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1.
Expert Rev Clin Pharmacol ; 12(9): 867-874, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31456441

RESUMO

Introduction: Hepatitis B virus is an important cause of liver disease and has numerous extra-hepatic manifestations. HBV leads to important morbidity and mortality in the general population and recent evidence suggests a role of HBV in the incidence and progression of chronic kidney disease. Areas covered: The mechanisms underlying the link between HBV and CKD remain unclear. Nucleos(t)ide analogues for the antiviral treatment of HBV are currently available; these drugs are provided with high efficacy even in patients with CKD. Expert opinion: A recent meta-analysis of clinical studies showed that HBV results in a greater risk of CKD in the general population. According to an updated review (studies were identified from PubMed, EMBASE, and the Cochrane database), we retrieved six clinical studies (n = 1,034,773 unique patients), adjusted RR, 1.41 (95% CI, 1.09; 1.82, P < 0.001). The significant heterogeneity observed precluded more definitive conclusions. Various mechanisms have been cited to explain the greater risk of CKD among HBsAg positive carriers. Novel evidence shows that untreated HBV and therapy with nucleos(t)ide analogues are associated with increased and decreased risk of end-stage renal disease in CKD population, respectively. We recommend that patients with HBV are assessed for kidney function and urinary changes at baseline and over the follow-up.


Assuntos
Antivirais/administração & dosagem , Hepatite B/complicações , Insuficiência Renal Crônica/etiologia , Progressão da Doença , Hepatite B/tratamento farmacológico , Hepatite B/virologia , Humanos , Incidência , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/etiologia , Falência Renal Crônica/virologia , Testes de Função Renal , Nucleosídeos/administração & dosagem , Nucleotídeos/administração & dosagem , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/virologia , Fatores de Risco
2.
Acta Gastroenterol Belg ; 82(2): 273-277, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31314188

RESUMO

BACKGROUND AND STUDY AIMS: The aim of this study was to enlighten the controversy about the renal safety of entecavir, tenofovir, and telbivudine treatments in chronic hepatitis B (CHB) patients by comparing these treatments in real-world conditions. PATIENTS AND METHODS: We retrospectively enrolled 104 treatment-naive patients with CHB monoinfection into our study. Patients were treated with entecavir monotherapy (n=38), tenofovir monotherapy (n=35), or telbivudine monotherapy (n=31). We then compared and statistically analyzed the effects of these drugs on the estimated glomerular filtration rate (eGFR) over a 24-month follow-up period. RESULTS: In the entecavir group, time-dependent change in eGFR was not statistically significant (p = 0.357). There was a statistically significant increase in eGFR in the telbivudine group at 12 months (p<0.001) and at 24 months (p<0.001) and, in contrast, a statistically significant decrease in the tenofovir group at 12 months (p<0.001) and at 24 months (p<0.001). There was no significant relationship between entecavir and eGFR change (p = 0.763). We found that tenofovir and telbivudine were independent predictors of eGFR change (decrease in eGFR, p<0.001 and increase in eGFR, p = 0.001, respectively). CONCLUSIONS: We recommend close follow-up of renal functions, especially for patients treated with tenofovir. Telbivudine was superior to the other drugs in terms of renal function. We conclude that an individualized therapy program considering treatment efficacy and side effects is the best option for patients.


Assuntos
Antivirais/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Nefropatias/induzido quimicamente , Rim/efeitos dos fármacos , Telbivudina/administração & dosagem , Tenofovir/administração & dosagem , Antivirais/efeitos adversos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Guanina/administração & dosagem , Guanina/efeitos adversos , Humanos , Rim/fisiopatologia , Nefropatias/patologia , Testes de Função Renal , Masculino , Estudos Retrospectivos , Telbivudina/efeitos adversos , Tenofovir/efeitos adversos , Timidina/administração & dosagem , Timidina/efeitos adversos , Resultado do Tratamento
3.
Nat Genet ; 51(6): 957-972, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31152163

RESUMO

Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.


