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1.
Am J Kidney Dis ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38788792

RESUMO

RATIONALE & OBJECTIVE: Established therapeutic interventions effectively mitigate the risk and progression of chronic kidney disease (CKD). Countries and regions have a compelling need for organizational structures that enable early identification of people with CKD who can benefit from these proven interventions. We aimed to report the current global status of CKD detection programs. STUDY DESIGN: A multinational cross-sectional survey. SETTING & PARTICIPANTS: Stakeholders, including nephrologist leaders, policymakers, and patient advocates from 167 countries, participating in the International Society of Nephrology (ISN) survey from June to September 2022. OUTCOMES: Structures for the detection and monitoring of CKD, including CKD surveillance systems in the form of registries, community-based detection programs, case-finding practices, and availability of measurement tools for risk identification. ANALYTICAL APPROACH: Descriptive statistics. RESULTS: Of all participating countries, 19% (n=31) reported CKD registries and 25% (n=40) reported implementing CKD detection programs as part of their national policies. There were variations in CKD detection program, with 50% (n=20) using a reactive approach (managing cases as identified) and 50% (n=20) actively pursuing case-finding in at-risk populations. Routine case-finding for CKD in high-risk populations was widespread, particularly for diabetes (n=152; 91%) and hypertension (n=148; 89%). Access to diagnostic tools, estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR), was limited, especially in low-income (LICs) and lower-middle-income (LMICs) countries, at primary (eGFR: LICs 22%, LMICs 39%, UACR: LICs 28%, LMICs 39%) and secondary/tertiary healthcare levels (eGFR: LICs 39%, LMICs 73%, UACR: LICs 44%, LMICs 70%), potentially hindering CKD detection. LIMITATIONS: A lack of detailed data prevented an in-depth analysis. CONCLUSION: This comprehensive survey highlights a global heterogeneity in the organization and structures (surveillance systems, detection programs and tools) for early identification of CKD. Ongoing efforts should be geared toward bridging such disparities to optimally prevent the onset and progression of CKD and its complications.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38769588

RESUMO

Kidney diseases have become a global epidemic with significant public health impact. Chronic kidney disease (CKD) is set to become the fifth largest cause of death by 2040, with major impacts on low-resource countries. This review is based on recent report of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) that uncovered gaps in key vehicles of kidney care delivery assessed using World Health Organization building blocks for health systems (financing, services delivery, workforce, access to essential medicines, health information systems, and leadership/governance). High-income countries had more centres for kidney replacement therapies (KRT), higher KRT access, higher allocation of public funds to KRT, larger workforce, more health information systems, and higher government recognition of CKD and KRT as health priorities than low-income nations. Evidence identified from the current ISN-GKHA initiative should serve as template for generating and advancing policies and partnerships to address the global burden of kidney disease. The results provide opportunities for kidney health policymakers, nephrology leaders, and organizations to initiate consultations to identify strategies for improving care delivery and access in equitable, and resource-sensitive manners. Policies to increase use of public funding for kidney care, lower cost of KRT, and increase workforce should be high-priority in low-resource nations, while strategies that expand access to kidney care and maintain current status of care should be prioritized in high-income countries. In all countries, the perspectives of people with CKD should be exhaustively explored to identify core kidney care priorities.

3.
Nephrology (Carlton) ; 29(3): 135-142, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38018697

RESUMO

AIM: Vascular and peritoneal access are essential elements for sustainability of chronic dialysis programs. Data on availability, patterns of use, funding models, and workforce for vascular and peritoneal accesses for dialysis at a global scale is limited. METHODS: An electronic survey of national leaders of nephrology societies, consumer representative organizations, and policymakers was conducted from July to September 2018. Questions focused on types of accesses used to initiate dialysis, funding for services, and availability of providers for access creation. RESULTS: Data from 167 countries were available. In 31 countries (25% of surveyed countries), >75% of patients initiated haemodialysis (HD) with a temporary catheter. Seven countries (5% of surveyed countries) had >75% of patients initiating HD with arteriovenous fistulas or grafts. Seven countries (5% of surveyed countries) had >75% of their patients starting HD with tunnelled dialysis catheters. 57% of low-income countries (LICs) had >75% of their patients initiating HD with a temporary catheter compared to 5% of high-income countries (HICs). Shortages of surgeons to create vascular access were reported in 91% of LIC compared to 46% in HIC. Approximately 95% of participating countries in the LIC category reported shortages of surgeons for peritoneal dialysis (PD) access compared to 26% in HIC. Public funding was available for central venous catheters, fistula/graft creation, and PD catheter surgery in 57%, 54% and 54% of countries, respectively. CONCLUSION: There is a substantial variation in the availability, funding, workforce, and utilization of vascular and peritoneal access for dialysis across countries regions, with major gaps in low-income countries.


