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1.
Toxins (Basel) ; 12(2)2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32085542

RESUMO

The American Urological Association guidelines for the management of non-neurogenic overactive bladder (OAB) recommend the use of OnabotulinumtoxinA, sacral neuromodulation (SNM), and peripheral tibial nerve stimulation (PTNS) as third line treatment options with no treatment hierarchy. The current study used network meta-analysis to compare the efficacy of these three modalities for managing adult OAB syndrome. We performed systematic literature searches of several databases from January 1995 to September 2019 with language restricted to English. All randomized control trials that compared any dose of OnabotulinumtoxinA, SNM, and PTNS with each other or a placebo for the management of adult OAB were included in the study. Overall, 17 randomized control trials, with a follow up of 3-6 months in the predominance of trials (range 1.5-24 months), were included for analysis. For each trial outcome, the results were reported as an average number of episodes of the outcome at baseline. Compared with the placebo, all three treatments were more efficacious for the selected outcome parameters. OnabotulinumtoxinA resulted in a higher number of complications, including urinary tract infection and urine retention. Compared with OnabotulinumtoxinA and PTNS, SNM resulted in the greatest reduction in urinary incontinence episodes and voiding frequency. However, comparison of their long-term efficacy was lacking. Further studies on the long-term effectiveness of the three treatment options, with standardized questionnaires and parameters are warranted.

3.
Sci Total Environ ; 706: 135522, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31864998

RESUMO

BACKGROUND: The association between incident chronic kidney disease (CKD) or end-stage renal disease (ESRD) and exposure to outdoor air pollution is under debate. We aimed to examine this relationship based on a systematic review with random-effects meta-analysis. METHODS: We screened the literature on long-term air pollution exposure assessment in the general population using an electronic search of PubMed, Medline, Embase, and Cochrane Library from inception to 20 October 2019. Observational studies investigating the association between long-term exposure to gaseous (CO, SO2, NO2, O3) or particulate (PM2.5 or PM10) outdoor air pollutants and CKD, ESRD, or renal dysfunction were included, and summary risks were estimated. RESULTS: Of 4419 identified articles, 23 met our inclusion criteria after screening and 14 were included in the meta-analysis. Pooled effect estimates had the following summary risk ratios (RRs) for CKD: 1.10 (95% confidence intervals [CI] 1.00, 1.21; derived from four studies) per 10 µg/m3 increase in PM2.5 and 1.16 (95% CI 1.05, 1.29; derived from four studies) for PM10; 1.31 (95% CI 0.86, 2.00; derived from two studies) per 10 ppm increase in CO; and 1.11 (95% CI 1.09, 1.14; derived from three studies) per 10 ppb increase in NO2. For the pooled effect on eGFR, increases in PM10 and PM2.5 (of 10 µg/m3) were associated with eGFR decline by -0.83 (95% CI -1.54, -0.12; derived from two studies) and -4.11 (95% CI -12.64, 4.42; derived from two studies) mL/min/1.73 m2, respectively. CONCLUSIONS: Air pollution was observed to be associated with CKD and renal function decline. Although more longitudinal studies are required, we argue that air pollution is pernicious to kidney health.


Assuntos
Falência Renal Crônica , Poluentes Atmosféricos , Poluição do Ar , Exposição Ambiental , Humanos , Estudos Longitudinais , Razão de Chances , Material Particulado
4.
Artigo em Inglês | MEDLINE | ID: mdl-31705576

