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OBJECTIVE: Sodium-glucose-cotransporter 2 (SGLT-2) inhibitors are widely used for diabetes management especially because their effects go beyond glucose control. More recently, their indications and usage have expanded to heart failure (HF) and renal dysfunction therapy in patients both with and without diabetes. Beneficial effects, especially for HF readmission, accrue very early in their treatment trajectory, and this has promoted their use in the hospital setting. Data on their safety and efficacy for inpatient use are accumulating but have lagged behind the outpatient data for their use. The objective of this counterpoint piece is to highlight areas of benefit for starting or continuing SGLT-2 inhibitors in the inpatient setting. METHODS: Discussion after literature review of available studies with a focus on HF outcomes and SGLT-2 inhibitor use. RESULTS: The benefits of starting or continuing an SGLT-2 inhibitor in the inpatient setting are well documented, mainly in HF. Similar data are not available for glucose or renal outcomes alone. Starting in the hospital allows the ability to titrate medications with similar effects, such as diabetes and HF agents, as well as reducing treatment inertia to obtain and start new medications after patients are discharged home. It is important to choose patients appropriately and hold these drugs when patients are without nutrition or on low-carbohydrate diets which can lead to diabetic ketoacidosis. CONCLUSION: In the right setting, using an SGLT-2 inhibitor in the hospital can affect multiple aspects of a patient's treatment trajectory and should be a consideration.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Hipoglucemiantes/uso terapéutico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Pacientes Internos , Glucosa/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
Chronic kidney disease (CKD) is common in patients with heart failure and often results in left ventricular diastolic dysfunction (LVDD). However, the mechanisms responsible for cardiac damage in CKD-LVDD remain to be elucidated. Epigenetic alterations may impose long-lasting effects on cellular transcription and function, but their exact role in CKD-LVDD is unknown. We investigate whether changes in cardiac site-specific DNA methylation profiles might be implicated in cardiac abnormalities in CKD-LVDD. CKD-LVDD and normal control pigs (n = 6 each) were studied for 14 wk. Renal and cardiac hemodynamics were quantified by multidetector CT and echocardiography. In randomly selected pigs (n = 3/group), cardiac site-specific 5-methylcytosine (5mC) immunoprecipitation (MeDIP)- and mRNA-sequencing (seq) were performed, followed by integrated (MeDiP-seq/mRNA-seq analysis), and confirmatory ex vivo studies. MeDIP-seq analysis revealed 261 genes with higher (fold change > 1.4; P < 0.05) and 162 genes with lower (fold change < 0.7; P < 0.05) 5mC levels in CKD-LVDD versus normal pigs, which were primarily implicated in vascular endothelial growth factor (VEGF)-related signaling and angiogenesis. Integrated MeDiP-seq/mRNA-seq analysis identified a select group of VEGF-related genes in which 5mC levels were higher, but mRNA expression was lower in CKD-LVDD versus normal pigs. Cardiac VEGF signaling gene and VEGF protein expression were blunted in CKD-LVDD compared with controls and were associated with decreased subendocardial microvascular density. Cardiac epigenetic changes in VEGF-related genes are associated with impaired angiogenesis and cardiac microvascular rarefaction in swine CKD-LVDD. These observations may assist in developing novel therapies to ameliorate cardiac damage in CKD-LVDD.NEW & NOTEWORTHY Chronic kidney disease (CKD) often leads to left ventricular diastolic dysfunction (LVDD) and heart failure. Using a novel translational swine model of CKD-LVDD, we characterize the cardiac epigenetic landscape, identifying site-specific 5-methylcytosine changes in vascular endothelial growth factor (VEGF)-related genes associated with impaired angiogenesis and cardiac microvascular rarefaction. These observations shed light on the mechanisms of cardiac microvascular damage in CKD-LVDD and may assist in developing novel therapies for these patients.
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Insuficiencia Cardíaca , Rarefacción Microvascular , Insuficiencia Renal Crónica , Disfunción Ventricular Izquierda , Porcinos , Animales , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Rarefacción Microvascular/complicaciones , Rarefacción Microvascular/genética , 5-Metilcitosina , Insuficiencia Renal Crónica/genética , Epigénesis Genética , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/complicaciones , ARN MensajeroRESUMEN
BACKGROUND AND AIMS: Transvenous lead extraction (TLE) has become a pivotal part of a comprehensive lead management strategy, dealing with a continuously increasing demand. Nonetheless, the literature about the long-term impact of TLE on survivals is still lacking. Given these knowledge gaps, the aim of our study was to analyse very long-term mortality in patients undergoing TLE in public health perspective. METHODS: This prospective, single-centre, observational study enrolled consecutive patients with cardiac implantable electronic device (CIED) who underwent TLE, from January 2005 to January 2021. The main goal was to establish the independent predictors of very long-term mortality after TLE. We also aimed at assessing procedural and hospitalization-related costs. RESULTS: We enrolled 435 patients (mean age 70 ± 12 years, with mean lead dwelling time 6.8 ± 16.7 years), with prevalent infective indication to TLE (92%). Initial success of TLE was achieved in 98% of population. After a median follow-up of 4.5 years (range: 1 month-15.5 years), 150 of the 435 enrolled patients (34%) died. At multivariate analysis, death was predicted by: age (≥77 years, OR: 2.55, CI: 1.8-3.6, p < 0.001), chronic kidney disease (CKD) defined as severe reduction of estimated glomerular filtration rate (eGFR <30 mL/min/1.73 m2 , OR: 1.75, CI: 1.24-2.4, p = 0.001) and systolic dysfunction assessed before TLE defined as left ventricular ejection fraction (LVEF) <40%, OR: 1.78, CI 1.26-2.5, p = 0.001. Mean extraction cost was 5011 per patient without reimplantation and 6336 per patient with reimplantation respectively. CONCLUSIONS: Our study identified three predictors of long-term mortality in a high-risk cohort of patients with a cardiac device infection, undergoing successful TLE. The future development of a mortality risk score before might impact on public health strategy.
