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1.
Chirurgia (Bucur) ; 115(2): 246-251, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32369729

RESUMO

Intraoperative monitoring of parathyroid hormone can confirm the complete excision of hyperfunctional parathyroid tissue, as the plasma half-life of PTH is approximately 5 minutes. The purpose of this study was to analyse the values of parathormon (PTH) and the intraoperative impact in patients with secondary hyperparathyroidism of renal cause (sHPT). A series of 86 patients who were hospitalised in our clinic between February 2015 to December 2018, were included in the study rom. All patients underwent surgery with PTH monitoring. PTH was determined preoperatively, intraoperatively 15 minutes after parathyroidectomy and postoperatively. Out of a total of 86 patients, 6 patients had non-functional renal transplant. 81 patients were operated on per primam and 5 patients were operated for disease recurrence. There were 77 total parathyroidectomies and 4 subtotal parathyroidectomies. One patient had 5 parathyroid glands. There were 4 patients with recurrent hyper-plastic tissue excision. Blood samples were collected intraoperatively through the puncture of the jugular vein. The PTH value was determined by the Elecsys PTH STATÃÂî test. The mean value of preoperative PTH was 1658 pg / mL and decreased to 46.5 pg / mL at the end of the operation. Subsequently, the level of PTH harvested at 3-6 months increased slightly to 59.8 pg / mL. 80 (93%) of patients had elevated preoperative calcium values. Recurrent hyperparathyroidism was found in 1 of the 4 patients who underwent subtotal parathyroidectomy. IPTH value is influenced by the intraoperative manipulation of the parathyroid glands, the individual variability of PTH half-life and the physiological state of the patient. The decrease of PTH measured intraoperatively at 15 minutes after harvest with at least 90% of the preoperative value indicates the success of a total parathyroidectomy, with normalisation of calcium and PTH.


Assuntos
Hiperparatireoidismo Secundário/sangue , Hiperparatireoidismo Secundário/cirurgia , Hormônio Paratireóideo/sangue , Paratireoidectomia , Insuficiência Renal/sangue , Humanos , Hiperparatireoidismo Secundário/etiologia , Monitorização Intraoperatória/métodos , Paratireoidectomia/métodos , Insuficiência Renal/complicações
2.
PLoS One ; 15(4): e0230998, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32251482

RESUMO

BACKGROUND: Renal failure is common in patients seeking help in medical emergency departments. Decreased renal function is associated with increased mortality in patients with heart failure or sepsis. In this study, the association between renal function (reflected by estimated glomerular filtration rate (eGFR) at the time of admission) and clinical outcome was evaluated. METHODS/OBJECTIVES: Data was used from a prospective, multi-national, observational cohort of patients treated in three medical emergency departments of tertiary care centers. The eGFR was calculated from the creatinine at the time of admission (using the Chronic Kidney Disease-Epidemiology Collaboration equation,CKD-EPI). Uni- and multivariate regression models were used for eGFR and 30-day mortality, in hospital mortality, length of stay and intensive care unit admission rate. RESULTS: 6983 patients were included. The 30-day mortality was 1.8%, 3.5%, 6.9%, 11.1%, 13.6%, and 14.2% in patients with eGFR of above 90, 60-89, 45-59, 30-44, 15-29, and <15 ml/min/1.73m2, respectively. Using multivariate regression, the adjusted odds ratio (OR) was 2.31 (for 15-29 ml/min/1.73m2, 95% confidence interval 1.36 to 3.90, p = 0.002) and 3.73 (for eGFR <15ml/min/1.73m2 as compared to >90 ml/min/1.73m2, 95% CI 2.04 to 6.84, p<0.001). For 10 ml/min/1.73m2 decrease in eGFR the OR for the 30-day mortality was 1.15 (95% CI1.09 to 1.22, p<0.001).The eGFR was also significantly associated with in-hospital mortality, the percentage of ICU-admissions, and with a longer hospital stay. No association was found with hospital readmission within 30 days. As limitations, only eGFR at admission was available and the number of patients on hemodialysis was unknown. CONCLUSION: Reduced eGFR at the time of admission is a strong and independent predictor for adverse outcome in this large population of patients admitted to medical emergency departments.


Assuntos
Taxa de Filtração Glomerular , Insuficiência Renal/mortalidade , Insuficiência Renal/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Creatinina/sangue , Serviço Hospitalar de Emergência , Feminino , Florida/epidemiologia , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Paris/epidemiologia , Estudos Prospectivos , Insuficiência Renal/sangue , Fatores de Risco , Suíça/epidemiologia , Centros de Atenção Terciária
3.
Ann Hematol ; 99(4): 737-741, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32030447

RESUMO

For patients with pure red cell aplasia (PRCA), cyclosporine (CsA) is the first line therapy. Occasionally, some patients who suffer from renal insufficiency cannot tolerate CsA. To explore the efficacy and tolerance of sirolimus treatment for those patients, twelve PRCA patients with renal insufficiency from May 2014 to May 2018 in Peking Union Medical College Hospital were enrolled, treated with sirolimus, and followed up at the median time of 16 (10-50) months. Eleven patients (91.7%) responded to sirolimus, with 58.3% complete response (CR) and 41.7% partial response (PR). The median time to achieve the optimum effect was 4 (1-7) months. The serum creatinine level remained stable or even reduced during the treatment period for eleven patients. Seven patients (58.3%) reported adverse events during sirolimus therapy, including increased blood glucose, infection, skin rash, elevated triglyceride or total cholesterol, and elevated serum creatinine compared with baseline. No treatment-related death was noticed during the follow-up time. Three patients relapsed with an overall response rate of 75.0% at 1 year. These results suggested that sirolimus was effective and tolerable for patients with PRCA complicated with renal insufficiency.