RESUMO

RATIONALE: Glycosylation on immunoglobulins is important for the immune function. In this study, we developed and validated a method for the absolute quantification of IgA subclasses and relative quantification of IgA-Fc glycopeptides by using affinity purification and ultrahigh-performance liquid chromatography/tandem mass spectrometry (UHPLC/MS/MS). Only micro-volumes of plasma were required from each sample and we also applied the method to discover IgA and IgA-glycopeptide profiles in patients with chronic kidney diseases and IgA nephropathy. METHODS: Peptide M affinity beads were used to purify IgA, and a cost-effective peptide analogue was added as internal standard. With an efficient on-bead digestion process, purified samples were analyzed by UHPLC/MS/MS in multiple reaction monitoring mode. RESULTS: Correlation coefficients were greater than 0.999 for the IgA1 and IgA2 calibration curves and greater than 0.994 for glycopeptide regression curves. Intraday and interday precisions for IgA1 and IgA2 were <1.6% and <5.1% RSD, respectively. Intraday and interday accuracies ranged from 102.6 to 114.9% and 103.5 to 113.5% for IgA1 and IgA2, respectively. Stabilities of IgA1 and IgA2 at -80°C for 7 to 15 days ranged from 96.0 to 109.4%, respectively. The Pearson's correlation coefficient was 0.916 when comparing the IgA quantification results of the 30 clinical samples by using ELISAs and the developed UHPLC/MS/MS method. Compared with healthy controls, IgA and IgA-glycopeptides showed different profiles in patients with chronic kidney diseases and IgA nephropathy. CONCLUSIONS: The developed method showed good validation results, and the absolute quantification results of IgA correlated with those from ELISA. The pilot application study showed that IgA and IgA-glycopeptides can be potential biomarker candidates for kidney diseases, and more clinical sample applications are worth investigating.

5.
Int Urol Nephrol ; 51(11): 2015-2025, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31578673

RESUMO

PURPOSE: Mammalian target of rapamycin (mTOR) inhibitors were previously considered a potential therapy for autosomal dominant polycystic kidney disease (ADPKD), but prior studies remained controversial about their efficacy. We performed an updated meta-analysis regarding the therapeutic and adverse effects of mTOR inhibitors in patients with ADPKD. METHODS: We systematically searched Cochrane Library, PubMed, EMBASE, and Medline for randomized controlled trials (RCTs) comparing mTOR inhibitors to placebo in ADPKD patients up to August 2019. We calculated weighted mean differences (WMDs) for total kidney volume (TKV), estimated glomerular filtration rates (eGFRs), and weighted odds ratios (ORs) for treatment-related complications between the treatment and the placebo groups, using the random effects model. RESULTS: We retrieved a total of 9 RCTs enrolling 784 ADPKD patients receiving rapamycin, sirolimus, or everolimus between 2009 and 2016. The WMDs of TKV and eGFR from baseline to the last measurement were - 31.54 mL (95% confidence interval [CI] - 76.79 to 13.71 mL) and 2.81 mL/min/1.73 m2 (95% CI - 1.85 to 7.46 mL/min/1.73 m2), respectively. Patients receiving mTOR inhibitors had a significantly increased risk of any adverse effects (OR 5.92, 95% CI 3.53-9.94), with the most common ones being aphthous stomatitis (OR 15.45, 95% CI 9.68-24.66) and peripheral edema (OR 3.49, 95% CI 1.31-9.27) compared to placebo users. CONCLUSIONS: mTOR inhibitors did not significantly influence renal progression in patients with ADPKD, but were associated with a higher risk of complications. Whether mTOR inhibitors can be an add-on option or second-line agents remain undetermined.

6.
J Clin Med ; 8(10)2019 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-31627462

RESUMO

BACKGROUND: AST-120 (Kremezin), which is an oral spherical carbon adsorbent, has been reported to have the potential for retarding disease progression in patients with chronic kidney disease. We aimed to evaluate its efficacy and safety in this study. METHODS: We systematically searched for randomized controlled trials published in PubMed, Embase, and Cochrane databases. The primary outcomes were the renal outcome and all-cause mortality, and the change in serum indoxyl sulfate (IS) levels. The safety outcome was also evaluated in terms of reported major adverse events. A random-effects model was used when heterogeneity was expected. RESULTS: Eight studies providing data for 3349 patients were included in the meta-analysis. The risk ratio of renal outcome and all-cause mortality were 0.97 (95% CI: 0.88-1.07; 6 trials) and 0.94 (0.73-1.20; 5 trials), respectively. Furthermore, the weighted mean change in IS levels from baseline to the end of the study was -0.28 mg/dL (95% CI: -0.46 to -0.11; 4 trials). CONCLUSIONS: This study provides evidence that AST-120 can effectively lower IS levels but still controversial in terms of slowing disease progression and all-cause mortality. Except for dermatological events, the incidence of adverse events did not differ significantly between the AST-120 and placebo groups.

