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1.
Medicine (Baltimore) ; 99(2): e18709, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31914079

RESUMO

Kidney handling of electrolytes varies in different stages of chronic kidney disease (CKD). Diabetes mellitus (DM) plays an important role in CKD. Fractional excretion (FE) is an important means in clinical practice. The relationship between FE of electrolytes in patients at different stages of CKD is worth further investigating.We designed a cross-sectional study in 1 teaching hospital, consecutive CKD patients were enrolled between February 2016 and January 2017. Including clinical demographic features, laboratory examination including spot urine electrolytes, blood biochemistries, and relevant medications were determined.A total of 762 CKD patients completed the study. Of these, 218 (28.6%) had DM. Participants were grouped according to estimated glomerular filtration rate into 7 categories: hyperfiltration (HF), CKD1, CKD2, CKD3a, CKD3b, CKD4, and CKD5. Groups HF, CKD1, 2, 3a, 3b, 4 and 5 contained 83, 143, 192, 94, 82, 82, and 86 patients, respectively. FE of electrolytes tended to increase along with the decline of renal function (CKD1-CKD5) (P < .001). The relationship was similar between the DM and non-DM groups. Diabetic patients demonstrated higher FE of magnesium compared with non-DM subjects at CKD2 and CKD5 (P < .05).CKD patients showed a progressive increase in the FE of electrolytes; FE of magnesium seemed to increase more among diabetic patients with CKD, and could be a potential predictor of CKD progression.


Assuntos
Eletrólitos/metabolismo , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Progressão da Doença , Eletrólitos/urina , Feminino , Humanos , Magnésio/metabolismo , Masculino , Pessoa de Meia-Idade , Índice de Gravidade de Doença
2.
Life Sci ; 241: 117109, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31786195

RESUMO

AIMS: This study aimed to identify interstitial molecules that were responsible for the deterioration of the esiantimated glomerular filtration rate (eGFR) in diabetic nephropathy (DN). MATERIALS AND METHODS: Weighted gene co-expression network analysis (WGCNA) was used to link the tubulointerstitial gene expression profile of DN to eGFR values. The relationship of eGFR with each sub-domain regulator in the network was analyzed with the linear regression model. Gene sets enrichment analysis (GSEA) was applied to detect the molecular changes mostly relating to the essential regulators. KEY FINDINGS: Four co-expression modules were found strongly correlating with eGFR values. Genes from these modules were over-represented in fibrosis-related biological processes (extracellular matrix (ECM) organization and cell adhesion) and pathways (integrin signaling and ECM-receptor interaction). Of sub-domains in the gene interaction network, the expression of hypoxia-inducible factor 1A (HIF1A) was most negatively correlated with eGFR (R2 = 0.417, P = 0.026). The positive correlations between HIF1A and its target genes were found, indicating an enhanced transcriptional activity of HIF1A. We also found that HIF1A positively correlated with CCAAT enhancer binding protein delta (CEBPD) (r = 0.731, P = 0.011), an activator of HIF1A transcription. Moreover, GSEA showed that samples with high HIF1A expression were enriched with fibrosis associated signaling, like ECM-receptor interaction and cell adhesion. Intriguingly, vascular epithelial growth factor A (VEGFA) expression decreased while HIF1A increased (R2 = 0.733, P = 0.001), suggesting VEGFA loss may exacerbate hypoxia and stimulate HIF1A induction. SIGNIFICANCE: The present study suggested that interstitial HIF1A may be involved in renal interstitial fibrosis in DN.


Assuntos
Nefropatias Diabéticas/genética , Fibrose/fisiopatologia , Taxa de Filtração Glomerular/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Rim/patologia , Adulto , Idoso , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/fisiopatologia , Feminino , Fibrose/genética , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Taxa de Filtração Glomerular/fisiologia , Humanos , Nefropatias/patologia , Masculino , Pessoa de Meia-Idade , Fator A de Crescimento do Endotélio Vascular/genética
3.
Chemosphere ; 238: 124603, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31442773

RESUMO

Environmental pollution is a risk factor for kidney dysfunction. However, the combined toxicity of air pollutants on kidney function is scarce. We estimated the relationship between combined toxicity of air pollutants and kidney function among adult women (n = 7071, 18-65 years old) in Mianyang City, Southwest China. We measured serum concentrations of uric acid, urea, creatinine, and cystatin C, and we calculated the individual estimated glomerular filtration rate (eGFR) using a cystatin C-based equation developed specifically for Chinese patients with CKD equation. Air pollution data were collected to calculate the individual average daily dose (ADD) of pollutants based on the air quality complex index (AQCI). Mean AQCI was higher in winter and lower in summer, and followed the monthly and seasonal trends of air pollutants. Concomitantly, individual ADD was also higher in winter and lower in summer, and the seasonal differences were reflected in the levels of kidney biomarkers (including uric acid, urea, creatinine, cystatin C, and eGFR). With an interquartile range (IQR: 1.04-1.50 m3/day/kg) increases of ADD, the serum concentrations of uric acid, urea, creatinine, and cystatin C increase [B (95%CI): 1.774 (0.318, 3.231) umol/L, 0.218 (0.1888, 0.247) mmol/L, 1.501 (1.016, 1.986) umol/L, and 0.006 (0.003, 0.009) mg/L, respectively], whereas eGFR decreases [B (95%CI): -0.776 (-1.106, -0.446) mL/min/1.73 m2]. Totally, the relationship between combined toxicity of air pollutants and kidney function in Chinese adult women suggests that the toxicity of combined air pollutants inversely affects kidney function, which might accelerate the risk of CKD.