Assuntos
Derivação Arteriovenosa Cirúrgica , Falência Renal Crônica , Nefrologia , Diálise Peritoneal , Humanos , Diálise Renal , Peritônio , Cateteres de Demora , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Derivação Arteriovenosa Cirúrgica/efeitos adversos
4.
BMC Nephrol ; 25(1): 159, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720263

RESUMO

BACKGROUND: There is a lack of contemporary data describing global variations in vascular access for hemodialysis (HD). We used the third iteration of the International Society of Nephrology Global Kidney Health Atlas (ISN-GKHA) to highlight differences in funding and availability of hemodialysis accesses used for initiating HD across world regions. METHODS: Survey questions were directed at understanding the funding modules for obtaining vascular access and types of accesses used to initiate dialysis. An electronic survey was sent to national and regional key stakeholders affiliated with the ISN between June and September 2022. Countries that participated in the survey were categorized based on World Bank Income Classification (low-, lower-middle, upper-middle, and high-income) and by their regional affiliation with the ISN. RESULTS: Data on types of vascular access were available from 160 countries. Respondents from 35 countries (22% of surveyed countries) reported that > 50% of patients started HD with an arteriovenous fistula or graft (AVF or AVG). These rates were higher in Western Europe (n = 14; 64%), North & East Asia (n = 4; 67%), and among high-income countries (n = 24; 38%). The rates of > 50% of patients starting HD with a tunneled dialysis catheter were highest in North America & Caribbean region (n = 7; 58%) and lowest in South Asia and Newly Independent States and Russia (n = 0 in both regions). Respondents from 50% (n = 9) of low-income countries reported that > 75% of patients started HD using a temporary catheter, with the highest rates in Africa (n = 30; 75%) and Latin America (n = 14; 67%). Funding for the creation of vascular access was often through public funding and free at the point of delivery in high-income countries (n = 42; 67% for AVF/AVG, n = 44; 70% for central venous catheters). In low-income countries, private and out of pocket funding was reported as being more common (n = 8; 40% for AVF/AVG, n = 5; 25% for central venous catheters). CONCLUSIONS: High income countries exhibit variation in the use of AVF/AVG and tunneled catheters. In low-income countries, there is a higher use of temporary dialysis catheters and private funding models for access creation.


Assuntos
Derivação Arteriovenosa Cirúrgica , Saúde Global , Diálise Renal , Diálise Renal/economia , Humanos , Falência Renal Crônica/terapia , Falência Renal Crônica/economia , Dispositivos de Acesso Vascular/economia , Nefrologia , Países Desenvolvidos , Países em Desenvolvimento
5.
Clin Genet ; 103(2): 256-257, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36354001

RESUMO

The study identifies a non-consanguineous multigenerational family of the Lua ethnic group in Northern Thailand with three members affected with hypoplastic-hypocalcified amelogenesis imperfecta, cone-rod dystrophy, and harboring a novel homozygous missense variant, c.1475G>A p.(Gly492Asp), in CNNM4, indicating Jalili syndrome. We report features including advanced dental age, crossbite, developmental delay, expanding genotypic and phenotypic spectra of Jalili syndrome, and perform the prenatal genetic testing that helps avoid unnecessary pregnancy termination.


Assuntos
Amelogênese Imperfeita , Proteínas de Transporte de Cátions , Distrofias de Cones e Bastonetes , Retinose Pigmentar , Humanos , Distrofias de Cones e Bastonetes/genética , Amelogênese Imperfeita/diagnóstico , Amelogênese Imperfeita/genética , Retinose Pigmentar/genética , Proteínas de Transporte de Cátions/genética
6.
Sleep Breath ; 27(3): 913-921, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35896858

RESUMO

BACKGROUND: Diagnosis of obstructive sleep apnea requires polysomnography which has limited availability. We aimed to develop and validate a risk score in predicting clinically significant OSA among the Thai population. METHODS: We reviewed polysomnographic studies performed in adults diagnosed with OSA in King Chulalongkorn Memorial Hospital from 2017 to 2019. 1798 and 450 patients were randomly enrolled in development and validation cohorts, respectively. A risk score was developed using multiple factor analysis and logistic regression. The NH-OSA score was externally validated at the Bangkok Christian Hospital. We compared its performance to existing screening scores (STOP-BANG, Berlin Questionnaire, Epworth Sleepiness Scale (ESS), and NoSAS score). RESULT: The NH-OSA score allocates 1 point for having neck circumference ≥ 13 inches (in women) or 15 inches (in men), 4 points for the presence of hypertension, 3 or 5 or 7 points for having a body mass index of 23-24.9, 25-30, ≥ 30 kg/m2, respectively, 9 points for the presence of moderate or severe snoring, and 5 points for age ≥ 40 years. With a cutoff value at 14 points, the sensitivity and specificity were 82.1% and 68.7%, respectively. The AUC was 0.75 (0.73-0.78). Both internal and external validation study revealed high AUC of 0.74 (0.68-0.80) and 0.75 (0.60-0.90), respectively. These were greater when compared to STOP-BANG, Berlin Questionnaire, ESS, and NoSAS score. CONCLUSION: NH-OSA is a newly developed tool which has good performance in predicting clinically significant OSA with high validity among the Thai population. It could help screen patients at risk of OSA for further investigation.


