RESUMO
BACKGROUND: Depression is prevalent across the spectrum of Chronic Kidney Disease and associated with poorer outcomes. There is limited evidence regarding the most effective interventions and care pathways for depression in Chronic Kidney Disease. OBJECTIVES: To investigate how depression is identified and managed in adults with Chronic Kidney Disease. DESIGN: Scoping review. METHODS: Systematic search of eight databases with pre-defined inclusion criteria. Data relevant to the identification and/or management of depression in adults with Chronic Kidney Disease were extracted. RESULTS: Of 2147 articles identified, 860 were included. Depression was most identified using self-report screening tools (n = 716 studies, 85.3%), with versions of the Beck Depression Inventory (n = 283, 33.7%) being the most common. A total of 123 studies included data on the management of depression, with nonpharmacological interventions being more frequently studied (n = 55, 45%). Cognitive Behavioural Therapy (n = 15) was the most common nonpharmacological intervention, which was found to have a significant effect on depressive symptoms compared to controls (n = 10). However, how such approaches could be implemented as part of routine care was not clear. There was limited evidence for antidepressants use in people with Chronic Kidney Disease albeit in a limited number of studies. CONCLUSIONS: Depression is commonly identified using validated screening tools albeit differences exist in reporting practices. Evidence regarding the management of depression is mixed and requires better-quality trials of both pharmacological and nonpharmacological approaches. Understanding which clinical care pathways are used and their evidence, may help facilitate the development of kidney care specific guidelines for the identification and management of depression.
Assuntos
Terapia Cognitivo-Comportamental, Insuficiência Renal Crônica, Adulto, Humanos, Depressão/diagnóstico, Depressão/terapia, Insuficiência Renal Crônica/complicações, Insuficiência Renal Crônica/terapia, Antidepressivos/uso terapêutico, RimRESUMO
Uromodulin, also known as the Tamm-Horsfall protein, is predominantly expressed in epithelial cells of the kidney. It is secreted mainly in the urine, although small amounts are also found in serum. Uromodulin plays an important role in maintaining renal homeostasis, particularly in salt/water transport mechanisms and is associated with salt-sensitive hypertension. It also regulates urinary tract infections, kidney stones, and the immune response in the kidneys or extrarenal organs. Uromodulin has been shown to be associated with the renal function, age, nephron volume, and metabolic abnormalities and has been proposed as a novel biomarker for the tubular function or injury. These findings suggest that uromodulin is a key molecule underlying the mechanisms or therapeutic approaches of chronic kidney disease, particularly nephrosclerosis and diabetic nephropathy, which are causes of end-stage renal disease. This review focuses on the current understanding of the role of uromodulin from a biological, physiological, and pathological standpoint.
Assuntos
Cálculos Renais, Insuficiência Renal Crônica, Humanos, Uromodulina/metabolismo, Rim/metabolismo, Insuficiência Renal Crônica/etiologia, HomeostaseRESUMO
INTRODUCTION: Glomerulonephritis are the third cause of chronic kidney disease (CKD) requiring dialysis in Brazil. Mineral and bone disorder (MBD) is one of the complications of CKD and is already present in the early stages. Assessment of carotid intima-media thickness (CIMT) and flow-mediated vasodilatation (FMV) are non-invasive ways of assessing cardiovascular risk. HYPOTHESIS: Patients with primary glomerulonephritis (PG) have high prevalence of atherosclerosis and endothelial dysfunction, not fully explained by traditional risk factors, but probably influenced by the early onset of MBD. OBJECTIVE: To evaluate the main markers of atherosclerosis in patients with PG. METHOD: Clinical, observational, cross-sectional and controlled study. Patients with PG were included and those under 18 years of age, pregnants, those with less than three months of follow-up and those with secondary glomerulonephritis were excluded. Those who, at the time of exams collection, had proteinuria higher than 6 grams/24 hours and using prednisone at doses higher than 0.2 mg/kg/day were also excluded. RESULTS: 95 patients were included, 88 collected the exams, 1 was excluded and 23 did not undergo the ultrasound scan. Patients with PG had a higher mean CIMT compared to controls (0.66 versus 0.60), p = 0.003. After multivariate analysis, age and values for systolic blood pressure (SBP), FMV and GFR (p = 0.02); and FMV and serum uric acid (p = 0.048) remained statistically relevant. DISCUSSION AND CONCLUSION: The higher cardiovascular risk in patients with PG was not explained by early MBD. Randomized and multicentric clinical studies are necessary to better assess this hypothesis.