Assuntos
Poluentes Atmosféricos/toxicidade , Poluição do Ar/análise , Exposição Ambiental/efeitos adversos , Taxa de Filtração Glomerular/fisiologia , Adolescente , Adulto , Idoso , Algoritmos , Biomarcadores/sangue , China , Creatinina/sangue , Cistatina C/sangue , Feminino , Humanos , Rim/patologia , Pessoa de Meia-Idade , Fatores de Risco , Ureia/sangue , Ácido Úrico/sangue , Adulto Jovem
4.
J Pharm Biomed Anal ; 177: 112889, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31568966

RESUMO

This work presents the development of a methodology for the accurate and precise quantification of the renal biomarker Cystatin C in human urine by Isotope Dilution Mass Spectrometry (IDMS). The procedure is based on the addition of a known quantity of the proteotypic peptide ALDFAVG*EYNK labelled with 13C2-glycine to the urine sample followed by protein hydrolysis using trypsin. Then, preconcentration and purification of the isotope diluted peptide was carried out by a selective monoclonal antibody bound to magnetic beads and final measurement was done after injection of the sample in a HPLC-MS/MS triple quadrupole instrument. The isotopic distribution of the isotope diluted proteotypic peptide was measured by low resolution selected reaction monitoring. Using this aquisition mode, the bandpass of the first quadrupole was widened (FWHM =13 u) so the whole isotopic clusters for both the natural abundance and the labelled peptides entered the collision cell. The proposed acquisition mode provided similar accuracy and precision than the regular SRM mode (FWHM =0.7 u) but a higher sensitivity was observed. The purification of the sample by antibody based enrichment of the target peptide was shown to remove interfering compounds more efficiently in comparison with a sample purification based on semipreparative liquid chromatography. Using 5 ng of the labelled peptide it was possible to quantify Cystatin C in human urine in patients with normal and impaired renal function. Recoveries from 100 to 104% were obtained in samples containing from 90 to 700 µg L-1 of Cystatin C with relative standard deviations from 0.5 to 6%. The stability of Cystatin C in urine samples was evaluated under different storage conditions showing that only when the urine samples were stored at room temperature during more than 10 days, a significant degradation of Cystatin C was observed.


Assuntos
Cistatina C/urina , Nefropatias/diagnóstico , Manejo de Espécimes/efeitos adversos , Espectrometria de Massas em Tandem/métodos , Biomarcadores/química , Biomarcadores/urina , Isótopos de Carbono/química , Cromatografia Líquida de Alta Pressão , Cistatina C/química , Taxa de Filtração Glomerular/fisiologia , Humanos , Técnicas de Diluição do Indicador , Rim/fisiopatologia , Nefropatias/fisiopatologia , Nefropatias/urina , Estabilidade Proteica , Manejo de Espécimes/métodos , Temperatura Ambiente , Fatores de Tempo
5.
Int Braz J Urol ; 45(6): 1227-1237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31808412

RESUMO

INTRODUCTION: Children with a solitary post-nephrectomy kidney (SNK) are at potential risk of developing kidney disease later in life. In response to the global decline in the number of nephrons, adaptive mechanisms lead to renal injury. The aim of this study was to determine the prevalence and time of onset of high blood pressure (HBP), proteinuria, glomerular filtration rate (GFR) disruption and renal tubular acidosis (RTA) in children with SNK. MATERIALS AND METHODS: After obtaining the approval from our institution's ethics committee, we reviewed the medical records of patients under 18 years of age who underwent unilateral nephrectomy between January 2005 and December 2015 in three university hospitals. RESULTS: We identifi ed 43 patients, 35 (81.4%) cases of unilateral nephrectomy (UNP) were due to a non-oncologic pathology and Wilm's tumor was identified in 8 (18.6%) cases. In patients with non-oncologic disease, 9.3% developed de novo hypertension, with an average time of onset of 7.1 years, 25% developed proteinuria de novo, with an average time of onset of 2.2 years. For GFR, 21.8% presented deterioration of the GFR in an average time of 3.4 years. Ten (43.5%) patients developed some type of de novo renal injury after UNP. Patients with oncolo-gic disease developed the conditions slowly and none of them developed proteinuria. CONCLUSIONS: Taking into account the high rate of long term postoperative renal injury, it can be considered that nephrectomy does not prevent this disease. The follow-up of children with SNK requires a multidisciplinary approach and long-term surveillance to detect renal injury.


