Your browser doesn't support javascript.
loading
Montrer: 20 | 50 | 100
Résultats 1 - 20 de 4.861
Filtrer
1.
Ned Tijdschr Geneeskd ; 1682024 Jun 17.
Article de Néerlandais | MEDLINE | ID: mdl-38888413

RÉSUMÉ

Almost all laboratories in The Netherlands report an estimated glomerular filtration rate (eGFR) whenever a value for plasma creatinine is requested. This formula is based on gender and age, besides the plasma creatinine concentration, and sometimes also a correction for race is applied. While this GFR reporting improved the recognition of chronic kidney disease, the formulas used have intrinsic limitations. Moreover, recently a novel formula that obviates the need for a correction factor for race has been proposed. In this article the strengths and weaknesses of plasma creatinine and formulas based on that are discussed, following ten frequently asked questions.


Sujet(s)
Créatinine , Débit de filtration glomérulaire , Humains , Débit de filtration glomérulaire/physiologie , Créatinine/sang , Facteurs sexuels , Facteurs âges , Femelle , Maladies du rein/diagnostic , Maladies du rein/physiopathologie , Maladies du rein/sang
4.
J Clin Lab Anal ; 38(7): e25032, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38525922

RÉSUMÉ

BACKGROUND: Kidney disease is fairly unique due to the lack of symptoms associated with disease activity, and it is therefore dependent on biological monitoring. Dried biofluids, particularly dried capillary blood spots, are an accessible, easy-to-use technology that have seen increased utility in basic science research over the past decade. However, their use is yet to reach the kidney patient population clinically or in large-scale discovery science initiatives. The aim of this study was to systematically evaluate the existing literature surrounding the use of dried biofluids in kidney research. METHODS: A systematic literature review was conducted using three search engines and a predefined search term strategy. Results were summarised according to the collection method, type of biofluid, application to kidney disease, cost, sample stability and patient acceptability. RESULTS: In total, 404 studies were identified and 67 were eligible. In total, 34,739 patients were recruited to these studies with a skew towards male participants (> 73%). The majority of samples were blood, which was used either for monitoring anti-rejection immunosuppressive drug concentrations or for kidney function. Dried biofluids offered significant cost savings to the patient and healthcare service. The majority of patients preferred home microsampling when compared to conventional monitoring. CONCLUSION: There is an unmet need in bringing dried microsampling technology to advance kidney disease despite its advantages. This technology provides an opportunity to upscale patient recruitment and longitudinal sampling, enhance vein preservation and overcome participation bias in research.


Sujet(s)
Dépistage sur goutte de sang séché , Maladies du rein , Humains , Dépistage sur goutte de sang séché/méthodes , Maladies du rein/sang , Maladies du rein/diagnostic
5.
Int Urol Nephrol ; 56(6): 2075-2083, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38281310

RÉSUMÉ

BACKGROUND: The blood-urea-nitrogen (BUN)-to-serum-albumin (ALB) ratio (BAR) has been identified as a novel indicator of both inflammatory and nutritional status, exhibiting a correlation with adverse cardiovascular outcomes. This study aims to investigate the potential predictive value of BAR levels at admission for the development of CIN in patients undergoing coronary angiography (CAG) or percutaneous coronary intervention (PCI). METHODS: Retrospective data were collected from patients who were admitted and underwent CAG or PCI between January 2018 and December 2022 at the Cardiac Medical Center of Union Hospital of Fujian Medical University, and the patients were divided into CIN and non-CIN groups. The BAR was computed by dividing the BUN count by the ALB count. Using multiple variable logistic regression, risk variables associated with the development of CIN were found. RESULTS: A total of 156 patients developed CIN (7.78%). The development of CIN was predicted by a BAR ratio > 4.340 with a sensitivity of 84.0% and a specificity of 70.2%, according to receiver operating characteristic (ROC) analysis. BAR, female gender, diuretic use, and statin medication use were found to be independent predictors of CIN using multifactorial analysis. CONCLUSIONS: When patients are receiving CAG/PCI, BAR is a simple-to-use marker that can be used independently to predict the presence of CIN.