Assuntos
Apneia Obstrutiva do Sono , População do Sudeste Asiático , Masculino , Adulto , Humanos , Feminino , Tailândia , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Sensibilidade e Especificidade , Inquéritos e Questionários , Programas de Rastreamento
7.
Asian Pac J Allergy Immunol ; 41(2): 168-178, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34284591

RESUMO

BACKGROUND: The excretion of trimethylamine N-oxide (TMAO) (uremic toxin) into the intestine might be enhanced, due to the limited renal elimination in chronic kidney disease (CKD), possibly induced TMAO reductase (a TMAO-neutralizing enzyme) in gut bacteria. Detection of TMAO reductase in serum could be used as a biomarker of gut permeability defect. OBJECTIVE: To explore the correlation between serum TMAO reductase, gut leakage, and systemic inflammation in CKD. METHODS: Mouse models of gut leakage; including 5/6 nephrectomy-induced chronic kidney disease (CKD), a model without colitis, and 1.5% dextran sulfate solution (DSS), a colitis model, were performed. In parallel, serum samples from patients with chronic hemodialysis (n = 48) and the healthy control (n = 20) were analyzed. RESULTS: Gut-leakage (FITC-dextran, endotoxemia, and reduced intestinal tight junction protein) was detected in both CKD and DSS models. While TMAO reductase and TMAO were elevated in the serum of both mouse models and patients, TMAO reductase correlated with TMAO, gut- leakage, and serum IL-6 only in mice but not in patients. Notably, endotoxemia was used as a surrogate marker of gut leakage in patients. In patients, TMAO reductase and TMAO did not correlate with serum IL-6 and vascular complications using the ankle-brachial index and cardio-ankle vascular index. CONCLUSIONS: Serum TMAO reductase was elevated in CKD mice and patients with CKD. Serum TMAO reductase was correlated with TMAO and gut-leakage only in mice but not in patients. Further studies in patients are needed to determine the benefit of serum TMAO reductase in patients with CKD.


Assuntos
Colite , Endotoxemia , Mucosite , Insuficiência Renal Crônica , Camundongos , Animais , Sulfato de Dextrana , Interleucina-6 , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Inflamação/metabolismo , Biomarcadores
8.
Nephrol Dial Transplant ; 37(8): 1429-1442, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35138387

RESUMO

BACKGROUND: Although pathogenic gut microbiota causes gut leakage, increases translocation of uremic toxins into circulation and accelerates CKD progression, the local strain of Lactobacillus rhamnosus L34 might attenuate gut leakage. We explored the effects of L34 on kidney fibrosis and levels of gut-derived uremic toxins (GDUTs) in 5/6 nephrectomy (5/6Nx) mice. METHODS: At 6 weeks post-5/6Nx in mice, either L34 (1 × 106 CFU) or phosphate buffer solution (as 5/6Nx control) was fed daily for 14 weeks. In vitro, the effects of L34-conditioned media with or without indoxyl sulfate (a representative GDUT) on inflammation and cell integrity (transepithelial electrical resistance; TEER) were assessed in Caco-2 (enterocytes). In parallel, the effects on proinflammatory cytokines and collagen expression were assessed in HK2 proximal tubular cells. RESULTS: At 20 weeks post-5/6Nx, L34-treated mice showed significantly fewer renal injuries, as evaluated by (i) kidney fibrosis area (P < 0.01) with lower serum creatinine and proteinuria, (ii) GDUT including trimethylamine-N-oxide (TMAO) (P = 0.02) and indoxyl sulfate (P < 0.01) and (iii) endotoxin (P = 0.03) and serum TNF-α (P = 0.01) than 5/6Nx controls. Fecal microbiome analysis revealed an increased proportion of Bacteroidetes in 5/6Nx controls. After incubation with indoxyl sulfate, Caco-2 enterocytes had higher interleukin-8 and nuclear factor κB expression and lower TEER values, and HK2 cells demonstrated higher gene expression of TNF-α, IL-6 and collagen (types III and IV). These indoxyl sulfate-activated parameters were attenuated with L34-conditioned media, indicating the protective role of L34 in enterocyte integrity and renal fibrogenesis. CONCLUSION: L34 attenuated uremia-induced systemic inflammation by reducing GDUTs and gut leakage that provided renoprotective effects in CKD.