Assuntos
Aterosclerose, Glomerulonefrite, Insuficiência Renal Crônica, Adulto, Feminino, Humanos, Aterosclerose/complicações, Espessura Intima-Media Carotídea, Estudos Transversais, Glomerulonefrite/complicações, Diálise Renal, Fatores de Risco, Ácido ÚricoRESUMO
Creatinine-based estimated glomerular filtration rate equations (eGFRcreatinine) are used to measure excretory kidney function in clinical practice. Despite inter and intra-patient variability, eGFRcreatinine has excellent clinical utility and provides the basis for the classification system for chronic kidney disease (CKD), for kidney function monitoring, treatment interventions and referral pathways. The 4-variable modification of diet in renal disease (MDRD) eGFRcreatinine equation was introduced in 2000 and recommended by the National Institute for Health and Care Excellence (NICE) in 2008. Subsequently, the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) eGFRcreatinine equation was introduced in 2009 and is more accurate than MDRD in patients with mild and moderate CKD. In 2014, NICE recommended that CKD-EPI eGFRcreatinine replace MDRD eGFRcreatinine in routine clinical practice across England. Both equations originally incorporated adjustments for age, gender and ethnicity. However, the evidence for ethnicity adjustment has been increasingly questioned, and in 2021 NICE recommended that kidney function should be estimated by CKD-EPI eGFRcreatinine without using ethnicity adjustment. Recently, a CKD-EPI equation has been presented without ethnicity adjustment; however, this has not been validated outside of North America and NICE continues to recommend CKD-EPI 2009. We review the status of eGFRcreatinine in clinical practice, including the limitations of eGFRcreatinine and the rationale for removal of ethnicity adjustment and the potential impact of this change on clinical care for patients with kidney disease.
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Etnicidade, Insuficiência Renal Crônica, Humanos, Taxa de Filtração Glomerular, Creatinina/metabolismo, InglaterraRESUMO
Purpose: Efficacy of exercise to improve renal health and filtration remains understudied in adults with moderate-stages (stages G3a-b) of chronic kidney disease (CKD). Acute exercise may contribute clinically relevant information for exercise-related augmentation of renal health and filtration in CKD. Urine epidermal growth factor (uEGF) and cystatin C (CyC) are proposed to be more direct biomarkers of renal health and filtration. This study aimed to determine the influence of continuous moderate-intensity exercise (CMIE) and high-intensity interval exercise (HIIE) on traditional and novel biomarkers of renal health and filtration in moderate-stages of CKD. Methods: Twenty CKD participants completed 30 minutes of both CMIE and HIIE. Blood and urine samples were obtained pre, 1-hour, and 24-hours post-exercise. Traditional-serum creatinine (sCr) urine creatinine, novel-uEGF, uEGF ratio (uEGFr), and CyC. Estimates of glomerular filtration rate (eGFR)-modification of diet in renal disease (MDRD) and the CKD-Epidemiology (CKD-EPI)-responses were compared pre, 1 hr, and 24 hr post-exercise. Results: Relative to pre-exercise measures, uEGF remained unchanged in both exercise conditions. However, uEGFr was 5.4% greater 24-hours after HIIE (P = .05), while uEGFr remained unchanged with CMIE. sCr decreased 6 to 19% 1-hour post-exercise in both conditions (P = .009). On average renal filtration increased in eGFR-MDRD (7.2 ± 2.0 ml/min/1.73 m2) (P = .007) and eGFR-CKD-EPI (8.6 ± 2.3 ml/min/1.73 m2) 1-hour post-exercise (P = .009). Conclusion: By clinical estimates, renal filtration in CKD was not normalized but transiently improved regardless of exercise condition, with HIIE eliciting transient improvements in renal health.
