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1.
Kidney Int Rep ; 9(4): 1047-1056, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38765576

RESUMEN

Introduction: This retrospective study on patients with biopsy-proven lupus nephritis (LN) aimed to assess the probability of sustained clinical remission (sCR) and to investigate sCR effects on disease flares and impaired kidney function (IKF). Methods: sCR was defined as clinical-Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) = 0 and estimated glomerular filtration rate (eGFR) >60 ml/min per 1.73 m2 lasting ≥1 year; IKF: eGFR <60 ml/min per 1.73 m2 for >3 months. We analyzed the probability of achieving and maintaining sCR, and the yearly risk of flare. Cox models were used to identify predictors of sCR and IKF with variables analyzed as time-dependent covariates when appropriate. Results: Of 303 patients followed-up with for 14.8 (interquartile range: 9.8-22) years, 257 (84.8%) achieved sCR. The probability of achieving sCR progressively increased over time reaching 90% at 15 years. Baseline age (hazard ratio [HR]: 1.017; 95% confidence interval [CI]: 0.005-1.029; P = 0.004), hydroxychloroquine intake (HR: 1.385; 95% CI: 1.051-1.825; P = 0.021), and absence of arterial hypertension (HR: 0.699; 95% CI: 0.532-0.921; P = 0.011) were independent predictors of sCR. Among patients who achieved sCR, 142 (55.3%) developed a lupus flare after a median time of 3.6 (2.3-5.9) years. In the remaining 115 patients, sCR persisted for 9.5 (5.8-14.5) years. The probability of sCR to persist at 15 years was 38%. SLE flare risk decreased to 10%, 5%, and 2% in patients with sCR lasting <5, 5 to 10, and >10 years, respectively. At the last observation, 57 patients (18.81%) had IKF. sCR achievement (HR: 0.18, P < 0.001) and its duration (HR: 0.83, P < 0.001) were protective against IKF. Conclusion: sCR is an achievable target in LN management and protects against IKF. The longer the sCR, the higher the chance of its persistence and the lower the risk of SLE flares.

2.
J Clin Ultrasound ; 51(9): 1553-1559, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37724945

RESUMEN

OBJECTIVE: To investigate the relationship between the specific ultrasonic manifestations of lower limb joints and impaired kidney function in gouty arthritis. METHODS: In this cross-sectional study, 408 patients with gouty arthritis were divided into two groups based on the status of renal function: normal group (n = 240) and renal impairment (n = 168) group. All patients underwent ultrasound examination of the bilateral knee, ankle, and first metatarsophalangeal joints to detect ultrasound features of double-contour sign (DC) and tophus. Multiple logistic regression analysis was conducted to assess the association between kidney dysfunction and ultrasound features. A number of potential clinical confounders were adjusted in the model. RESULTS: Univariable conditional logistic regression produces several significant risk factors of impaired kidney function which were the highest and current lever of serum urate acid, course of disease, frequency of attack, hyperlipidemia, hypertension, diabetes, coronary heart disease, presence of multiple tophus, and DC (P < 0.05). After correcting the course of disease and other risk factors, tophus was still an independent risk factor of impaired kidney function and the multivariable adjusted odds ratios (95% CI) was 1.789 (1.005-3.185, P = 0.05), however, the association was not significant in DC (OR = 1.098, 95% CI: 0.668-1.803, P = 0.71). CONCLUSION: The ultrasound feature of tophus was associated with kidney dysfunction in patients with gout, independent of clinical risk factors, which may be helpful in guiding clinical practice.


Asunto(s)
Artritis Gotosa , Gota , Humanos , Artritis Gotosa/complicaciones , Artritis Gotosa/diagnóstico por imagen , Estudios Transversales , Ácido Úrico , Gota/complicaciones , Gota/diagnóstico por imagen , Riñón/diagnóstico por imagen
3.
Front Pharmacol ; 14: 1147980, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37033654