Assuntos
Imunossupressores/uso terapêutico , Aplasia Pura de Série Vermelha/tratamento farmacológico , Insuficiência Renal/etiologia , Sirolimo/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Creatinina/sangue , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Erupção por Droga/etiologia , Avaliação de Medicamentos , Substituição de Medicamentos , Feminino , Humanos , Hiperglicemia/induzido quimicamente , Hipertrigliceridemia/induzido quimicamente , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Recidiva , Aplasia Pura de Série Vermelha/complicações , Indução de Remissão , Insuficiência Renal/sangue , Estudos Retrospectivos , Sirolimo/efeitos adversos , Resultado do Tratamento
4.
Diabetes Res Clin Pract ; 161: 108011, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31991151

RESUMO

AIMS: The association of blood glucose in advanced diabetic kidney disease (DKD) is unclear. This study investigated the association between blood glucose and renal endpoints in DKD patients. METHODS: This retrospective cohort study enrolled type 2 diabetic patients with advanced DKD with an estimated glomerular filtration rate (eGFR) between 30 and 90 ml/min/1.73 m2 and urine albumin-to-creatinine ratio (UACR) of 300-5000 mg/g. We classified patients into 2 groups according to their 1-year average HbA1c: <7% and >7%. We followed up the patients until the occurrence of primary renal endpoints. RESULTS: A total of 345 patients were included in the analysis for the period 2012-2018. Mean baseline eGFR was 58 ml/min/1.73 m2 and mean albuminuria levels were 1146 and 1313 mg/g, respectively. Median study duration was 3 years. The risk of primary renal endpoints was not decreased in patients with HbA1c less than 7% with an adjusted hazard ratio (aHR) of 0.62, 95% CI 0.26-1.45. The risks of persistent eGFR lower than 15 ml/min/1.73 m2 and doubling of serum creatinine level were similar between 2 group with aHR of 0.58 (95% CI 0.19-1.83) and 0.61 (95% CI 0.26-1.44), respectively. CONCLUSIONS: Intensive blood sugar control did not prevent renal failure in advanced DKD.


Assuntos
Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Rim/fisiopatologia , Idoso , Albuminúria/sangue , Albuminúria/complicações , Albuminúria/fisiopatologia , Biomarcadores/análise , Biomarcadores/sangue , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Insuficiência Renal/sangue , Insuficiência Renal/complicações , Insuficiência Renal/diagnóstico , Estudos Retrospectivos
5.
Nephrol Dial Transplant ; 34(Suppl 3): iii2-iii11, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31800080

RESUMO

There have been significant recent advances in our understanding of the mechanisms that maintain potassium homoeostasis and the clinical consequences of hyperkalemia. In this article we discuss these advances within a concise review of the pathophysiology, risk factors and consequences of hyperkalemia. We highlight aspects that are of particular relevance for clinical practice. Hyperkalemia occurs when renal potassium excretion is limited by reductions in glomerular filtration rate, tubular flow, distal sodium delivery or the expression of aldosterone-sensitive ion transporters in the distal nephron. Accordingly, the major risk factors for hyperkalemia are renal failure, diabetes mellitus, adrenal disease and the use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or potassium-sparing diuretics. Hyperkalemia is associated with an increased risk of death, and this is only in part explicable by hyperkalemia-induced cardiac arrhythmia. In addition to its well-established effects on cardiac excitability, hyperkalemia could also contribute to peripheral neuropathy and cause renal tubular acidosis. Hyperkalemia-or the fear of hyperkalemia-contributes to the underprescription of potentially beneficial medications, particularly in heart failure. The newer potassium binders could play a role in attempts to minimize reduced prescribing of renin-angiotensin inhibitors and mineraolocorticoid antagonists in this context.


Assuntos
Insuficiência Cardíaca/sangue , Insuficiência Cardíaca/complicações , Hiperpotassemia , Potássio/sangue , Insuficiência Renal/complicações , Saúde Global , Taxa de Filtração Glomerular , Homeostase , Humanos , Hiperpotassemia/sangue , Hiperpotassemia/epidemiologia , Hiperpotassemia/etiologia , Incidência , Insuficiência Renal/sangue , Insuficiência Renal/fisiopatologia , Fatores de Risco
6.
J. bras. nefrol ; 41(4): 481-491, Out.-Dec. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1056601