Assuntos
Estudos de Associação Genética/métodos , Predisposição Genética para Doença , Locos de Características Quantitativas , Característica Quantitativa Herdável , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/fisiopatologia , Mapeamento Cromossômico , Grupo com Ancestrais do Continente Europeu , Estudo de Associação Genômica Ampla , Taxa de Filtração Glomerular , Humanos , Padrões de Herança , Testes de Função Renal , Fenótipo , Polimorfismo de Nucleotídeo Único , Insuficiência Renal Crônica/urina , Uromodulina/urina
4.
BMC Complement Altern Med ; 19(1): 118, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170978

RESUMO

BACKGROUND: Hirudin, an extract from Hirudo spp., is an anticoagulant used to treat a variety of renal diseases, including diabetic nephropathy (DN). Currently, hirudin has to be used at high dosages to treat DN because it poorly targets the kidneys, although at high dosages it can have severe side effects. Developing a targeted drug delivery system for hirudin, then, could boost its positive therapeutic effects while lowering the risk of side effects. Liposomes have been demonstrated to have significant renal targeting potential, but here we show that a hirudin-loaded liposome is an effective delivery method for patients with DN. METHOD: In this study, we prepared a hirudin/liposome complex and tested its efficacy by injecting it into a rat model. We then compared the renal accumulation of hirudin between complex-injected rat models and rat models that received injections of hirudin alone. We also investigated the mechanisms behind the complex's effects. RESULT: The hirudin/liposome complex increased the accumulation of hirudin in kidney tissues and relieved the renal injury in DN rat models. Moreover, the hirudin/liposome complex down-regulated the expression of TGF-ß1 and VEGF in the kidneys. CONCLUSION: We demonstrated that a hirudin/liposome complex can have a significant positive effect on DN. The mechanism may be that the complex inhibits the expression of VEGF and TGF-ß1.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Fibrinolíticos/administração & dosagem , Hirudinas/administração & dosagem , Animais , Glicemia , Diabetes Mellitus Experimental/complicações , Nefropatias Diabéticas/patologia , Avaliação Pré-Clínica de Medicamentos , Fibrinolíticos/farmacocinética , Hirudinas/farmacocinética , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Testes de Função Renal , Lipossomos , Masculino , Ratos Sprague-Dawley , Fator de Crescimento Transformador beta1/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
5.
Clin Interv Aging ; 14: 905-913, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190776

RESUMO

Purpose: The prevalence of depression and the relationship between depression and kidney function and health-related quality of life (HRQOL) are not well understood in elderly patients with predialysis chronic kidney disease (CKD). This study aimed to evaluate the prevalence of depression and the association between depression and kidney function and HRQOL. Patients and methods: In this cross-sectional study, 1079 elderly participants with CKD were recruited at 32 clinical centers located within 26 cities throughout 24 provinces in China. Demographic information and laboratory analyses were collected. Symptoms of depression were assessed using the 15-item Geriatric Depression Scale (GDS-15). HRQOL was evaluated using the Kidney Disease Quality of Life-36 (KDQOL-36) instrument. Results: The prevalence of depression was 23.0%. The estimated glomerular filtration rate (eGFR) was negatively correlated with the GDS score whether it was treated as a categorical variable (r=-0.097, P=0.001) or as a continuous variable (r=-0.100, P=0.001). Marital status, education level, history of CVD and diabetes, CKD stage and proteinuria confirmed to be independent and significant predictors of depression in patients with CKD. Compared with CKD 1-2 patients, we observed an increase of 0.541 and 4.171 in the odds for developing depression in patients CKD 4 (odds ratio [OR] =1.541; P=0.031) and CKD 5 (odds ratio [OR] =5.171; P<0.001), respectively. We observed negative and significant correlations with the GDS score for the following components: PCS (r=-0.370, P<0.001), MCS (r=-0.412, P<0.001), burden of kidney disease (r=-0.403, P<0.001), symptoms and problems of kidney disease (r=-0.360, P<0.001) and effects of kidney disease (r=-0.355, P<0.001). Depression was an independent and significant predictor of all the subcomponents of the HRQOL. Conclusions: The prevalence of depression in elderly patients with CKD was high and was negatively correlated with kidney function. Depression had a major negative impact on HRQOL.


Assuntos
Depressão/epidemiologia , Qualidade de Vida , Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Estudos Prospectivos , Fatores Socioeconômicos
6.
Expert Rev Clin Pharmacol ; 12(8): 805-813, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31242039

RESUMO

Objective: To evaluate the predictive performance of eight renal function equations to describe amikacin elimination in a large standard population with a wide range of age. Methods: Retrospective study of adult hospitalized patients treated with amikacin and monitored in the clinical pharmacokinetics laboratory of a pharmacy service. Renal function was calculated as Cockcroft-Gault with total, adjusted and ideal body weight, MDRD-4, CKD-EPI, rLM, BIS1, and FAS. One compartment model with first-order elimination, including interindividual variability on clearance and volume of distribution and combined residual error model was selected as a base structural model. A pharmaco-statistical analysis was performed following a non-linear mixed effects modeling approach (NONMEM 7.3 software). Results: 198 patients (61 years [18-93]) and 566 measured amikacin plasma concentrations were included. All the estimated glomerular filtration rate and creatinine clearance equations evaluated described properly the data. The linear relationship between clearance and glomerular filtration rate based on rLM showed a statistically significant improvement in the fit of the data. rLM must be evaluated carefully in renal failure for amikacin dose adjustment. Conclusions: Revised Lund-Malmö (rLM) and CKD-EPI showed the superior predictive performance of amikacin drug elimination comparing to all the alternative metrics evaluated.