7.
Nat Commun ; 10(1): 4332, 2019 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-31551414

RESUMO

PTEN is frequently mutated in prostate cancer. The tumor suppressor function of PTEN is attributed to its lipid phosphatase activity that counters PI3K action. Here, we report a PTEN-ARID4B-PI3K axis in which PTEN inhibits expression of ARID4B, while ARID4B is a transcriptional activator of the PI3K subunit genes PIK3CA and PIK3R2 that are crucial for activation of the PI3K/AKT pathway. Reciprocal binding of ARID4B and histone H1 to the PIK3CA and PIK3R2 promoters modulates chromatin condensation, suggesting a mechanism by which ARID4B activates these promoters. Functional analyses reveals that ARID4B is required for prostate tumorigenesis when PTEN is deficient. The biological significance is further substantiated by the existence of a PTEN/ARID4B/PIK3CA three-gene signature that improves the predictive power for prostate cancer recurrence in patients. In summary, we identify ARID4B as a master regulator in the PTEN-PI3K pathway, thus providing a potential therapeutic target for prostate cancer carrying PTEN mutations.


Assuntos
Antígenos de Neoplasias/metabolismo , Proteínas de Neoplasias/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Neoplasias da Próstata/genética , Animais , Antígenos de Neoplasias/genética , Histonas/metabolismo , Humanos , Masculino , Camundongos Knockout , Proteínas de Neoplasias/genética , PTEN Fosfo-Hidrolase/genética , Neoplasias da Próstata/metabolismo , Transdução de Sinais
8.
Arch Toxicol ; 93(9): 2535-2544, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31473767

RESUMO

Developmental delay has been associated with inefficient arsenic methylation capacity in preschool children. Folate and vitamin B12 are important nutrients that produce s-adenosylmethionine during single-carbon metabolism and provide methyl groups for arsenic methylation. The aim of the present study was to explore whether plasma folate and vitamin B12 levels influence arsenic methylation capacity and in turn are related to developmental delay in preschool children. A case-control study was conducted in 178 children with developmental delay and 88 normal children, who were recruited from Shin Kong Wu Ho-Su Memorial Teaching Hospital from August 2010 to March 2014. Arsenite (AsIII), arsenate (AsV), monomethylarsonic acid (MMAV), and dimethylarsinic acid (DMAV) in the urine was determined by high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Plasma folate and vitamin B12 levels were measured using a SimulTRAC-SNB radioassay. The results show that the combination of high plasma folate and high vitamin B12 levels were correlated with efficient arsenic methylation capacity (low MMAV %, low InAs %, and high DMAV %). High MMAV % significantly increased and high DMAV % and secondary methylation index decreased the odds ratio (OR) of developmental delay in a dose-dependent manner in both low plasma folate and low vitamin B12 (low/low) groups; the multivariate OR and 95% confidence interval were 5.01 (0.83-30.06), 0.21 (0.04-1.23), and 0.20 (0.03-1.20), respectively. This is the first study to show that the combination of high plasma folate and high vitamin B12 levels increases arsenic methylation capacity and indirectly decreases the OR of developmental delay in preschool children.

9.
Medicine (Baltimore) ; 98(29): e16311, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31335677

RESUMO

BACKGROUND/OBJECTIVE: Hyperuricemia has been proven to be an independent risk factor for chronic kidney disease (CKD). However, the role of hyperuricemia in the progression of CKD remains unclear. Thus, we performed a systematic review and meta-analysis to evaluate the efficacy and safety of febuxostat, a first line urate-lowering agent, in CKD patients with hyperuricemia. METHODS: We have systematically searched for randomized controlled trials assessing the efficacy and safety of febuxostat versus control in CKD patients with hyperuricemia through MEDLINE, PubMed, EMBASE, and Cochrane databases. All statistical analyses were conducted by using the statistical package Review Manager, version 5.3.5. Heterogeneity was assessed using the Cochrane Q and I tests and summary statistics were reported with 95% confidence interval. Two-tailed test was used for analysis and a P value of <.05 is considered statistically significant. RESULTS: Eleven eligible trials with 1317 participants were included in the meta-analysis. A significant reduction in serum uric acid was found in the febuxostat treated group. Also, a significant higher eGFR was found in the febuxostat treated group among CKD stage 3 and 4 patients. No significant difference of major complication or death was identified between treatment and control groups. CONCLUSIONS: The meta-analysis showed that other than its urate-lowering effect, febuxostat presented a reno-protective effect in CKD patients. More studies with larger sample sizes and higher quality are required to clarify the role of febuxostat use in the progression of CKD.