Assuntos
Lacticaseibacillus rhamnosus , Insuficiência Renal Crônica , Animais , Anti-Inflamatórios , Células CACO-2 , Meios de Cultivo Condicionados , Modelos Animais de Doenças , Fibrose , Humanos , Indicã , Inflamação/patologia , Inflamação/prevenção & controle , Camundongos , Nefrectomia , Insuficiência Renal Crônica/patologia , Fator de Necrose Tumoral alfa
9.
Blood Purif ; 51(1): 47-54, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-33857940

RESUMO

INTRODUCTION: Uncontrolled systemic inflammation may occur in severe coronavirus disease 19 (COVID-19). We have previously shown that endotoxemia, presumably from the gut, may complicate COVID-19. However, the role of endotoxin adsorbent (EA) therapy to mitigate organ dysfunction in COVID-19 has not been explored. METHODS: We conducted a retrospective observational study in COVID-19 patients who received EA therapy at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand, between March 13 and April 17, 2020. Relevant clinical and laboratory data were collected by inpatient chart review. RESULTS: Among 147 hospitalized COVID-19 patients, 6 patients received EA therapy. All of the 6 patients had severe COVID-19 infection with acute respiratory distress syndrome (ARDS). Among these, 5 of them were mechanically ventilated and 4 had complications of secondary bacterial infection. The endotoxin activity assay (EAA) results of pre-EA therapy ranged from 0.47 to 2.79. The choices of EA therapy were at the discretion of attending physicians. One patient was treated with oXiris® along with continuous renal replacement therapy, and the others received polymyxin B hemoperfusion sessions. All patients have survived and were finally free from the mechanical ventilation as well as had improvement in PaO2/FiO2 ratio and decreased EAA level after EA therapy. CONCLUSIONS: We demonstrated the clinical improvement of severe COVID-19 patients with elevated EAA level upon receiving EA therapy. However, the benefit of EA therapy in COVID-19 ARDS is still unclear and needs to be elucidated with randomized controlled study.


Assuntos
COVID-19/terapia , Endotoxemia/terapia , Hemoperfusão/métodos , SARS-CoV-2 , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Adsorção , COVID-19/complicações , Cuidados Críticos/métodos , Endotoxemia/etiologia , Feminino , Heparina/administração & dosagem , Humanos , Masculino , Membranas Artificiais , Pessoa de Meia-Idade , Polimixina B/administração & dosagem , Terapia de Substituição Renal , Síndrome do Desconforto Respiratório/etiologia , Estudos Retrospectivos , Resultado do Tratamento
10.
Nephrology (Carlton) ; 27(7): 621-631, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35238113

RESUMO

BACKGROUND: Spiritual well-being (SWB), an individual's understanding of the meaning and purpose of life, may help patients with chronic or terminal illnesses cope with their diseases. This study aimed to assess SWB in patients on peritoneal dialysis (PD), as well as its relationship with patient characteristics and patient-reported outcomes (PRO). METHODS: The data were obtained from questionnaires that formed part of the PD Outcomes and Practice Patterns Study (PDOPPS). Measures used in this study were SWB scores derived from the WHO quality of life, spirituality, religiousness and personal beliefs (WHOQOL-SRPB) tool including 32 items from eight facets; physical (PCS) and mental component summary (MCS) scores of the 12-Item Short-Form Health Survey (SF-12), Center of Epidemiologic Studies Depression Scale-10 (CES-D-10) scores, burden of kidney disease scores and functional status scores. RESULTS: Overall, 529 out of 848 participants (62%) completely responded to the questionnaires and were included in the analysis. Over two-thirds of PD patients (70%) had moderate or higher SWB scores. The SWB scores were significantly lower in patients with age >65 years and unemployed status. SWB scores positively correlated with higher PCS, MCS, burden of kidney disease scores and functional status scores, while negatively correlated with depression scores by CES-D-10 scale. Patients who reported significant depressive symptoms (CES-D-10 score ≥ 10) had significantly lower SWB scores. CONCLUSION: Better SWB was significantly associated with better health-related QOL (HRQOL) and the absence of depressive symptoms. SWB may be an essential consideration in the delivery of high-quality PD.


Assuntos
Diálise Peritoneal , Qualidade de Vida , Idoso , Humanos , Medidas de Resultados Relatados pelo Paciente , Diálise Peritoneal/efeitos adversos , Espiritualidade , Inquéritos e Questionários
11.
Acta Neurochir (Wien) ; 164(4): 1055-1067, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35258691

RESUMO

BACKGROUND: Transcranial anterior clinoidectomy is a conventional microsurgical approach for treatment of paraclinoid aneurysms. The endoscopic endonasal approach (EEA) is an alternative method for clipping intracranial aneurysms. No analysis has been conducted to anatomically compare approaches with respect to treating paraclinoid aneurysms. The surgical anatomical exposures of the paraclinoid region during transcranial extradural anterior clinoidectomy (EAC) and the endoscopic endonasal transplanum-cavernous approach (EETC) are described and quantitatively assessed. METHOD: Seven cadaveric heads underwent EAC and EETC. Measurements included the area of exposure, volume of surgical freedom, angle of attack, ophthalmic artery (OphA) origin, and coronal exposure angle of the internal carotid artery (ICA). RESULTS: The EETC provided a larger area of exposure than the EAC (100.1±24.9 vs 76.1±12.9 mm2, p = 0.04). The EAC provided a higher volume of surgical freedom and greater angle of attack than the EETC in all neurovascular parameters, including the OphA, superior hypophyseal artery (SHA), distal ICA, and distal dural ring (all p < 0.001). The OphA origin was intradural in 85.7% and extradural in 14.3% of specimens. With regard to the coronal angle of exposure, the EAC exposed the OphA and SHA in the upper lateral quadrant (67.9±7.8° and 80.6±4.5°, respectively) and the distal ICA in the upper medial and upper lateral quadrants (92±7.5°). The EEA exposed the OphA, SHA, and distal ICA in the upper medial and lower medial quadrants (130.4±10.7°, 68.4±10.8°, and 58±11.4°, respectively). CONCLUSIONS: The EAC and EETC each offer specific advantages for paraclinoid region exposure. The EAC is appropriate for paraclinoid aneurysms that occur at the dorsolateral surface of the paraclinoid ICA. The EETC is an alternative approach for aneurysms that occur along medial surface of the paraclinoid ICA (e.g., carotid cave and SHA aneurysms). The EETC provides greater surgical exposure to the medial aspect of the paraclinoid ICA.