Assuntos
Amicacina/administração & dosagem , Antibacterianos/administração & dosagem , Nefropatias/complicações , Modelos Biológicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Amicacina/farmacocinética , Antibacterianos/farmacocinética , Creatinina/metabolismo , Relação Dose-Resposta a Droga , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Dinâmica não Linear , Estudos Retrospectivos , Distribuição Tecidual , Adulto Jovem
7.
JAMA ; 321(21): 2136, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31162564
8.
Neurología (Barc., Ed. impr.) ; 34(5): 300-308, jun. 2019. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-180846

RESUMO

Introducción: La acetona cianohidrina (ACH) es una sustancia tóxica resultante de la hidrólisis enzimática de linamarina, contenido en las raíces de yuca (Manihot esculenta Crantz); su consumo a largo plazo se asocia con 2 trastornos neurológicos: konzo y la neuropatía atáxica tropical. Estudios anteriores han evaluado las alteraciones conductuales después del consumo de esta sustancia, pero los efectos tóxicos sobre los procesos fisiológicos se desconocen. Método: Se asignaron 32 ratas Wistar macho a 4 grupos experimentales (n = 8): un grupo vehículo (solución salina 0,3 ml/rata, ip) y 3 grupos con ACH (PubChem CID: 6406) a concentraciones de 10, 15 y 20 mM, durante 28 días, cada 24 h. Se evaluó la actividad motora espontánea en campo abierto y la coordinación motora en pruebas de rotarod y nado a 0, 7, 14, 21 y 28 días de tratamiento. Al final de las pruebas conductuales (día 28) se tomaron muestras de sangre por punción transcardiaca para evaluar la función renal y hepática. Resultados: La ACH promovió alteraciones en la actividad locomotora y promovió tanto el nado lateral como la conducta de giro en la prueba de nado los días 21 y 28 del tratamiento. La ACH incrementó los parámetros de la función renal y hepática de una manera dependiente de la concentración, excepto la glucosa y la bilirrubina total. Conclusión: Estos datos indican que el contenido de este compuesto tóxico contenido en las raíces de yuca podría ser potencialmente peligroso bajo el consumo a largo plazo en sujetos vulnerables


Introduction: Acetone cyanohydrin (ACH) is a toxic substance present in cassava roots (Manihot esculenta Crantz) which results from enzymatic hydrolysis of linamarin. Long-term consumption is associated with 2 neurological disorders: konzo and tropical ataxic neuropathy. Previous studies have evaluated behavioural alterations linked to ACH consumption, but the toxic effects of this substance on physiological processes remain unknown. Method: 32 male Wistar rats were assigned to 4 experimental groups (n = 8 per group): a vehicle group (0.3 mL saline solution, IP) and 3 ACH groups (PubChem CID: 6406) dosed at 10, 15, and 20 mM/24h for 28 days. We evaluated spontaneous motor activity with the open field test and motor coordination with the rotarod and forced swimming tests at 0, 7, 14, 21, and 28 days of treatment. At the end of the assessment period (day 28), blood samples were collected by transcardiac puncture to evaluate kidney and liver function. Results: ACH caused alterations in locomotor activity and promoted both lateral swimming and spinning in the forced swimming test at 21 and 28 days of treatment. Furthermore, it led to an increase in the levels of the parameters of kidney and liver function in a concentration-dependent manner, except for glucose and total bilirubin. Conclusion: Our results suggest that long-term consumption of this toxic compound present in cassava roots may be potentially dangerous for vulnerable subjects


Assuntos
Animais , Ratos , Atividade Motora/efeitos dos fármacos , Fígado/efeitos dos fármacos , Rim/efeitos dos fármacos , Neurotoxinas/isolamento & purificação , Acetona/efeitos adversos , Manihot/efeitos adversos , Ratos Wistar , Extratos Vegetais/farmacocinética , Modelos Animais de Doenças , Testes de Função Renal/estatística & dados numéricos , Testes de Função Hepática/estatística & dados numéricos , Testes de Toxicidade Aguda/métodos
9.
Transplant Proc ; 51(5): 1314-1316, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31056244