RESUMEN

Background: Nirmatrelvir/ritonavir has demonstrated effectiveness in high-risk patients with coronavirus disease 2019 (COVID-19). However, investigations on the efficacy and safety of nirmatrelvir/ritonavir in patients with kidney dysfunction are limited. Methods: Data were collected from the patients admitted to a COVID-19 referral center in Shanghai, China. Patients were at least 18 years of age and had a baseline estimated glomerular filtration rate (eGFR) of <60 ml/min/1·73 m2. The primary endpoint was a composite of all-cause mortality, intensive care unit admission, or cardiovascular events. The secondary endpoint was viral shedding. Results: Among the 195 participants, 73 received nirmatrelvir/ritonavir. A lower risk of the primary endpoint was observed in nirmatrelvir/ritonavir recipients compared with non-recipients [adjusted HR 0.56 (95% CI: 0.32-0.96); p = 0.035]. Nirmatrelvir/ritonavir recipients experienced a shorter duration of viral shedding [adjusted HR 3·70 (95%CI: 2.60-5.28); p < 0.001) and faster viral load clearance versus non-recipients. Among the nirmatrelvir/ritonavir users, earlier initiation of nirmatrelvir/ritonavir within 5 days since COVID-19 diagnosis was related with shorter viral shedding time (adjusted HR 7.84 [95% CI: 3.28-18.76]; p < 0.001) compared to late initiation. No patients reported serious adverse events during treatment. Conclusion: Our findings support the early initiation of nirmatrelvir/ritonavir for high-risk patients with impaired kidney function. This could improve patient outcomes and shorten the viral shedding period.

4.
Eur Clin Respir J ; 10(1): 2181291, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36861117

RESUMEN

Purpose: Co-morbidities are common in chronic obstructive pulmonary disease (COPD) and are associated with increased morbidity and mortality. The aim of the present study was to explore the prevalence of several comorbid conditions in severe COPD, and to investigate and compare their associations with long-term mortality. Methods: In May 2011 to March 2012, 241 patients with COPD stage 3 or 4 were included in the study. Information was collected on sex, age, smoking history, weight and height, current pharmacological treatment, number of exacerbations the recent year and comorbid conditions. At December 31st, 2019, mortality data (all-cause and cause specific) were collected from the National Cause of Death Register. Data were analyzed using Cox-regression analysis with gender, age, previously established predictors of mortality and comorbid conditions as independent variables, and all-cause mortality and cardiac and respiratory mortality, respectively, as dependent variables. Results: Out of 241 patients, 155 (64%) were deceased at the end of the study period; 103 patients (66%) died of respiratory disease and 25 (16%) of cardiovascular disease. Impaired kidney function was the only comorbid condition independently associated with increased all-cause mortality (HR (95% CI) 3.41 (1.47-7.93) p=0.004) and respiratory mortality (HR (95%CI) 4.63 (1.61 to 13.4), p = 0.005). In addition, age ≥70, BMI <22 and lower FEV1 expressed as %predicted were significantly associated with increased all-cause and respiratory mortality. Conclusion: In addition to the risk factors high age, low BMI and poor lung function; impaired kidney function appears to be an important risk factor for mortality in the long term, which should be taken into account in the medical care of patients with severe COPD.

5.
Clin Immunol ; 248: 109271, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36806705

RESUMEN

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.


Asunto(s)
COVID-19 , Humanos , SARS-CoV-2 , Subgrupos Linfocitarios , Recuento de Linfocitos , Riñón , Estudios Retrospectivos
6.
Front Nutr ; 9: 966018, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36267903

RESUMEN

Propelled by an ever-growing awareness about the importance of following dietary recommendations meeting specific biological requirements linked to a person health status, interest in personalized nutrition is on the rise. Soilless biofortification of vegetables has opened the door to the potential for adapting vegetable production to specific dietary requirements. The evolution of vegetables biofortification toward tailored food is examined focusing on some specific categories of people in a context of personalized nutrition instead to simple describe developments in vegetables biofortification with reference to the single element or compound not adequately present in the daily diet. The concepts of bioavailability and bioaccessibility as a useful support tool for the precision biofortification were detailed. Key prospects for challenges ahead aiming to combine product quality and sustainable are also highlighted. Hydroponically cultivation of vegetables with low potassium content may be effective to obtain tailored leafy and fruit vegetable products for people with impaired kidney function. Simultaneous biofortification of calcium, silicon, and boron in the same vegetable to obtain vegetable products useful for bone health deserve further attention. The right dosage of the lithium in the nutrient solution appears essential to obtain tailored vegetables able to positively influence mental health in groups of people susceptible to mental illness. Modulate nitrogen fertilization may reduce or enhance nitrate in vegetables to obtain tailored products, respectively, for children and athletes. Future research are needed to produce nickel-free vegetable products for individuals sensitized to nickel. The multidisciplinary approach toward tailored foods is a winning one and must increasingly include a synergy between agronomic, biological, and medical skills.