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Desfibriladores Implantables , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Desfibriladores Implantables/efectos adversos , Estudios Prospectivos , Volumen Sistólico , Función Ventricular Izquierda , Factores de Riesgo , Resultado del Tratamiento , Estudios RetrospectivosRESUMEN
BACKGROUND: Patients with chronic kidney diseases (CKD) are susceptible to the toxic drug effects if given unadjusted doses. Although Pakistan harbors a high burden of CKD patients, there is limited information available on the frequency, pattern and factors associated with unadjusted drug doses among CKD patients. METHODS: This cross-sectional study conducted at Sandeman Provincial Hospital, Quetta included 303 non-dialysis ambulatory CKD patients (glomerular filtration rate < 60 ml/min/1.73m2). The patients' data were collected through a purpose designed data collection form. The appropriateness of doses was checked against the renal drug handbook-2018, Kidney Disease Improving Global Outcomes guidelines, British National Formulary-2022, and manufacturer leaflets. Data were analysed by SPSS 23 and multiple binary logistic regression analysis was used to assess the factors associated with receiving inappropriate high doses. A p-value < 0.05 was considered statistically significant. RESULTS: The patients received a total of 2265 prescription lines, with a median of eight different drugs per patient (interquartile range: 6-9 drugs). A total of 34.5% (783/2265) drugs required dose adjustment. Of these, doses were not adjusted for 56.1% (440) drugs in 162 (53.4%) patients. The most common pharmacological class of drugs requiring dose adjustment were antibiotics (79.1%), followed by antidiabetics (59.2%), diuretics (57.0%), angiotensin converting enzyme inhibitors (56.9%), beta blockers (56.9%), analgesics (56.0%), angiotensin receptor blockers (55.2%), domperidone (53.9%) and antihyperlipidmics (46.1%). Patient's age of 41-60 (OR = 5.76) and > 60 years (OR = 9.49), hypertension (OR = 2.68), diabetes mellitus (OR = 3.47) and cardiovascular diseases (OR = 2.82) had statistically significant association (p-value < 0.05) with inappropriate high doses. CONCLUSION: The high frequency of inappropriate high doses suggests an important quality gap in medication dosing for patients with ND-CKD at the study site. Special attention should be paid to the drugs and patients with identified risk factors for receiving inappropriate high doses.
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Riñón , Insuficiencia Renal Crónica , Humanos , Insuficiencia Renal Crónica/tratamiento farmacológico , Insuficiencia Renal Crónica/epidemiología , Tasa de Filtración Glomerular , Pakistán/epidemiología , Estudios Transversales , Persona de Mediana Edad , Antibacterianos/efectos adversos , Hipoglucemiantes/efectos adversos , Antihipertensivos/efectos adversos , Riñón/efectos de los fármacos , Adulto , Anciano , Prescripción Inadecuada , Comorbilidad , Diabetes Mellitus/tratamiento farmacológico , Diabetes Mellitus/epidemiología , Hipertensión/tratamiento farmacológico , Hipertensión/epidemiología , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiologíaRESUMEN
BACKGROUND: An elevated coronary artery calcification score (CACS) is associated with increased cardiovascular disease risk in patients with CKD. However, the relationship between CACS and CKD progression has not been elucidated. METHODS: We studied 1936 participants with CKD (stages G1-G5 without kidney replacement therapy) enrolled in the KoreaN Cohort Study for Outcome in Patients With CKD. The main predictor was Agatston CACS categories at baseline (0 AU, 1-100 AU, and >100 AU). The primary outcome was CKD progression, defined as a ≥50% decline in eGFR or the onset of kidney failure with replacement therapy. RESULTS: During 8130 person-years of follow-up, the primary outcome occurred in 584 (30.2%) patients. In the adjusted cause-specific hazard model, CACS of 1-100 AU (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.04 to 1.61) and CACS >100 AU (HR, 1.42; 95% CI, 1.10 to 1.82) were associated with a significantly higher risk of the primary outcome. The HR associated with per 1-SD log of CACS was 1.13 (95% CI, 1.03 to 1.24). When nonfatal cardiovascular events were treated as a time-varying covariate, CACS of 1-100 AU (HR, 1.31; 95% CI, 1.07 to 1.60) and CACS >100 AU (HR, 1.46; 95% CI, 1.16 to 1.85) were also associated with a higher risk of CKD progression. The association was stronger in older patients, in those with type 2 diabetes, and in those not using antiplatelet drugs. Furthermore, patients with higher CACS had a significantly larger eGFR decline rate. CONCLUSION: Our findings suggest that a high CACS is associated with significantly increased risk of adverse kidney outcomes and CKD progression.