Sujet(s)
Azote uréique sanguin , Produits de contraste , Valeur prédictive des tests , Sérumalbumine , Humains , Femelle , Mâle , Études rétrospectives , Sujet âgé , Adulte d'âge moyen , Produits de contraste/effets indésirables , Sérumalbumine/analyse , Sérumalbumine/métabolisme , Coronarographie/effets indésirables , Maladies du rein/induit chimiquement , Maladies du rein/sang , Maladie coronarienne/sang , Intervention coronarienne percutanée
6.
Immunol Res ; 72(3): 476-489, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38135837

RÉSUMÉ

Diagnosis of renal fibrosis can only be verified by kidney biopsy, but biomarkers for non-invasive evaluation remain unsatisfactory. Patients with fibrosis often have abnormalities of the lymphatic vascular system and associated immune function. We describe here a lymphatic marker as a candidate biomarker for fibrosis. After assessing and grading the fibrosis scores, testing serum soluble lymphatic vessel endothelial hyaluronan receptor1 (sLYVE1) level, and collecting clinical information, the association between sLYVE1 and renal fibrosis was analyzed. Logistic regression analysis was used to screen variables. Diagnosis models with or without sLYVE1 were built, and nomograms were plotted. Calibration curve, C-index, and DCA were performed to assess the models. A total of 298 patients were enrolled in the study, of which 199 were included in the training cohort and 99 patients in the validation cohort. Serum sLYVE1 levels markedly elevated with increasing fibrosis grade (p<0.05). ROC analysis of sLYVE1 showed an AUC of 0.791 and 0.846 with optimal cut-off value of 405.25 ng/mL and 498.55 ng/mL for the prediction of moderate-to-severe renal fibrosis (MSF) and severe renal fibrosis (SF), respectively. The diagnostic nomogram model without sLYVE1 (model 1) included traditional clinical determinants (C-index: 0.658 for MSF; 0.603 for SF). A combination of model 1 and sLYVE1 (model 2) improved predictive performance (C-index: 0.847 for MSF; 0.856 for SF). Calibration curve and DCA demonstrated a better consistency accuracy and clinical benefit of model 2 than model 1. Serum sLYVE1 may be identified as a potential biomarker of renal fibrosis. Models incorporating sLYVE1 may be beneficial for a more accurate non-invasive diagnosis of renal fibrosis.


Sujet(s)
Marqueurs biologiques , Fibrose , Rein , Protéines du transport vésiculaire , Humains , Marqueurs biologiques/sang , Mâle , Femelle , Adulte d'âge moyen , Études rétrospectives , Études transversales , Rein/anatomopathologie , Protéines du transport vésiculaire/sang , Adulte , Maladies du rein/diagnostic , Maladies du rein/sang , Courbe ROC , Sujet âgé , Nomogrammes
7.
J Gerontol A Biol Sci Med Sci ; 78(9): 1701-1707, 2023 08 27.
Article de Anglais | MEDLINE | ID: mdl-37190783

RÉSUMÉ

BACKGROUND: Serum growth differentiation factor 15 (GDF15) is associated with age-related adverse outcomes. However, renal function has not been thoroughly evaluated in studies addressing the association between GDF15 and mortality. We aimed to clarify whether GDF15 is associated with total mortality after carefully controlling renal function markers. METHODS: We divided 1 801 community-dwelling Japanese older adults into quartiles according to their serum GDF15 concentrations. The correlation of GDF15 with renal function and inflammation markers was assessed by calculating Spearman correlation coefficients. Cumulative survival rates of the quartiles were estimated. In a Cox regression analysis adjusted for confounders, the association between GDF15 and mortality was evaluated. The discriminative capacity of GDF15 for the prediction of mortality was assessed with receiver-operating characteristic analysis. RESULTS: GDF15 was correlated with cystatin C (r = 0.394), ß2-microglobulin (r = 0.382), C-reactive protein (r = 0.124), and interleukin-6 (r = 0.166). The highest GDF15 quartile showed poor survival compared to the others. Older adults with higher GDF15 were associated with an increased mortality risk, independent of demographics and clinically relevant variables (hazard ratio [95% confidence interval]: 1.98 [1.09-3.59]). This significant association disappeared when additionally adjusted for cystatin C (1.65 [0.89-3.05]) or ß2-microglobulin (1.69 [0.91-3.12]). The ability to predict mortality was approximately comparable between GDF15 (area under the curve: 0.667), cystatin C (0.691), and ß2-microglobulin (0.715). CONCLUSIONS: Serum GDF15 is associated with total mortality in older Japanese after adjustment for major confounders. The increased mortality risk in older adults with higher GDF15 may be partly attributed to decreased renal function.