Assuntos
Nefrectomia/efeitos adversos , Rim Único/epidemiologia , Rim Único/fisiopatologia , Acidose Tubular Renal/epidemiologia , Acidose Tubular Renal/fisiopatologia , Adolescente , Idade de Início , Criança , Pré-Escolar , Colômbia/epidemiologia , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Hipertensão/epidemiologia , Hipertensão/fisiopatologia , Lactente , Recém-Nascido , Masculino , Período Pós-Operatório , Prevalência , Prognóstico , Proteinúria/epidemiologia , Proteinúria/fisiopatologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco
6.
Urologiia ; (5): 72-78, 2019 Dec.
Artigo em Russo | MEDLINE | ID: mdl-31808636

RESUMO

INTRODUCTION: and Objectives: to date there have been several hypotheses on the causes of kidney stone formation. Compromised intrarenal blood flow might play one of major roles in stone formation. Advances in software and 3D technologies have unveiled the nature of contrast medium flow in the intrarenal structures. Mathematical analysis and 3D rendering of computed tomography (CT) scans was utilized for inrarenal contrast medium flow assessment in patients with stone kidney disease. This study aimed at assessing split glomerular filtration rate (sGFR) in patients at the initial stage of stone kidney disease (SKD). sGFR was measured by means of mathematical analysis of 3D rendering abdominal contrast enhanced CT scans. As well as that, possible correlations between irregular inrarenal contrast medium flow and causes of stone formation were considered. MATERIALS AND METHODS: 23 patients of both sexes with stone kidney disease (SKD) were recruited. They underwent US/Dopler investigation of the kidneys and the bladder, plain X-ray, histopathological evaluation of the tissues (those patients who were operated on), spectroscopic analysis of the stone(s). Mathematical analysis of 3D rendering of CT scans was utilized for sGFR assessment (sGFR reference value: 0,55% of contrast medium per second). Inclusion criteria are as follows: 1) newly diagnosed SKD; 2) stone size less than 1,5-2,0 cm 3) stones that do not block urine flow 4) non-operated young patients; 5) patients free of comorbidities. Inclusion criteria were set to mitigate the effects of other factors that might influence on intrarenal blood flow and conduct the study per se. RESULTS: Mathematical analysis of 3D rendering of CT scans allowed to elucidate changes in sGFR in 22 (95,6%) patients out of 23. HypErfiltration (hyperF) was detected in 10 (43,5%) patients, hypOfiltration (hypoF) was detected in 11(47,8%) patients. sGFR values were statistically significantly different in these groups both on the left (p=0,000142) and on the right (p=0,00068). No significant gender differences were observed (hypoF group aged 25-67 years with the mean age of 43,5 years; hyperF group aged 17-57 years with the mean age of 39 years (p=0,563). Ultrasound Doppler renal resistive index in renal arteries was within the normal range in both groups with no statistically significant difference between the groups. However, 1 patient demonstrated no sGFR changes. Another patient had hyporfiltration on the left (0,48%) and hyperfiltration on the right (0,62%) Conclusions: sGFR alterations (hypo- or hyperfiltration) were detected in the majority of the patients with SKD (95,6%). This in turn might be suggestive of compromised intrarenal blood flow. Further studies are needed to elucidate the optimal management of these patients.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Rim/diagnóstico por imagem , Rim/fisiologia , Tomografia Computadorizada por Raios X/métodos , Adolescente , Adulto , Idoso , Pré-Escolar , Meios de Contraste , Feminino , Humanos , Cálculos Renais , Masculino , Pessoa de Meia-Idade , Adulto Jovem
7.
Adv Clin Exp Med ; 28(12): 1657-1666, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31851790

RESUMO

BACKGROUND: Diagnosing acute kidney injury (AKI) in preterm newborns, who are particularly susceptible to renal damage, is a serious challenge as there is no definite consensus about the diagnostic criteria. OBJECTIVES: The objective of this study was to measure the values for selected urinary biomarkers and estimated glomerular filtration rate (eGFR) among a population of preterm infants with uncomplicated clinical course as well as to determine whether these markers depend on birth weight (BW), gestational age (GA), postnatal age (PNA), or gender. MATERIAL AND METHODS: The prospective study was carried out in neonatal intensive care unit (NICU). The evaluation included 57 children that were divided into 3 categories according to BW: low birth weight (LBW) - 1501-2500 g (22 infants); very low birth weight (VLBW) - 1000-1500 g (25 infants); and extremely low birth weight (ELBW) - 750-999 g (10 infants). Urine samples were collected daily between the 4th and 28th day of life for measurements of creatinine (Cr), neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), and human kidney injury molecule 1 (hKIM1). RESULTS: The values of the 3 urine tubular biomarkers, serum creatinine and eGFR were taken in substantially healthy preterm infants with normal kidney function at 4 time intervals during the neonatal period. Their correlations were determined and a multivariable regression analysis was carried out with respect to BW, GA, PNA, and gender. Trends of the studied markers in terms of PNA and BW were also assessed with the Jonckheere-Terpstra test. CONCLUSIONS: Glomerular and tubular function in preterm neonates during the 1st month of life is significantly influenced by BW, GA, PNA, and gender.


