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1.
Int J Mol Sci ; 24(17)2023 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-37686418

RESUMO

This study aims to highlight the impact of physicochemical properties on the behaviour of nanopharmaceuticals and how much carrier structure and physiochemical characteristics weigh on the effects of a formulation. For this purpose, two commercially available nanosimilar formulations of Doxil and their respective carriers were compared as a case study. Although the two formulations were "similar", we detected different toxicological effects (profiles) in terms of in vitro toxicity and immunological responses at the level of cytokines release and complement activation (iC3b fragment), that could be correlated with the differences in the physicochemical properties of the formulations. Shedding light on nanosimilar key quality attributes of liposome-based materials and the need for an accurate characterization, including investigation of the immunological effects, is of fundamental importance considering their great potential as delivery system for drugs, genes, or vaccines and the growing market demand.


Assuntos
Doxorrubicina , Polietilenoglicóis , Doxorrubicina/farmacologia , Excipientes , Lipossomos
2.
Anal Bioanal Chem ; 414(1): 385-397, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33547482

RESUMO

Validation of analytical methods for measurements of microplastics (MP) is severely hampered because of a general lack of reference materials, RM. There is a great need to develop such reference materials. This study presents a concept of three-component kit with immobilised MP in solid NaCl, a surfactant and clean water that can be applied for the production of many types of MP RMs. As proof of concept, an RM for polyethylene terephthalate (PET) particles in water was prepared and evaluated for its homogeneity. The particles ranged from 30 µm (Feretmin) to about 200 µm adapted by wet sieving. A specific number of PET particles were immobilized in about 0.29 g of solid NaCl by freeze-drying 1 mL of a NaCl suspension. By using manual and automated counting, twenty reconstituted 1-L water samples were evaluated for homogeneity with respect to number of PET particles from 30 µm to > 200 µm/L of water. The number of particles was 730 ± 120 (mean ± one standard deviation (SD); n = 10) and 865 ± 155 particles (n = 10) obtained by optical microscopy in two independent laboratories. This corresponded to relative SDs of 16.4 and 17.9% and a mean of 797 ± 151 particles (18.9% RSD, for n = 20). Homogeneity studies of the NaCl carrier without reconstitution resulted in 794 ± 60 particles (7.5% RSD). The homogeneity of PET in the salt carrier was also evaluated directly with respect to mass of PET per vial using an ultra-micro balance. An average mass of 293 ± 41 µg of PET was obtained (14, % RSD for n = 14). Micrographs were recorded to demonstrate the absence of major sources of contamination of the RM components. Information about the particle size distribution and particle shapes was obtained by laser diffraction (LD) and dynamic image analysis (DIA). In addition, the identity of the PET polymer was confirmed by Raman and FT-IR spectroscopy. The RM was developed for a large-scale inter-laboratory comparison of PET particles in water (ILC). Based on the homogeneity results, the material was found to be sufficiently homogeneous to be of meaningful use in the ILC. In a 3-day process, more than 500 samples of PET particles in the NaCl carrier were prepared with good potential for further upscaling with respect to the number of vials or with other kinds of polymers. The stability of PET was not evaluated but it was deemed to be stable for the duration of the ILC.

3.
J Appl Toxicol ; 42(12): 2030-2044, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35929361

RESUMO

Microplastics (MPs) represent a worldwide emerging relevant concern toward human and environmental health due to their intentional or unintentional release. Human exposure to MPs by inhalation is predicted to be among the most hazardous. MPs include both engineered, or primary MPs, and secondary MPs, materials obtained by fragmentation from any plastic good. The major part of the environmental MPs is constituted by the second ones that are irregular in size, shape and composition. These features make the study of the biological impact of heterogenous MPs of extremely high relevance to better estimate the real toxicological hazards of these materials on human and environmental organisms. The smallest fractions of plastic granules, relying on the micron-sized scale, can be considered as the most abundant component of the environmental MPs, and for this reason, they are typically used to perform toxicity tests using in vitro systems representative of an inhalation exposure scenario. In the present work, MPs obtained from industrial treatment of waste plastics (wMPs < 50 µm) were investigated, and after the physico-chemical characterization, the cytotoxic, inflammatory and genotoxic responses, as well as the modality of wMPs interactions with alveolar lung cells, were determined. Obtained results indicated that, at high concentrations (100 µg/ml) and prolonged exposure time (48 h), wMPs affect biological responses by inducing inflammation and genotoxicity, as a result of the cell-wMP interactions, also including the uptake of the smaller particles.