RESUMO

INTRODUCTION: Renal scintigraphy is used to evaluate split renal function. A computed tomography (CT) examination is also carried out for donor safety and appropriate transplantation surgery, and the renal volume (CT volumetry) can be obtained at that time. In this study, we evaluated donor kidney function by inulin clearance (Cin) before and after donor nephrectomy in living donor renal transplantation, and the predictive role of CT volumetry was compared with diethylenetriamine pentaacetic acid (DTPA). METHOD: From November 2005 to April 2018, 34 cases of living donor transplantation conducted at Fukuoka University Hospital were retrospectively studied. The donated kidney weight was measured in 25 cases, and postoperative Cin was measured in 19 cases. RESULTS: The average donor age was 51.7 years old (from 35 to 71). Preoperative Cin and postoperative Cin of donors were 86.3 mL/min/1.73 m2 (from 59.5 to 138.3) and 52.3 (from 40.5 to 76.6), respectively. The average CT volumetry of donated kidneys was 153.9 mL (from 107.8 to 219.3). Correlations of weight and DTPA and CT volumetry of donated kidneys were r = 0.033 (P = .8770) and r = 0.763 (P < .0001), respectively. Correlations of glomerular filtration rate of DTPA and CT volumetry and Cin of postoperative donor residual kidneys were r = 0.66 (P = .002) and r = 0.555 (P = .014). CONCLUSION: There was a significant correlation between CT volumetry and the weight of the removed kidneys, and a correlation between Cin after donor nephrectomy and CT volumetry of the remaining kidneys, but it did not exceed the predictive role of DTPA. However, it was suggested that it is worthy to use as a preoperative examination for split renal function equivalent to DTPA.


Assuntos
Testes de Função Renal/métodos , Transplante de Rim/métodos , Rim/diagnóstico por imagem , Rim/fisiologia , Doadores Vivos , Adulto , Idoso , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nefrectomia/métodos , Cuidados Pré-Operatórios/métodos , Estudos Retrospectivos , Coleta de Tecidos e Órgãos/métodos
10.
Transplant Proc ; 51(5): 1331-1336, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31076148

RESUMO

BACKGROUND: The albumin to creatinine ratio (ACR) has been shown to be an important prognostic marker in kidney disease. The ACR has been shown to predict graft failure and patient death after kidney transplant. METHODS: From March 1, 2011, to December 31, 2013, we checked the urine ACR and blood for highly sensitive C-reactive protein in 93 kidney recipients who regularly follow up at out institute. We tested the linear correlations of these parameters with estimated glomerular filtration rate. Furthermore, we used multivariate linear regression to examine its value in predicting graft function. Finally, we used receiver operating characteristic curve analysis to validate their predictive value on creatinine clearance > 45 mL/min. RESULTS: With multivariate linear regression, the latest estimated glomerular filtration rate has a strong linear relationship with initial ACR (B = -0.032; P = .02), suggesting each unit rise in ACR with a decrease in creatinine clearance by 0.032 mL/min. To investigate their value in predicting good functional graft defined as creatinine clearance >45 mL/min, a receiver operating characteristic curve analysis was applied on these parameters. The area under curve for age is 0.496, for body weight is 0.539, and for highly sensitive C-reactive protein is 0.582, which are all around the chance of 0.5 by flipping coins. The area under ACR curve is 0.825, better than above parameters, and only second to serum creatinine level. CONCLUSIONS: Urine ACR is a simple and effective measure to predict graft function after a kidney transplant. It has similar independent strong correlations to creatinine clearance comparing with serum creatinine without requirement of a blood draw.


Assuntos
Albuminúria/urina , Creatinina/urina , Sobrevivência de Enxerto , Testes de Função Renal/métodos , Transplante de Rim , Adulto , Feminino , Taxa de Filtração Glomerular , Humanos , Nefropatias/urina , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Curva ROC , Urinálise
11.
Int J Occup Environ Med ; 10(2): 80-88, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31041925