RESUMO

Abstract Introduction: It is unclear whether residual renal function (RRF) in dialysis patients can attenuate the metabolic impact of the long 68-hour interdialytic interval, in which water, acid, and electrolyte accumulation occurs. Objective: to evaluate serum electrolyte levels, water balance, and acid-base status in dialytic patients with and without RRF over the long interdialytic interval (LII). Methodology: this was a single-center, cross-sectional, and analytical study that compared patients with and without RRF, defined by diuresis above 200 mL in 24 hours. Patients were weighed and serum samples were collected for biochemical and gasometric analysis at the beginning and at the end of the LII. Results: 27 and 24 patients with and without RRF were evaluated, respectively. Patients without RRF had a higher increase in serum potassium during the LII (2.67 x 1.14 mEq/L, p < 0.001), reaching higher values at the end of the study (6.8 x 5.72 mEq/L, p < 0.001) and lower pH value at the beginning of the interval (7.40 x 7.43, p = 0.018). More patients with serum bicarbonate < 18 mEq/L (50 x 14.8%, p = 0.007) and mixed acid-base disorder (57.7 x 29.2%, p = 0.042), as well as greater interdialytic weight gain (14.67 x 8.87 mL/kg/h, p < 0.001) and lower natremia (137 x 139 mEq/L, p = 0.02) at the end of the interval. Calcemia and phosphatemia were not different between the groups. Conclusion: Patients with RRF had better control of serum potassium, sodium, acid-base status, and volemia throughout the LII.


Resumo Introdução: Não se sabe ao certo se a função renal residual (FRR) de pacientes dialíticos pode atenuar o impacto metabólico do maior intervalo interdialítico (MII) de 68 horas, no qual ocorre acúmulo de volume, ácidos e eletrólitos. Objetivo: Avaliar os níveis séricos de eletrólitos, balanço hídrico e status ácido-básico de pacientes dialíticos com e sem FRR ao longo do MII. Metodologia: Tratou-se de estudo unicêntrico, transversal e analítico, que comparou pacientes com e sem FRR, definida como diurese acima de 200 mL em 24 horas. Para tal, os pacientes foram pesados e submetidos à coleta de amostras séricas para análise bioquímica e gasométrica no início e fim do MII. Resultados: Foram avaliados 27 e 24 pacientes com e sem FRR, respectivamente. Pacientes sem FRR apresentaram maior aumento de potássio sérico durante o MII (2,67 x 1,14 mEq/L, p < 0,001) atingindo valores mais elevados no fim (6,8 x 5,72 mEq/L, p < 0,001); menor valor de pH no início do intervalo (7,40 x 7,43, p = 0,018), maior proporção de pacientes com bicarbonato sérico < 18 mEq/L (50 x 14,8 %, p = 0,007) e distúrbio ácido-básico misto (70,8 x 42,3 %, p = 0,042), além de maior ganho de peso interdialítico (14,67 x 8,87 mL/kg/h, p < 0,001) e menor natremia (137 x 139 mEq/L, p = 0,02) no fim do intervalo. A calcemia e fosfatemia não foram diferentes entre os grupos. Conclusão: Pacientes com FRR apresentaram melhor controle dos níveis séricos de potássio, sódio, status ácido-básico e da volemia ao longo do MII.


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Equilíbrio Hidroeletrolítico/fisiologia , Diálise Renal/efeitos adversos , Insuficiência Renal/sangue , Rim/fisiopatologia , Fosfatos/sangue , Potássio/sangue , Sódio/sangue , Desequilíbrio Ácido-Base/fisiopatologia , Bicarbonatos/sangue , Ganho de Peso , Cálcio/sangue , Estudos Transversais , Progressão da Doença , Insuficiência Renal/fisiopatologia , Insuficiência Renal/urina , Insuficiência Renal/terapia , Rim/metabolismo , Rim/química , Testes de Função Renal/métodos
7.
Rev Med Suisse ; 15(673): 2210-2212, 2019 Nov 27.
Artigo em Francês | MEDLINE | ID: mdl-31778052

RESUMO

Since 2017 the world suffers from a piperacillin/tazobactam shortage. Cefepime is then proposed as a broad spectrum antibiotic alternative. Up to 15 % of the patients under treatment develop neurotoxicity, mostly in kidney failure settings. Cefepime serum concentration and electroencephalogram guide diagnosis. Treatment consists in withholding or reducing the dose. Most of the patients recover without neurologic sequelae.


Assuntos
Encefalopatias/induzido quimicamente , Cefepima/efeitos adversos , Antibacterianos/efeitos adversos , Antibacterianos/provisão & distribução , Antibacterianos/uso terapêutico , Encefalopatias/sangue , Encefalopatias/diagnóstico , Cefepima/administração & dosagem , Cefepima/sangue , Cefepima/uso terapêutico , Humanos , Insuficiência Renal/sangue , Insuficiência Renal/complicações , Insuficiência Renal/tratamento farmacológico
8.
Drug Metab Lett ; 13(2): 111-122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31613735

RESUMO

BACKGROUND: Clinical development of lesinurad, a selective uric acid reabsorption inhibitor, required analysis of lesinurad in plasma from special patient populations. METHODS: EMA and FDA bioanalytical method validation guidance have recommended studying matrix effects on quantitation if samples from special patient populations are to be analyzed. In addition to lesinurad (plasma protein binding 98.2%), the matrix effects from special population plasma on the quantitation of verapamil (PPB 89.6%), allopurinol and oxypurinol (PPB negligible) were also investigated. RESULTS: The plasma from special population patients had no matrix effects on the three quantification methods with stable isotope labeled internal standard, protein precipitation extraction, and LC-MS/MS detection. The validated lesinurad plasma quantification method was successfully applied for the pharmacokinetic evaluations to support the clinical studies in renal impaired patients. CONCLUSION: Special population plasma did not affect quantitation of drugs with a wide range of plasma protein binding levels in human plasma. With the confirmation that there is no impact on quantification from the matrix, the bioanalytical method can be used to support the pharmacokinetic evaluations for clinical studies in special populations.