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Enfermedad de la Arteria Coronaria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Insuficiencia Renal Crónica/etiología , Calcificación Vascular/complicaciones , Anciano , Estudios de Cohortes , Progresión de la Enfermedad , Humanos , Modelos de Riesgos Proporcionales , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/terapia , Factores de Riesgo , Calcificación Vascular/etiologíaRESUMEN
BACKGROUND: Repeated administration of cisplatin causes CKD. In previous studies, we reported that the kidney-secreted survival protein renalase (RNLS) and an agonist peptide protected mice from cisplatin-induced AKI. METHODS: To investigate whether kidney-targeted delivery of RNLS might prevent cisplatin-induced CKD in a mouse model, we achieved specific delivery of a RNLS agonist peptide (RP81) to the renal proximal tubule by encapsulating the peptide in mesoscale nanoparticles (MNPs). We used genetic deletion of RNLS, single-cell RNA sequencing analysis, and Western blotting to determine efficacy and to explore underlying mechanisms. We also measured plasma RNLS in patients with advanced head and neck squamous cell carcinoma receiving their first dose of cisplatin chemotherapy. RESULTS: In mice with CKD induced by cisplatin, we observed an approximate 60% reduction of kidney RNLS; genetic deletion of RNLS was associated with significantly more severe cisplatin-induced CKD. In this severe model of cisplatin-induced CKD, systemic administration of MNP-encapsulated RP81 (RP81-MNP) significantly reduced CKD as assessed by plasma creatinine and histology. It also decreased inflammatory cytokines in plasma and inhibited regulated necrosis in kidney. Single-cell RNA sequencing analyses revealed that RP81-MNP preserved epithelial components of the nephron and the vasculature and suppressed inflammatory macrophages and myofibroblasts. In patients receiving their first dose of cisplatin chemotherapy, plasma RNLS levels trended lower at day 14 post-treatment. CONCLUSIONS: Kidney-targeted delivery of RNLS agonist RP81-MNP protects against cisplatin-induced CKD by decreasing cell death and improving the viability of the renal proximal tubule. These findings suggest that such an approach might mitigate the development of CKD in patients receiving cisplatin cancer chemotherapy.
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Cisplatino/efectos adversos , Monoaminooxidasa/metabolismo , Insuficiencia Renal Crónica/inducido químicamente , Insuficiencia Renal Crónica/prevención & control , Secuencia de Aminoácidos , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Línea Celular , Cisplatino/administración & dosificación , Creatinina/sangre , Modelos Animales de Enfermedad , Expresión Génica/efectos de los fármacos , Tasa de Filtración Glomerular , Receptor Celular 1 del Virus de la Hepatitis A/sangre , Humanos , Riñón/efectos de los fármacos , Riñón/metabolismo , Riñón/patología , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Monoaminooxidasa/deficiencia , Monoaminooxidasa/genética , Nanocápsulas/administración & dosificación , Péptidos/administración & dosificación , Péptidos/genética , Insuficiencia Renal Crónica/patologíaRESUMEN
BACKGROUND: Semiquantitative visual inspection for glomerulosclerosis, interstitial fibrosis, and arteriosclerosis is often used to assess chronic changes in native kidney biopsies. Morphometric evaluation of these and other chronic changes may improve the prognostic assessment. METHODS: We studied a historical cohort of patients who underwent a native kidney biopsy between 1993 and 2015 and were followed through 2021 for ESKD and for progressive CKD (defined as experiencing 50% eGFR decline, temporary dialysis, or ESKD). Pathologist scores for the percentages of globally sclerosed glomeruli (GSG), interstitial fibrosis and tubular atrophy (IFTA), and arteriosclerosis (luminal stenosis) were available. We scanned biopsy sections into high-resolution images to trace microstructures. Morphometry measures were percentage of GSG; percentage of glomerulosclerosis (percentage of GSG, ischemic-appearing glomeruli, or segmentally sclerosed glomeruli); percentage of IFTA; IFTA foci density; percentage of artery luminal stenosis; arteriolar hyalinosis counts; and measures of nephron size. Models assessed risk of ESKD or progressive CKD with biopsy measures adjusted for age, hypertension, diabetes, body mass index, eGFR, and proteinuria. RESULTS: Of 353 patients (followed for a median 7.5 years), 75 developed ESKD and 139 experienced progressive CKD events. Visually estimated scores by pathologists versus morphometry measures for percentages of GSG, IFTA, and luminal stenosis did not substantively differ in predicting outcomes. However, adding percentage of glomerulosclerosis, IFTA foci density, and arteriolar hyalinosis improved outcome prediction. A 10-point score using percentage of glomerulosclerosis, percentage of IFTA, IFTA foci density, and any arteriolar hyalinosis outperformed a 10-point score based on percentages of GSG, IFTA, and luminal stenosis >50% in discriminating risk of ESKD or progressive CKD. CONCLUSION: Morphometric characterization of glomerulosclerosis, IFTA, and arteriolar hyalinosis on kidney biopsy improves prediction of long-term kidney outcomes.