Sujet(s)
Cystatine C , Facteur-15 de croissance et de différenciation , Maladies du rein , Sujet âgé , Humains , Marqueurs biologiques , Peuples d'Asie de l'Est , Facteur-15 de croissance et de différenciation/sang , Vie autonome , Maladies du rein/sang , Maladies du rein/mortalité , Mortalité
8.
EBioMedicine ; 90: 104537, 2023 Apr.
Article de Anglais | MEDLINE | ID: mdl-37001235

RÉSUMÉ

BACKGROUND: Observational studies have investigated the effect of serum lipids on kidney function, but these findings are limited by confounding, reverse causation and have reported conflicting results. Mendelian randomization (MR) studies address this confounding problem. However, they have been conducted mostly in European ancestry individuals. We, therefore, set out to investigate the effect of lipid traits on the estimated glomerular filtration rate (eGFR) based on serum creatinine in individuals of African ancestry. METHODS: We used the two-sample and multivariable Mendelian randomization (MVMR) approaches; in which instrument variables (IV's) for the predictor (lipid traits) were derived from summary-level data of a meta-analyzed African lipid GWAS (MALG, n = 24,215) from the African Partnership for Chronic Disease Research (APCDR) (n = 13,612) & the Africa Wits-IN-DEPTH partnership for Genomics studies (AWI-Gen) dataset (n = 10,603). The outcome IV's were computed from the eGFR summary-level data of African-ancestry individuals within the Million Veteran Program (n = 57,336). A random-effects inverse variance method was used in our primary analysis, and pleiotropy was adjusted for using robust and penalized sensitivity testing. The lipid predictors for the MVMR were high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides (TG). FINDINGS: We found a significant causal association between genetically predicted low-density lipoprotein (LDL) cholesterol and eGFR in African ancestry individuals ß = 1.1 (95% CI [0.411-1.788]; p = 0.002). Similarly, total cholesterol (TC) showed a significant causal effect on eGFR ß = 1.619 (95% CI [0.412-2.826]; p = 0.009). However, the IVW estimate showed that genetically predicted HDL-C ß = -0.164, (95% CI = [-1.329 to 1.00]; p = 0.782), and TG ß = -0.934 (CI = [-2.815 to 0.947]; p = 0.33) were not significantly causally associated with the risk of eGFR. In the multivariable analysis inverse-variance weighted (MVIVW) method, there was evidence for a causal association between LDL and eGFR ß = 1.228 (CI = [0.477-1.979]; p = 0.001). A significant causal effect of Triglycerides (TG) on eGFR in the MVIVW analysis ß = -1.3 ([-2.533 to -0.067]; p = 0.039) was observed as well. All the causal estimates reported reflect a unit change in the outcome per a 1 SD increase in the exposure. HDL showed no evidence of a significant causal association with eGFR in the MVIVW method (ß = -0.117 (95% CI [-1.252 to 0.018]; p = 0.840)). We found no evidence of a reverse causal impact of eGFR on serum lipids. All our sensitivity analyses indicated no strong evidence of pleiotropy or heterogeneity between our instrumental variables for both the forward and reverse MR analysis. INTERPRETATION: In this African ancestry population, genetically predicted higher LDL-C and TC are causally associated with higher eGFR levels, which may suggest that the relationship between LDL, TC and kidney function may be U-shaped. And as such, lowering LDL_C does not necessarily improve risk of kidney disease. This may also imply the reason why LDL_C is seen to be a poorer predictor of kidney function compared to HDL. In addition, this further supports that more work is warranted to confirm the potential association between lipid traits and risk of kidney disease in individuals of African Ancestry. FUNDING: Wellcome (220740/Z/20/Z).


Sujet(s)
Africains , Maladies du rein , Rein , Lipides , Humains , Africains/génétique , Cholestérol/sang , Cholestérol HDL/sang , Cholestérol LDL/sang , Étude d'association pangénomique , Débit de filtration glomérulaire/physiologie , Rein/physiopathologie , Maladies du rein/sang , Maladies du rein/ethnologie , Maladies du rein/génétique , Maladies du rein/physiopathologie , Lipides/sang , Lipides/génétique , Analyse de randomisation mendélienne , Polymorphisme de nucléotide simple , Répartition aléatoire , Facteurs de risque , Triglycéride/sang
9.
Biol Pharm Bull ; 46(2): 194-200, 2023.
Article de Anglais | MEDLINE | ID: mdl-36724948

RÉSUMÉ

Higher amounts of circulating ultrafilterable platinum (fPt) are found in patients with renal dysfunction receiving a constant dose of oxaliplatin. However, the increased systemic fPt levels do not increase oxaliplatin-induced toxicities. We hypothesized that renal dysfunction has minimal effect on the elimination rate of reactive fPt, and that the DNA-binding capacity is one of the properties of reactive Pt species. This study aimed to quantify DNA-reactive fPt in plasma and to evaluate the impact of severe renal dysfunction on its pharmacokinetics. The pharmacokinetics of oxaliplatin was assessed in rats with bilateral nephrectomy (BNx) and in a hemodialysis patient who received mFOLFOX7 therapy for advanced metastatic gastric cancer. The platinum concentrations were determined using inductively coupled plasma-mass spectrometry. The amount of DNA-reactive fPt in the plasma was evaluated by the reaction between plasma and calf thymus DNA. Compared to the sham group in rats, the BNx group had significantly higher plasma total fPt concentrations at 24 h after drug administration. However, there was no significant difference in the plasma levels of DNA-reactive fPt between the two groups. In a hemodialysis patient, the plasma levels of total fPt decreased to 35.9 and 7.3% at 2 and 14 d after treatment, respectively. The plasma level of DNA-reactive fPt also decreased to 1.9 and 0.6%, respectively, on these days. This study showed that severe renal dysfunction has a limited effect on the plasma levels of DNA-reactive fPt after oxaliplatin administration.