Assuntos
Plásticos , Poluentes Químicos da Água , Humanos , Plásticos/toxicidade , Células A549 , Poluentes Químicos da Água/toxicidade , Microplásticos/toxicidade , Pulmão , Monitoramento Ambiental
4.
Part Fibre Toxicol ; 18(1): 23, 2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34134756

RESUMO

BACKGROUND: Widespread use of silver in its different forms raises concerns about potential adverse effects after ingestion, the main exposure route for humans. The aim of this study was to investigate in CD-1 (ICR) male mice the tissue distribution and in vivo effects of 4-week oral exposure to 0.25 and 1 mg Ag/kg bw 10 nm citrate coated silver nanoparticles (AgNPs) and 1 mg Ag/kg bw silver acetate (AgAc) at the end of treatment (EoT) and after 4 weeks of recovery. RESULTS: There were no treatment-related clinical signs and mortality, and no significant effects on body and organ weights at the EoT and after recovery. Treatment-related changes in hematology and clinical chemistry were found after recovery, the most relevant being a dose-dependent lymphopenia and increased triglycerides in AgNP-treated mice, and increased levels of urea in all treated groups, associated with decreased albumin only in AgAc-treated mice. At the EoT the highest silver concentration determined by Triple Quadrupole ICP-MS analysis was found in the brain, followed by testis, liver, and spleen; much lower concentrations were present in the small intestine and kidney. Tissue silver concentrations were slightly higher after exposure to AgAc than AgNPs and dose dependent for AgNPs. After recovery silver was still present in the brain and testis, highlighting slow elimination. No histopathological changes and absence of silver staining by autometallography were observed in the organs of treated mice. At the EoT GFAP (astrocytes) immunoreactivity was significantly increased in the hippocampus of AgNP-treated mice in a dose-dependent manner and Iba1 (microglial cells) immunoreactivity was significantly increased in the cortex of 1 mg/kg bw AgNP-treated mice. After recovery, a significant reduction of Iba1 was observed in the cortex of all treated groups. TEM analysis of the hippocampus revealed splitting of basement membrane of the capillaries and swelling of astrocytic perivascular end-feet in 1 mg/kg bw AgNP- and AgAc-treated mice at the EoT. CONCLUSIONS: Our study revealed accumulation and slow clearance of silver in the brain after oral administration of 10 nm AgNPs and AgAc at low doses in mice, associated with effects on glial cells and ultrastructural alterations of the Blood-Brain Barrier.


Assuntos
Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Administração Oral , Animais , Encéfalo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Distribuição Tecidual
5.
Ecotoxicol Environ Saf ; 225: 112775, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536794

RESUMO

Microplastic pollution represents a global problem with negative impacts on aquatic environment and organisms' health. To date, most of the laboratory toxicological studies on microplastics (MPs) have made use of single commercial micro and nano-polymers, which do not reflect the heterogeneity of environmental MPs. To improve the relevance of the hazard assessment, micrometer-sized plastic particles of miscellaneous non-reusable waste plastics, with size <100 µm and <50 µm (waste microplastics, wMPs), were characterized by microscopic and spectroscopic techniques and tested on developing zebrafish and Xenopus laevis by FET and FETAX assays respectively. Moreover, the modalities of wMP interaction with the embryonic structures, as well as the histological lesions, were explored by light and electron microscopy. We have shown that wMPs had very heterogeneous shapes and sizes, were mainly composed of polyethylene and polypropylene and contained metal and organic impurities, as well as submicrometric particle fractions, features that resemble those of environmental occurring MPs. wMPs (0.1-100 mg/L) caused low rate of mortality and altered phenotypes in embryos, but established species-specific biointeractions. In zebrafish, wMPs by adhering to chorion were able to delay hatching in a size and concentration dependent manner. In Xenopus embryos, which open stomodeum earlier than zebrafish, wMPs were accumulated in intestinal tract, where produced mechanical stress and stimulated mucus overproduction, attesting an irritation response. Although wMP biointeractions did not interfere with morphogenesis processes, further studies are needed to understand the underlying mechanisms and long-term impact of these, or even smaller, wMPs.