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Riñón , Insuficiencia Renal Crónica , Humanos , Pronóstico , Constricción Patológica/patología , Riñón/patología , Biopsia/métodos , FibrosisRESUMEN
OBJECTIVES: Chronic kidney disease (CKD) is a common cause of restless leg syndrome (RLS). RLS is under-recognized, misdiagnosed and undertreated disorder in our locality. In this study, we aimed to determine the prevalence of RLS due to CKD and its predictors. METHODS: This cross-sectional study included 520 patients [male = 200; female = 320; age: 48.45 ± 3.63yrs; uremia duration: 6.44 ± 1.65yrs; CKD5D = 400; CKD3D = 120). RLS diagnosis was done by clinical interviewing according to International RLS Study Group criteria. All underwent detailed biochemical testing and iron and ferritin levels' measurements. Insomnia, depression and anxiety severities were assessed using insomnia sleep index (ISI), Beck Depression Inventory (BDI-II) and State-Trait Anxiety Inventory for Adults (STAI-AD) scales. RESULTS: RLS was found in 22.31% [ESKD = 26%, CKD3D = 10%]. Insomnia, depression and anxiety were found in 76.15%, 91.15% and 44.23%, respectively. Insomnia was correlated with depression (r = 0.488, p = 0.001) and anxiety (r = 0.360, p = 0.006) but not RLS. Multiple linear regression analysis showed that ESKD (OR = 3.8, 95%CI = 2.5-8.5, p = 0.001), inadequate dialysis (OR = 4.6, 95%CI = 3.5-8.6, p = 0.001), hyperparathyroidism (OR = 5.1, 95%CI 3.2-13.7, p = 0.0001) and peripheral neuropathy (OR = 5.6, 95%CI = 3.8-12.8, p = 0.0001) were independently associated with RLS. CONCLUSION: The prevalence of RLS with CKD is 22.31%. It is 2.6 times more frequent and severe with ESKD compared to CKD3D. It seems that RLS may occur early with CKD and becomes worse with progressive kidney impairment. Also, insomnia, depression and anxiety are common with CKD, however, their severities were not correlated with RLS. Predictors for RLS were ESKD, inadequacy of dialysis, hyperparathyroidism and peripheral neuropathy.
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Enfermedades del Sistema Nervioso Periférico , Insuficiencia Renal Crónica , Síndrome de las Piernas Inquietas , Trastornos del Inicio y del Mantenimiento del Sueño , Adulto , Humanos , Masculino , Femenino , Persona de Mediana Edad , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/complicaciones , Síndrome de las Piernas Inquietas/etiología , Síndrome de las Piernas Inquietas/complicaciones , Estudios Transversales , Egipto/epidemiología , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/epidemiología , Prevalencia , Enfermedades del Sistema Nervioso Periférico/complicacionesRESUMEN
BACKGROUND: Total knee arthroplasty (TKA) in end-stage renal disease is associated with complications. Controversy exists whether elective TKA should be performed while patients are on hemodialysis (HD) or following renal transplant (RT). This study compares TKA outcomes in HD versus RT patients. METHODS: A national database was retrospectively reviewed using International Classification of Diseases codes to identify HD and RT patients who underwent primary TKA from 2010 to 2018. Demographics, comorbidities, and hospital factors were compared using Wald and Chi-squared tests. The primary outcome was in-hospital mortalities while secondary outcomes included quality outcomes and medical/surgical complications. Multivariate regressions were used to determine independent associations. Significance was determined with a 2-tailed P value of .05. There were 13,611 patients who underwent TKA (61.1 HD and 38.9% RT). Patients who had RT were younger, had fewer comorbidities, and more likely to have private insurance. RESULTS: The RT patients had a lower rate of mortality (odds ratio (OR) 0.23, P < .01)), complications (OR 0.63, P < .01), cardiopulmonary complications (OR 0.44, P = .02), sepsis (OR 0.22, P < .001), and blood transfusion (OR 0.35, P < .001) during the index hospitalization. This cohort was also found to have decreased length of stay (-2.0 days, P < .001), non-home discharge (OR 0.57, P < .001), and hospital cost (-$5,300, P < .001). Patients who had RT had a lower rate of readmission (OR 0.54, P < .001), periprosthetic joint infection (OR 0.50, P < .01), and surgical site infection (OR 0.37, P < .001) within 90 days. CONCLUSION: These findings suggest that HD patients are a high-risk population in TKA compared to RT patients and warrant stringent perioperative monitoring.