Assuntos
Insuficiência Hepática/metabolismo , Insuficiência Renal/metabolismo , Tioglicolatos/sangue , Triazóis/sangue , Uricosúricos/sangue , Alopurinol/farmacocinética , Calibragem , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida de Alta Pressão/normas , Ensaios Clínicos como Assunto , Insuficiência Hepática/sangue , Insuficiência Hepática/fisiopatologia , Humanos , Rim/metabolismo , Rim/fisiopatologia , Fígado/metabolismo , Fígado/fisiopatologia , Oxipurinol/sangue , Oxipurinol/farmacocinética , Padrões de Referência , Insuficiência Renal/sangue , Insuficiência Renal/fisiopatologia , Reabsorção Renal , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodos , Espectrometria de Massas em Tandem/normas , Tioglicolatos/farmacocinética , Triazóis/farmacocinética , Uricosúricos/farmacocinética , Verapamil/sangue , Verapamil/farmacocinética
9.
Braz J Med Biol Res ; 52(10): e8845, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31576907

RESUMO

Regucalcin is a soluble protein that is principally expressed in hepatocytes. Studies of regucalcin have mainly been conducted in animals due to a lack of commercially available kits. We aimed to develop an enzyme-linked immunosorbent assay (ELISA) to quantify serum regucalcin in patients with hepatitis B virus (HBV)-related disease. High-titer monoclonal antibodies and a polyclonal antibody to regucalcin were produced, a double-antibody sandwich ELISA method was established, and serum regucalcin was determined in 47 chronic hepatitis B (CHB) patients, 91 HBV-related acute-on-chronic liver failure (HBV-ACLF) patients, and 33 healthy controls. The ELISA demonstrated an appropriate linear range, and high levels of reproducibility, sensitivity, specificity, accuracy, and stability. The median serum regucalcin concentrations in HBV-ACLF and CHB patients were 5.46 and 3.76 ng/mL, respectively (P<0.01), which were much higher than in healthy controls (1.72 ng/mL, both P<0.01). For the differentiation of CHB patients and healthy controls, the area under curve (AUC) was 0.86 with a cut-off of 2.42 ng/mL, 85.7% sensitivity, and 78.8% specificity. In contrast, the AUC of alanine aminotransferase (ALT) was lower (AUC=0.80, P=0.01). To differentiate ACLF from CHB, the AUC was 0.72 with a cut-off of 4.26 ng/mL, 77.0% sensitivity, and 61.2% specificity while the AUC of ALT was 0.41 (P=0.07). Thus, we have developed an ELISA that is suitable for measuring serum regucalcin and have shown that serum regucalcin increased with the severity of liver injury due to HBV-related diseases, such that it appears to be more useful than ALT as a marker of liver injury.


Assuntos
Proteínas de Ligação ao Cálcio/sangue , Hepatite B Crônica/sangue , Insuficiência Renal/sangue , Adolescente , Adulto , Idoso , Anticorpos Antivirais/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/virologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
10.
Am J Physiol Heart Circ Physiol ; 317(4): H695-H704, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31398059

RESUMO

High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease (CAVD). However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. The experimental design consisted of administering a uremia-inducing diet, with or without phosphate enrichment, to rats for 7 wk. Forty-two rats were fed with a phosphate-enriched uremic regimen that caused renal insufficiency and hyperphosphatemia. Another 42 rats were fed with a phosphate-depleted uremic regimen, which induces similar severity of renal insufficiency, but without its related mineral disorder. Aortic valves were evaluated at several points during the time of diet administration. In the second part, additional 54 rats were fed a phosphate-enriched diet for various time periods and were then switched to a phosphate-depleted diet to complete 7 wk of uremic diet. Osteoblast-like phenotype, inflammation, and eventually valve calcification were observed only in rats that were fed with a phosphate-enriched regimen. Significant valve calcification was observed only in rats that were fed a phosphate-enriched diet for at least 4 wk. Valve calcification was observed only when the switch to a phosphate-depleted regimen occurred after osteoblast markers and activation of Akt and ERK intracellular signaling pathways had already been found in the valve. Phosphate is essential for the initiation of the calcification process. However, when osteoblast markers are already expressed in valve tissue, phosphate depletion will not halt the disease.NEW & NOTEWORTHY High serum levels of phosphate are associated with uremia-induced calcific aortic valve disease. However, it is not clear whether hyperphosphatemia is required in all phases of the process. Our aim was to determine the effects of phosphate and phosphate depletion at different phases of valve disease. Our findings indicated that phosphate is essential for the initiation of the process that includes macrophage accumulation and osteoblast phenotype. Furthermore, hyperphosphatemia is dispensable beyond a certain phase of the process, a point of "no return" after which phosphate depletion does not prevent calcification. This point is relatively early in the course of calcification, when no calcification is apparent, but the inflammation, osteoblast markers, and activation of ERK and Akt pathways have already been identified. Our findings emphasize the complexity of the calcification process and suggest that different mediators might be required during different phases and that the role of phosphate precedes the actual calcification.