Assuntos
Insuficiência Renal Crônica, Adulto, Humanos, Exercício Físico, BiomarcadoresRESUMO
Background: Cannabis consumption for recreational and medical use is increasing worldwide. However, the long-term effects on kidney health and disease are largely unknown. Materials and Methods: Post hoc analysis of cannabis use as a risk factor for kidney disease was performed using data from the Assessment, Serial Evaluation, and Subsequent Sequelae of Acute Kidney Injury (ASSESS-AKI) study that enrolled hospitalized adults with and without acute kidney injury from four U.S. centers during 2009-2015. Associations between self-reported cannabis consumption and the categorical and continuous outcomes were determined using multivariable Cox regression and linear mixed models, respectively. Results: Over a mean follow-up of 4.5±1.8 years, 94 participants without chronic kidney disease (CKD) (estimated glomerular filtration rate [eGFR] >60 mL/min/1.73 m2) who consumed cannabis had similar rates of annual eGFR decline versus 889 nonconsumers (mean difference=-0.02 mL/min/1.73 m2/year, p=0.9) and incident CKD (≥25% reduction in eGFR compared with the 3-month post-hospitalization measured eGFR and achieving CKD stage 3 or higher) (adjusted hazard ratio [aHR]=1.2; 95% confidence interval [CI]=0.7-2.0). Nineteen participants with CKD (eGFR <60 mL/min/1.73 m2) who consumed cannabis had more rapid eGFR decline versus 597 nonconsumers (mean difference=-1.3 mL/min/1.73 m2/year; p=0.02) that was not independently associated with an increased risk of CKD progression (≥50% reduction in eGFR compared with the 3-month post-hospitalization eGFR, reaching CKD stage 5, or receiving kidney replacement therapy) (aHR=1.6; 95% CI=0.7-3.5). Cannabis consumption was not associated with the rate of change in urine albumin to creatinine ratio (UACR) over time among those with (p=0.7) or without CKD (p=0.4). Conclusions: Cannabis consumption did not adversely affect the kidney function of participants without CKD but was associated with a faster annual eGFR decline among participants with CKD. Cannabis consumption was not associated with changes in UACR over time, incident CKD, or progressive CKD regardless of baseline kidney function. Additional research is needed to investigate the kidney endocannabinoid system and the impact of cannabis use on kidney disease outcomes.
Assuntos
Injúria Renal Aguda, Cannabis, Insuficiência Renal Crônica, Adulto, Humanos, Estudos Retrospectivos, Rim, Insuficiência Renal Crônica/epidemiologia, Insuficiência Renal Crônica/complicações, Injúria Renal Aguda/complicaçõesRESUMO
PURPOSE: To evaluate the test-retest reliability and validity of the Patient Generated Index (PGI) in individuals with Chronic Kidney Disease (CDK) undergoing hemodialysis. METHODS: Through a non-experimental study with repeated measures, PGI was applied twice to assess internal consistency and test-retest reliability. Correlations with the Kidney Disease Quality of Life Short Form (KDQOL-SF), the Human Activity Profile (HAP) questionnaire, the Social Participation Scale, and the Glittre ADL Test were used. RESULTS: 91 individuals with CKD were evaluated. There was high reliability for the PGI (ICC= 0.97) PGI correlated with KQDOL - SF in Functional Capacity r = 0.38 (p < 0.001), Emotional Well-Being r = 0.31 (p = 0.003), Social Aspect r = 0.22 (p = 0.036), Emotional Function r = 0.22 (p = 0.038) and Effect of Kidney Disease r = 0.21 (p = 0.042), and Physical scores r = 0.24 (p = 0.021)), Mental r = 0.21 (p = 0.05) and General r = 0.22 (p = 0.037) summarized. There was a significant correlation between PGI and HAP r = 0.40 (p < 0.001) and the Social Participation Scale r = -0.36 (p < 0.001). There was no correlation between the PGI and Glittre ADL scores r = 0.12 (p = 0.247). CONCLUSION: In adults receiving hemodialysis, the PGI proved to be an accurate and reliable instrument for the assessment of the quality of life from the perspective of the patient.IMPLICATIONS FOR REHABILITATIONAlthough hemodialysis treatment is associated with increased survival and symptom control, there is a significant change in the patient's lifestyle.In order to provide a more focused view of the individual, the Patient Generated Index (PGI) was created to evaluate the quality of life.PGI is reliable and correlates with KQDOL - SF and the Social Participation Scale in this population.