7.
Eur J Haematol ; 109(5): 576-585, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-36054308

RESUMEN

The myeloproliferative neoplasms are associated with chronic kidney disease but whether clonal haematopoiesis of indeterminate potential (CHIP) is associated with impaired kidney function is unknown. In the Danish General Suburban Population Study (N = 19 958) from 2010 to 2013, 645 individuals were positive for JAK2V617F (N = 613) or CALR (N = 32) mutations. Mutation-positive individuals without haematological malignancy were defined as having CHIP (N = 629). We used multiple and inverse probability weighted (IPW)-adjusted linear regression analysis to estimate adjusted mean (95% confidence interval) differences in estimated glomerular filtration rate (eGFR; ml/min/1.73 m2 ) by mutation status, variant allele frequency (VAF%), blood cell counts, and neutrophil-to-lymphocyte ratio (NLR). We performed 11-year longitudinal follow-up of eGFR in all individuals. Compared to CHIP-negative individuals, the mean differences in eGFR were -5.6 (-10.3, -0.8, p = .02) for CALR, -11.9 (-21.4, -2.4, p = 0.01) for CALR type 2, and -10.1 (-18.1, -2.2, p = .01) for CALR with VAF ≥ 1%. The IPW-adjusted linear regression analyses showed similar results. NLR was negatively associated with eGFR. Individuals with CALR type 2 had a worse 11-year longitudinal follow-up on eGFR compared to CHIP-negative individuals (p = .004). In conclusion, individuals with CALR mutations, especially CALR type 2, had impaired kidney function compared to CHIP-negative individuals as measured by a lower eGFR at baseline and during 11-year follow-up.


Asunto(s)
Calreticulina , Trombocitemia Esencial , Calreticulina/genética , Hematopoyesis Clonal/genética , Dinamarca/epidemiología , Estudios de Seguimiento , Humanos , Janus Quinasa 2/genética , Riñón/metabolismo , Mutación , Trombocitemia Esencial/genética
8.
Kidney Int Rep ; 7(4): 848-856, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35497809

RESUMEN

Introduction: Complement has been implicated in systemic lupus erythematosus (SLE) pathogenesis on the basis of the associations with inherited complement defects and genome-wide association study risk alleles, glomerular deposits, reduced serum levels, and occasional reports of retinal drusen. This study examined drusen in SLE and their clinical significance. Methods: This cross-sectional observational study compared individuals with SLE recruited from renal and rheumatology clinics with hospital controls. Participants were reviewed for clinical features and underwent imaging with a nonmydriatic retinal camera. Deidentified images were examined by 2 trained graders for drusen number and size using a grid overlay. Results: The cohort with SLE (n = 65) comprised 55 women (85%) and 10 men (15%) with a median age of 47 years (interquartile range 35-59), where 23 (35%) were of southern European or Asian ancestry, and 32 (49%) had biopsy-proven lupus nephritis. Individuals with SLE had higher mean drusen numbers than controls (27 ± 60, 3 ± 9, respectively, P = 0.001), more drusen counts ≥10 (31, 48% and 3, 5%, respectively, P < 0.001), and more medium-large drusen (14, 22% and 3, 5%, respectively, P < 0.001). In SLE, mean drusen counts were higher, and drusen were larger, with an estimated glomerular filtration rate (eGFR) <90 ml/min per 1.73 m2 (P = 0.02, P = 0.02, respectively) or class IV nephritis (P = 0.03, P = 0.02). Conclusion: Drusen composition resembles that of glomerular immune deposits. CFH controls complement activation in the extracellular matrix and CFH risk variants are shared by drusen in macular degeneration and by SLE. CFH represents a possible treatment target for SLE especially with renal impairment.