Assuntos
Lesão Renal Aguda , Taxa de Filtração Glomerular , Recém-Nascido Prematuro , Lesão Renal Aguda/diagnóstico , Biomarcadores/sangue , Biomarcadores/urina , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Recém-Nascido de Baixo Peso , Recém-Nascido , Masculino , Estudos Prospectivos
8.
Mayo Clin Proc ; 94(11): 2189-2198, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31668448

RESUMO

OBJECTIVE: To classify subjects in a general population per their renal function and characterize the cardiac biomarker levels, left ventricular function and cardiovascular outcomes over a 10.2 year follow-up period (interquartile range, 5.1-11.4 years). METHODS: This was a retrospective review of a population-based random sample of residents aged ≥45 years. Data were collected between January 1, 1997, and December 31, 2000. One thousand nine hundred eighty-one individuals were classified based on estimated glomerular filtration rate (eGFR) into group I (>90 mL/min/1.73 m2), group II (60 to 89 mL/min/1.73 m2) and group III (<60 mL/min/1.73 m2; chronic kidney disease [CKD]). Age/sex-adjusted baseline characteristics, tertiles of N-terminal pro B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) and their interactions with eGFR were examined. Outcomes measured included incident myocardial infarction (MI), congestive heart failure, stroke, and all-cause mortality. RESULTS: Eight hundred nineteen patients were classified as group I, 1036 as group II, and 126 of 1981 (6.4%) as group III or CKD. Subjects in group III were older and had a higher incidence of hypertension, diabetes, and MI at baseline. Over a 10.2-year follow-up period, CKD was associated with an increased risk of MI (hazard ratio, 1.95; 95% CI, 1.2-3.14; P=.006) and composite cardiovascular outcomes including MI, congestive heart failure, stroke, and all-cause mortality (hazard ratio, 1.38; 95% CI, 1.05-1.83 ;P=.02). Subjects with NT-proBNP or hs-TnT in the third tertile were at greater risk of cardiovascular events without significant interactions between eGFR and levels of NT-proBNP and hs-TnT. CONCLUSION: Subjects with CKD had significantly elevated cardiac biomarkers and were at an increased risk of MI and adverse cardiovascular events. This warrants future studies to investigate whether these cardiac biomarkers could identify high-risk CKD patients for aggressive management of cardiovascular risk factors.


Assuntos
Doenças Cardiovasculares/sangue , Taxa de Filtração Glomerular/fisiologia , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Insuficiência Renal Crônica/sangue , Idoso , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Estudos Retrospectivos , Fatores de Risco
9.
Nat Med ; 25(11): 1753-1760, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700174

RESUMO

Chronic kidney disease is common in the general population and associated with excess cardiovascular disease (CVD), but kidney function does not feature in current CVD risk-prediction models. We tested three formulae for estimated glomerular filtration rate (eGFR) to determine which was the most clinically informative for predicting CVD and mortality. Using data from 440,526 participants from UK Biobank, eGFR was calculated using serum creatinine, cystatin C (eGFRcys) and creatinine-cystatin C. Associations of each eGFR with CVD outcome and mortality were compared using Cox models and adjusting for atherosclerotic risk factors (per relevant risk scores), and the predictive utility was determined by the C-statistic and categorical net reclassification index. We show that eGFRcys is most strongly associated with CVD and mortality, and, along with albuminuria, adds predictive discrimination to current CVD risk scores, whilst traditional creatinine-based measures are weakly associated with risk. Clinicians should consider measuring eGFRcys as part of cardiovascular risk assessment.


Assuntos
Doenças Cardiovasculares/diagnóstico , Taxa de Filtração Glomerular/fisiologia , Falência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/diagnóstico , Adulto , Idoso , Albuminúria/complicações , Albuminúria/diagnóstico , Albuminúria/fisiopatologia , Albuminúria/urina , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Biomarcadores/urina , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/fisiopatologia , Creatinina/metabolismo , Feminino , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Fatores de Risco
10.
Medicine (Baltimore) ; 98(42): e17588, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626129

RESUMO

In 2014/2015, tyrosine kinase inhibitors (TKIs) were introduced as a secondary treatment for refractory differentiated thyroid cancer (DTC) in Japan. While renal dysfunction is an adverse event of TKI, data on this adverse event in TKI-treated DTC remains insufficient. Here, we investigated renal function in patients undergoing TKI treatment for DTC and evaluated the efficacy of dose reduction/withdrawal for cases of renal dysfunction.A total of 73 cases of radioactive iodine-refractory DTC treated with sorafenib (n = 22) or lenvatinib (n = 51) were included. Patient data evaluated were TKI treatment period, estimated glomerular filtration rate (eGFR) before and after TKI therapy, incidence and degree (maximum value at time of TKI treatment) of proteinuria, and albumin levels before and after TKI therapy were compared.The mean ΔeGFR was -6.75% with lenvatinib and +5.90% with sorafenib. It was not significant (P = .15). The mean Δalbumin was -8.90% and -5.85% with lenvatinib and sorafenib, respectively; there was no significant difference between the lenvatinib and sorafenib groups (P = .77). According to our program of TKI dose reduction and withdrawal, all patients except 2 with diabetes were successfully continuing treatment.Overall, the present results demonstrated that renal function is negatively affected by long-term TKI treatment for RAI-refractory DTC. However, heightened proteinuria, decreased eGFR and albumin levels, and significant but apparently reversible renal dysfunction were more frequent with lenvatinib than sorafenib.