Assuntos
Febuxostat/farmacologia , Taxa de Filtração Glomerular/efeitos dos fármacos , Insuficiência Renal Crônica , Progressão da Doença , Supressores da Gota/farmacologia , Humanos , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/fisiopatologia , Ácido Úrico/sangue
10.
Int J Mol Sci ; 20(11)2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31195684

RESUMO

The kidney harbors one of the strongest circadian clocks in the body. Kidney failure has long been known to cause circadian sleep disturbances. Using an adenine-induced model of chronic kidney disease (CKD) in mice, we probe the possibility that such sleep disturbances originate from aberrant circadian rhythms in kidney. Under the CKD condition, mice developed unstable behavioral circadian rhythms. When observed in isolation in vitro, the pacing of the master clock, the suprachiasmatic nucleus (SCN), remained uncompromised, while the kidney clock became a less robust circadian oscillator with a longer period. We find this analogous to the silencing of a strong slave clock in the brain, the choroid plexus, which alters the pacing of the SCN. We propose that the kidney also contributes to overall circadian timekeeping at the whole-body level, through bottom-up feedback in the hierarchical structure of the mammalian circadian clocks.


Assuntos
Relógios Circadianos/fisiologia , Rim/fisiologia , Adenina , Animais , Modelos Animais de Doenças , Masculino , Camundongos Endogâmicos C57BL , Proteínas Circadianas Period/metabolismo , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/fisiopatologia , Núcleo Supraquiasmático/fisiopatologia
11.
Nat Commun ; 10(1): 2437, 2019 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164646

RESUMO

Gratings, one of the most important energy dispersive devices, are the fundamental building blocks for the majority of optical and optoelectronic systems. The grating period is the key parameter that limits the dispersion and resolution of the system. With the rapid development of large X-ray science facilities, gratings with periodicities below 50 nm are in urgent need for the development of ultrahigh-resolution X-ray spectroscopy. However, the wafer-scale fabrication of nanogratings through conventional patterning methods is difficult. Herein, we report a maskless and high-throughput method to generate wafer-scale, multilayer gratings with period in the sub-50 nm range. They are fabricated by a vacancy epitaxy process and coated with X-ray multilayers, which demonstrate extremely large angular dispersion at approximately 90 eV and 270 eV. The developed new method has great potential to produce ultrahigh line density multilayer gratings that can pave the way to cutting edge high-resolution spectroscopy and other X-ray applications.

12.
BMC Nephrol ; 20(1): 203, 2019 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-31167651

RESUMO

BACKGROUND: Infection is the second most common cause of mortality for patients with end-stage renal disease (ESRD), accompanying with immune dysfunction. Endothelin (EDN) is known to be related to inflammation; however, it is unknown whether genetic variants of the EDN gene family are associated with increased risk of hospitalized infection events. METHODS: Nineteen tagging single-nucleotide polymorphisms (tSNPs) of the EDN gene family were selected for genotyping a cohort of 190 ESRD patients. Patient demographics were recorded, the subtypes of infection events were identified, and association analysis between the EDN genetic variants and hospitalized infection events was performed. RESULTS: In this study, 106 patients were hospitalized for infection events. The leading events were pneumonia, bacteremia, and cellulitis. The minor allele of rs260741, rs197173, and rs926632 SNPs of EDN3 were found to be associated with reduced risk of hospitalized bacteremia events. CONCLUSIONS: The minor allele of rs260741, rs197173, and rs926632 in EDN3 were associated with reduced risk of hospitalized bacteremia events in ESRD patients.