9.
BMC Nephrol ; 23(1): 107, 2022 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-35300612

RESUMEN

BACKGROUND: In the era of combination antiretroviral therapy (ART), the incidence, manifestations and severity of kidney diseases have dramatically changed in people living with HIV (PLWH). Little is known about the incidence of impaired kidney function (IKF) measured by serum creatine-based estimated glomerular filtration rate (eGFR) in PLWH. METHODS: In this systematic review and meta-analysis, we searched PubMed, Ovid, Medline, Embase and Web of Science for studies published before May 7th, 2021, with estimates of incidence of IKF among PLWH. We independently reviewed each study for quality by using the Newcastle-Ottawa scale. The incidence and 95% confidence intervals (CIs) were calculated using random-effects model. RESULTS: Sixty out of 3797 identifiable studies were eligible for the meta-analysis. A total of 19 definitions of IKF were described and categorized into three types: the threshold of eGFR, an absolute or percent decrease in eGFR, and certain eGFR threshold combined with decrement in eGFR. The eGFR< 60 ml/min/1.73m2 was the most widely used definition or criterion for IKF, by which the pooled incidence rate of IKF was 12.50 (95%CI: 9.00-17.36) per 1000 person years (PYs). The second most-studied outcome was a > 25% decrease in eGFR, followed by eGFR< 90 ml/min/1.73m2, eGFR< 30 ml/min/1.73m2 and a combination of eGFR threshold plus decreased eGFR. The reported incidence rates of IKF differ widely by different definitions of IKF. The highest pooled incidence was observed for those with > 25% decrease in eGFR, while the lowest was observed in those with eGFR < 30 ml/min/1.73m2. Substantial heterogeneity was identified across most estimates. CONCLUSION: Our study provides a comprehensive summary of eGFR-based definitions and incidence rates of IKF in PLWH, not only promoting our understanding of IKF, but also underscoring needs for a concerted action to unify definitions and outcomes of IKF and their applications in AIDS care.


Asunto(s)
Infecciones por VIH , Insuficiencia Renal , Femenino , Tasa de Filtración Glomerular , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Incidencia , Riñón , Masculino
10.
BMC Nephrol ; 22(1): 37, 2021 01 21.
Artículo en Inglés | MEDLINE | ID: mdl-33478431

RESUMEN

BACKGROUND: This study estimated the prevalence and risk factors for decreased estimated glomerular filtration rate (eGFR) in those without known hypertension, type 2 diabetes mellitus, or heavy proteinuria as a surrogate marker for chronic kidney disease of unknown cause (CKDu) among adults in the North of Peru. METHODS: A cross-sectional study was conducted following the Disadvantaged Populations eGFR Epidemiology (DEGREE) Study protocol. Low eGFR was defined based on a single eGFR ≤60 mL/min/1.7m2 estimated using the CKD-EPI equation. Environmental conditions related to CKDu (i.e., work in agriculture or sugarcane, water source, heat intolerance, and pesticide exposure) were evaluated, in addition to traditional risk factors for CKD (i.e., smoking, heavy drinking, physical activity, hypertension, type 2 diabetes mellitus, urolithiasis, among others). RESULTS: A total of 1514 subjects were included in the study, mean age 45.1 (SD: 16.4), and 55.2% were females. Overall, only 26 cases (1.7%; 95%CI: 1.1-2.5%) had an eGFR < 60 mL/min/1.7m2 compatible with CKD definition; when those with hypertension and type-2 diabetes or heavy proteinuria were excluded, according to the DEGREE protocol, the estimate fell to 0.9% (95%CI: 0.4-1.5%). Low physical activity levels (OR = 1.99; 95%CI: 1.18-3.34), hypertension (OR = 2.07; 1.26-3.41), and urolithiasis (OR = 1.97; 95%CI: 1.18-3.27) were factors associated with low eGFR. CONCLUSIONS: A low population-based prevalence of low eGFR (as a surrogate for CKDu), both in rural and urban settings areas, in the Northern Peru, was found. Low physical activity levels, hypertension and urolithiasis were factors associated with low eGFR. Interventions to prevent CKD cases may be focused on well-known CV risk factors and urolithiasis.


Asunto(s)
Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/epidemiología , Adulto , Estudios Transversales , Femenino , Tasa de Filtración Glomerular , Humanos , Masculino , Persona de Mediana Edad , Perú/epidemiología , Prevalencia , Insuficiencia Renal Crónica/fisiopatología , Factores de Riesgo
11.
Eur J Heart Fail ; 21(10): 1248-1258, 2019 10.
Artículo en Inglés | MEDLINE | ID: mdl-31476097