Assuntos
Artéria Carótida Interna , Aneurisma Intracraniano , Artéria Carótida Interna/cirurgia , Humanos , Aneurisma Intracraniano/cirurgia , Artéria Oftálmica/cirurgia , Hipófise
12.
Int J Mol Sci ; 23(24)2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36555628

RESUMO

Uremic toxins and gut dysbiosis in advanced chronic kidney disease (CKD) can induce gut leakage, causing the translocation of gut microbial molecules into the systemic circulation. Lipopolysaccharide (LPS) and (1→3)-ß-D-glucan (BG) are the major gut microbial molecules of Gram-negative bacteria and fungi, respectively, and can induce inflammation in several organs. Here, the fibrosis in the kidney, liver, and heart was investigated in oral C. albicans-administered 5/6 nephrectomized (Candida-5/6 Nx) mice. At 20 weeks post 5/6 Nx, Candida-5/6 Nx mice demonstrated increased 24 h proteinuria, liver enzymes, and serum cytokines (TNF-α, IL-6, and IL-10), but not weight loss, systolic blood pressure, hematocrit, serum creatinine, or gut-derived uremic toxins (TMAO and indoxyl sulfate), compared to in 5/6 Nx alone. The gut leakage in Candida-5/6 Nx was more severe, as indicated by FITC-dextran assay, endotoxemia, and serum BG. The areas of fibrosis from histopathology, along with the upregulated gene expression of Toll-like receptor 4 (TLR-4) and Dectin-1, the receptors for LPS and BG, respectively, were higher in the kidney, liver, and heart. In vitro, LPS combined with BG increased the supernatant IL-6 and TNF-α, upregulated the genes of pro-inflammation and pro-fibrotic processes, Dectin-1, and TLR-4 in renal tubular (HK-2) cells and hepatocytes (HepG2), when compared with LPS or BG alone. This supported the pro-inflammation-induced fibrosis and the possible LPS-BG additive effects on kidney and liver fibrosis. In conclusion, uremia-induced leaky gut causes the translocation of gut LPS and BG into circulation, which activates the pro-inflammatory and pro-fibrotic pathways, causing internal organ fibrosis. Our results support the crosstalk among several organs in CKD through a leaky gut.


Assuntos
Insuficiência Renal Crônica , beta-Glucanas , Camundongos , Animais , Lipopolissacarídeos , Candida/metabolismo , Glucanos , Receptor 4 Toll-Like , Fator de Necrose Tumoral alfa , Toxinas Urêmicas , Interleucina-6 , Insuficiência Renal Crônica/metabolismo , Fibrose , beta-Glucanas/metabolismo , Inflamação , Modelos Animais de Doenças
13.
Int J Mol Sci ; 23(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35269654

RESUMO

A chronic kidney disease (CKD) causes uremic toxin accumulation and gut dysbiosis, which further induces gut leakage and worsening CKD. Lipopolysaccharide (LPS) of Gram-negative bacteria and (1➔3)-ß-D-glucan (BG) of fungi are the two most abundant gut microbial molecules. Due to limited data on the impact of intestinal fungi in CKD mouse models, the influences of gut fungi and Lacticaseibacillus rhamnosus L34 (L34) on CKD were investigated using oral C. albicans-administered 5/6 nephrectomy (5/6Nx) mice. At 16 weeks post-5/6Nx, Candida-5/6Nx mice demonstrated an increase in proteinuria, serum BG, serum cytokines (tumor necrotic factor-α; TNF-α and interleukin-6), alanine transaminase (ALT), and level of fecal dysbiosis (Proteobacteria on fecal microbiome) when compared to non-Candida-5/6Nx. However, serum creatinine, renal fibrosis, or gut barrier defect (FITC-dextran assay and endotoxemia) remained comparable between Candida- versus non-Candida-5/6Nx. The probiotics L34 attenuated several parameters in Candida-5/6Nx mice, including fecal dysbiosis (Proteobacteria and Bacteroides), gut leakage (fluorescein isothiocyanate (FITC)-dextran), gut-derived uremic toxin (trimethylamine-N-oxide; TMAO) and indoxyl sulfate; IS), cytokines, and ALT. In vitro, IS combined with LPS with or without BG enhanced the injury on Caco-2 enterocytes (transepithelial electrical resistance and FITC-dextran permeability) and bone marrow-derived macrophages (supernatant cytokines (TNF-α and interleukin-1 ß; IL-1ß) and inflammatory genes (TNF-α, IL-1ß, aryl hydrocarbon receptor, and nuclear factor-κB)), compared with non-IS activation. These injuries were attenuated by the probiotics condition media. In conclusion, Candida administration worsens kidney damage in 5/6Nx mice through systemic inflammation, partly from gut dysbiosis-induced uremic toxins, which were attenuated by the probiotics. The additive effects on cell injury from uremic toxin (IS) and microbial molecules (LPS and BG) on enterocytes and macrophages might be an important underlying mechanism.