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Artroplastia de Reemplazo de Cadera , Artroplastia de Reemplazo de Rodilla , Trasplante de Riñón , Humanos , Artroplastia de Reemplazo de Rodilla/efectos adversos , Estudios Retrospectivos , Trasplante de Riñón/efectos adversos , Factores de Riesgo , Diálisis Renal/efectos adversos , Tiempo de Internación , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Readmisión del Paciente , Artroplastia de Reemplazo de Cadera/efectos adversosRESUMEN
Fifty years ago, in July 1973, providing care to patients with end stage kidney disease changed dramatically with the implementation of legislation (PL 92-603) that deemed chronic renal disease to be a disability and provided coverage under Medicare for the treatment of the disease. In this article, we discuss the impact of the implementation of PL 92-603.
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Fallo Renal Crónico , Insuficiencia Renal Crónica , Anciano , Humanos , Estados Unidos , Aniversarios y Eventos Especiales , Medicare , Fallo Renal Crónico/terapiaRESUMEN
Autosomal dominant polycystic kidney disease (ADPKD) is the most common congenital kidney disorder, generally caused by mutations in the PKD1 and PKD2 genes, coding for polycystins 1 and 2. Its pathogenesis is accompanied by alterations of the cAMP, mTOR, MAPK/ERK, and JAK/STAT pathways. ADPKD is clinically characterized by the formation of many growing cysts with kidney enlargement and a progressive damage to the parenchyma, up to its complete loss of function, and the onset of end-stage renal disease (ESRD). The current aim of ADPKD therapy is the inhibition of cyst development and retardation of chronic kidney disease progression. Several drugs have been recently included as potential therapies for ADPKD including metformin, the drug of choice for the treatment of type 2 diabetes mellitus, according to its potential inhibitory effects on cystogenesis. In this review, we summarize preclinical and clinical evidence endorsing or rejecting metformin administration in ADPKD evolution and pathological mechanisms. We explored the biology of APDKD and the role of metformin in slowing down cystogenesis searching PubMed and Clinical Trials to identify relevant data from the database inception to December 2020. From our research analysis, evidence for metformin as emerging cure for ADPKD mainly arise from preclinical studies. In fact, clinical studies are still scanty and stronger evidence is awaited. Its effects are likely mediated by inhibition of the ERK pathway and increase of AMPK levels, which are both linked to ADPKD pathogenesis.
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Diabetes Mellitus Tipo 2 , Metformina , Riñón Poliquístico Autosómico Dominante , Insuficiencia Renal Crónica , Humanos , Riñón/metabolismo , Metformina/farmacología , Metformina/uso terapéutico , Mutación , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Riñón Poliquístico Autosómico Dominante/genética , Riñón Poliquístico Autosómico Dominante/metabolismoRESUMEN
BACKGROUND: Advanced kidney disease is an emerging problem in people living with HIV despite sustained viral suppression. METHODS: We performed a prospective cohort study to identify people living with HIV with advanced kidney disease according to the Kidney Disease Improving Global Outcomes criteria and to assess disease progression over a 48-week period following the offer of targeted multidisciplinary management. RESULTS: From our cohort of 3090 individuals, 55 (1.8%, 95% confidence interval [CI] 1.31-2.25) fulfilled the inclusion criteria. Most were male (83.6%), and the median (interquartile range [IQR]) age was 58 (53.25-66.75) years. Nadir CD4 T-cell count was 135.5 (IQR 43.5-262.75) cells/µl, current CD4 T-cell count was 574 (IQR 438.5-816) cells/µl, and 96% had maintained HIV viral suppression. The most frequent comorbidity was arterial hypertension (85.5%). Inadequate antiretroviral dose was detected in three individuals (5.5%), and drug-drug interactions were recorded in eight (14.5%), mainly involving the use of cobicistat (n = 5 [9%]). Four individuals (7%) required modification of their concomitant treatment. Seven (13%) had to start or resume follow-up with a nephrologist. Nine participants (16.4%) experienced an improvement in kidney disease stage, three individuals (5.5%) underwent renal transplantation, and one (2%) started haemodialysis. CONCLUSIONS: Our results show that a multidisciplinary approach, including a critical review of treatment and evaluation of specific requirements, could be useful for anticipating drug-drug interactions and toxicities and for reducing death and hospitalization in people living with HIV with advanced kidney disease.