Assuntos
Taxa de Filtração Glomerular/fisiologia , Radioisótopos do Iodo/uso terapêutico , Nefropatias/etiologia , Compostos de Fenilureia/uso terapêutico , Proteínas Tirosina Quinases/antagonistas & inibidores , Quinolinas/uso terapêutico , Sorafenibe/uso terapêutico , Neoplasias da Glândula Tireoide/terapia , Idoso , Substituição de Medicamentos , Feminino , Seguimentos , Humanos , Nefropatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Tolerância a Radiação , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/complicações , Neoplasias da Glândula Tireoide/diagnóstico , Tomografia Computadorizada por Raios X , Resultado do Tratamento
11.
Clin Nephrol ; 92(5): 237-242, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31549627

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is associated with a subclinical inflammatory state, which contributes to increased mortality in CKD patients. The purpose of this study was to examine the association between chosen cytokines, such as IFN-γ, IL-10, IL-2p70, IL-6, and kidney function as well as the body composition and nutritional markers in patients with CKD and diabetes mellitus type 2. MATERIALS AND METHODS: 21 patients with diabetes mellitus type 2 and CKD stage 3b - 5, with estimated glomerular filtration rate (eGFR) lower than 45 mL/min/1.72m2, not being treated with dialysis were included in the study. Body composition was assessed by bioimpedance spectroscopy (Body Composition Monitor - Fresenius Medical Care). RESULTS: Significant, negative correlations between lean tissue index (LTI) and IFN-γ concentrations (r = -0.52, p = 0.021) as well as IL-6 concentrations (r = -0.46, p = 0.047) were observed. Only the IL-6 levels significantly correlated with kidney function expressed by eGFR (r = -0.47, p = 0.034). We observed a significant positive correlation between IL-6 level and IFN-γ (r = 0.51, p = 0.019) as well as with high-sensitivity C-reactive protein (hsCRP) levels (r = 0.48, p = 0.029). The IL-10 level significantly correlated with hsCRP (r = 0.53, p = 0.015). CONCLUSION: In CKD patients with diabetes mellitus type 2 during conservative treatment, IL-6 levels were associated with kidney function expressed by eGFR. IL-6 levels and IFN-γ levels negatively correlated with the amount of muscle mass. Cytokines did not show any association with the amount of fat tissue this study.


Assuntos
Composição Corporal/fisiologia , Citocinas/sangue , Diabetes Mellitus Tipo 2/complicações , Insuficiência Renal Crônica , Taxa de Filtração Glomerular/fisiologia , Humanos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia
12.
Br J Anaesth ; 123(5): 584-591, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31521337

RESUMO

BACKGROUND: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation. METHODS: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss. RESULTS: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min-1 (1.73 m)-2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]). CONCLUSIONS: RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia. CLINICAL TRIAL REGISTRATION: ISRCTN30083294.


Assuntos
Precondicionamento Isquêmico/métodos , Transplante de Rim , Traumatismo por Reperfusão/prevenção & controle , Adolescente , Adulto , Idoso , Aloenxertos , Método Duplo-Cego , Europa (Continente) , Feminino , Seguimentos , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/fisiologia , Rim/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Tempo , Resultado do Tratamento , Adulto Jovem
13.
Transplant Proc ; 51(8): 2667-2670, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31477426

RESUMO

BACKGROUND: Elevated levels of plasma homocysteine could, through homocysteine oxidation, induce the overproduction of reactive oxygen species, leading to a reduction in glutathione-related antioxidants, and may impair graft functions in patients with renal transplants. The purpose of this study was to determine whether plasma homocysteine, glutathione, or its related antioxidants were related to graft functions in patients with renal transplants. PATIENTS AND METHODS: We recruited 66 patients (mean age 48.4 years) with renal transplants (mean transplant duration 8.3 years). Patients were divided into 2 groups, based on their estimated glomerular filtration rate (eGFR): the moderate graft function group (eGFR ≥ 60 mL/min/1.73 m2, n = 37) and low graft function group (eGFR < 60 mL/min/1.73 m2, n = 29). We then determined their fasting levels of the following: malondialdehyde (MDA), homocysteine, cysteine, pyridoxal 5'-phosphate (PLP), glutathione (GSH), oxidized glutathione (GSSG), GSH/GSH ratio, glutathione peroxidase (GSH-Px) activity. RESULTS: We found in the low graft function group significantly higher levels of plasma homocysteine, cysteine, GSH, and GSH/GSSG ratios. But an intergroup difference was not found regarding levels of MDA, PLP, GSSG, and GSH-Px activity. After adjusting for potential confounders, the increased plasma homocysteine and GSH levels were independently associated with lower eGFR. No interaction existed between homocysteine and GSH levels in association with eGFR. CONCLUSION: Increased plasma homocysteine and GSH levels appeared to be independent indicators of decreased graft functions in patients with renal transplants.


