smartphone/instrumentação
20.
Ecotoxicol Environ Saf ; 191: 110237, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-31986454

RESUMO

Extensive antibiotic exposure in the general population has been documented by bio-monitoring, but data regarding antibiotic burden across three generations in families living in the same household are lacking. We investigated the distribution of antibiotics and the potential health risk among the three generations by selecting 691 participants from 256 households in Fuyang city, China. A total of 45 antibiotics and two metabolites were screened in urine samples through liquid chromatography electrospray tandem mass spectrometry. In total, 34 antibiotics were found in the samples with an overall detection frequency of 92.0%, and the detection frequencies of individual antibiotic ranged from 0.3% to 28.7%. Specifically, the concentrations of seven antibiotics (azithromycin, amoxicillin, oxytetracycline, levofloxacin, norfloxacin, trimethoprim and sulfamethoxazole) were extremely high (i.e., above 10, 000 ng/mL). The detection rates of tetracyclines were significantly different among the three generations, with parents having the highest detection rate. Penicillin V, chlortetracycline, doxycycline, enrofloxacin, and ciprofloxacin showed a higher detection frequency in parents, whereas tetracycline, danofloxacin, and ofloxacin were more likely to be found in grandparents. The proportions of the sum of the daily exposure dose of VAs and PVAs more than 1 µg/kg/d in children, parents, and grandparents were 31.6%, 39.5%, and 26.5%, respectively. A hazard index (HI) greater than 1 was observed in 14.7% children, which was less than the 23.6% in parents and slightly higher than the 11.8% in grandparents. Ciprofloxacin was the biggest contributor to HI among the three generations. Collectively, these findings indicate that households are widely exposed to various antibiotics in Fuyang city, where parents had the highest health risk associated with the disturbance of gut microbiota.


Assuntos
Antibacterianos/urina , Monitoramento Biológico/métodos , Poluentes Ambientais/urina , Drogas Veterinárias/urina , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Criança , Pré-Escolar , China , Creatinina/urina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores Sexuais , Inquéritos e Questionários , Adulto Jovem
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