Sujet(s)
Maladies du rein , Oxaliplatine , Animaux , Rats , ADN/sang , Maladies du rein/sang , Maladies du rein/traitement médicamenteux , Oxaliplatine/effets indésirables , Platine/sang
10.
Oxid Med Cell Longev ; 2022: 1197061, 2022.
Article de Anglais | MEDLINE | ID: mdl-35126806

RÉSUMÉ

BACKGROUND: Recent meta-analyses have shown that sodium-glucose cotransporter 2 (SGLT-2) inhibitors alleviate chronic kidney disease and acute kidney injury in diabetic patients. In this study, we aimed to investigate the effect of empagliflozin on renal ischemia/reperfusion (I/R) in nondiabetic rats and find the possible mechanisms. Experimental Approach. Eighteen male Wistar rats were randomly divided into three groups, including healthy control, ischemic control, and empagliflozin-treated group. Thirty minutes of bilateral renal ischemia was induced by clamping the renal hilum. Forty-eight hours after reopening the clamps, rats' blood samples and tissue specimens were collected. Empagliflozin 10 mg/kg was administered by gavage, 2 hours before ischemia and 24 hours after the first dose. RESULTS: I/R injury led to a significant rise in serum creatinine and blood urea nitrogen which was significantly decreased after treatment with empagliflozin. Empagliflozin also alleviated tubulointerstitial and glomerular damage and significantly decreased tissue histology scores. Empagliflozin decreased the increased levels of malondialdehyde, interleukin 1ß, and tumor necrosis factor α. SGLT2 inhibition increased the decreased expression of nuclear factor erythroid 2-related factor 2 and PPARG coactivator 1 alpha that conduct antioxidant defense and mitochondrial biogenesis, respectively. Furthermore, empagliflozin markedly increased LC3-II/LC3-I and bcl2/bax ratios, showing its beneficial effect on activation of autophagy and inhibition of apoptosis. Despite its effects on diabetic nephropathy, empagliflozin did not activate the Sestrin2/AMP-activated protein kinase pathway in this study. CONCLUSION: Empagliflozin improved renal I/R injury in nondiabetic rats in this study by promoting autophagy and mitochondrial biogenesis and attenuation of oxidative stress, inflammation, and apoptosis.


Sujet(s)
Antioxydants/administration et posologie , Autophagie/effets des médicaments et des substances chimiques , Composés benzhydryliques/administration et posologie , Glucosides/administration et posologie , Maladies du rein/complications , Maladies du rein/traitement médicamenteux , Biogenèse des organelles , Lésion d'ischémie-reperfusion/complications , Lésion d'ischémie-reperfusion/traitement médicamenteux , Inhibiteurs du cotransporteur sodium-glucose de type 2/administration et posologie , Animaux , Apoptose/effets des médicaments et des substances chimiques , Azote uréique sanguin , Créatinine/sang , Modèles animaux de maladie humaine , Interleukine-1 bêta/métabolisme , Maladies du rein/sang , Mâle , Malonaldéhyde/métabolisme , Stress oxydatif/effets des médicaments et des substances chimiques , Rats , Rat Wistar , Lésion d'ischémie-reperfusion/sang , Transduction du signal/effets des médicaments et des substances chimiques , Résultat thérapeutique , Facteur de nécrose tumorale alpha/métabolisme
11.
Anal Biochem ; 643: 114580, 2022 04 15.
Article de Anglais | MEDLINE | ID: mdl-35149001

RÉSUMÉ

The pharmacodynamics, 1H NMR metabolomics and endogenous network pharmacology strategy approaches were integrated to investigate the preventive mechanism of Gushudan (GSD) on kidney-yang-deficiency-syndrome (KYDS) rats in this study. Firstly, the KYDS rat model was achieved by hydrocortisone induction, and the efficacy of GSD on KYDS model rats was assessed by the pharmacodynamic indicators. Next, the comprehensive untargeted serum metabolic profile of rats was obtained in 1H NMR metabolomics study, 29 potential biomarkers closely associated with KYDS were identified, which were mainly involved in carbohydrate metabolism, amino acid metabolism and intestinal flora metabolism. In addition, the potential biomarkers-targets-pathways-disease metabolic network was further investigated for deeper understanding the preventive effects of GSD on KYDS rats and its mechanism, which was further obtained for the important targets related to biomarkers and diseases such as NOS3, PTGS2 and CXCL8, and important metabolic pathways such as glyoxylate and dicarboxylate metabolism, arginine and proline metabolism, and microbial metabolism in diverse environments. Finally, compared with our previous anti-osteoporosis study of GSD, it suggested that some similar metabolic pathways, which would provide some scientific reference of the existence of the kidney-bone axis under the traditional Chinese medicine (TCM) theory of "kidney dominates bone".