Assuntos
Função Retardada do Enxerto/sangue , Taxa de Filtração Glomerular/fisiologia , Glutationa/sangue , Homocisteína/sangue , Transplante de Rim , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
14.
Transplant Proc ; 51(8): 2533-2538, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31471015

RESUMO

Kidney transplants from living donors have increased, but few studies have examined the long-term risks of live donor nephrectomy. This is the first study to report the blood pressure (BP) changes associated with cardiovascular disease and linked to chronic kidney disease (CKD) 1 year after live donor nephrectomy. This study examined a prospective cohort of patients who underwent donor nephrectomy between March 1, 2006, and December 31, 2016, at the Severance Hospital, Seoul, South Korea. CKD was defined as a glomerular filtration rate (GFR) of < 60 mL/min/1.73m2. Patients with a history of hypertension or CKD or an estimated GFR < 60 mL/min/1.73m2 were excluded; those examined after 1 year post-nephrectomy were included in the study population. Among 420 patients who underwent donor nephrectomy, 137 (32.6%) developed a first-time onset of a GFR < 60 mL/min/1.73m2 by the first year after surgery. After propensity score-matching the age, systolic BP (P < .001) and pulse pressure (P = .006) were significantly associated with the groups with newly developed CKD. Systolic BP and pulse pressure decreased significantly at 1 year after donor nephrectomy. These differences decreased after donor nephrectomy, possibly lowering the risk of cardiovascular disease.


Assuntos
Pressão Sanguínea , Transplante de Rim , Doadores Vivos , Nefrectomia/efeitos adversos , Coleta de Tecidos e Órgãos/efeitos adversos , Adulto , Doenças Cardiovasculares/etiologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Pontuação de Propensão , Estudos Prospectivos , Insuficiência Renal Crônica/etiologia , República da Coreia
15.
Int Heart J ; 60(5): 1022-1029, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484858

RESUMO

Optical coherence tomography (OCT)-guided percutaneous coronary intervention (PCI) may increase contrast volume. However, the impact of OCT-guided PCI on the decline in kidney function (DKF) in actual clinical practice remains unclear.Among 1,003 consecutive patients who underwent either OCT-guided or intravascular ultrasound (IVUS)-guided PCI in our institute, we identified 202 propensity score-matched pairs adjusted by baseline factors. The incidence of DKF was compared between the OCT-guided PCI group and the IVUS-guided PCI group. DKF was defined as an increase in serum creatinine level of ≥ 0.5 mg/dL or a relative increase of ≥ 25% over baseline within 48 hours (acute DKF) or 1 month (sustained DKF) after PCI.Baseline characteristics, including the prevalence of chronic kidney disease (54% versus 46%, P = 0.09), were comparable between the OCT- and IVUS-guided PCI groups except for the age. The contrast volume was comparable between the two groups (153 ± 56 versus 144 ± 60 mL, P = 0.09), although it was significantly greater in the OCT-guided PCI group in patients with acute coronary syndrome (ACS; 175 ± 55 versus 159 ± 43 mL, P = 0.04). The incidence of acute DKF (0.5% versus 2.5%, P = 0.22) and sustained DKF (5.0% versus 10.4%, P = 0.31) was comparable between the two groups. Multivariate analysis demonstrated that ACS (odds ratio 4.74, 95% confidence interval 2.72-8.25, P < 0.001) was a predictor of sustained DKF.Compared with IVUS-guided PCI, OCT-guided PCI did not increase the incidence of DKF in actual clinical practice, although the increased contrast volume was observed in ACS cases.


Assuntos
Síndrome Coronariana Aguda/cirurgia , Lesão Renal Aguda/induzido quimicamente , Meios de Contraste/efeitos adversos , Intervenção Coronária Percutânea/métodos , Tomografia de Coerência Óptica/métodos , Ultrassonografia de Intervenção/métodos , Centros Médicos Acadêmicos , Síndrome Coronariana Aguda/diagnóstico por imagem , Lesão Renal Aguda/epidemiologia , Idoso , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Incidência , Japão , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Razão de Chances , Segurança do Paciente/estatística & dados numéricos , Intervenção Coronária Percutânea/efeitos adversos , Pontuação de Propensão , Estudos Retrospectivos , Medição de Risco , Cirurgia Assistida por Computador/efeitos adversos , Cirurgia Assistida por Computador/métodos , Tomografia de Coerência Óptica/efeitos adversos , Ultrassonografia de Intervenção/efeitos adversos
16.
Int Heart J ; 60(5): 1037-1042, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31484863

RESUMO

Although high-sensitivity C-reactive protein (hs-CRP) has been used to predict the risk of adverse cardiac events in patients with coronary artery disease (CAD) after percutaneous coronary interventions (PCIs), little is known about the association between hs-CRP and long-term outcomes in patients with preserved renal function.Here, we studied 1,153 patients with stable CAD and preserved renal function (estimated glomerular filtration rate: > 60 mL/minute/1.73 m2) who underwent their first PCI between 2000 and 2011. Those with available data on preprocedural hs-CRP were included. Patients were assigned to tertiles according to preprocedural hs-CRP levels. The incidence of major adverse cardiac events (MACE), including all-cause death and nonfatal myocardial infarction, was evaluated. During a median follow-up period of 7.5 years, Kaplan-Meier curves showed ongoing divergence in the rates of MACE among the hs-CRP tertiles (hs-CRP < 0.05 mg/L, 12.1%; 0.05-0.17 mg/L, 12.1%; > 0.17 mg/L, 21.6%; log-rank P = 0.003). After adjusting for the established cardiovascular risk factors, hs-CRP levels were found to be associated with a higher incidence of MACE (hazard ratio [HR]: 3.65, 95% confidence interval [CI]: 1.77-7.07; P = 0.0008) and a higher rate of all-cause mortality (HR: 5.14, 95% CI: 2.38-10.30; P < 0.0001).In conclusion, this long-term registry showed that preprocedural hs-CRP measurement is clinically useful for long-term risk assessments in patients with stable CAD and preserved renal function.