Assuntos
Diálise Renal, Insuficiência Renal Crônica, Adulto, Humanos, Qualidade de Vida/psicologia, Reprodutibilidade dos Testes, Insuficiência Renal Crônica/terapia, Emoções, Inquéritos e QuestionáriosRESUMO
BACKGROUND: The optimal loading dose of digoxin in patients with reduced kidney function is unknown. Tertiary references recommend reduced loading doses; however, these recommendations are based on immunoassays that are falsely elevated by the presence of digoxin-like immunoreactive substances, a problem that is minimized in modern assays. OBJECTIVE: To determine whether chronic kidney disease (CKD) or acute kidney injury (AKI) is associated with supratherapeutic digoxin concentrations after a digoxin loading dose. METHODS: A retrospective analysis on patients who received an intravenous loading dose of digoxin with a digoxin concentration collected 6 to 24 hours after the end of the dose. Patients were stratified into 3 groups: AKI, CKD, and non-AKI/CKD (NKI) based on glomerular filtration rate and serum creatinine. The primary outcome was frequency of supratherapeutic digoxin concentrations (>2 ng/mL) and secondary outcomes included frequency of adverse events. RESULTS: A total of 146 digoxin concentrations were included (AKI = 59, CKD = 16, NKI = 71). Frequencies of supratherapeutic concentrations were similar between groups (AKI: 10.2%, CKD: 18.8%, NKI: 11.3%; P = 0.61). Pre-planned logistic regression demonstrated no significant relationship between kidney function group and the development of a supratherapeutic concentration (AKI: odds ratio [OR]: 1.3, 95% confidence interval [CI]: 0.4-4.5; CKD: OR 4.3, 95% CI: 0.7-23). CONCLUSION AND RELEVANCE: This is the first study in routine clinical practice evaluating the relationship between kidney function and digoxin peak concentrations that differentiates AKI from CKD. We did not find a relationship between kidney function and peak concentrations; however, the group with CKD was underpowered.
Assuntos
Injúria Renal Aguda, Insuficiência Renal Crônica, Humanos, Estudos Retrospectivos, Digoxina/efeitos adversos, Injúria Renal Aguda/induzido quimicamente, Fatores de Risco, Taxa de Filtração GlomerularRESUMO
BACKGROUND AND AIM: It is feared that among chronic kidney disease patients undergoing hemodialysis, arteriovenous fistula (AVF) itself could contribute to pulmonary hypertension (PH). The impact of AVF location on PH is yet to be assessed. We hypothesize that patients with proximal AVF have higher access blood flow and hence higher pulmonary arterial systolic pressure (PASP) than those with distal AVF. We aimed to compare the PASP between patients with proximal and distal AVF. METHODS: In this cross-sectional study, PASP was estimated using Doppler echocardiography and blood flow in the AVF was assessed by Doppler ultrasound. PASP was modeled by multivariate linear regression. AVF location was the primary exposure of interest. RESULTS: Out of 89 patients undergoing hemodialysis, 72 (81%) had PH defined as PASP >35 mmHg. The mean blood flow in proximal and distal AVF was, respectively, 1240 and 783 mL/min (mean difference 457 mL/min, p < 0.001). Mean PASP in patients with proximal AVF was 16.6 mmHg higher than those with distal AVF (p < 0.001, 95% CI 8.3-24.9). There was a positive correlation between access blood flow and PASP (r = 0.28, p = 0.007). If access blood flow was included as a covariate in the multivariate model, the association between AVF location and PASP ceased to exist. CONCLUSION: Patients with proximal AVF have a significantly higher PASP than those with distal AVF, and this could be attributed to the higher blood flow in proximal AVF compared to distal AVF.