RESUMEN

AIMS: An implantable cardioverter-defibrillator (ICD) is recommended for reducing the risk of sudden cardiac death (SCD) in myocardial infarction (MI) patients with a left ventricular ejection fraction (LVEF) ≤ 30%, as well as patients with a LVEF ≤ 35% and heart failure symptoms. Diabetes and/or impaired kidney function may confer additional SCD risk. We assessed the association between these two risk factors with SCD and non-SCD among MI survivors taking account of age and LVEF. METHODS AND RESULTS: A total of 17 773 patients from the High-Risk MI Database were evaluated. Overall, diabetes and estimated glomerular filtration rate < 60 mL/min/1.73 m2 , individually and together, conferred a higher risk of SCD [adjusted competing risk: hazard ratio (HR) 1.23, 1.23, and 1.32, respectively; all P < 0.03] and non-SCD (HR 1.34, 1.52, and 2.13, respectively; all P < 0.0001). Annual SCD rates in patients with LVEF > 35% and with diabetes, impaired kidney function, or both (2.0%, 2.5% and 2.7%, respectively) were comparable to rates observed in patients with LVEF 30-35% but no such risk factors (1.7%). However, these patients had also similarly higher non-SCD rates, such that the ratio of SCD to non-SCD was not increased. Importantly, this ratio was mostly dependent on age, with higher overall ratios in youngest subgroups (0.89 in patients < 55 years vs. 0.38 in patients ≥ 75 years), regardless of risk factors. CONCLUSION: Although MI survivors with LVEF > 35% with diabetes, impaired kidney function, or both are at increased risk of SCD, the risk of non-SCD risk is even higher, suggesting an extension of the current indication for an ICD to them is unlikely to be worthwhile. MI survivors with low LVEF and aged < 55 years are likely to have the greatest potential benefit from ICD implantation.


Asunto(s)
Muerte Súbita Cardíaca/epidemiología , Complicaciones de la Diabetes/mortalidad , Insuficiencia Cardíaca/mortalidad , Infarto del Miocardio/complicaciones , Adulto , Factores de Edad , Anciano , Femenino , Humanos , Incidencia , Pruebas de Función Renal , Masculino , Persona de Mediana Edad , Medición de Riesgo , Factores de Riesgo , Sobrevivientes , Sístole
12.
Kidney Blood Press Res ; 43(4): 1245-1254, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30078009

RESUMEN

BACKGROUND/AIMS: Kidney dysfunction is an important risk factor for cardiovascular disease and end-stage renal disease. This study investigated whether dietary salt intake predicts deterioration of kidney function in the general population. METHODS: In all, 12 126 subjects with a normal estimated glomerular filtration rate (eGFR ≥60 mL/min per 1.73m2) attending an annual check-up were enrolled in the study and were followed-up for a median of 1754 days; the endpoint was the development of impaired kidney function (eGFR < 60 mL/min per 1.73m2). Individual salt intake was estimated using spot urine analysis. RESULTS: At baseline, mean (± SD) salt intake and eGFR were 10.6 ± 3.4 g/day and 80.8 ± 12.9 mL/min per 1.73m2, respectively. During the follow-up period, 1384 subjects (25.2 per 1000 person-years) developed impaired kidney function. Multivariate Cox hazard regression analysis revealed salt intake as a significant predictor of the new onset of kidney impairment (hazard ratio 1.045; 95% confidence interval 1.025-1.065). Subjects were divided into two groups based on salt intake; the incidence of impaired kidney function was higher in the group with high than low salt intake (P < 0.001, log-rank test). Multivariate Cox hazard regression analysis indicated a 29% increased risk of developing impaired kidney function in the high-salt group. Multivariate linear regression analysis showed a significant correlation between salt intake and yearly decline in eGFR (ß = 0.060, P < 0.001). CONCLUSION: Salt intake is associated with the development of impaired kidney function in the general population, independent of its effects on blood pressure. Salt restriction may help prevent the development of impaired kidney function.


Asunto(s)
Tasa de Filtración Glomerular/fisiología , Insuficiencia Renal Crónica/inducido químicamente , Cloruro de Sodio Dietético/efectos adversos , Adulto , Presión Sanguínea , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal Crónica/epidemiología
13.
Diabetes Metab Res Rev ; 34(8): e3052, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30064156