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Infecciones por VIH , Insuficiencia Renal Crónica , Anciano , Recuento de Linfocito CD4 , Cobicistat/uso terapéutico , Estudios de Cohortes , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Insuficiencia Renal Crónica/epidemiología , Insuficiencia Renal Crónica/terapia , Carga ViralRESUMEN
BACKGROUND: Changes in renal microvascular perfusion are involved in several kidney diseases. Contrast-enhanced ultrasonography (CEUS) quantitative analysis can enable the estimation of renal microvascular perfusion non-invasively. However, to date, few pediatric patients with renal disease have been subjected to CEUS quantitative analysis. This study aimed to explore the feasibility of CEUS in evaluating renal microvascular perfusion in pediatric patients and paving its way to clinical practice. METHODS: Seventeen pediatric patients with chronic kidney disease (CKD) and five children without kidney disease were consecutively examined using CEUS. Quantitative analysis of CEUS images based on time-intensity curve (TIC) fittings was performed using specialized software. Quantitative parameters of wash-in microvascular blood flow, including A, k, B, and TtoPk, were generated from three regions of interest (ROIs) each in the cortex and medulla of each kidney. RESULTS: CEUS was performed in all children successfully and safely without the use of sedatives. All parameters (A, B, k, and TtoPk) demonstrated no statistical differences among the three sampling ROIs in the renal cortex and medulla. All parameters (A, B, k, and TtoPk) showed no statistical differences between the left and right sides of kidneys both in cortices and medullas. Comparing with patients with CKD stage 3-5, both control group and patients with CKD stage 1-2 had significantly higher values of parameter A in the renal cortex (p = 0.025 and p = 0.031, respectively). In control group and patients stage 1-2, the values of parameters k in the renal cortices were significantly higher than that in the renal medullas, while in patients with CKD stage 3-5, parameter k showed no statistically significant differences between the renal cortex and medulla (p = 0.173). CONCLUSION: CEUS is safe and practicable in pediatric patients with chronic kidney disease. Renal microvascular perfusion estimated by CEUS could be a robust approach in the evaluation of pediatric renal diseases. Parameters A and k derived from CEUS quantitative analysis can provide great potential in non-invasive assessment of renal microvascular perfusion impairment in pediatric CKD.
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Medios de Contraste , Insuficiencia Renal Crónica , Humanos , Niño , Estudios de Factibilidad , Ultrasonografía/métodos , Riñón/diagnóstico por imagen , Riñón/irrigación sanguínea , Insuficiencia Renal Crónica/diagnóstico por imagen , Perfusión/métodosRESUMEN
BACKGROUND: There is a general assumption that periodontal disease is highly prevalent among patients with chronic renal failure undergoing hemodialysis. The aim of the study to estimate the frequency of periodontitis in patients on hemodialysis among a sample of the Egyptian population, as well as the correlation between different clinical parameters of periodontal status with serum creatinine and blood urea. This may rule out the bidirectional relationship between periodontitis and renal failure in patients on hemodialysis. METHODS: The study was conducted on 263 hemodialysis patients (165 males and 98 females) at three dialysis centers in Benha Governorate, Egypt (Benha Hospital, Tukh hospital, Qalyub hospital). Periodontal parameters including plaque index (PI), gingival index (GI), clinical attachment level (CAL), and probing pocket depth (PPD) had been recorded in these patients. Serum urea and creatinine levels had been measured, the data had been collected and undergone statistical analysis. RESULTS: Frequency of periodontitis was 85.6% with stage III is the most prevalent stage. There was a significant positive strong correlation between age and periodontitis stage (rs = 0.707, p < 0.001). There was a positive correlation between clinical parameters and serum creatinine level. CONCLUSION: In the present study, a high frequency of periodontitis had been found among ESRD patients on hemodialysis in the severe form (stage III) periodontitis. There was a significant direct correlation between the severity of periodontitis and CAL with a duration of hemodialysis. There was a weak insignificant association between periodontal indices (PD, BOP, and plaque score) and duration of hemodialysis.
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Fallo Renal Crónico , Periodontitis , Estudios Transversales , Índice de Placa Dental , Egipto/epidemiología , Femenino , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/terapia , Masculino , Pérdida de la Inserción Periodontal/epidemiología , Bolsa Periodontal/epidemiología , Periodontitis/epidemiología , Diálisis RenalRESUMEN
Patients with chronic kidney disease (CKD) have a high cardiovascular mortality. CKD and heart failure (HF) coexist in up to 50% of patients, and both associate with inflammation. We aimed to define the cardiac phenotype of a novel swine model of CKD and test the hypothesis that inflammation of renal origin propels the development of precursors of HF in CKD. CKD was induced in 14 pigs, which were followed for 14 wk. Renal (multidetector computed tomography) and cardiac (echocardiography) hemodynamics were quantified before and 8 wk after single intrarenal administration of placebo or a biopolymer-fused peptide inhibitor of NF-κB that blocks NF-κB activity and decreases inflammatory activity (SynB1-ELP-p50i). Blood was collected to quantify cytokines (TNF-α, monocyte chemoattractant protein-1, and interleukins), markers of inflammation (C-reactive protein), and biomarkers of HF (atrial and brain natriuretic peptides). Pigs were then euthanized, and kidneys and hearts were studied ex vivo. Normal pigs were used as time-matched controls. Renal dysfunction in CKD was accompanied by cardiac hypertrophy and fibrosis, diastolic dysfunction, increased renal and cardiac expression of TNF-α, monocyte chemoattractant protein-1, and interleukins, canonical and noncanonical mediators of NF-κB signaling, circulating inflammatory factors, and biomarkers of HF. Notably, most of these changes were improved after intrarenal SynB1-SynB1-ELP-p50i, although cardiac inflammatory signaling remained unaltered. The translational traits of this model support its use as a platform to test novel technologies to protect the kidney and heart in CKD. A targeted inhibition of renal NF-κB signaling improves renal and cardiac function, suggesting an inflammatory renal-cardio axis underlying early HF pathophysiology in CKD.NEW & NOTEWORTHY Chronic kidney disease (CKD) is a progressive disorder with high cardiovascular morbidity and mortality. This work supports the role of inflammatory cytokines of renal origin in renal-cardio pathophysiology in CKD and that the heart may be a target. Furthermore, it supports the feasibility of a new strategy in a translational fashion, using targeted inhibition of renal NF-κB signaling to offset the development of cardiac injury in CKD.