13.
Transplant Proc ; 51(5): 1472-1474, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31084921

RESUMO

INTRODUCTION: The immunosuppressant agents in kidney transplantation (KT) may lead to various complications such as opportunistic infections and malignancies. BK virus associated nephropathy is a significant complication following KT, and it can result in graft failure. BK virus causes tubulointerstitial nephritis, ureter stenosis, and even graft failure in KT recipients with impaired immune system. We described a 63-year-old woman, who was a hepatitis C carrier and on dialysis for 22 years before KT, who received cadaveric-donor KT 2 years previously. She reported decreasing urine output and general weakness. The serum creatinine level was slightly increased from 2.94 to 4.38 mg/dL. METHODS: Immunosuppressant medications including prednisolone, everolimus, cyclosporin, and mycophenolate sodium were continued as maintenance therapy post KT. Kidney biopsy was performed due to deterioration of graft function. RESULTS: The kidney biopsy showed consistent results with early-stage polyomavirus nephropathy, characterized by focal viral cytopathic changes with positive immunohistochemical signals and mesangial proliferative glomerulonephritis, immune-complex-mediated (Fig 1 and Fig 2). Negative C4d staining at peritubular capillary was reported. The dosage of mycophenolate sodium was tapered from 720 to 360 mg daily and that of everolimus increased from 0.5 to 1.0 mg daily due to BK viral infection with BK nephropathy. The serum creatinine level was 2.75 mg/dL after treatment. CONCLUSION: Early detection of BK nephropathy and decreasing immunosuppressant agents are the mainstay of treatment. Substituting leflunomide for mycophenolate sodium and increasing dosage of everolimus has been proposed to solve BK nephropathy. We presented that the use of leflunomide in such situation is in a timely manner.


Assuntos
Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim , Infecções por Polyomavirus/imunologia , Infecções Tumorais por Vírus/imunologia , Vírus BK , Everolimo/uso terapêutico , Feminino , Humanos , Transplante de Rim/efeitos adversos , Leflunomida/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Nefrite Intersticial/imunologia , Nefrite Intersticial/virologia , Infecções Oportunistas/imunologia , Transplante Homólogo/efeitos adversos
14.
J Hazard Mater ; 375: 224-232, 2019 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-31075550

RESUMO

This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m2 estimated glomerular filtration rate (eGFR) for three or more consecutive months. Plasma selenium and red blood cell cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined via HPLC-HG-AAS and were summed to determine the total urinary arsenic concentration. Plasma selenium was positively correlated to eGFR, and subjects with high plasma selenium levels (>243.90 µg/L) had a significantly lower odds ratio (OR) and 95% confidence interval (CI) (0.23, 0.13-0.42) for CKD compared to those with low plasma selenium levels (≤ 196.70 µg/L). High plasma selenium and low red blood cell cadmium or lead concentrations interacted to decrease the OR and 95% CI for CKD (0.12, 0.06-0.26; 0.09, 0.04-0.19). High plasma selenium and low red blood cell lead levels also interacted to increase the eGFR (20.70, 15.56-26.01 mL/min/1.73 m2). This study is the first to suggest that selenium modifies the eGFR and OR in CKD induced by environmental toxicants.

15.
J Neurovirol ; 25(4): 612-615, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31069707

RESUMO

End-stage renal disease (ESRD) has a major impact on health and affects more than 600,000 people in the USA. The current mainstay treatments include dialysis and kidney transplantation (KT), and patients who have received KT have a higher quality of life and a lower mortality risk than those on chronic dialysis. Therefore, KT is considered the more preferred treatment modality for patients with ESRD. However, even though KT results in a higher long-term survival rate, the use of immunosuppressants is associated with various complications, including opportunistic infections and malignancies, which may lead to a higher risk of death in the first year after transplantation. Progressive multifocal leukoencephalopathy (PML) is a rare complication following KT, with an incidence of 0.027% in KT recipients. We present a case of PML following immunosuppressant therapy in a patient who received KT.