RESUMEN

BACKGROUND: The visceral adiposity index (VAI) is considered to be a reliable indicator of adipose tissue dysfunction and cardiometabolic disease risk. The aim of this study was to evaluate its usefulness in assessing cardiometabolic risk in a sample of elderly women living in a rural-urban community in central Poland. METHODS: A total of 365 women aged 65 to 74 years were included in this cross-sectional study. All patients were interviewed to obtain their history of diabetes mellitus, myocardial infarction, stroke, and revascularization. For all participants, anthropometric measurements were performed, then body mass index (BMI) and waist/hip ratio were calculated. Blood pressure was measured on the arm and on both ankles, and the ankle/brachial index was calculated. Blood samples were collected for the assessment of glycemia, lipid profile, and creatinine level. In patients with elevated fasting glucose, the test was repeated, or an oral glucose tolerance test was performed where appropriate. Finally, carotid intima-media thickness was measured in all women. RESULTS: The VAI of participants was significantly correlated with a history of myocardial infarction, higher carotid intima-media thickness, diabetes, prediabetes, and impaired kidney function. Furthermore, VAI demonstrated a better correlation with these endpoints than BMI or waist circumference. CONCLUSIONS: The VAI can be considered a useful tool for the assessment of cardiometabolic disease risk in elderly women, with a score of ≥2.71 representing the cut-off point for identifying females at high risk. In such patients, screening for cardiovascular disease, abnormal glucose metabolism, and impaired kidney function should be routine practice.


Asunto(s)
Adiposidad/fisiología , Enfermedades Cardiovasculares/diagnóstico , Indicadores de Salud , Grasa Intraabdominal/patología , Síndrome Metabólico/diagnóstico , Anciano , Envejecimiento/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/patología , Estudios Transversales , Femenino , Humanos , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/patología , Obesidad Abdominal/complicaciones , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/patología , Medición de Riesgo
14.
Expert Rev Clin Pharmacol ; 10(7): 737-752, 2017 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-28447486

RESUMEN

INTRODUCTION: In addition to tailored clinical trials in patients on chronic hemodialysis (HD) during drug development, clinician-initiated post-marketing studies and case reports on individual pharmacokinetic (PK) assessments provide an important source of information about drug dialysability and individualized dose recommendations in this vulnerable population. Areas covered: First, factors that may alter drug exposure in HD patients are explained. Second, available regulatory and methodological guidelines for PK assessments in this population are summarized. Third, a 4-step approach is proposed to develop individual dose recommendations for HD patients receiving drugs without data from a PK study: (1) literature search, (2) model-based dosage decisions, (3) validation and refinement through concentration monitoring, and (4) publication of relevant observations. Fourth, clinician-initiated PK assessments and case reports to evaluate and individualize use of drugs in HD patients are reviewed, and recommendations to enhance their quality are discussed. Expert commentary: Guidance on collecting and reporting PK information in individual HD patients is warranted to ensure completeness and consistency of such PK studies. A checklist and template for easy-to-implement PK calculations and pharmacometric modeling is provided to facilitate evaluation and individualization of dosing strategies in these patients.


Asunto(s)
Modelos Biológicos , Preparaciones Farmacéuticas/administración & dosificación , Diálisis Renal , Lista de Verificación , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Humanos , Preparaciones Farmacéuticas/metabolismo , Farmacocinética , Guías de Práctica Clínica como Asunto
15.
J Clin Pharmacol ; 57(4): 524-535, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27681484

RESUMEN

The purpose of the present study was to evaluate the pharmacokinetics of beraprost sodium (BPS) and its active enantiomer, BPS-314d, in Japanese subjects with impaired kidney function. The plasma and urine concentrations of BPS and BPS-314d were measured following the single oral administration of 120 µg of BPS as the sustained-release tablet, TRK-100STP, under fasting conditions to 18 subjects with impaired kidney function (stage 2, 3, and 4 chronic kidney disease [CKD] as categorized by the estimated glomerular filtration rate) and to 6 age-, body weight-, and gender-matched subjects with normal kidney function (stage 1 CKD). The Cmax values (mean ± SD) of BPS in stage 1, 2, 3, and 4 CKD, respectively, were 84.9 ± 22.9, 119.8 ± 36.4, 190.6 ± 137.3, and 240.2 ± 110.5 pg/mL; its AUC0-48h were 978 ± 226, 1252 ± 427, 1862 ± 964, and 1766 ± 806 pg·h/mL, respectively, and its cumulative urinary excretion rates were 0.704 ± 0.351%, 0.638 ± 0.292%, 0.485 ± 0.294%, and 0.159 ± 0.136%. The Cmax values of BPS-314d were 22.4 ± 6.4, 30.8 ± 8.5, 46.7 ± 30.6, and 54.4 ± 25.2 pg/mL, its AUC0-48h were 155 ± 56, 226 ± 67, 341 ± 176, and 329 ± 143 pg·h/mL, and its cumulative urinary excretion rates were 0.428 ± 0.242%, 0.349 ± 0.179%, 0.356 ± 0.270%, and 0.096 ± 0.099%, respectively. Adverse events were reported in 2 subjects with stage 2 CKD and 1 subject with stage 4 CKD. The Cmax and AUC0-48h of BPS and BPS-314d were higher based on the severity of impaired kidney function. No relationship was observed between the incidence of adverse events and the severity, and tolerability was confirmed. We consider that dose adjustment is not necessary, but BPS is more carefully treated in patients with impaired kidney function.