Assuntos
Angioplastia Coronária com Balão/mortalidade , Angioplastia Coronária com Balão/métodos , Proteína C-Reativa/metabolismo , Causas de Morte , Doença da Artéria Coronariana/terapia , Idoso , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Biomarcadores/sangue , Estudos de Coortes , Angiografia Coronária/métodos , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/mortalidade , Taxa de Filtração Glomerular/fisiologia , Hospitais Universitários , Humanos , Japão , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento
17.
J Physiol Anthropol ; 38(1): 12, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31488191

RESUMO

BACKGROUND: Mitochondrial DNA 5178 (Mt5178) C/A polymorphism is reportedly associated with longevity in the Japanese population. The objective of this study was to investigate whether Mt5178 C/A polymorphism influences the effect of physiological aging on renal function in male Japanese health checkup examinees. METHODS: A total of 404 male subjects (mean age ± SD, 53.9 ± 7.8 years; range, 29-76 years) were selected from among individuals visiting the hospital for regular medical checkups. After Mt5178 C/A genotyping, a cross-sectional study assessing the joint effects of Mt5178 C/A polymorphism and aging on renal function was then conducted. Renal function was evaluated by estimated glomerular filtration rate (eGFR). Subjects were divided into three age groups (< 50, 50-59, ≥ 60 years). RESULTS: In simple linear regression analysis, a significant negative association between aging and eGFR was observed in both Mt5178C and Mt5178A genotypic men (P < 0.001 and P = 0.003, respectively). However, in multiple linear regression analysis, a significant effect of aging on reduced eGFR was observed only in Mt5178C genotypic men (P < 0.001). Logistic regression analysis showed that, in the case of reduced eGFR defined as < 75 mL/min/1.73 m2, reduced eGFR was dependent on aging in both Mt5178C and Mt5178A genotypic men (P for trend < 0.001 and P for trend = 0.002, respectively). After adjusting for smoking status and alcohol consumption, reduced eGFR was also dependent on aging in both Mt5178C and Mt5178A genotypic men (P for trend < 0.001 and P for trend = 0.014, respectively). However, in reduced eGFR defined as < 90 mL/min/1.73 m2, reduced eGFR was dependent on aging only in Mt5178C genotypic men (P for trend < 0.001). CONCLUSIONS: This cross-sectional study suggests that Mt5178 C/A polymorphism modulates the effects of physiological aging on kidney function in Japanese men.


Assuntos
DNA Mitocondrial/genética , Taxa de Filtração Glomerular/fisiologia , Longevidade/genética , Polimorfismo de Nucleotídeo Único/genética , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , Grupo com Ancestrais do Continente Asiático/estatística & dados numéricos , Estudos Transversais , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade
18.
Hypertension ; 74(4): 872-879, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31378102

RESUMO

Chronic kidney disease is a strong risk factor for cardiovascular disease (CVD), but clinical kidney measures (estimated glomerular filtration rate and albuminuria) do not fully reflect the multiple aspects of kidney tubules influencing cardiovascular health. Applied methods are needed to integrate numerous tubule biomarkers into useful prognostic scores. In SPRINT (Systolic Blood Pressure Intervention Trial) participants with chronic kidney disease at baseline (estimated glomerular filtration ratecr&cys <60 mL/minute per 1.73 m2), we measured 8 biomarkers from urine (α1M [α1M microglobulin], ß2M [ß2M microglobulin], umod [uromodulin], KIM-1 [kidney injury molecule-1], MCP-1 [monocyte chemoattractant protein-1], YKL-40 [chitinase-3-like protein-1], NGAL [neutrophil gelatinase-associated lipocalin], and IL-18 [interleukin 18]) and 2 biomarkers from serum (intact parathyroid hormone, iFGF-23 [intact fibroblast growth factor-23]). We used an unsupervised method, exploratory factor analysis, to create summary scores of tubule health dimensions. Adjusted Cox models evaluated each tubule score with CVD events, heart failure, and all-cause mortality. We examined CVD discrimination using Harrell C-statistic. Factor analysis of 10 biomarkers from 2376 SPRINT-chronic kidney disease participants identified 4 unique dimensions of tubular health: tubule injury/repair (NGAL, IL-18, YKL-40), tubule injury/fibrosis (KIM-1, MCP-1), tubule reabsorption (α1M, ß2M), and tubular reserve/mineral metabolism (umod, intact parathyroid hormone, iFGF-23). After adjustment for CVD risk factors, estimated glomerular filtration rate, and albumin-to-creatinine ratio, 2 of the 4 tubule scores were associated with CVD (hazard ratio per SD; reabsorption, 1.21 [1.06-1.38]; reserve, 1.24 (1.08-1.38]), 1 with heart failure (reserve, 1.41 [1.13-1.74]), and none with mortality. Compared with a base model (C-statistic=0.674), adding estimated glomerular filtration rate and albumin-to-creatinine ratio improved the C-statistic (C=0.704; P=0.001); further adding tubule scores additionally improved the C-statistic (C=0.719; P=0.009). In the setting of chronic kidney disease, dimensions of tubule health quantified using factor analysis improved CVD discrimination beyond contemporary kidney measures. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01206062.