Assuntos
Derivação Arteriovenosa Cirúrgica, Hipertensão Pulmonar, Falência Renal Crônica, Insuficiência Renal Crônica, Humanos, Diálise Renal/efeitos adversos, Falência Renal Crônica/complicações, Falência Renal Crônica/terapia, Pressão Arterial, Estudos Transversais, Derivação Arteriovenosa Cirúrgica/efeitos adversos, Hipertensão Pulmonar/diagnóstico por imagem, Hipertensão Pulmonar/etiologia, Insuficiência Renal Crônica/complicações, Insuficiência Renal Crônica/terapiaRESUMO
Cardiac alteration due to chronic kidney disease is described by tissue fibrosis. This remodeling involves myofibroblasts of various origins, including epithelial or endothelial to mesenchymal transitions. In addition, obesity and insulin resistance together or separately seem to exacerbate cardiovascular risk in chronic kidney disease (CKD). The main objective of this study was to assess if pre-existing metabolic disease exacerbates CKD-induced cardiac alterations. In addition, we hypothesised that endothelial to mesenchymal transition participates in this enhancement of cardiac fibrosis. Rats fed cafeteria type diet for 6 months underwent a subtotal nephrectomy at 4 months. Cardiac fibrosis was evaluated by histology and qRT-PCR. Collagens and macrophages were quantified by immunohistochemistry. Endothelial to mesenchymal transitions were assessed by qRT-PCR (CD31, VE-cadherin, α-SMA, nestin) and also by CD31 immunofluorescence staining. Rats fed with cafeteria type regimen were obese, hypertensive and insulin resistant. Cardiac fibrosis was predominant in CKD rats and was highly majored by cafeteria regimen. Collagen-1 and nestin expressions were higher in CKD rats, independently of regimen. Interestingly, in rats with CKD and cafeteria diet we found an increase of CD31 and α-SMA co-staining with suggest an implication of endothelial to mesenchymal transition during heart fibrosis. We showed that rats already obese and insulin resistant had an enhanced cardiac alteration to a subsequent renal injury. Cardiac fibrosis process could be supported by a involvement of the endothelial to mesenchymal transition phenomenon.
Assuntos
Insulinas, Síndrome Metabólica, Insuficiência Renal Crônica, Ratos, Animais, Nestina, Síndrome Metabólica/patologia, Remodelação Ventricular, Insuficiência Renal Crônica/patologia, Rim/patologia, Fibrose, Obesidade/complicações, Obesidade/patologia, Transição Epitelial-MesenquimalRESUMO
This study was conducted to compare the differences of the whole blood zinc concentration in patients with chronic kidney disease (CKD) as compared to healthy controls, and to explore the correlations of the whole blood zinc level with coronary artery calcification (CAC) and cardiovascular event (CVE) in CKD patients. A total of 170 CKD patients and 62 healthy controls were recruited. The whole blood zinc concentration was determined in using atomic absorption spectroscopy (AAS) method. The degrees of CAC were evaluated by Agatston score based on computed tomography (CT). Regular follow-up visits were performed to record the incidence of CVE, and risk factors were analyzed by COX proportional hazard model and Kaplan-Meier survival curve. There were statistically significant lower zinc levels in CKD patients than in healthy population. The prevalence of CAC was 58.82% in CKD patients. Correlation analysis showed that dialysis duration, intact parathyroid hormone (iPTH), alkaline phosphatase (ALP), 25-hydroxyvitamin D3 (25(OH)D3), neutrophil-lymphocyte ratio (NLR), total cholesterol (TC), and high-sensitive C-reactive protein (Hs-CRP) were positively correlated with CAC, while albumin (ALB), hemoglobin (Hb), and zinc levels were negatively associated with CAC. Further COX proportional hazard model demonstrated that moderate to severe CAC, NLR, phosphate, 25(OH)D3, iPTH, and high-density lipoprotein (HDL) were associated with an increased risk for CVE, while zinc levels, Hb, and ALB were inversely associated with a reduced risk for CVE. Kaplan-Meier curve showed that low zinc (zinc < 86.62 µmol/L) patients and moderate to severe CAC patients had lower survival respectively. Our study found the lower levels of zinc and higher prevalence of CAC in CKD patients; the low zinc is involved in the high incidence rate of moderate to severe CAC and CVE in CKD patients.