Asunto(s)
Epoprostenol/análogos & derivados , Insuficiencia Renal/sangre , Insuficiencia Renal/orina , Administración Oral , Anciano , Preparaciones de Acción Retardada , Epoprostenol/administración & dosificación , Epoprostenol/farmacocinética , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/administración & dosificación , Inhibidores de Agregación Plaquetaria/farmacocinética , Unión Proteica/fisiología , Insuficiencia Renal/tratamiento farmacológico
16.
Artículo en Inglés | MEDLINE | ID: mdl-27303364

RESUMEN

BACKGROUND: Diabetes is a leading risk factor for impaired kidney function, an indicator of chronic kidney disease. The aim of this study was to examine the association between type 2 diabetes (T2D) and impaired kidney function among adults in sub-Saharan Africa (SSA). METHODS: Participants were enrolled from Ghana, Kenya, and Nigeria. Impaired kidney function was based on an estimated glomerular filtration rate <60 ml/min/1.73 m(2). Using logistic regression models, we conducted case-control analyses to estimate the multivariate-adjusted association of T2D and kidney function. RESULTS: We used data from 4815 participants for whom the mean (SD) age was 48 (15) years, 41% were male and 46% had T2D. Those with T2D were more likely to have impaired kidney function [13.4% (95% CI: 11.9-14.7)] compared to those without T2D [4.8% (95% CI: 4.0-5.6)], p-value <0.001. The multivariate odds ratio of impaired kidney function among those with type 2 diabetes was 1.50 (95% CI: 1.17-1.91) p-value = 0.001, compared to those without T2D. Also, individuals with T2D who were at least 60 years old, obese, hypertensive or dyslipidemic were more likely to have impaired kidney function compared to those without T2D. CONCLUSION: T2D was associated with 50% increased risk of impaired kidney function in this sample of adults from SSA. Interventions targeted at prevention, early diagnosis, and management of T2D are likely to reduce the burden of kidney disease in SSA.

17.
J Cardiothorac Vasc Anesth ; 29(5): 1236-47, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26119403

RESUMEN

OBJECTIVES: The authors investigated whether zero-balance ultrafiltration (Z-BUF) during bypass significantly improves clinical and cost outcomes or biomarkers of kidney injury for patients with preoperative kidney impairment (estimated glomerular filtration rate [eGFR]<60 mL/minute) undergoing cardiac surgery. DESIGN: A single-center randomized controlled trial recruited, patients between 2010 and 2013, with a 12-months follow-up. SETTING: Hospital. PARTICIPANTS: One hundred ninety-nine patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: Patients were assigned randomly to receive zero-balance ultrafiltration (Z-BUF) or not, with stratification for degree of kidney dysfunction and diabetes. MEASUREMENTS AND MAIN RESULTS: The authors assessed clinical efficacy and kidney function biomarkers. Cumulative probability of discharge from the intensive care unit (ICU) was assessed by Kaplan-Meier plots and was found not to be significantly different between the two trial arms (p = 0.61). After adjusting for EuroSCORE, diabetes, eGFR, cardioplegia types and type of surgery in a Cox proportional hazard model, hazard ratios (HR) for ICU length of stay between the Z-BUF and no-Z-BUF groups was not significantly different: HR (95% CI): 0.89 (0.66, 1.20; p = 0.44). In contrast, significant reductions in postoperative chest infections and the composite of clinical endpoints (death, strokes, and myocardial infarctions) in the Z-BUF group were observed. In addition, Z-BUF significantly abrogated the rise in the kidney damage markers urinary NGAL/creatinine ratio, urea, creatinine and eGFR during CPB and adverse events risks. CONCLUSIONS: Z-BUF during bypass surgery is associated with significant reductions in morbidity and biomarkers of CPB-induced acute kidney injury soon after CPB, which are indicative of clearance of inflammatory/immune mediators from the circulation.