Assuntos
Valva Aórtica/patologia , Calcinose/etiologia , Doenças das Valvas Cardíacas/etiologia , Hiperfosfatemia/complicações , Fosfatos/sangue , Insuficiência Renal/complicações , Adenina , Animais , Valva Aórtica/metabolismo , Calcinose/sangue , Calcinose/patologia , Progressão da Doença , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Doenças das Valvas Cardíacas/sangue , Doenças das Valvas Cardíacas/patologia , Hiperfosfatemia/sangue , Masculino , Osteoblastos/metabolismo , Osteoblastos/patologia , Fosfatos/deficiência , Fósforo na Dieta , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Insuficiência Renal/sangue , Fatores de Tempo
11.
Saudi J Kidney Dis Transpl ; 30(4): 825-831, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31464239

RESUMO

Paraprotein gap is sometimes used as a screening tool in some autoimmune diseases, cancers, and screening for latent infections. The increase in the paraprotein gap in these diseases was hypothesized to be the result of increased levels of immunoglobulins, raising the total serum protein without any changes in serum albumin. Our aim was to assess the overall survival using novel chemotherapy, bortezomib compared to traditional ones and to assess if paraprotein gap could be used as a predictor of survival. Finally, we aimed to assess factors that could predict renal response in this population.


Assuntos
Mieloma Múltiplo/sangue , Paraproteínas/metabolismo , Insuficiência Renal/sangue , Microglobulina beta-2/sangue , Idoso , Antineoplásicos/uso terapêutico , Biomarcadores/sangue , Bortezomib/uso terapêutico , Feminino , Humanos , Masculino , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/mortalidade , Inibidores de Proteassoma/uso terapêutico , Insuficiência Renal/diagnóstico , Insuficiência Renal/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
12.
BMC Res Notes ; 12(1): 462, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358035

RESUMO

OBJECTIVE: The aim of this study was to estimate the prevalence of renal insufficiency using estimated glomerular filtration rate (eGFR) among adult outpatients with normal SCr. RESULTS: A total of 414 patients with normal SCr were included in the study. Mean GFR (ml/min/1.73 m2) was 116.8 ± 43.5 using the MDRD equation and 90.5 ± 33.1 by the C-G formula. According to the MDRD formula, mild renal insufficiency (i.e. eGFR 60-89.9 ml/min/1.73 m2) was found in 21.5% of the patients and moderate renal insufficiency (i.e. eGFR 30-59.9 ml/min/1.73 m2) was found in 7.7%. According to the Cockcroft-Gault (C-G) formula, mild renal insufficiency was found in 38.2% and moderate renal insufficiency in 16.9% of the patients with normal SCr. In multivariate analysis, older age, female sex, a family history of kidney disease or other chronic diseases and high systolic blood pressure were associated with prevalent renal insufficiency depending on the formula used to estimate GFR. This study demonstrates the substantial prevalence of impaired renal function among Ethiopian adult outpatients with normal SCr. Including calculated estimates of GFR in routine laboratory reporting may help to facilitate the identification and thus optimal management of patients with renal insufficiency.


Assuntos
Rim/fisiopatologia , Insuficiência Renal/epidemiologia , Insuficiência Renal/fisiopatologia , Adulto , Fatores Etários , Idoso , Creatinina/sangue , Estudos Transversais , Etiópia/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Pacientes Ambulatoriais , Prevalência , Insuficiência Renal/sangue , Insuficiência Renal/diagnóstico , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
13.
Nutr J ; 18(1): 42, 2019 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-31351493

RESUMO

BACKGROUND: Chronic Kidney Disease (CKD), characterized by an impaired kidney function, is associated with low testosterone levels. This study investigated the association between dietary patterns, testosterone levels, and severity of impaired kidney function among middle-aged and elderly men. METHODS: This cross-sectional study used the database from a private health-screening institute in Taiwan between 2008 and 2010. Men aged 40 years old and older (n = 21,376) with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73 m2 and proteinuria were selected. Among 21,376 men, 256 men had available measurements of testosterone levels. Dietary assessment was conducted using a food frequency questionnaire and three dietary patterns (fried-processed, vege-seafood, and dairy-grain dietary patterns) were identified using principal component analysis. RESULTS: Men in the lower tertiles (T1 and T2) of eGFR had significantly decreased testosterone levels by 0.8 (95% CI: - 1.40, - 0.20) and 0.9 nmol/L (95% CI: - 1.43, - 0.33). Furthermore, serum triglycerides (TG) levels were inversely associated with testosterone levels (ß = - 0.51, 95% CI: - 0.77, - 0.24). Men in the higher tertile of fried-processed dietary pattern scores were associated with decreased testosterone levels by 0.8 nmol/L (95% CI: - 1.40, - 0.16), reduced testosterone-to-TG (T/TG) ratio by 1.8 units (95% CI: - 2.99, - 0.53), and increased risk of moderate/severe impaired kidney function (eGFR < 60 mL/min/1.73 m2) and proteinuria severity by 1.35 (95% CI: 1.15, 1.58) and 1.18 (95% CI: 1.02, 1.37) times respectively. In contrast, the vege-seafood dietary pattern was negatively associated with severity of impaired kidney function and proteinuria after multivariable adjustment, but had no association with testosterone levels and T/TG ratio. CONCLUSIONS: The fried-processed dietary pattern is negatively associated with testosterone levels but positively associated with the severity of impaired kidney function. However, the vege-seafood and dairy-grain dietary patterns appear to have beneficial effects.