Assuntos
Lacticaseibacillus rhamnosus , Insuficiência Renal Crônica , Uremia , Animais , Células CACO-2 , Candida , Citocinas , Disbiose/microbiologia , Glucanos , Humanos , Lacticaseibacillus rhamnosus/fisiologia , Lipopolissacarídeos/toxicidade , Camundongos , Fator de Necrose Tumoral alfa/efeitos adversos , Toxinas Urêmicas
14.
Transpl Infect Dis ; 23(1): e13388, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32585765

RESUMO

We report a case of COVID-19 in kidney transplant patient in Thailand. A 58-year-old 2 years post-kidney transplant recipient, with maintenance immunosuppression of tacrolimus, mycophenolate mofetil (MMF), and prednisolone, presented with acute diarrhea which followed by fever on day 12. Symptoms of pneumonia together with lymphopenia from complete blood count were developed on day 7 after onset of fever with the x-ray finding of bilateral multifocal patchy infiltration. COVID-19 infection has been confirmed by reverse real-time polymerase chain reaction (PCR) in nasal swab as well as found in stool. Darunavir together with ritonavir, hydroxychloroquine, azithromycin, and favipiravir was initiated on the first day of admission at primary hospital. Patient has been transferred to our hospital on day 2 of admission in which tacrolimus together with MMF was discontinued. High-flow nasal cannula oxygen therapy was required on days 4-5 of hospitalization. Tocilizumab was administered after rising of serum IL-6 level. Symptoms of pneumonia were improved in which no oxygen treatment required from day 10 of hospitalization. Drug interaction between tacrolimus and anti-viral treatment leads to severely high level of tacrolimus which caused reversible acute kidney injury (AKI) after supportive treatment.


Assuntos
Amidas/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Transplante de Rim , Pirazinas/uso terapêutico , Transplantados , Amidas/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Antivirais/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Pirazinas/administração & dosagem , SARS-CoV-2
15.
J Clin Lab Anal ; 35(4): e23729, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33590941

RESUMO

INTRODUCTION: Chronic kidney disease (CKD) is a significant global health issue. As the prevalence of renal replacement therapy (RRT) in Thailand is increasing, early detection and management of CKD is the most important step to prevent CKD progression and the need for RRT. Current diagnostic tests for CKD are non-specific and expensive. We aimed to develop and validate antibody-based-albumin point-of-care testing (POCT) to detect patients with impaired kidney function at early stage. METHODS: The prototype strip test was developed under the concept of competitive lateral flow immunochromatography assay, or strip test. Monoclonal antibodies (MAbs) to human serum albumin (HSA) were harvested from the hybridomas of spleen cells from immunized mice and mouse myeloma cells. Presence of MAbs was detected by enzyme-linked immunosorbent assay (ELISA). Spot urine was obtained from patients with kidney disease, type I, or type II Diabetes Mellitus upon their visit at King Chulalongkorn Memorial Hospital during 2018-2019. All samples were analyzed for urine albumin with our POCT (CU microalbumin) and the other two commercial POCTs (Microalbu PHAN and MICRAL). The results were validated against standard method for urine microalbumin measurement. A urine microalbumin concentration of less than 20 ug/ml was defined as normal. The sensitivity, specificity, and predictive values were calculated in comparison with the standard laboratory method. RESULT: A total of 100 adult patients were included. CU microalbumin had a sensitivity of 86%, a specificity of 94%, and a positive predictive value of 96%. Our POCT showed good correlation with the laboratory results. CONCLUSION: CU microalbumin correlated well with the standard method for quantitative measurement of urine albumin. Therefore, it has the potential for early screening of CKD, especially in primary health care facilities in resource limited settings.