Asunto(s)
Lesión Renal Aguda/prevención & control , Procedimientos Quirúrgicos Cardíacos , Puente Cardiopulmonar , Enfermedad de la Arteria Coronaria/cirugía , Insuficiencia Renal/terapia , Ultrafiltración/métodos , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/etiología , Anciano , Anciano de 80 o más Años , Enfermedad de la Arteria Coronaria/complicaciones , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Humanos , Periodo Intraoperatorio , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Insuficiencia Renal/complicaciones , Estudios Retrospectivos , Método Simple Ciego , Reino Unido/epidemiología
18.
Artículo en Chino | WPRIM (Pacífico Occidental) | ID: wpr-462083

RESUMEN

Objective To investigate the risk factors for occurring cerebral microbleeds( CMBs)in patients with ischemic stroke Methods A total of 184 consecutive patients with ischemic stroke admitted from January 2012 to January 2014 in General Hospital of Beijing Military Command were enrolled prospec-tively. They were divided into either a CMB group( n=60 )or a non-CMB group( n=124 )according to whether head MRI magnetic sensitive weighted imaging( SWI)revealed CMBs or not. The general clinical data and serum biochemical results of the patients in both groups were collected. Renal creatinine clearance ( Ccr)was calculated,and the data of both groups were analyzed by the univariate and multivariate analyses. Results (1)The results of univariate analysis showed that there were significant differences in age(63 ± 10 vt. 58 ± 10 ),male( 65. 0%[ 39/60 ]vs. 49. 2%[ 61/124 ]),the incidence of leukoaraiosis( LA ) (73. 3%[44 cases]vs. 47. 6%[59 cases]),and serum homocysteine(Hcy)levels(20 ± 8 vs. 16 ± 6μmol/L)between the CMB group and the non-CMB group(P<0. 05). The Ccr level(89 ± 10 mL/(min·1.73m2)of the CMB group was lower than(106 ±6mL/(min·1.73m2)of the non-CMB group. There was significant difference(P <0. 05).(2)Multivariate logistic regression analysis showed that age(OR,1. 103,95%CI1. 024—1. 989,P =0. 028),LA(OR,3. 121,95%CI 1. 310—7. 436;P <0. 05)and impaired kidney function(OR,1. 890,95%CI 1. 358—3. 076;P<0. 01)were the independent risk factors for the occurrence of CMBs in patients with ischemic stroke. Conclusion Age,LA and impaired kidney function are the independent risk factors for occurring CMBs in patients with ischemic stroke.

19.
Afr Health Sci ; 11 Suppl 1: S28-33, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-22135641

RESUMEN

BACKGROUND: HIV related renal disease is a common occurrence in patients with HIV infection. It is the third leading cause of end stage renal disease among African-American males between the ages of 20 and 64 years in USA. Renal function impairment has been reported at all stages of HIV infection. The aim of this study is to determine the relationship between severity of renal function impairment and CD4 cell count in HIV infected patients. METHOD: HIV patients presenting at University of Benin Teaching Hospital Benin, City Nigeria from 1(st) January to 30(th) June 2007 were randomly selected and screened for renal functional impairment (RFI). Those with RFI detected by glomerular filtration rate < 60 ml/min/1.73 m(2) or urine protein creatinine ratio 3 200 were stratified into mild, moderate and severe RFI. Forty patients from each stratum and forty HIV infected patients with normal renal functions were recruited as subjects and control respectively. Their clinical and laboratory parameters were evaluated. The data obtained were analysed using SPSS vs 15.0. RESULTS: Of the HIV patients screened, 53.3% had renal functional impairment. of these, 40.2% had mild, 37.7% had moderate and 22.2% had severe impairment in their renal functions respectively Their mean age was 36.0 ± 8.8 years. The CD4 cell count was found to be 309.75 ± 268.71/ul, 188.45 ± 173.12/ul, and 141.10 ± 126.01/ul among subjects with mild, moderate and severe RFI respectively. The CD4 cell count in control group was 319.05 ± 248.41/ul. The difference was statistically significant. (p = <0.001). CD4 cell count had a significant positive correlation with GFR (r = 0.32, p = 0.042). However, there was a negative correlation between CD4 cell count and proteinuria but this was not statistically significant (r = 0.09, p = 0.173). CONCLUSION: Severity of RFI has a positive correlation with degree of immunosuppression in HIV infected patients.


Asunto(s)
Recuento de Linfocito CD4 , Infecciones por VIH/embriología , Hospitales de Enseñanza , Enfermedades Renales/fisiopatología , Índice de Severidad de la Enfermedad , Adulto , Comorbilidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nigeria , Adulto Joven
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