Sujet(s)
Médicaments issus de plantes chinoises/analyse , Maladies du rein/métabolisme , Métabolomique , Pharmacologie des réseaux , Déficit du Yang/métabolisme , Animaux , Médicaments issus de plantes chinoises/métabolisme , Médicaments issus de plantes chinoises/pharmacocinétique , Maladies du rein/sang , Maladies du rein/diagnostic , Mâle , Spectroscopie par résonance magnétique du proton , Rats , Rat Sprague-Dawley , Déficit du Yang/sang , Déficit du Yang/diagnostic
12.
Sci Rep ; 12(1): 1815, 2022 02 02.
Article de Anglais | MEDLINE | ID: mdl-35110648

RÉSUMÉ

Citrate has been proposed as anticoagulation of choice in continuous renal replacement therapy (CRRT). However, little is known about the pharmacokinetics (PK) and metabolism of citrate in liver failure patients who require CRRT with regional citrate anticoagulation (RCA). This prospective clinical PK study was conducted at King Chulalongkorn Memorial Hospital between July 2019 to April 2021, evaluating seven acute liver failure (ALF) and seven acute-on-chronic liver failure (ACLF) patients who received CRRT support utilizing RCA as an anticoagulant at a citrate dose of 3 mmol/L. For evaluation of the citrate PK, we delivered citrate for 120 min and then stopped for a further 120 min. Total body clearance of citrate was 152.5 ± 50.9 and 195.6 ± 174.3 mL/min in ALF and ACLF, respectively. The ionized calcium, ionized magnesium, and pH slightly decreased after starting citrate infusion and gradually increased to baseline after stopping citrate infusion. Two of the ACLF patients displayed citrate toxicity during citrate infusion, while, no ALF patient had citrate toxicity. In summary, citrate clearance was significantly decreased in critically ill ALF and ACLF patients receiving CRRT. Citrate use as an anticoagulation in these patients is of concern for the risk of citrate toxicity.


Sujet(s)
Anticoagulants/pharmacocinétique , Acide citrique/pharmacocinétique , Thérapie de remplacement rénal continue , Maladies du rein/thérapie , Défaillance hépatique aigüe/thérapie , Foie/métabolisme , Insuffisance hépatique aigüe sur chronique/sang , Insuffisance hépatique aigüe sur chronique/diagnostic , Insuffisance hépatique aigüe sur chronique/physiopathologie , Insuffisance hépatique aigüe sur chronique/thérapie , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Anticoagulants/administration et posologie , Anticoagulants/effets indésirables , Acide citrique/administration et posologie , Acide citrique/effets indésirables , Thérapie de remplacement rénal continue/effets indésirables , Maladie grave , Femelle , Humains , Maladies du rein/sang , Maladies du rein/diagnostic , Maladies du rein/physiopathologie , Foie/physiopathologie , Défaillance hépatique aigüe/sang , Défaillance hépatique aigüe/diagnostic , Défaillance hépatique aigüe/physiopathologie , Mâle , Taux de clairance métabolique , Adulte d'âge moyen , Études prospectives , Résultat thérapeutique
14.
PLoS One ; 17(1): e0262847, 2022.
Article de Anglais | MEDLINE | ID: mdl-35061855

RÉSUMÉ

BACKGROUND: Somatic tissue oxygen saturation (SstO2) is associated with systemic hypoperfusion. Kidney dysfunction may lead to increased mortality and morbidity in patients who undergo living donor liver transplantation (LDLT). We investigated the clinical utility of SstO2 during LDLT for identifying postoperative kidney dysfunction. PATIENTS AND METHODS: Data from 304 adults undergoing elective LDLT between January 2015 and February 2020 at Seoul St. Mary's Hospital were retrospectively collected. Thirty-six patients were excluded based on the exclusion criteria. In total, 268 adults were analyzed, and 200 patients were 1:1 propensity score (PS)-matched. RESULTS: Patients with early kidney dysfunction had significantly lower intraoperative SstO2 values than those with normal kidney function. Low SstO2 (< 66%) 1 h after graft reperfusion was more highly predictive of early kidney dysfunction than the values measured in other intraoperative phases. A decline in the SstO2 was also related to kidney dysfunction. CONCLUSIONS: Kidney dysfunction after LDLT is associated with patient morbidity and mortality. Our results may assist in the detection of early kidney dysfunction by providing a basis for analyzing SstO2 in patients undergoing LDLT. A low SstO2 (< 66%), particularly 1 h after graft reperfusion, was significantly associated with early kidney dysfunction after surgery. SstO2 monitoring may facilitate the identification of early kidney dysfunction and enable early management of patients.