Assuntos
Doenças Cardiovasculares/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/metabolismo , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Creatinina/metabolismo , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/metabolismo , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/fisiopatologia , Risco , Taxa de Sobrevida
19.
J Vet Intern Med ; 33(5): 2105-2116, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31444986

RESUMO

BACKGROUND: Glomerular filtration rate (GFR) is the most sensitive indicator of initial renal function decline during chronic kidney disease (CKD), but conventional protocols for measuring GFR are labor-intensive and stressful for the dog. OBJECTIVES: To assess the diagnostic potential for detecting CKD with simplified GFR protocols based on iohexol plasma clearance. ANIMALS: Seventeen CKD-positive and 23 CKD-negative dogs of different breeds and sex. METHODS: Prospective nonrandomized study. Plasma iohexol was measured 5, 15, 60, 90, and 180 minutes after injection. Glomerular filtration rate was calculated using 5 samples (GFR5 ) or simplified protocols based on 1, 2, or 3 samples. The GFR5 and simplified GFR were compared by Bland-Altmann and concordance correlation coefficient (CCC) analysis, and diagnostic accuracy for CKD by receiver operating characteristic curves. A gray zone for each protocol was bounded by the fourth quartile of the CKD-positive population (lower cutoff) and the first quartile of the CKD-negative population (upper cutoff). RESULTS: All simplified protocols gave reliable GFR measurements, comparable to reference GFR5 (CCC >0.92). Simplified protocols which included the 180-minutes sampling granted the best GFR measure (CCC: 0.98), with strong diagnostic potential for CKD (area under the receiver operating characteristic curve ± SE: 0.98 ± 0.01). A double cutoff including a zone of CKD uncertainty guaranteed reliable diagnosis outside the gray area and identified borderline dogs inside it. CONCLUSIONS: The simplified GFR protocols offer an accurate, hands-on tool for CKD diagnosis in dogs. The gray zone might help decision-making in the management of early kidney dysfunction.


Assuntos
Doenças do Cão/diagnóstico , Taxa de Filtração Glomerular/veterinária , Iohexol/farmacocinética , Insuficiência Renal Crônica/veterinária , Animais , Doenças do Cão/sangue , Cães , Feminino , Taxa de Filtração Glomerular/fisiologia , Masculino , Estudos Prospectivos , Insuficiência Renal Crônica/diagnóstico
20.
Clin Drug Investig ; 39(11): 1117-1123, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31435905

RESUMO

BACKGROUND: The orally active dual endothelin receptor antagonist aprocitentan targets a novel pathway in the treatment of hypertension and could be a key player in the treatment of salt/volume-dependent hypertension. Its pharmacokinetic profile supports a once-daily dosing strategy. OBJECTIVE: As hypertensive patients may also experience concomitant renal disease, the objectives of this study were to evaluate the pharmacokinetics and tolerability of aprocitentan in subjects with severe renal function impairment (SRFI) and compare these with matched healthy subjects. DESIGN, SETTING, PARTICIPANTS: In this open-label, single-center, phase 1 study (NCT03165071) eight subjects with SRFI (mean estimated glomerular filtration rate [eGFR] 21.9 mL/min/1.73 m2) and eight healthy subjects (mean eGFR 94.9 mL/min/1.73 m2) received a single dose of 50 mg of aprocitentan followed by an observation period of up to 17 days. Plasma pharmacokinetic parameters of aprocitentan were derived by noncompartmental analysis of the plasma concentration-time profiles. Differences in pharmacokinetic parameters were explored using geometric means ratio (GMR) and 90% confidence intervals (CIs) with SRFI subjects as test group and healthy subjects as reference group. Safety and tolerability evaluations included adverse events (AEs), electrocardiograms, vital signs, and clinical laboratory tests. RESULTS: All 16 subjects received aprocitentan and completed the study. The pharmacokinetics of aprocitentan were similar in SRFI and healthy subjects with maximum plasma concentrations reached at 7.6 h and 5.0 h, respectively. Maximum plasma concentrations did not differ as indicated by a GMR (90% CI) of 1.04 (0.85-1.28). Due to a slightly lower observed clearance in SRFI subjects, half-life was longer (53.2 h compared to 47.4 h in healthy subjects), while exposure expressed as area under the curve was 34% higher (GMR 90% CI 1.13-1.58). There were no differences in plasma protein binding (> 99% bound). Aprocitentan was well tolerated in subjects with SRFI with no notable difference compared to healthy subjects. CONCLUSIONS: Based on these single-dose results, subjects with mild, moderate, or severe renal function can be included in clinical studies without the need for dose adjustment.


Assuntos
Antagonistas dos Receptores de Endotelina/farmacocinética , Rim/efeitos dos fármacos , Pirimidinas/farmacocinética , Insuficiência Renal/metabolismo , Sulfonamidas/farmacocinética , Adulto , Antagonistas dos Receptores de Endotelina/uso terapêutico , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim/fisiologia , Masculino , Pessoa de Meia-Idade , Pirimidinas/uso terapêutico , Insuficiência Renal/tratamento farmacológico , Sulfonamidas/uso terapêutico
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