Assuntos
Albuminúria/diagnóstico , Diagnóstico Precoce , Testes Imediatos , Insuficiência Renal Crônica/diagnóstico , Animais , Feminino , Humanos , Cinética , Camundongos Endogâmicos BALB C , Insuficiência Renal Crônica/urina , Albumina Sérica Humana/urina
16.
J Ren Nutr ; 31(6): 679-686, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-33642190

RESUMO

OBJECTIVES: Protein-energy wasting (PEW) is defined as the loss of body protein and energy reserves associated with kidney disease. However, the extent to which PEW contributes to increased mortality among peritoneal dialysis (PD) patients remains unclear. METHODS: This is a retrospective cohort study from 2012 to 2020. The PEW was diagnosed by applying at least 3 of the 4 following criteria: (1) altered serum biochemistry indicated by a serum albumin level of <3.5 g/L; (2) decreased body mass status identified by a body mass index (BMI) of <23 kg/m2 or <10% total body fat; (3) muscle wasting defined by the lean tissue index, calculated as a lean tissue mass normalized to the height-squared in the <10th percentile of the reference population; and (4) low dietary protein intake determined by the normalized protein equivalent of a total nitrogen appearance of <0.8 g/kg/day. The Malnutrition Inflammation Score (MIS) was also examined as an alternative tool for assessment of PEW. RESULTS: The average age of the 555 participants was 57.5 ± 12.6 years. The prevalence of PEW was 27.3%, with 196 deaths observed during the mean follow-up of 25.5 months. Patients with PEW who fulfilled at least 3 of the 4 listed criteria had a higher risk of death in the unadjusted model (hazard ratio 1.61, 95% confidence interval 1.19-2.18, P = .002). However, these associations were attenuated after adjusting for potential confounders. Regarding the individual PEW criterion, decreased serum albumin and low muscle mass were significantly associated with mortality in the multivariable models. In contrast, decreased body mass and low protein intake were not associated with a higher risk of death. High MIS (≥5 points) and each one-point increase in the MIS were also significantly associated with higher risk of death in both unadjusted and adjusted models. CONCLUSIONS: Among PD patients, the presence of PEW was not a better predictor of all-cause mortality than either the altered serum biochemistry (albumin) or low muscle mass criteria. The MIS performed well as an independent predictor of death and might be an option for assessment of PEW status in the PD population.


Assuntos
Diálise Peritoneal , Desnutrição Proteico-Calórica , Adulto , Idoso , Proteínas Alimentares , Humanos , Pessoa de Meia-Idade , Estado Nutricional , Desnutrição Proteico-Calórica/epidemiologia , Diálise Renal , Estudos Retrospectivos
17.
Sleep Breath ; 23(2): 687-693, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30484015

RESUMO

PURPOSE: Preeclampsia-eclampsia remains one of the leading causes of maternal and perinatal morbidity and mortality. Emerging evidence suggests that obstructive sleep apnea (OSA), which has been linked to hypertension in the general population, may play role in hypertensive disorders in pregnancy, including preeclampsia-eclampsia. However, little research has been conducted in Asia (no data in Thailand) on the effects of OSA on preeclampsia-eclampsia. We aimed to examine the association between OSA and preeclampsia-eclampsia among Thai pregnant women. METHODS: We conducted a large prospective cohort study among Thai pregnant women who were in the second trimester of singleton pregnancy. The Berlin Questionnaire was administered to evaluate the risk for OSA. Preeclampsia-eclampsia was diagnosed by standard clinical assessment. Multivariate models were applied in adjustment for confounding factors. RESULTS: Enrolled were 1345 pregnant women. The overall prevalence of high risk for OSA was 10.1% (95% confidence intervals [CIs] 8.5-11.7), and it was significantly associated with pre-pregnancy body mass index and score on the Perceived Stress Scale. An adjusted odds ratio (OR) for preeclampsia-eclampsia in women with high risk for OSA was 2.72 (95% CI 1.33-5.57). CONCLUSIONS: Pregnant women with high risk for OSA are at increased risks for preeclampsia-eclampsia compared to those with low risk for OSA. Our results support a role for screening for OSA by BQ during antenatal care.


Assuntos
Pré-Eclâmpsia/etiologia , Apneia Obstrutiva do Sono/complicações , Adulto , Estudos de Coortes , Feminino , Humanos , Pré-Eclâmpsia/epidemiologia , Gravidez , Gravidez de Alto Risco , Estudos Prospectivos , Fatores de Risco , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia , Tailândia , Adulto Jovem
18.
Crit Care ; 22(1): 279, 2018 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-30367647