Assuntos
Dieta/efeitos adversos , Dieta/métodos , Insuficiência Renal Crônica/sangue , Testosterona/sangue , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/sangue , Índice de Gravidade de Doença , Taiwan
14.
Bull Exp Biol Med ; 167(2): 267-271, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31236876

RESUMO

Prognostic value of N-terminal fragment of the prohormone brain-type natriuretic peptide (NT-proBNP) was analyzed in patients with multiple myeloma complicated by dialysisdependent renal failure. The prospective study included 20 patients with newly diagnosed multiple myeloma. The concentrations of NT-proBNP were measured before antimyeloma chemotherapy. The median age of the patients was 67 (63-76) years. The median glomerular filtration rate was 4 (4, 5) ml/min/1.73 m2. For overall survival, the area under ROC curve was 0.75 and the cut-off point was 7000 pg/ml. At median follow-up of 17.3 months, the overall survival was 76.6±14.8 and 27.3±13.4% (p=0.02) for cases with NT-proBNP levels below and above the cut-off point, respectively. There were no cases of death due to cardiovascular causes. We concluded that the increase in serum concentration of NT-proBNP>7400 pg/ml is associated with the severity of kidney damage and the risk of non-cardiac mortality.


Assuntos
Mieloma Múltiplo/sangue , Mieloma Múltiplo/patologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Idoso , Biomarcadores/sangue , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Diálise Renal , Insuficiência Renal/sangue , Insuficiência Renal/patologia
15.
Can J Cardiol ; 35(9): 1097-1105, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31230825

RESUMO

BACKGROUND: Acute heart failure (HF) patients with renal insufficiency and risk factors for diuretic resistance may be most likely to derive incremental improvement in congestion with the addition of spironolactone. METHODS: The Aldosterone Targeted Neurohormonal Combined with Natriuresis Therapy in Heart Failure (ATHENA-HF) trial randomized 360 acute HF patients with reduced or preserved ejection fraction to spironolactone 100 mg daily or usual care for 96 hours. The current analysis assessed the effects of study therapy within tertiles of baseline estimated glomerular filtration rate (eGFR) and subgroups at heightened risk for diuretic resistance. RESULTS: Across eGFR tertiles, there was no incremental benefit of high-dose spironolactone on any efficacy endpoint, including changes in log N-terminal pro-B-type natriuretic peptide and signs and symptoms of congestion (all P for interaction ≥ 0.06). High-dose spironolactone had no significant effect on N-terminal pro-B-type natriuretic peptide reduction regardless of blood pressure, diabetes mellitus status, and loop diuretic dose (all P for interaction ≥ 0.38). In-hospital changes in serum potassium and creatinine were similar between treatment groups for all GFR tertiles (all P for interaction ≥ 0.18). Rates of inpatient worsening HF, 30-day worsening HF, and 60-day all-cause mortality were numerically higher among patients with lower baseline eGFR, but relative effects of study treatment did not differ with renal function (all P for interaction ≥ 0.27). CONCLUSIONS: High-dose spironolactone did not improve congestion over usual care among patients with acute HF, irrespective of renal function and risk factors for diuretic resistance. In-hospital initiation or continuation of spironolactone was safe during the inpatient stay, even when administered at high doses to patients with moderate renal dysfunction.


Assuntos
Resistência a Medicamentos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Renal/complicações , Espironolactona/administração & dosagem , Creatinina/sangue , Relação Dose-Resposta a Droga , Seguimentos , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/fisiopatologia , Humanos , Antagonistas de Receptores de Mineralocorticoides/administração & dosagem , Estudos Prospectivos , Insuficiência Renal/sangue , Insuficiência Renal/fisiopatologia , Fatores de Risco , Volume Sistólico/fisiologia , Resultado do Tratamento
16.
BMC Pharmacol Toxicol ; 20(1): 27, 2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-31064405

RESUMO

BACKGROUND: Thromboprophylaxis dosing strategies using enoxaparin in elderly patients with renal disease are limited, while dose adjustments or monitoring of anti-Xa levels are recommended. We sought to evaluate the efficacy and safety of enoxaparin 20 mg versus 30 mg subcutaneously daily by comparing anti-Xa levels, thrombosis and bleeding. METHODS: We conducted a prospective, single-blinded, single-center randomized clinical trial including non-surgical patients, 70 years of age or older, with renal disease requiring thromboprophylaxis. Patients were randomized to receive either 20 mg or 30 mg of enoxaparin. The primary endpoint was peak anti-Xa levels on day 3. Secondary endpoints included trough anti-Xa levels on day 3, achievement of within range prophylactic target peak anti-Xa levels and the occurrence of hemorrhage, thrombosis, thrombocytopenia or hyperkalemia during hospitalization. RESULTS: Thirty-two patients were recruited and sixteen patients were randomized to each arm. Mean peak anti-Xa level was significantly higher in 30 mg arm (n = 13) compared to the 20 mg arm (n = 11) 0.26 ± 0.11, 95%CI (0.18-0.34), versus 0.14 ± 0.09, 95CI (0.08-0.19) UI/ml, respectively; p = 0.004. Mean trough anti-Xa level was higher in 30 mg arm (n = 10) compared to the 20 mg arm (n = 16), 0.06 ± 0.03, 95CI (0.04-0.08) versus 0.03 ± 0.03, 95CI (0.01-0.05) UI/ml, respectively; p = 0.044. Bleeding events reported in the 30 mg arm were one retroperitoneal bleed requiring multiple transfusions, and in the 20 mg arm one hematuria. No thrombotic events were reported. CONCLUSION: Peak anti-Xa levels provided by enoxaparin 20 mg were lower than the desired range for thromboprophylaxis in comparison to enoxaparin 30 mg. TRIAL REGISTRATION: The trial was retrospectively registered on ClinicalTrials.gov identifier: NCT03158792 . Registered: May 18, 2017.