RESUMO

BACKGROUND: Many workers, particularly those working in manufacture of fertilizers, explosives, rubber, pesticides, textiles, and employees of petrochemical industries are exposed to ammonia in their workplaces. Toxic responses of hematopoietic system and kidney following occupational exposure to this chemical have not been thoroughly investigated. OBJECTIVE: To determine the relationship between long-term occupational exposure to low levels of ammonia and hematological parameters and kidney function. METHODS: In this cross-sectional study, 119 randomly selected, male petrochemical workers and 131 office employees (comparison group) were examined. Urine and blood samples were taken from all participants for urinalysis, complete blood count (CBC), serum calcium level, and blood urea nitrogen (BUN) and plasma creatinine. Personal, environmental, and peak ammonia exposure were also measured. RESULTS: The median personal, environmental, and peak occupational exposure to ammonia were 0.23, 0.16, and 65.50 mg/m3, respectively, among the exposed group. No significant difference was observed between the exposed and unexposed participants in terms of hematological parameters and urinalysis. Conversely, calcium and BUN, while within the normal range, were significantly higher in the exposed than in the comparison group. CONCLUSION: Occupational exposure to low atmospheric concentrations of ammonia was associated with subtle, sub-clinical, pre-pathologic changes in kidney function. Possible longterm consequences and ramifications of these effects require further investigation.


Assuntos
Amônia/toxicidade , Rim/efeitos dos fármacos , Exposição Ocupacional/análise , Adulto , Contagem de Células Sanguíneas , Nitrogênio da Ureia Sanguínea , Cálcio/sangue , Creatinina/sangue , Estudos Transversais , Humanos , Testes de Função Renal , Masculino
12.
Int J Occup Environ Med ; 10(2): 89-93, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-31041926

RESUMO

Lead exposure is associated with several health hazards among workers with different individual responses. We conducted this study to determine the possible effects of lead exposure on hematological parameters and kidney function of a group of Egyptian ammunition workers and the interaction of aminolevulinic acid dehydratase (ALAD) G177C gene polymorphisms as an effect modifier. Significant differences were observed between exposed workers with ALAD1-1 and ALAD1-2 genotypes in terms of blood lead level, hematological parameters and kidney function. It seems that δ-ALAD gene polymorphism may be an effect modifier and a marker of genetic susceptibility to lead toxicity.


Assuntos
Chumbo/sangue , Exposição Ocupacional , Polimorfismo Genético , Sintase do Porfobilinogênio/genética , Biomarcadores/sangue , Estudos Transversais , Egito , Predisposição Genética para Doença , Humanos , Rim/efeitos dos fármacos , Testes de Função Renal , Chumbo/toxicidade , Masculino , Pessoa de Meia-Idade
13.
Medicine (Baltimore) ; 98(21): e15465, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124929

RESUMO

This study aimed to explore the diagnostic performance of the ratio of renal resistive index (RRI) to semiquantitative power Doppler ultrasound (PDU) score in predicting acute kidney injury (AKI) 3 in critically ill patients.This study was a prospective, observational study that included 101 critically ill patients. RRI and semiquantitative PDU score were measured within 6 hours following admission to the intensive care unit (ICU). The ratio of RRI to PDU (RRI/PDU) was calculated as follows: RRI / PDU. If PDU score was 0, the RRI/PDU was 1. Meanwhile, AKI was defined according to the Kidney Disease Improving Global Outcomes criteria.Median RRI/PDU was 0.234 (0.190, 0.335) in patients with AKI 0-2 and 0.636 (0.411, 0.738) in patients with AKI 3 (P < .001). As assessed by the area under the receiver operator characteristic curves (AUC), RRI/PDU performed best in diagnosing AKI 3 [AUC = 0.935 (95% CI: 0.868-0.974)]. Optimal cuto for RRI/PDU was > 0.37, and the sensitivity and specificity were 90.5% and 90.0%, respectively. In 93 patients, except for 8 patients with a PDU score of 0, the AUC of RRI/PDU [0.938 (95% CI: 0.868-0.977)] was superior to the PDU score (0.905 [95% CI: 0.826-0.956], P = .133), RRI [0.782 (95% CI: 0.684-0.861), P = .016], serum creatinine [0.801 (95% CI: 0.705-0.877), P = .017], or 6 hours AKI stage (0.876 [95% CI: 0.791-0.935], P = .110) in predicting AKI 3 on D5.In our study, RRI, PDU score, RRI/PDU, and 6 hours AKI stage were useful in predicting AKI 3. Furthermore, RRI/PDU may be a better predictor of AKI 3.