RESUMO

BACKGROUND: Recent randomized trials have not found that polymyxin B hemoperfusion (PMX-HP) improves outcomes for patients with sepsis. However, it remains unclear whether the therapy could provide benefit for highly selected patients. Monocyte human leukocyte antigen (mHLA-DR) expression, a critical step in the immune response, is decreased during sepsis and leads to worsening sepsis outcomes. One recent study found that PMX-HP increased mHLA-DR expression while another found that the treatment removed HLA-DR-positive cells. METHODS: We conducted a randomized controlled trial in patients with blood endotoxin activity assay (EAA) level ≥ 0.6. Patients in the PMX-HP group received a 2-h PMX-HP treatment plus standard treatment for 2 consecutive days. Patients in the non-PMX-HP group received only standard treatment. The primary outcome compared the groups on median change in mHLA-DR expression between day 3 and baseline. Secondary outcomes compared the groups on the mean or median change in CD11b expression, neutrophil chemotaxis, presepsin, cardiovascular Sequential Organ Failure Assessment (CVS SOFA) score, vasopressor dose, and EAA level between day 3 and baseline. We further compared the groups on mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and major adverse kidney events (MAKE 28), measured on day 28. RESULTS: Fifty-nine patients were randomized to PMX-HP (n = 29) and non-PMX-HP (n = 30) groups. At baseline, mHLA-DR expression, CD11b, neutrophil chemotaxis, and clinical parameters were comparable between groups. The median change in mHLA-DR expression between day 3 and baseline was higher in PMX-HP patients than in patients receiving standard therapy alone (P = 0.027). The mean change in CD11b between day 3 and baseline was significantly lower in the PMX-HP group than in the non-PMX-HP group (P = 0.002). There were no significant changes from baseline in neutrophil chemotaxis, presepsin, CVS SOFA scores, vasopressor doses, or EAA level between groups. On day 28 after enrollment, mortality, ICU-free days, ventilator-free days, dialysis dependence status, renal recovery, serum creatinine, vasopressor-free days, and MAKE 28 were comparable between groups. CONCLUSION: PMX-HP improved mHLA-DR expression in severe sepsis patients. Future studies should examine the potential benefit of PMX-HP in patients with low mHLA-DR expression. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02413541 . Registered on 3 March 2015.


Assuntos
Antígenos HLA-DR/efeitos dos fármacos , Polimixina B/farmacologia , Sepse/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Feminino , Antígenos HLA-DR/análise , Antígenos HLA-DR/sangue , Hemoperfusão/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Polimixina B/uso terapêutico , Estatísticas não Paramétricas , Tailândia
19.
Drugs Aging ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38926293

RESUMO

In an era marked by a global demographic shift towards an aging society, there is a heightened prevalence of chronic kidney disease (CKD) among older adults. The burden of CKD spans from kidney-related complications to impacting psychological well-being, giving rise to depressive symptoms and caregiver burnout. This article delves into CKD prevention strategies within the context of aging, contributing to the discourse by exploring its multifaceted aspects. The prevention of CKD in the older adults necessitates a comprehensive approach. Primary prevention is centered on the modification of risk factors, acknowledging the intricate interplay of various comorbidities. Secondary prevention focuses on early CKD identification. Tertiary prevention aims to address factors contributing to CKD progression and complications, emphasizing the importance of timely interventions. This comprehensive strategy aims to enhance the quality of life for individuals affected by CKD, decelerating the deterioration of functional status. By addressing CKD at multiple levels, this approach seeks to effectively and compassionately care for the aging population.

20.
BMJ Open ; 14(5): e078393, 2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38760033

RESUMO

INTRODUCTION: Metformin is a first-line antihyperglycaemic agent for type 2 diabetes (T2DM). In addition to glycaemic control, it offers benefits related to cardiovascular health, weight neutrality and metabolic syndrome. However, its benefits in kidney transplant recipients remain unclear as metformin use is controversial in this population due to a lack of evidence and there are recommendations against its use in patients with poor kidney function. Hence, we seek to describe a protocol for a systematic review, which will assess the impact of metformin use on graft survival and mortality in kidney transplant recipients. METHODS: This protocol was guided by the standards of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Protocols 2015. We will search empirical databases such as MEDLINE, Embase, Cochrane Library, CINAHL and Web of Science Core Collection for relevant studies conducted in kidney transplant recipients using metformin, which report outcomes related to graft and patient survival. All studies meeting these criteria in adults and published in English from inception to 2023 will be included in our review. We will employ the Cochrane Risk of Bias Tool 2 for randomised controlled trials and the Risk of Bias in Non-randomised Studies of Intervention for non-randomised studies. We will present our data and study characteristics in a table format and determine if a meta-analysis can be performed by clinical and methodological heterogeneity, using the I2 statistics. If a meta-analysis cannot be performed, we will provide a narrative synthesis of included studies using the Synthesis Without Meta-Analysis Reporting Guideline. ETHICS AND DISSEMINATION: Ethical approval will not be required for this review as the data used will be extracted from already published studies with publicly accessible data. As this study will assess the impact of metformin use on graft and patient survival in kidney transplant recipients, evidence gathered through it will be disseminated using traditional approaches that include open-access peer-reviewed publication, scientific presentations and a report. We will also disseminate our findings to appropriate academic bodies in charge of publishing guidelines related to T2DM and transplantation, as well as patient and research centred groups. PROSPERO REGISTRATION NUMBER: CRD42023421799.


Assuntos
Diabetes Mellitus Tipo 2 , Sobrevivência de Enxerto , Hipoglicemiantes , Transplante de Rim , Metformina , Revisões Sistemáticas como Assunto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/mortalidade , Metformina/uso terapêutico , Sobrevivência de Enxerto/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Projetos de Pesquisa , Transplantados
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