Assuntos
Anticoagulantes/administração & dosagem , Enoxaparina/administração & dosagem , Fator Xa/análise , Insuficiência Renal/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Enoxaparina/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Masculino , Insuficiência Renal/sangue , Método Simples-Cego , Trombose/prevenção & controle , Resultado do Tratamento
17.
Oxid Med Cell Longev ; 2019: 8219283, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31089418

RESUMO

Chronic kidney disease (CKD) is accompanied by a disturbed redox homeostasis, especially in end-stage patients, which is associated with pathological complications such as anemia, atherosclerosis, and muscle atrophy. However, limited evidence exists about redox disturbances before the end stage of CKD. Moreover, the available redox literature has not yet provided clear associations between circulating and tissue-specific (muscle) oxidative stress levels. The aim of the study was to evaluate commonly used redox status indices in the blood and in two different types of skeletal muscle (psoas, soleus) in the predialysis stages of CKD, using an animal model of renal insufficiency, and to investigate whether blood redox status indices could be reflecting the skeletal muscle redox status. Indices evaluated included reduced glutathione (GSH), oxidized glutathione (GSSG), glutathione reductase (GR), catalase (CAT), total antioxidant capacity (TAC), protein carbonyls (PC), and thiobarbituric acid reactive substances (TBARS). Results showed that blood GSH was higher in the uremic group compared to the control (17.50 ± 1.73 vs. 12.43 ± 1.01, p = 0.033). In both muscle types, PC levels were higher in the uremic group compared to the control (psoas: 1.086 ± 0.294 vs. 0.596 ± 0.372, soleus: 2.52 ± 0.29 vs. 0.929 ± 0.41, p < 0.05). The soleus had higher levels of TBARS, PC, GSH, CAT, and GR and lower TAC compared to the psoas in both groups. No significant correlations in redox status indices between the blood and skeletal muscles were found. However, in the uremic group, significant correlations between the psoas and soleus muscles in PC, GSSG, and CAT levels emerged, not present in the control. Even in the early stages of CKD, a disturbance in redox homeostasis was observed, which seemed to be muscle type-specific, while blood levels of redox indices did not seem to reflect the intramuscular condition. The above results highlight the need for further research in order to identify the key mechanisms driving the onset and progression of oxidative stress and its detrimental effects on CKD patients.


Assuntos
Músculo Esquelético/metabolismo , Insuficiência Renal/sangue , Insuficiência Renal/metabolismo , Animais , Catalase/metabolismo , Modelos Animais de Doenças , Feminino , Dissulfeto de Glutationa/metabolismo , Oxirredução , Carbonilação Proteica , Coelhos , Uremia/sangue
18.
Circ Heart Fail ; 12(5): e005544, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31091993

RESUMO

BACKGROUND: PENK (proenkephalin) is a stable surrogate for enkephalins, endogenous opioid peptides, which exert cardiodepressive effects and improve renal function. PENK has been associated with heart failure (HF) severity and renal dysfunction. We therefore hypothesized that PENK could be associated with deterioration of kidney function and could have a role as a novel renal marker in HF. METHODS AND RESULTS: In 2180 patients with HF of a large multicenter cohort (BIOSTAT-CHF [A Systems Biology Study to Tailored Treatment in Chronic Heart Failure]), the relationship between PENK and clinical variables, plasma and urinary biomarkers, and clinical end points was established. Data were validated in a separate cohort of 1703 patients with HF. PENK was elevated (>80 pmol/L, 99th percentile) in 1245 (57%) patients. Higher PENK was associated with more advanced HF and glomerular and tubular dysfunction. The strongest independent predictor of PENK was estimated glomerular filtration rate. Others were plasma NGAL (neutrophil gelatinase-associated lipocalin) and NT-proBNP (N-terminal pro-B-type natriuretic peptide; all P<0.001). Using correlation heatmaps and hierarchical cluster analyses, PENK clustered with estimated glomerular filtration rate, creatinine, NGAL, galectin-3, and urea. Higher PENK was independently associated with increased risk of deterioration of kidney function between baseline and 9 months (odds ratio, 1.29 [1.02-1.65] per PENK doubling; P=0.038; defined as >25% decrease in estimated glomerular filtration rate) and mortality (hazard ratio, 1.23 [1.07-1.43] per doubling; P=0.004). Analyses in the validation cohort yielded comparable findings. CONCLUSIONS: Higher PENK levels are associated with more severe HF, with glomerular and tubular renal dysfunction, with incidence of a deterioration of kidney function, and with mortality. These findings suggest that the opioid system might be involved in deteriorating kidney function in HF.