Sujet(s)
Maladies du rein , Rein/métabolisme , Transplantation hépatique , Donneur vivant , Saturation en oxygène , Complications postopératoires , Femelle , Humains , Maladies du rein/sang , Maladies du rein/étiologie , Maladies du rein/mortalité , Mâle , Adulte d'âge moyen , Complications postopératoires/sang , Complications postopératoires/étiologie , Complications postopératoires/mortalité , Études rétrospectives , Séoul/épidémiologie
15.
Molecules ; 27(2)2022 Jan 16.
Article de Anglais | MEDLINE | ID: mdl-35056874

RÉSUMÉ

Heavy metals intoxication causes several health problems that necessitate finding new protective and therapeutic approaches. This study aimed to evaluate the impact of Musa sp. leaves extract (MLE) on hepato-renal toxicities induced by cadmium (Cd) in male mice. The phytochemical screening, metal chelating activity (MCA), and the median lethal dose (LD50) of MLE were determined. Fifty CD-1 male mice were used and intraperitoneally (i.p.) injected with MLE (1000 to 5000 mg/kg b.wt) for MLE LD50 determination. Another 50 mice were used for evaluating the effect of MLE on Cd toxicity. Blood samples were collected for hematological, liver, and kidney functions assessments. Liver tissue homogenates were used for determination of oxidant/antioxidant parameters. Liver and kidney tissues were harvested for histopathological and molecular investigations. MLE showed potent in vitro antioxidant activities. The MCA and LD50 of the MLE were 75 µg/mL and 3000 mg/kg b.wt, respectively. MLE showed beneficial therapeutic activity against hepato-renal toxicities in Cd-intoxicated mice, evidenced by improving the hematological, biochemical, histopathological, and molecular alterations.


Sujet(s)
Antioxydants/pharmacologie , Chélateurs/pharmacologie , Lésions hépatiques dues aux substances/prévention et contrôle , Maladies du rein/prévention et contrôle , Musa/composition chimique , Extraits de plantes/pharmacologie , Feuilles de plante/composition chimique , Animaux , Antioxydants/composition chimique , Antioxydants/usage thérapeutique , Hémogramme , Cadmium/toxicité , Intoxication au cadmium/prévention et contrôle , Chélateurs/composition chimique , Chélateurs/usage thérapeutique , Lésions hépatiques dues aux substances/sang , Lésions hépatiques dues aux substances/anatomopathologie , Cyclooxygenase 1/génétique , Cyclooxygenase 1/métabolisme , Enzymes/métabolisme , Maladies du rein/sang , Maladies du rein/induit chimiquement , Maladies du rein/anatomopathologie , Dose létale 50 , Mâle , Protéines membranaires/génétique , Protéines membranaires/métabolisme , Souris , Facteur de transcription NF-kappa B/génétique , Facteur de transcription NF-kappa B/métabolisme , Stress oxydatif/effets des médicaments et des substances chimiques , Extraits de plantes/composition chimique , Extraits de plantes/usage thérapeutique , Facteur de croissance transformant bêta-1/génétique , Facteur de croissance transformant bêta-1/métabolisme
16.
Clin J Am Soc Nephrol ; 17(1): 27-37, 2022 01.
Article de Anglais | MEDLINE | ID: mdl-34759008

RÉSUMÉ

BACKGROUND AND OBJECTIVES: Biomarkers for noninvasive assessment of histopathology and prognosis are needed in patients with kidney disease. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Using a proteomics assay, we measured a multimarker panel of 225 circulating plasma proteins in a prospective cohort study of 549 individuals with biopsy-confirmed kidney diseases and semiquantitative assessment of histopathology. We tested the associations of each biomarker with histopathologic lesions and the risks of kidney disease progression (defined as ≥40% decline in eGFR or initiation of KRT) and death. RESULTS: After multivariable adjustment and correction for multiple testing, 46 different proteins were associated with histopathologic lesions. The top-performing markers positively associated with acute tubular injury and interstitial fibrosis/tubular atrophy were kidney injury molecule-1 (KIM-1) and V-set and Ig domain-containing protein 2 (VSIG2), respectively. Thirty proteins were significantly associated with kidney disease progression, and 35 were significantly associated with death. The top-performing markers for kidney disease progression were placental growth factor (hazard ratio per doubling, 5.4; 95% confidence interval, 3.4 to 8.7) and BMP and activin membrane-bound inhibitor (hazard ratio, 3.0; 95% confidence interval, 2.1 to 4.2); the top-performing markers for death were TNF-related apoptosis-inducing ligand receptor-2 (hazard ratio, 2.9; 95% confidence interval, 2.0 to 4.0) and CUB domain-containing protein-1 (hazard ratio, 2.4; 95% confidence interval, 1.8 to 3.3). CONCLUSION: We identified several plasma protein biomarkers associated with kidney disease histopathology and adverse clinical outcomes in individuals with a diverse set of kidney diseases. PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2021_12_28_CJN09380721.mp3.