Assuntos
Doença da Artéria Coronariana, Insuficiência Renal Crônica, Calcificação Vascular, Humanos, Fatores de Risco, ZincoRESUMO
Receptor interacting protein kinase 3 (RIPK3) is an intracellular kinase at the crossroads of cell death and inflammation. RIPK3 contains a RIP homotypic interaction motif (RHIM) domain which allows interactions with other RHIM-containing proteins and a kinase domain that allows phosphorylation of target proteins. RIPK3 may be activated through interaction with RHIM-containing proteins such as RIPK1, TRIF and DAI (ZBP1, DLM-1) or through RHIM-independent mechanisms in an alkaline intracellular pH. RIPK3 mediates necroptosis and promotes inflammation, independently of necroptosis, through either activation of NFκB or the inflammasome. There is in vivo preclinical evidence of the contribution of RIPK3 to both acute kidney injury (AKI) and chronic kidney disease (CKD) and to the AKI-to-CKD transition derived from RIPK3 deficient mice or the use of small molecule RIPK3 inhibitors. In these studies, RIPK3 targeting decreased inflammation but kidney injury improved only in some contexts. Clinical translation of these findings has been delayed by the potential of some small molecule inhibitors of RIPK3 kinase activity to trigger apoptotic cell death by inducing conformational changes of the protein. A better understanding of the conformational changes in RIPK3 that trigger apoptosis, dual RIPK3/RIPK1 inhibitors or repurposing of multiple kinase inhibitors such as dabrafenib may facilitate clinical development of the RIPK3 inhibition concept for diverse inflammatory diseases, including kidney diseases.
Assuntos
Injúria Renal Aguda, Insuficiência Renal Crônica, Animais, Camundongos, Apoptose, Fosforilação, InflamaçãoRESUMO
Gut dysbiosis is common in patients with chronic kidney disease (CKD) and is associated with uremic toxin production, inflammation, oxidative stress, and cardiovascular disease development. Therefore, healthy dietary patterns are essential modulators of gut microbiota. In this context, studies suggest that consuming berry fruits, rich in polyphenols and nutrients, may positively affect the gut microbiota, promoting the selective growth of beneficial bacteria and improving clinical status. However, studies on the effects of berry fruits on gut microbiota in CKD are scarce, and a better understanding of the possible mechanisms of action of berry fruits on gut microbiota is needed to guide future clinical studies and clinical practice in CKD. The objective was to discuss how berry fruits (blueberry, cranberry, raspberry, and strawberry) could be a therapeutic strategy to modulate the gut microbiota and possibly reverse the dysbiosis in CKD. Overall, available evidence shows that berry fruits can promote an increase in diversity by affecting the abundance of mucus-producing bacteria and short-chain fatty acids. Moreover, these fruits can increase the expression of mRNA involved in tight junctions in the gut such as occludin, tight junction protein 1 (TJP1), and mucin. Studies on the exact amount of berries leading to these effects show heterogeneous findings. However, it is known that, with 5 mg/day, it is already possible to observe some effects in animal models. Wild berries could possibly improve the uremic condition by reducing the levels of uremic toxins via modulation of the gut microbiota. In the long term, this could be an excellent strategy for patients with CKD. Therefore, clinical studies are encouraged to evaluate better these effects on CKD as well as the safe amount of these fruits in order to promote a better quality of life or even the survival of these patients.
Assuntos
Mirtilos Azuis (Planta), Fragaria, Microbioma Gastrointestinal, Insuficiência Renal Crônica, Rubus, Vaccinium macrocarpon, Animais, Humanos, Frutas, Disbiose, Qualidade de Vida, Insuficiência Renal Crônica/tratamento farmacológico, Insuficiência Renal Crônica/metabolismo, Insuficiência Renal Crônica/microbiologiaRESUMO
OBJECTIVE: African Americans are more likely to develop end-stage kidney disease (ESKD) than whites and face multiple inequities regarding ESKD treatment, renal replacement therapy (RRT), and overall care. This study focused on determining gaps in participants' knowledge of their chronic kidney disease and barriers to RRT selection in an effort to identify how we can improve health care interventions and health outcomes among this population. METHODS: African American participants undergoing hemodialysis were recruited from an ongoing research study of hospitalized patients at an urban Midwest academic medical center. Thirty-three patients were interviewed, and the transcribed interviews were entered into a software program. The qualitative data were coded using template analysis to analyze text and determine key themes. Medical records were used to obtain demographic and additional medical information. RESULTS: Three major themes emerged from the analysis: patients have limited information on ESKD causes and treatments, patients did not feel they played an active role in selecting their initial dialysis unit, and interpersonal interactions with the dialysis staff play a large role in overall unit satisfaction. DISCUSSION: Although more research is needed, this study provides information and suggestions to improve future interventions and care quality, specifically for this population.