Assuntos
Biomarcadores/sangue , Encefalinas/sangue , Insuficiência Cardíaca/sangue , Precursores de Proteínas/sangue , Insuficiência Renal/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Biomarcadores/urina , Estudos de Coortes , Encefalinas/metabolismo , Feminino , Taxa de Filtração Glomerular , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/urina , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Precursores de Proteínas/metabolismo , Insuficiência Renal/etiologia , Insuficiência Renal/metabolismo , Insuficiência Renal/urina
19.
Biosci Rep ; 39(4)2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-30936264

RESUMO

The present study was designed to look at the hematological disorders in gentamicin nephrotoxicity model, as kidney is considered as one of the hemopoietic organs. In a previous study, novel and classical kidney injury biomarkers were utilized to evaluate the nephroprotective potential of Carica papaya leaf extract (CPLE) in the same model in albino rats. Gentamicin (100 mg/kg, subcutaneously, for 21 consecutive days) resulted in significant decreases in red blood cell (RBC) count, hemoglobin concentration (HGB), and packed cell volume (PCV) value, with minimal alterations in erythrocytic indices. Leucogram showed leukocytosis, granulocytosis, and thrombocytopenia. Erythropoietin (EPO) levels were also drastically decreased by the end of the experimental course. Serum iron, unsaturated iron-binding capacity (UIBC), total iron binding capacity (TIBC), transferrin saturation %, and serum transferrin concentration values were significantly decreased in contrast to ferritin, which was increased. When concurrently administered with gentamicin, CPLE (150 and 300 mg/kg, orally via gastric tube, for 21 days) significantly protected against the drastic effects of the former on the blood profile with improving potentials on erythrogram, leukogram, thrombocytes, EPO, iron and its indices, in a dose-dependent manner. These data may suggest CPLE as an appreciated blood homeostatic and nephroprotective agent from a natural source that could be a good remedy in conditions associated with blood disorders.


Assuntos
Carica/química , Doenças Hematológicas/tratamento farmacológico , Ferro/sangue , Nefropatias/tratamento farmacológico , Anemia/sangue , Anemia/tratamento farmacológico , Anemia/patologia , Animais , Plaquetas/metabolismo , Plaquetas/patologia , Eritropoetina/sangue , Gentamicinas/farmacologia , Doenças Hematológicas/sangue , Doenças Hematológicas/patologia , Humanos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Ratos , Insuficiência Renal/sangue , Insuficiência Renal/tratamento farmacológico , Insuficiência Renal/patologia , Transferrina/metabolismo
20.
Biopharm Drug Dispos ; 40(5-6): 176-187, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30985942

RESUMO

We previously verified a physiologically based pharmacokinetic (PBPK) model for mirabegron in healthy subjects using the Simcyp Simulator by incorporating data on the inhibitory effect on cytochrome P450 (CYP) 2D6 and a multi-elimination pathway mediated by CYP3A4, uridine 5'-diphosphate-glucuronosyltransferase (UGT) 2B7 and butyrylcholinesterase (BChE). The aim of this study was to use this PBPK model to assess the magnitude of drug-drug interactions (DDIs) in an elderly population with severe renal impairment (sRI), which has not been evaluated in clinical trials. We first determined the system parameters, and meta-analyses of literature data suggested that the abundance of UGT2B7 and the BChE activity in an elderly population with sRI was almost equivalent to and 20% lower than that in healthy young subjects, respectively. Other parameters, such as the CYP3A4 abundance, for an sRI population were used according to those built into the Simcyp Simulator. Second, we confirmed that the PBPK model reproduced the plasma concentration-time profile for mirabegron in an sRI population (simulated area under the plasma concentration-time curve (AUC) was within 1.5-times that of the observed value). Finally, we applied the PBPK model to simulate DDIs in an sRI population. The PBPK model predicted that the AUC for mirabegron with itraconazole (a CYP3A4 inhibitor) was 4.12-times that in healthy elderly subjects administered mirabegron alone, and predicted that the proportional change in AUC for desipramine (a CYP2D6 substrate) with mirabegron was greater than that in healthy subjects. In conclusion, the PBPK model was verified for the purpose of DDI assessment in an elderly population with sRI.


Assuntos
Acetanilidas/farmacocinética , Agonistas de Receptores Adrenérgicos beta 3/farmacocinética , Modelos Biológicos , Insuficiência Renal/metabolismo , Tiazóis/farmacocinética , Acetanilidas/sangue , Adolescente , Agonistas de Receptores Adrenérgicos beta 3/sangue , Adulto , Idoso , Envelhecimento/metabolismo , Butirilcolinesterase/metabolismo , Inibidores do Citocromo P-450 CYP2D6/sangue , Inibidores do Citocromo P-450 CYP2D6/farmacocinética , Citocromo P-450 CYP3A/metabolismo , Inibidores do Citocromo P-450 CYP3A/sangue , Inibidores do Citocromo P-450 CYP3A/farmacocinética , Desipramina/sangue , Desipramina/farmacocinética , Interações Medicamentosas , Feminino , Genfibrozila/sangue , Genfibrozila/farmacocinética , Glucuronosiltransferase/metabolismo , Humanos , Itraconazol/sangue , Itraconazol/farmacocinética , Lorazepam/sangue , Lorazepam/farmacocinética , Masculino , Pessoa de Meia-Idade , Insuficiência Renal/sangue , Tiazóis/sangue , Adulto Jovem , Zidovudina/sangue , Zidovudina/farmacocinética
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