18.
J Vasc Surg ; 69(4): 1282-1292, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30905366

RESUMO

OBJECTIVE: Patients with end-stage renal disease need vascular access to ensure sufficient blood flow during hemodialysis (HD). Patients who are poor candidates for arteriovenous access creation require long-term catheter placement. Problems such as dialysate recirculation, thrombosis, catheter-related infections, and malfunction can occur with HD catheters. Different tip designs (step, split, and symmetrical) have been developed to ameliorate the catheter-related problems. The aim of the study was to compare the efficacy and safety of split-tip, step-tip, and symmetrical-tip HD catheters. METHODS: The PubMed, Embase, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were searched for studies published before November 2017. Studies comparing the clinical and rheologic outcomes of step-, split-, or symmetrical-tip catheters in patients undergoing HD were included in this meta-analysis. We conducted meta-analyses using random-effects models. The primary outcomes were catheter survival time and incidence of functioning catheters. The secondary outcomes were delivered blood flow rate, blood recirculation rate, and incidence of catheter-related complications. RESULTS: Seven randomized controlled trials and one retrospective study with a total of 988 patients were included. No significant differences were observed in the delivered blood flow rate (weighted mean difference, -5.37 mL/min; 95% confidence interval [CI], -23.75 to 13.02), incidence of catheter-related infections (risk ratio [RR], 1.18; 95% CI, 0.63-2.22), or incidence of catheter-related thrombosis (RR, 1.29; 95% CI, 0.64-2.59) between step-tip catheters and advanced (both split-tip and symmetrical-tip) catheters. Moreover, a meta-analysis of the incidence of functioning catheters at 1 month, 6 months, and 12 months revealed that the outcome of step-tip catheter use was better than that of split-tip catheter use, but with a significant difference only at 6 months (RR, 1.22; 95% CI, 1.02-1.46). CONCLUSIONS: None of the catheter types exhibited unique features that can enhance their suitability for application. Hence, catheters can be selected by also considering different factors, including costs, ease of procedures, expertise of the clinician, and education and preference of the patient.


Assuntos
Cateterismo Venoso Central/instrumentação , Cateteres de Demora , Cateteres Venosos Centrais , Falência Renal Crônica/terapia , Diálise Renal/instrumentação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Venoso Central/efeitos adversos , Desenho de Equipamento , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
19.
Free Radic Biol Med ; 135: 235-244, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30878646

RESUMO

Traffic emission is responsible for most small-sized particulate matter (PM) air pollution in urban areas. Several recent studies have indicated that traffic-related PM may aggravate kidney disease. Furthermore, exposure to particulate air pollution may be related to the risk of chronic kidney disease (CKD). However, the underlying molecular mechanisms have not been adequately addressed. In the present study, we studied the mechanisms of renal damage that might be associated with exposure to PM. In a real world of whole-body exposure to traffic-related PM model for 3-6 months, PM in urban ambient air can affect kidney function and induce autophagy, endoplasmic reticulum (ER) stress and apoptosis in kidney tissues. Exposure to traffic-related diesel particulate matter (DPM) led to a reduction in cell viability in human kidney tubular epithelial cells HK-2. DPM increased mitochondrial reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Furthermore, DPM induced ER stress and activated the unfolded protein response (UPR) pathway. Eventually, DPM exposure induced caspase pathways and triggered apoptosis. In addition, DPM induced autophagy through the inhibition of the Akt/mTOR pathway. Autophagy inhibition resulted in significantly increased cytotoxicity and apoptosis. These findings suggest that air pollution in urban areas may cause nephrotoxicity and autophagy as a protective role in PM-induced cytotoxicity.

20.
Sci Rep ; 9(1): 2694, 2019 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-30804406

RESUMO

It remains unclear how different uses of angiotensin-converting inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) influence the progression of chronic kidney disease (CKD). This study explored CKD progression in a multicentre, longitudinal cohort study that included 2639 patients with CKD stage 1-5 and hypertension. Patients treated with ACEI or ARB for ≥90 days during a 6-mo period comprised the study group, or no treatment, comprised the control group. The study group was subdivided on the basis of treatment: ACEI monotherapy or ARB monotherapy. Progression of renal deterioration was defined by an average eGFR decline of more than 5 mL/min/1.73 m2/yr or the commencement of dialysis. With at least 1-year follow up, a progression of renal deterioration was demonstrated in 29.70% of the control group and 25.09% of the study group. Patients in the study group had significantly reduced progression of CKD with adjusted odds ratio 0.79 (95% confidence interval: 0.63-0.99). However, when ACEI monotherapy and ARB monotherapy were analyzed separately, none of their associations with CKD progression was statistically significant. In conclusion, ACEI or ARB monotherapy may retard the deterioration of renal function among patients with CKD and hypertension.

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