Assuntos
Negro ou Afro-Americano, Disparidades em Assistência à Saúde, Falência Renal Crônica, Terapia de Substituição Renal, Humanos, Falência Renal Crônica/etnologia, Falência Renal Crônica/terapia, Diálise Renal, Insuficiência Renal Crônica, Terapia de Substituição Renal/métodos, Disparidades em Assistência à Saúde/etnologia, Meio-Oeste dos Estados Unidos, Centros Médicos Acadêmicos, Conhecimentos, Atitudes e Prática em Saúde, Letramento em Saúde, Hospitalização, População Urbana, Educação de Pacientes como Assunto, Participação do PacienteRESUMO
PURPOSE: Cancer treatment with alpha-emitter-based radioligand therapies (α-RLTs) demonstrates promising tumor responses. Radiolabeled peptides are filtered through glomeruli, followed by potential reabsorption of a fraction by proximal tubules, which may cause acute kidney injury (AKI) and chronic kidney disease (CKD). Because tubular cells are considered the primary site of radiopeptides' renal reabsorption and potential injury, the current use of kidney biomarkers of glomerular functional loss limits the evaluation of possible nephrotoxicity and its early detection. This study aimed to investigate whether urinary secretion of tubular injury biomarkers could be used as an additional non-invasive sensitive diagnostic tool to identify unrecognizable tubular damage and risk of long-term α-RLT nephrotoxicity. METHODS: A bifunctional cyclic peptide, melanocortin 1 ligand (MC1L), labeled with [203Pb]Pb-MC1L, was used for [212Pb]Pb-MC1L biodistribution and absorbed dose measurements in CD-1 Elite mice. Mice were treated with [212Pb]Pb-MC1L in a dose-escalation study up to levels of radioactivity intended to induce kidney injury. The approach enabled prospective kidney functional and injury biomarker evaluation and late kidney histological analysis to validate these biomarkers. RESULTS: Biodistribution analysis identified [212Pb]Pb-MC1L reabsorption in kidneys with a dose deposition of 2.8, 8.9, and 20 Gy for 0.9, 3.0, and 6.7 MBq injected [212Pb]Pb-MC1L doses, respectively. As expected, mice receiving 6.7 MBq had significant weight loss and CKD evidence based on serum creatinine, cystatin C, and kidney histological alterations 28 weeks after treatment. A dose-dependent urinary neutrophil gelatinase-associated lipocalin (NGAL, tubular injury biomarker) urinary excretion the day after [212Pb]Pb-MC1L treatment highly correlated with the severity of late tubulointerstitial injury and histological findings. CONCLUSION: Urine NGAL secretion could be a potential early diagnostic tool to identify unrecognized tubular damage and predict long-term α-RLT-related nephrotoxicity.
Assuntos
Chumbo, Insuficiência Renal Crônica, Camundongos, Animais, Lipocalina-2/urina, Distribuição Tecidual, Detecção Precoce de Câncer, Biomarcadores, CreatininaRESUMO
BACKGROUND: The intestinal microbiome is involved in the pathogenesis of chronic kidney disease (CKD). Despite its importance, the microbiome of the small intestinal mucosa has been little studied due to sampling difficulties, and previous studies have mainly focused on fecal sources for microbiome studies. We aimed to characterize the small intestinal microbiome of CKD patients by studying the microbiome collected from duodenal and fecal samples of CKD patients and healthy controls. METHODS: Overall, 28 stage 5 CKD patients and 21 healthy participants were enrolled. Mucosal samples were collected from the deep duodenum during esophagogastroduodenoscopy and fecal samples were also collected. The 16S ribosomal RNA gene sequencing using Qiime2 was used to investigate and compare the microbial structure and metagenomic function of the duodenal and fecal microbiomes. RESULTS: The duodenal flora of CKD patients had decreased alpha diversity compared with the control group. On the basis of taxonomic composition, Veillonella and Prevotella were significantly reduced in the duodenal flora of CKD patients. The tyrosine and tryptophan metabolic pathways were enhanced in the urea toxin-related metabolic pathways based on the Kyoto Encyclopedia of Genes and Genomes database. CONCLUSION: The small intestinal microbiome in CKD patients is significantly altered, indicating that increased intestinal permeability and production of uremic toxin may occur in the upper small intestine of CKD patients.