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Cardiopatías/etiología , Riñón/metabolismo , FN-kappa B/metabolismo , Insuficiencia Renal Crónica/metabolismo , Animales , Apoptosis , Biomarcadores/sangre , Citocinas/genética , Citocinas/metabolismo , Dieta Alta en Grasa , Femenino , Fibrosis/etiología , Fibrosis/patología , Cardiopatías/metabolismo , Riñón/patología , Masculino , PorcinosRESUMEN
AIMS: We aimed to assess the impact of the severity of chronic kidney disease (CKD) with long-term clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). METHODS: We analyzed data on consecutive patients undergoing PCI enrolled in the Victorian Cardiac Outcomes Registry (VCOR) from January 2014 to December 2018. Patients were stratified into tertiles of renal function; estimated glomerular filtration (eGFR) ≥60, 30-59 and < 30 ml/min/1.73 m2 (including dialysis). The primary outcome was long-term all-cause mortality obtained from linkage with the Australian National Death Index (NDI). The secondary endpoint was a composite of 30 day major adverse cardiac and cerebrovascular events. RESULTS: We identified a total of 51,480 patients (eGFR ≥60, n = 40,534; eGFR 30-59, n = 9,521; eGFR <30, n = 1,425). Compared with patients whose eGFR was ≥60, those with eGFR 30-59 and eGFR<30 were on average older (77 and 78 vs. 63 years) and had a greater burden of cardiovascular risk factors. Worsening CKD severity was independently associated with greater adjusted risk of long-term NDI mortality: eGFR<30 hazard ratio 4.21 (CI 3.7-4.8) and eGFR 30-59; 1.8 (CI 1.7-2.0), when compared to eGFR ≥60, all p < .001. CONCLUSION: In this large, multicentre PCI registry, severity of CKD was associated with increased risk of all-cause mortality underscoring the high-risk nature of this patient cohort.
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Intervención Coronaria Percutánea , Insuficiencia Renal Crónica , Australia , Tasa de Filtración Glomerular , Humanos , Intervención Coronaria Percutánea/efectos adversos , Insuficiencia Renal Crónica/diagnóstico , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The potential long-term safety and efficacy of aliskiren in nondiabetic chronic kidney disease (CKD) are unknown. We sought to investigate the renoprotective effect of aliskiren on nondiabetic CKD patients. METHODS: In this open-label, parallel, randomized controlled trial, nondiabetic CKD Stages 3-4 patients were randomized to receive aliskiren added to an angiotensin II receptor blocker (ARB) at the maximal tolerated dose, or ARB alone. Primary outcome was the rate of change in estimated glomerular filtration rate (eGFR). Secondary endpoints included rate of change in urine protein-to-creatinine ratio (UPCR), cardiovascular events and hyperkalemia. Composite renal outcomes of doubling of baseline serum creatinine or a 40% reduction in eGFR or incident end-stage renal disease or death were analyzed as post hoc analysis. RESULTS: Seventy-six patients were randomized: 37 to aliskiren (mean age 55.1 ± 11.1 years) and 39 to control (mean age 55.0 ± 9.4 years). Their baseline demographics were comparable to eGFR (31.9 ± 9.0 versus 27.7 ± 9.0 mL/min/1.73 m2, P = 0.05) and UPCR (30.7 ± 12.6 versus 47.8 ± 2.8 mg/mmol, P = 0.33) for treatment versus control subjects. After 144 weeks of follow-up, there was no difference in the rate of eGFR change between groups. Six patients in the aliskiren group and seven in the control group reached the renal composite endpoint (16.2% versus 17.9%, P = 0.84). The cardiovascular event rate was 10.8% versus 2.6% (P = 0.217). The hyperkalemia rate was 18.9% versus 5.1% with an adjusted hazard ratio of 7.71 (95% confidence interval 1.14 to 52.3, P = 0.04) for the aliskiren arm. CONCLUSION: Aliskiren neither conferred additional renoprotective benefit nor increased adverse events, except for more hyperkalemia in nondiabetic CKD patients.