Assuntos
Microplásticos , Plásticos , Anfíbios , Animais , Plásticos/toxicidade , Polietileno , Peixe-Zebra
6.
Biomacromolecules ; 18(2): 452-460, 2017 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-28030952

RESUMO

Poly(d,l-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) are among the most studied systems for drug and gene targeting. So far, the synthesis of stable and uniform PLGA NPs has involved the use of a large excess of polyvinyl surfactants such as poly(vinyl alcohol) (PVA) and polyvinylpyrrolidone (PVP), whose removal requires multistep purification procedures of high ecological and economic impact. Hence the development of environment-friendly and cost-effective synthetic procedures for the synthesis of PLGA NPs would effectively boost their use in clinics. This work aims to address this issue by investigating more efficacious alternatives to the so far employed polyvinyl surfactants. More specifically, we developed an innovative synthetic process to achieve stable and uniformly distributed PLGA NPs that involves the use of calcium stearate (CSt), gaining benefits of its high biocompatibility and efficacy at low concentrations and avoiding consequently expensive purification steps. With the help of minimum quantities of polysorbate 60 and sorbitane monostearate, CSt-stabilized PLGA NPs with different sizes and structures were synthesized. The influence of CSt on the encapsulation efficiency of bioactive molecules has been also investigated. The effective encapsulation of both hydrophobic (curcumin) and hydrophilic (fibrinogen labeled with Alexa647) biomolecules into NPs was demonstrated by confocal microscopy, and their release quantified by spectrofluorimetric analyses. Finally, degradation and cytotoxicity studies showed that CSt stabilized NPs were stable under physiological conditions and with good biocompatibility, thus looking promising for further investigation as controlled release devices.


Assuntos
Portadores de Fármacos/química , Ácido Láctico/química , Macrófagos/citologia , Nanopartículas/química , Ácido Poliglicólico/química , Álcool de Polivinil/química , Ácidos Esteáricos/química , Animais , Proliferação de Células , Células Cultivadas , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Tensoativos
7.
Part Fibre Toxicol ; 13: 12, 2016 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-26926244

RESUMO

BACKGROUND: Silver nanoparticles (AgNPs) are an important class of nanomaterials used as antimicrobial agents for a wide range of medical and industrial applications. However toxicity of AgNPs and impact of their physicochemical characteristics in in vivo models still need to be comprehensively characterized. The aim of this study was to investigate the effect of size and coating on tissue distribution and toxicity of AgNPs after intravenous administration in mice, and compare the results with those obtained after silver acetate administration. METHODS: Male CD-1(ICR) mice were intravenously injected with AgNPs of different sizes (10 nm, 40 nm, 100 nm), citrate-or polyvinylpyrrolidone-coated, at a single dose of 10 mg/kg bw. An equivalent dose of silver ions was administered as silver acetate. Mice were euthanized 24 h after the treatment, and silver quantification by ICP-MS and histopathology were performed on spleen, liver, lungs, kidneys, brain, and blood. RESULTS: For all particle sizes, regardless of their coating, the highest silver concentrations were found in the spleen and liver, followed by lung, kidney, and brain. Silver concentrations were significantly higher in the spleen, lung, kidney, brain, and blood of mice treated with 10 nm AgNPs than those treated with larger particles. Relevant toxic effects (midzonal hepatocellular necrosis, gall bladder hemorrhage) were found in mice treated with 10 nm AgNPs, while in mice treated with 40 nm and 100 nm AgNPs lesions were milder or negligible, respectively. In mice treated with silver acetate, silver concentrations were significantly lower in the spleen and lung, and higher in the kidney than in mice treated with 10 nm AgNPs, and a different target organ of toxicity was identified (kidney). CONCLUSIONS: Administration of the smallest (10 nm) nanoparticles resulted in enhanced silver tissue distribution and overt hepatobiliary toxicity compared to larger ones (40 and 100 nm), while coating had no relevant impact. Distinct patterns of tissue distribution and toxicity were observed after silver acetate administration. It is concluded that if AgNPs become systemically available, they behave differently from ionic silver, exerting distinct and size-dependent effects, strictly related to the nanoparticulate form.