Assuntos
Microbioma Gastrointestinal, Insuficiência Renal Crônica, Humanos, RNA Ribossômico 16S/genética, Duodeno, Intestino Delgado, FezesRESUMO
AIM: To evaluate the association between trypsin-like protease (TLP) activity in the oral cavity as an indicator of periodontal health status and kidney function in Japanese workers. MATERIALS AND METHODS: This cross-sectional study included 1117 Japanese workers (mean age = 43.8 years). Tongue-swab TLP activity was quantified as a* value (the redness intensity of the matrix disc of the TLP activity assessment kit; a larger value indicates more intense enzymatic activity in the samples and poorer periodontal health status). Kidney function was assessed using the estimated glomerular filtration rate (eGFR; a lower value indicates poorer kidney function). We performed ordinal logistic regression analyses to assess the association of the a* value with three eGFR categories: ≥90, 60-89 and <60 mL/min/1.73 m2 . RESULTS: The prevalence for each eGFR category was as follows: ≥90 (31.6%), 60-89 (63.8%) and <60 mL/min/1.73 m2 (4.6%). After adjusting for potential confounders, the a* value was found to be significantly associated with reduced kidney function. The multivariable-adjusted odds ratio (95% confidence interval) for reduced kidney function was 1.12 (1.02-1.22) per unit increase in the a* value. CONCLUSIONS: Higher TLP activity was associated with reduced kidney function in Japanese workers.
Assuntos
Rim, Insuficiência Renal Crônica, Humanos, Adulto, Tripsina, Estudos Transversais, Japão/epidemiologia, Taxa de Filtração Glomerular, Boca, Insuficiência Renal Crônica/complicaçõesRESUMO
We aimed to assess the efficacy of eplerenone, a steroidal mineralocorticoid receptor antagonist known to reduce blood pressure and mitigate cardiovascular disease (CVD) progression, in retarding the progression of chronic kidney disease (CKD) and CVD in a rat model of type 4 cardiorenal syndrome (CRS). We grouped rats into four experimental categories: sham surgery, sham treatment with eplerenone, nephrectomy without eplerenone (Nx), and nephrectomy with eplerenone (Nx + EP). For the Nx + EP group, rats received five-sixths nephrectomy, inducing CKD and CVD conditions such as renal hypertension and hyperglycemia, and were then treated with eplerenone (100 mg/kg/day, orally) over 4 weeks after an initial 4-week observation period. Heart rate, blood pressure, blood sugar levels, and sympathetic nerve excitation were monitored biweekly. In addition, assessments of renal and cardiac tissues, including evaluation of renal tubulointerstitial injury, glomerular injury, and cardiomyocyte hypertrophy, were conducted at week 8. Eplerenone administration mitigated CKD and CVD progression in the Nx + EP group, evident by improved blood pressure (217.3 ± 5.4 versus 175.3 ± 5.6), blood sugar (121.8 ± 1.3 versus 145.6 ± 6.0) level, reduced sympathetic nerve excitation, and cardiomyocyte hypertrophy compared to the Nx group. However, renal tubulointerstitial injury, glomerular injury, and cardiovascular dysfunction, which were increased in rats with type 4 CRS, did not show significant changes with eplerenone treatment. Our study demonstrated that eplerenone treatment did not exacerbate type 4 CRS but improved blood pressure, blood sugar levels, sympathetic nerve excitation, and cardiomyocyte hypertrophy in this model.