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Insuficiencia Renal Crónica , Renina , Adulto , Anciano , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Tasa de Filtración Glomerular , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológicoRESUMEN
BACKGROUND: Aberrant microRNA (miRNA) expression affects biologic processes and downstream genes that are crucial to CKD initiation or progression. The miRNA miR-204-5p is highly expressed in the kidney but whether miR-204-5p plays any role in the development of chronic renal injury is unknown. METHODS: We used real-time PCR to determine levels of miR-204 in human kidney biopsies and animal models. We generated Mir204 knockout mice and used locked nucleic acid-modified anti-miR to knock down miR-204-5p in mice and rats. We used a number of physiologic, histologic, and molecular techniques to analyze the potential role of miR-204-5p in three models of renal injury. RESULTS: Kidneys of patients with hypertension, hypertensive nephrosclerosis, or diabetic nephropathy exhibited a significant decrease in miR-204-5p compared with controls. Dahl salt-sensitive rats displayed lower levels of renal miR-204-5p compared with partially protected congenic SS.13BN26 rats. Administering anti-miR-204-5p to SS.13BN26 rats exacerbated interlobular artery thickening and renal interstitial fibrosis. In a mouse model of hypertensive renal injury induced by uninephrectomy, angiotensin II, and a high-salt diet, Mir204 gene knockout significantly exacerbated albuminuria, renal interstitial fibrosis, and interlobular artery thickening, despite attenuation of hypertension. In diabetic db/db mice, administering anti-miR-204-5p exacerbated albuminuria and cortical fibrosis without influencing blood glucose levels. In all three models, inhibiting miR-204-5p or deleting Mir204 led to upregulation of protein tyrosine phosphatase SHP2, a target gene of miR-204-5p, and increased phosphorylation of signal transducer and activator of transcription 3, or STAT3, which is an injury-promoting effector of SHP2. CONCLUSIONS: These findings indicate that the highly expressed miR-204-5p plays a prominent role in safeguarding the kidneys against common causes of chronic renal injury.
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Nefropatías Diabéticas/metabolismo , Hipertensión/metabolismo , Riñón/metabolismo , Riñón/patología , MicroARNs/metabolismo , Nefroesclerosis/metabolismo , Adulto , Albuminuria/genética , Animales , Arterias/patología , Presión Sanguínea/efectos de los fármacos , Nefropatías Diabéticas/patología , Femenino , Fibrosis , Técnicas de Silenciamiento del Gen , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Masculino , Ratones , Ratones Noqueados , MicroARNs/antagonistas & inhibidores , MicroARNs/genética , Persona de Mediana Edad , Nefroesclerosis/etiología , Nefroesclerosis/patología , Fosforilación , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Factor de Transcripción STAT3/metabolismo , Transducción de Señal , Cloruro de Sodio Dietético/administración & dosificación , Regulación hacia ArribaRESUMEN
Besides renal disease, gastrointestinal (GI) disorders are frequently reported in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD). Related gastrointestinal symptoms tend to increase as the renal disease progresses. Also, in patients with ESRD, the modality of dialysis is related to particular forms of GI disorders.The kidney can interact with the digestive organs through functional endogenous systems such as the 'kidney-colon axis' and the 'kidney-liver axis'. Digestive diseases are one of the visible manifestations of the disturbance between hemostatic, hemodynamic and immunological balance in such patients.No clear management guidelines currently exist for many of the gastrointestinal problems that accompany renal failure. This review aims to describe the particular aspects of GI diseases present in CKD/ESRD. We focus our discussion in the specificities of epidemiology, diagnosis, and prognosis of such disorders between the different segments of the digestive system.
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Enfermedades Gastrointestinales/epidemiología , Fallo Renal Crónico/epidemiología , Insuficiencia Renal Crónica/epidemiología , Progresión de la Enfermedad , Enfermedades Gastrointestinales/diagnóstico , Enfermedades Gastrointestinales/etiología , Humanos , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/diagnóstico , Pronóstico , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/etiología , Factores de RiesgoRESUMEN
BACKGROUNDS: There is a discrepancy between west and east on the relationship between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). This study aimed to find out the possible reason for this and to clarify the association between NAFLD and CKD by analyzing two population-based datasets from the US and China. METHODS: Two health examination datasets from China and the US were used. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2 or and/or abnormal albuminuria and/or overt proteinuria. Binary logistic regression was used to examine the association between NAFLD and CKD. RESULTS: A total of 60,965 participants were analyzed, including 11,844 from the US and 51,229 from China. The prevalence of NAFLD was 27.12% in the Chinese population and 36.08% in the US population (p < 0.001). The proportions of CKD and late stage CKD (stages 3-5) were higher in the US population than the Chinese one. NAFLD was independently associated with an increased risk of CKD in Chinese population, whereas in the US population, the NAFLD was not an independent risk factor of CKD. In subgroup analyses which excluded late stages CKD (stages 3-5), the risks of mild renal function decline became consistent: NAFLD was associated with early stages of CKD but not the late stages of CKD in both populations. CONCLUSION: NAFLD increased the risk of early stages of CKD in both Chinese and the US population. The conflicting results reported by previous studies might result from the different proportion of late stages of CKD.