Assuntos
Nanopartículas , Prata/farmacocinética , Prata/toxicidade , Acetatos/administração & dosagem , Acetatos/farmacocinética , Acetatos/toxicidade , Animais , Encéfalo/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Ácido Cítrico/química , Doenças da Vesícula Biliar/induzido quimicamente , Doenças da Vesícula Biliar/patologia , Hemorragia/induzido quimicamente , Hemorragia/patologia , Injeções Intravenosas , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Pulmão/metabolismo , Masculino , Camundongos Endogâmicos ICR , Necrose , Tamanho da Partícula , Povidona/química , Medição de Risco , Prata/administração & dosagem , Prata/sangue , Prata/química , Compostos de Prata/administração & dosagem , Compostos de Prata/farmacocinética , Compostos de Prata/toxicidade , Baço/metabolismo , Distribuição Tecidual
8.
Kidney Int ; 84(1): 164-73, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23447062

RESUMO

There are no adequate studies that have formally tested the performance of different estimating formulas in patients with type 2 diabetes both with and without overt nephropathy. Here we evaluated the agreement between baseline GFRs, GFR changes at month 6, and long-term GFR decline measured by iohexol plasma clearance or estimated by 15 creatinine-based formulas in 600 type 2 diabetics followed for a median of 4.0 years. Ninety patients were hyperfiltering. The number of those identified by estimation formulas ranged from 0 to 24:58 were not identified by any formula. Baseline GFR was significantly underestimated and a 6-month GFR reduction was missed in hyperfiltering patients. Long-term GFR decline was also underestimated by all formulas in the whole study group and in hyper-, normo-, and hypofiltering patients considered separately. Five formulas generated positive slopes in hyperfiltering patients. Baseline concordance correlation coefficients and total deviation indexes ranged from 32.1% to 92.6% and from 0.21 to 0.53, respectively. Concordance correlation coefficients between estimated and measured long-term GFR decline ranged from -0.21 to 0.35. The agreement between estimated and measured values was also poor within each subgroup considered separately. Thus, our study questions the use of any estimation formula to identify hyperfiltering patients and monitor renal disease progression and response to treatment in type 2 diabetics without overt nephropathy.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Taxa de Filtração Glomerular , Rim/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Humanos , Iohexol , Itália , Pessoa de Meia-Idade , Modelos Biológicos , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Eslovênia , Fatores de Tempo
9.
Water Res ; 222: 118848, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35901554

RESUMO

Since nanoplastics are currently considered potentially hazardous to the environment and human health, reliability of studies on nanoplastic exposure becomes crucial. However, analytical challenges limit our understanding of their formation and detection, thus hampering their biological interactions assessment. Here we provide a combined approach to quantitatively and qualitatively detect the release of nanoplastics in water matrix and, in particular, to measure direct exposure of consumers by simulated use of drinking water plastic bottles. We measured that the polyethylene sealing of the bottles released particles with a size distribution ranging from few hundreds nanometers up to about one micron and estimated a mass release in the order of few tenths of nanograms per opening/closing cycle. We observe that mechanical stress alters the physical-chemical characteristics of the generated secondary nanoplastics and degrades the material properties compared to the original bulk source, thus complicating their spectroscopic chemical identification. Our findings demonstrate that understanding material degradation processes is therefore crucial for identifying and quantifying nanoplastics in real samples. Moreover, methods allowing quantitative studies on the release of nanoplastic as a source of exposure are considered essential for proper assessment of their potential health hazards and to promote improvements in consumer products plastic packaging design.