Assuntos
Lesão Renal Aguda/diagnóstico , Testes de Função Renal/estatística & dados numéricos , Índice de Gravidade de Doença , Ultrassonografia Doppler/estatística & dados numéricos , Idoso , Área Sob a Curva , Creatinina/sangue , Feminino , Humanos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Sensibilidade e Especificidade , Resistência Vascular
14.
Medicine (Baltimore) ; 98(21): e15808, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31124979

RESUMO

Data on risk factors predicting rapid progression to end-stage renal disease (ESRD) or short-term kidney function decline (i.e., within 1 year) in chronic kidney disease (CKD) are rare but urgently needed to plan treatment. This study describes the association and predictive value of urinary uromodulin (uUMOD) for rapid progression of CKD.We assessed uUMOD, demographic/treatment parameters, estimated glomerular filtration rate (eGFR), and proteinuria in 230 CKD patients stage I-V. ESRD and 25% decline of eGFR was documented at the end of follow-up period and used as a composite endpoint. Association between logarithmic uUMOD and eGFR/proteinuria was calculated using linear regression analysis, adjusting for age, gender, and body mass index. We performed multivariable Cox proportional hazard regression analysis to evaluate the association of uUMOD with the composite endpoint. Therefore, patients were categorized into quartiles. The predictive value of uUMOD for the above outcomes was assessed using receiver-operating characteristic (ROC) curve analysis.Follow-up was 57.3 ±â€Š18.7 weeks, baseline age was 60 (18;92) years, and eGFR was 38 (6;156) mL/min/1.73 m. Forty-seven (20.4%) patients reached the composite endpoint. uUMOD concentrations were directly associated with eGFR and inversely associated with proteinuria (ß = 0.554 and ß = -0.429, P < .001). In multivariable Cox regression analysis, the first 2 quartiles of uUMOD concentrations had a hazard ratio (HR) of 3.589 [95% confidence interval (95% CI) 1.002-12.992] and 5.409 (95% CI 1.444-20.269), respectively, in comparison to patients of the highest quartile (≥11.45 µg/mL) for the composite endpoint. In ROC-analysis, uUMOD predicted the composite endpoint with good sensitivity (74.6%) and specificity (76.6%) at an optimal cut-off at 3.5 µg/mL and area under the curve of 0.786 (95% CI 0.712-0.860, P < .001).uUMOD was independently associated with ESRD/rapid loss of eGFR. It might serve as a robust predictor of rapid kidney function decline and help to better schedule arrangements for future treatment.


Assuntos
Falência Renal Crônica/etiologia , Testes de Função Renal/estatística & dados numéricos , Proteinúria/etiologia , Insuficiência Renal Crônica/urina , Uromodulina/urina , Adulto , Idoso , Área Sob a Curva , Estudos de Coortes , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Testes de Função Renal/métodos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Modelos de Riscos Proporcionais , Curva ROC , Insuficiência Renal Crônica/complicações , Fatores de Risco
15.
Gene ; 707: 198-204, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31075409

RESUMO

BACKGROUND: Drug-induced kidney injury (DIKI) can be manifested with progressive chronic kidney diseases or end-stage renal diseases. Understanding the molecular disarrangements caused by DIKI is an attractive point of interest. A class of non-coding RNA called microRNAs (miRNAs) is known to play a major role in regulation of gene expression and signaling pathways making miRNAs excellent targets for new therapeutic agents. AIM OF THE STUDY: We aimed to investigate the role of miRNA 21 and 181a in gentamicin (GNT) induced nephrotoxicity rat model and the protective effect of Dapagliflozin (DAPA) in modulating their expression through studying its effect on renal function as well as renal histopathological changes. MATERIALS AND METHODS: Wistar rats were used and divided into: naïve, DAPA, GNT and DAPA + GNT groups. In all studied groups, kidney function, oxidative stress, apoptosis markers and miRNAs' expression in serum and renal biopsies were investigated in addition to the histopathological studies to identify its early renoprotective effect. RESULTS: DAPA was found to improve kidney function, oxidative stress markers, decrease apoptosis of renal tubular cells and increase miR-21 but decrease the expression of miR-181a with restoration of the renal architecture after 14 days of treatment in GNT induced nephrotoxicity rat model. CONCLUSIONS: DAPA produced significant decrease in renal expression of miR-181a on the other hand it increased the expression of renal miR-21, this may introduce a novel early protective effect of DAPA against GNT-induced nephrotoxicity.