Sujet(s)
Maladies du rein/sang , Adulte , Sujet âgé , Marqueurs biologiques/sang , Biopsie , Femelle , Humains , Maladies du rein/anatomopathologie , Mâle , Adulte d'âge moyen
17.
CPT Pharmacometrics Syst Pharmacol ; 11(1): 94-103, 2022 01.
Article de Anglais | MEDLINE | ID: mdl-34793625

RÉSUMÉ

Remdesivir, a prodrug of the nucleoside analog GS-441524, plays a key role in the treatment of coronavirus disease 2019 (COVID-19). However, owing to limited information on clinical trials and inexperienced clinical use, there is a lack of pharmacokinetic (PK) data in patients with COVID-19 with special characteristics. In this study, we aimed to measure serum GS-441524 concentrations and develop a population PK (PopPK) model. Remdesivir was administered at a 200 mg loading dose on the first day followed by 100 mg from day 2, based on the package insert, in patients with an estimated glomerular filtration rate (eGFR) greater than or equal to 30 ml/min. In total, 190 concentrations from 37 Japanese patients were used in the analysis. The GS-441524 trough concentrations were significantly higher in the eGFR less than 60 ml/min group than in the eGFR greater than or equal to 60 ml/min group. Extracorporeal membrane oxygenation in four patients hardly affected the total body clearance (CL) and volume of distribution (Vd ) of GS-441524. A one-compartment model described serum GS-441524 concentration data. The CL and Vd of GS-441524 were significantly affected by eGFR readjusted by individual body surface area and age, respectively. Simulations proposed a dose regimen of 200 mg on day 1 followed by 100 mg once every 2 days from day 2 in patients with an eGFR of 30 ml/min or less. In conclusion, we successfully established a PopPK model of GS-441524 using retrospectively obtained serum GS-441524 concentrations in Japanese patients with COVID-19, which would be helpful for optimal individualized therapy of remdesivir.


Sujet(s)
AMP/analogues et dérivés , Adénosine/analogues et dérivés , Alanine/analogues et dérivés , Traitements médicamenteux de la COVID-19 , Maladies du rein/sang , Adénosine/sang , AMP/administration et posologie , AMP/pharmacocinétique , Sujet âgé , Sujet âgé de 80 ans ou plus , Alanine/administration et posologie , Alanine/pharmacocinétique , Surface corporelle , COVID-19/sang , Calendrier d'administration des médicaments , Oxygénation extracorporelle sur oxygénateur à membrane , Femelle , Débit de filtration glomérulaire , Humains , Japon , Mâle , Adulte d'âge moyen , Méthode de Monte Carlo , Médecine de précision , Études rétrospectives
18.
Bioengineered ; 12(2): 12702-12721, 2021 12.
Article de Anglais | MEDLINE | ID: mdl-34949157

RÉSUMÉ

The overuse of cisplatin (>50 mg/m2) is limited to nephrotoxicity, ototoxicity, gastrotoxicity, myelosuppression, and allergic reactions. The objective of this study was to investigate the nephroprotective effects of Daucus carota and Eclipta prostrata extracts on cisplatin-induced nephrotoxicity in Wistar albino rats. The study involved male Wistar albino rats of 8 weeks weighing 220-270 g. A single injection of 5 mg/kg was injected into the rats for nephrotoxicity. Rats were divided into four groups based on dose conentrations. Blood and urine samples of rats were collected on the 0, 7th, 14th, and 21st days for nephrological analysis. The results showed that Cis + DC/Cis + EP (600 mg/kg) significantly (p < 0.001) increased the body weight and reduced the kidney weight of cisplatin-induced nephrotoxicity in rats (p < 0.001) as compared to Cis group. The results showed that 600 mg/kg administration of Cis + DC/Cis +EP successfully (p < 0.005) improved the urine and plasmin creatinine, Na, and K level compared to the Cis group. Histopathological results confirmed that Cis + EP/Cis + DC effectively improved the renal abnormalities. It is concluded that the co-administration of Cis + EP extract showed exceptional nephroprotective effects at a dose rate of 600 mg/kg.