Assuntos
Água Potável , Poluentes Químicos da Água , Humanos , Microplásticos , Plásticos , Reprodutibilidade dos Testes , Poluentes Químicos da Água/análise
10.
Polymers (Basel) ; 14(6)2022 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-35335568

RESUMO

Micro- and nanoplastic (pMP and pNP, respectively) release is an emerging issue since these particles constitute a ubiquitous and growing pollutant, which not only threatens the environment but may have potential consequences for human health. In particular, there is concern about the release of secondary pMP and pNP from the degradation of plastic consumer products. The phenomenon is well-documented in relation to plastic waste in the environment but, more recently, reports of pMP generated even during the normal use of plastic food contact materials, such as water bottles, tea bags, and containers, have been published. So far, a validated and harmonized strategy to tackle the issue is not available. In this study, we demonstrate that plastic breakdown to pMP and pNP can occur during the normal use of polyethylene (PE) rice cooking bags and ice-cube bags as well as of nylon teabags. A multi-instrumental approach based on Raman microscopy, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and particular attention on the importance of sample preparation were applied to evaluate the chemical nature of the released material and their morphology. In addition, a simple method based on Fourier transform infrared (FT-IR) spectroscopy is proposed for pNP mass quantification, resulting in the release of 1.13 ± 0.07 mg of nylon 6 from each teabag. However, temperature was shown to have a strong impact on the morphology and aggregation status of the released materials, posing to scientists and legislators a challenging question: are they micro- or nanoplastics or something else altogether?

11.
Environ Int ; 123: 156-163, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30529840

RESUMO

Traffic-related emissions include gas and particles that can alter air quality and affect human and environmental health. Limited studies have demonstrated that particulate debris thrown off from brakes are toxic to higher plants. The acute phytotoxicity of brake pad wear debris (BPWD) investigated using cress seeds grown in soil contaminated with increasing concentrations of debris. Two types of pads were used: a commercially available phenol based pad and an innovative cement-based pad developed within of the LIFE+ COBRA project. The results suggested that even through the BPWD generated by the two pads were similar in and morphology, debris from traditional pads were more phytotoxic than that from cementitious pads, causing significant alterations in terms of root elongation and loss of plasma membrane integrity.


Assuntos
Lepidium sativum/efeitos dos fármacos , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Automóveis , Germinação/efeitos dos fármacos , Humanos , Material Particulado/química , Raízes de Plantas/efeitos dos fármacos , Raízes de Plantas/crescimento & desenvolvimento , Testes de Toxicidade
12.
Can J Vet Res ; 78(2): 153-5, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24688179

RESUMO

The objective of the present work was to determine the effect of Lactobacillus murinus strain LbP2 on canine fecal immunoglobulin A (IgA) levels. Seven dogs were orally treated with a 3-mL suspension of L. murinus LbP2 containing 5 × 10(9) colony-forming units on alternate days for 2 wk. Six dogs were treated with 3 mL of phosphate-buffered saline as placebo. Fecal samples were taken from the rectal ampulla on days 0 and 16, and the total canine fecal IgA concentration was determined with an immunoperoxidase assay kit. The IgA levels of individual dogs were compared with the nonparametric Wilcoxon test. Differences were considered significant when the P-value was less than 0.05. An increase in the total fecal IgA concentration was observed in the 7 dogs after treatment with L. murinus LbP2 (P = 0.01796). No differences were detected between the initial total fecal IgA values and those obtained at the end of placebo treatment. Thus, after oral administration L. murinus LbP2 showed potential immunomodulatory effects, an important property to assess in a microorganism being considered for use as a probiotic.


L'objectif de la présente étude était de déterminer l'effet de la souche Lactobacillus murinus LbP2 sur les niveaux d'immunoglobulines A (IgA) fécales chez le chien. Sept chiens ont reçu oralement 3 mL d'une suspension de L. murinus LbP2 contenant 5 × 109 unités formatrices de colonies à chaque 2 jours pendant 2 semaines. Six chiens ont reçu 3 mL de saline tamponnée comme placebo. Des échantillons de fèces ont été prélevés au niveau de l'ampoule rectale aux jours 0 et 16, et la concentration d'IgA canine totale déterminée au moyen d'une épreuve d'immunoperoxydase. Les niveaux d'IgA des chiens individuels ont été comparés avec le test non-paramétrique de Wilcoxon. Les différences étaient considérées significatives lorsque la valeur de P était inférieure à 0,05. Une augmentation dans la concentration d'IgA fécale totale a été observée dans les sept chiens après traitement avec L. murinus LbP2 (P = 0,01796). Aucune différence ne fut détectée entre les valeurs initiales des IgA fécales totales et celles à la fin du traitement avec le placebo. Ainsi, l'administration orale de L. murinus LbP2 montre des effets immunomodulateurs potentiels, une propriété intéressante à évaluer chez un microorganisme considéré pour usage comme probiotique.(Traduit par Docteur Serge Messier).