Assuntos
Lesão Renal Aguda/tratamento farmacológico , Compostos Benzidrílicos/administração & dosagem , Gentamicinas/efeitos adversos , Glucosídeos/administração & dosagem , MicroRNAs/genética , Lesão Renal Aguda/induzido quimicamente , Lesão Renal Aguda/genética , Lesão Renal Aguda/fisiopatologia , Animais , Apoptose/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/farmacologia , Testes de Função Renal , Masculino , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
16.
Internist (Berl) ; 60(5): 485-501, 2019 05.
Artigo em Alemão | MEDLINE | ID: mdl-30997523

RESUMO

Kidney diseases are among the most frequently reported diseases with a poor prognosis that are diagnosed too late. According to current Kidney Disease Improving Global Outcomes (KDIGO) guidelines, diagnosis and risk stratification are mainly based on functional markers (creatinine and cystatin C), which are used to determine the estimated glomerular filtration rate (eGFR) and the analysis of urinary albumin excretion as a marker of kidney damage. These methods have limitations that can complicate the interpretation of the results and can lead to a delay of the diagnosis as well as to a misinterpretation of the prognosis. Therefore, new damage markers are required that sensitively and specifically detect kidney damage and enable targeted treatment. Urinalysis complements the laboratory diagnostic spectrum of diseases of the kidneys and urinary tract. It is mainly used for screening and provides important information on localization (renal/postrenal) and differentiation of kidney diseases (glomerular/tubulointerstitial).


Assuntos
Creatinina/sangue , Cistatina C/sangue , Taxa de Filtração Glomerular/fisiologia , Nefropatias/diagnóstico , Testes de Função Renal/normas , Insuficiência Renal/diagnóstico , Biomarcadores/sangue , Humanos , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/fisiopatologia , Urinálise
17.
Phytother Res ; 33(6): 1648-1657, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30942510

RESUMO

Diabetes mellitus is a metabolic disease that manifested as hyperglycemia due to the defect in secretion or function of insulin. Studies have shown that saffron and its derivatives cause a significant reduction in plasma glucose levels in experimental models. The purpose of this study was to investigate the effect of the saffron extract on fasting plasma glucose (FPG), glycated hemoglobin level (HbA1c), lipid profile, liver enzymes, and renal function tests in type 2 diabetic patients. In this double-blind randomized clinical trial, 64 type 2 diabetic patients who were on oral anti-diabetic drugs were examined. Participants received either 15 mg of saffron or placebo capsules (two pills per day) for 3 months. Anthropometric indices, dietary intake, FPG, HbA1c, lipid profiles, liver enzymes (ALT, AST, ALP), and renal function (BUN, Cr.) tests were measured pre and post intervention after 3 months. Independent t test and paired t test were used for data analysis. After 3-months intervention, mean difference of FPG, Cholesterol, LDL-c, and LDL/HDL ratio between two groups showed significant reduction(p < 0.0001), but HbA1c, HDL-C, API, TG showed no significant differences (p > 0.05). In saffron group, FPG, HbA1c, cholesterol, LDL-c, and LDL/HDL ratio decreased significantly after 3-months intervention compare with baseline (p < 0.0001).


Assuntos
Crocus/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Rim/efeitos dos fármacos , Fígado/efeitos dos fármacos , Extratos Vegetais/uso terapêutico , Adulto , Idoso , Glicemia/análise , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Etanol/química , Jejum/sangue , Feminino , Hemoglobina A Glicada/efeitos dos fármacos , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Insulina/sangue , Rim/fisiologia , Testes de Função Renal , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Fígado/metabolismo , Fígado/fisiologia , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/química , Água/química
18.
Arch Ital Urol Androl ; 91(1): 30-34, 2019 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-30932421

RESUMO

OBJECTIVES: We evaluated the efficacy of sutureless laparoscopic partial nephrectomy (LPN), using a fibrin gel in order to minimize renal ischemia time and preserve kidney function. MATERIALS AND METHODS: Nineteen patients (mean age 58.3 ± 7.1) undergoing sutureless LPN using a fbrin gel were compared with a control group consisting of 21 patients (mean age 57.9 ± 7.5) subjected to LPN with standard suturing. Intraand post-operative data for the two groups were compared. The following parameters were recorded: patient demographics, Charlson Comorbidity Index, tumor characteristics according to the RENAL score, warm ischemia and operative times, estimated blood loss, mean hospital stay, post-operative complications referring to the Clavien-Dindo classification, renal function parameters pathologic and follow-up data. The main outcome measure was renal ischemia time and maintenance of kidney function. RESULTS: Median warm ischemia time was 13 minutes (range 11-19) in the group treated with fibrin gel and 19 (range 17- 29) in the control group, with a statistically significant difference (p < 0.001). The two groups were homogeneous in terms of the Charlson Comorbidity Index (4.6 vs 4.8) and RENAL score (9.6 vs 9.4). Median operative time differed significantly in the two groups, 183 minutes (range 145-218) in the group treated with fibrin gel and 201 (range 197-231) in the control group (p < 0.001). A negative surgical margin was reported in 18 patients (94.7%) in the group treated with fibrin gel and in 21 patients (100%) in the control group. No difference in renal function was found between the two groups. CONCLUSIONS: Sutureless LPN with fibrin gel can reduce warm ischemia and total operative time while preserving kidney function.