Sujet(s)
Cisplatine/effets indésirables , Daucus carota/composition chimique , Eclipta/composition chimique , Maladies du rein/induit chimiquement , Maladies du rein/traitement médicamenteux , Agents protecteurs/usage thérapeutique , Animaux , Poids/effets des médicaments et des substances chimiques , Créatinine/sang , Rein/effets des médicaments et des substances chimiques , Rein/anatomopathologie , Maladies du rein/sang , Maladies du rein/urine , Mâle , Taille d'organe/effets des médicaments et des substances chimiques , Extraits de plantes/pharmacologie , Extraits de plantes/usage thérapeutique , Potassium/urine , Agents protecteurs/pharmacologie , Rat Wistar , Sodium/urine , Miction/effets des médicaments et des substances chimiques
19.
Sci Rep ; 11(1): 22280, 2021 11 15.
Article de Anglais | MEDLINE | ID: mdl-34782668

RÉSUMÉ

This study aimed to assess the association of serum iron level (Iron) with the estimated glomerular filtration rate (eGFR) after bariatric surgery (BS). We reviewed 210 patients with mean age of 39.1 ± 10.6 years (body mass index, 41.4 ± 5.5 kg/m2) undergoing BS. The primary outcome was the relationship between Iron and eGFR at 12-month after surgery. Multiple linear regression analyses were performed using postoperative eGFR as dependent variables and using Iron and other variables (i.e., age) as independent variables. At 12-month follow-up, 94 patients were analyzed. BMI significantly decreased, whereas serum iron level significantly increased. Although the percentage of patients with eGFR of < 90 mL/min/1.73 m2 increased during the study period, no significant difference was found in postoperative 12-month eGFR. No correlations were noted between Iron and eGFR at baseline and postoperative 1 and 6 months, whereas a significant relationship was observed between Iron and postoperative 12-month eGFR. Multiple linear regression analyses revealed that Iron and presence of diabetes were the independent predictors of postoperative 12-month eGFR. This pilot study showed a positive association of postoperative serum iron level with renal function in this patient population. Further large-scale trials are needed to confirm the findings.


Sujet(s)
Marqueurs biologiques/sang , Gastrectomie/effets indésirables , Fer/sang , Maladies du rein/sang , Rein/physiopathologie , Laparoscopie/effets indésirables , Adulte , Femelle , Études de suivi , Humains , Maladies du rein/diagnostic , Maladies du rein/étiologie , Tests de la fonction rénale , Mâle , Adulte d'âge moyen , Soins postopératoires , Soins préopératoires , Pronostic , Courbe ROC , Études rétrospectives , Facteurs de risque
20.
Sci Rep ; 11(1): 20981, 2021 10 25.
Article de Anglais | MEDLINE | ID: mdl-34697364

RÉSUMÉ

Hematuria, either glomerular or extraglomerular, is defined as 3 or more red blood cells (RBCs)/high power field. Currently, urinalyses are commonly performed using automated urine sediment analyzers. To assess whether RBC counting by automated urine sediment analyzers is reliable for defining hematuria in glomerular disease, random specimen urinalyses of men with nephritic glomerular disease (7674 urinalyses) and bladder cancer (12,510 urinalyses) were retrospectively reviewed. Urine RBCs were counted by an automated urine sediment analyzer based on flow cytometry (UF-1000i, Sysmex Corporation) or digital image analysis (Cobas 6500, Roche Diagnostics GmbH). In about 20% of urine specimens, the specific gravity was less than 1.010, making the RBC counts unreliable. In the urine specimens with specific gravity ≥ 1.010, RBC counts measured using either UF-1000i or Cobas 6500 were well correlated with the positive grades in the dipstick blood test. However, at a trace, 1+, or higher positive dipstick tests for blood, RBC counts were graded significantly lower in glomerular disease than in bladder cancer. The findings suggest that RBC counting by UF-1000i or Cobas 6500 underestimates the severity of hematuria in glomerular disease, possibly because dysmorphic RBCs in glomerular disease are susceptible to hemolysis and/or fail to be properly recognized.


Sujet(s)
Hématurie/diagnostic , Maladies du rein/urine , Tumeurs de la vessie urinaire/urine , Sujet âgé , Études cas-témoins , Numération des érythrocytes , Femelle , Cytométrie en flux , Humains , Maladies du rein/sang , Mâle , Adulte d'âge moyen , Études rétrospectives , Tumeurs de la vessie urinaire/sang
SÉLECTION CITATIONS
DÉTAIL DE RECHERCHE
...