Assuntos
Cães/imunologia , Fezes/microbiologia , Imunoglobulina A/análise , Imunomodulação/imunologia , Lactobacillus/imunologia , Probióticos/farmacologia , Animais , Cães/microbiologia , Feminino , Masculino , Probióticos/administração & dosagem , Estatísticas não Paramétricas
13.
PLoS One ; 7(2): e32533, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22393413

RESUMO

Trials failed to demonstrate protective effects of investigational treatments on glomerular filtration rate (GFR) reduction in Autosomal Dominant Polycystic Kidney Disease (ADPKD). To assess whether above findings were explained by unreliable GFR estimates, in this academic study we compared GFR values centrally measured by iohexol plasma clearance with corresponding values estimated by Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) and abbreviated Modification of Diet in Renal Disease (aMDRD) formulas in ADPKD patients retrieved from four clinical trials run by a Clinical Research Center and five Nephrology Units in Italy. Measured baseline GFRs and one-year GFR changes averaged 78.6±26.7 and 8.4±10.3 mL/min/1.73 m(2) in 111 and 71 ADPKD patients, respectively. CKD-Epi significantly overestimated and aMDRD underestimated baseline GFRs. Less than half estimates deviated by <10% from measured values. One-year estimated GFR changes did not detect measured changes. Both formulas underestimated GFR changes by 50%. Less than 9% of estimates deviated <10% from measured changes. Extent of deviations even exceeded that of measured one-year GFR changes. In ADPKD, prediction formulas unreliably estimate actual GFR values and fail to detect their changes over time. Direct kidney function measurements by appropriate techniques are needed to adequately evaluate treatment effects in clinics and research.


Assuntos
Rim Policístico Autossômico Dominante/genética , Adulto , Estudos de Coortes , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Iohexol/metabolismo , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Nefrologia/métodos , Reprodutibilidade dos Testes , Projetos de Pesquisa , Resultado do Tratamento
14.
Diabetes Care ; 35(10): 2061-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22773704

RESUMO

OBJECTIVE: To describe the prevalence and determinants of hyperfiltration (glomerular filtration rate [GFR] ≥120 mL/min/1.73 m(2)), GFR decline, and nephropathy onset or progression in type 2 diabetic patients with normo- or microalbuminuria. RESEARCH DESIGN AND METHODS: We longitudinally studied 600 hypertensive type 2 diabetic patients with albuminuria <200 µg/min and who were retrieved from two randomized trials testing the renal effect of trandolapril and delapril. Target blood pressure (BP) was <120/80 mmHg, and HbA(1c) was <7%. GFR, albuminuria, and glucose disposal rate (GDR) were centrally measured by iohexol plasma clearance, nephelometry in three consecutive overnight urine collections, and hyperinsulinemic euglycemic clamp, respectively. RESULTS: Over a median (range) follow-up of 4.0 (1.7-8.1) years, GFR declined by 3.37 (5.71-1.31) mL/min/1.73 m(2) per year. GFR change was bimodal over time: a larger reduction at 6 months significantly predicted slower subsequent decline (coefficient: -0.0054; SE: 0.0009), particularly among hyperfiltering patients. A total of 90 subjects (15%) were hyperfiltering at inclusion, and 11 of 47 (23.4%) patients with persistent hyperfiltration progressed to micro- or macroalbuminuria versus 53 (10.6%) of the 502 who had their hyperfiltration ameliorated at 6 months or were nonhyperfiltering since inclusion (hazard ratio 2.16 [95% CI 1.13-4.14]). Amelioration of hyperfiltration was independent of baseline characteristics or ACE inhibition. It was significantly associated with improved BP and metabolic control, amelioration of GDR, and slower long-term GFR decline on follow-up. CONCLUSIONS: Despite intensified treatment, patients with type 2 diabetes have a fast GFR decline. Hyperfiltration affects a subgroup of patients and may contribute to renal function loss and nephropathy onset or progression. Whether amelioration of hyperfiltration is renoprotective is worth investigating.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Idoso , Albuminúria/complicações , Glicemia , Estudos de Coortes , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Glomérulos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade
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