Assuntos
Neoplasias Renais/cirurgia , Laparoscopia/métodos , Nefrectomia/métodos , Procedimentos Cirúrgicos sem Sutura/métodos , Idoso , Feminino , Fibrina/química , Seguimentos , Géis , Humanos , Isquemia/prevenção & controle , Testes de Função Renal , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Isquemia Quente/métodos
19.
J Vet Intern Med ; 33(3): 1530-1539, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31025445

RESUMO

BACKGROUND: Urine concentration (UC) provides clinically useful information concerning hydration status and renal function of animals. OBJECTIVES: To characterize the clinical performance of urine specific gravity measured by optical refractometry (USG-R ) or Multistix-SG urine reagent dipstick (USG-D ), urine electrical conductivity using an OAKTON Con 6 conductivity handheld meter (UEC ), urine color (UColor ) using a custom-designed 8-point color chart, and urine creatinine concentration (UCreat ) for assessing UC in dairy cattle. ANIMALS: 20 periparturient Holstein-Friesian cows. METHODS: Urine was obtained by perineal stimulation or urethral catheterization and urine osmolality (UOsm , reference method), USG-R , USG-D , UEC , UColor , and UCreat determined. Diagnostic test performance was evaluated using Spearman's rho and logistic regression to determine the area under the receiver operating curve (AUC) and optimal cut point for diagnosing hypohydration (UOsm ≥800 mOsm/kg). P < .05 was considered significant. RESULTS: The best performing test for diagnosing hypohydration was USG-R (AUC = 0.90) at an optimal cut point ≥1.030. The second-best performing test was UEC (AUC = 0.82) at a cut point of ≥23.7 mS/cm, followed by UCreat (AUC = 0.76) at a cut point of ≥95.3 mg/dL, and UColor (AUC = 0.74) at a cut point of ≥4 on an 8-point scale. Urine specific gravity measured by dipstick performed poorly (AUC = 0.63). CONCLUSIONS AND CLINICAL IMPORTANCE: USG-R and UEC provide practical and sufficiently accurate methods for measuring UC in dairy cattle. Urine color had moderate clinical utility as a no-cost cow-side method for assessing UC, whereas dipstick refractometry is not recommended for assessing UC.


Assuntos
Bovinos/urina , Cor , Estado de Hidratação do Organismo , Gravidade Específica , Urinálise/veterinária , Animais , Creatinina/urina , Condutividade Elétrica , Feminino , Testes de Função Renal/veterinária , Sensibilidade e Especificidade , Urinálise/instrumentação , Urinálise/métodos
20.
BMJ Case Rep ; 12(3)2019 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-30936328

RESUMO

Immunoglobulin A nephropathy (IgAN) is the most commonly diagnosed glomerulonephritis worldwide. It is usually idiopathic and may be associated with many other diseases. Recently, biological agents including tumour necrosis factor alpha (TNFα) inhibitors have been identified as a potential cause for IgAN. We report the case of a 39-year-old woman who presented with renal dysfunction and visible haematuria. She had a background of Crohn's disease (CD) and had been on adalimumab for 4 years following a right hemicolectomy. Subsequently, she underwent a renal biopsy that demonstrated IgAN and adalimumab was ceased. Following a flare in her CD, she was commenced on infliximab, which led to remission of the IgAN and CD. This is the first case to demonstrate the occurrence of IgAN as a complication of a TNFα inhibitor (adalimumab) that remained in remission despite the commencement of a second TNFα inhibitor (infliximab).


Assuntos
Adalimumab/efeitos adversos , Doença de Crohn/cirurgia , Fármacos Gastrointestinais/uso terapêutico , Glomerulonefrite por IGA/induzido quimicamente , Infliximab/uso terapêutico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Adalimumab/uso terapêutico , Adulto , Biópsia , Colectomia , Doença de Crohn/tratamento farmacológico , Doença de Crohn/fisiopatologia , Feminino , Glomerulonefrite por IGA/patologia , Humanos , Testes de Função Renal , Resultado do Tratamento
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