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Association between GLIM-defined malnutrition and hospitalizations in kidney transplant candidates: A post hoc analysis of a cohort study.
Dávalos-Yerovi, V, Pérez-Sáez, MJ, Faura-Vendrell, A, Muns-Cornellas, MD, Duran, X, Sánchez-Rodríguez, D, Pascual, J, Marco, E, ,
JPEN. Journal of parenteral and enteral nutrition. 2023;(6):802-811
Abstract
BACKGROUND Malnutrition is frequent in patients with chronic kidney disease (CKD) and has a negative impact on morbidity, mortality, and quality of life. The objective of this study was to assess the value of the Global Leadership Initiative for Malnutrition (GLIM) criteria to predict hospitalizations and mortality in candidates to kidney transplant during their first year on the waiting list. METHODS This was a post hoc analysis of 368 patients with advanced CKD. The main study variables were malnutrition, according to the GLIM criteria; number of hospital admissions during the first year on the waiting list; and mortality at the end of follow-up. Kaplan-Meier survival curves and binary logistic regression were performed, adjusting for age, frailty status, handgrip strength, and Charlson Index as potential confounders. RESULTS The prevalence of malnutrition was 32.6%. Malnutrition was associated with increased risk of hospitalizations during the first year on the waiting list (odds ratio [OR] = 3.33 [95% CI = 1.34-8.26]), which persisted after adjustment for age and frailty status (adjusted OR = 3.61 [95% CI = 1.38-10.7]), age and handgrip strength (adjusted OR = 3.39 [95% CI = 1.3-8.85]), and age and Charlson Index (adjusted OR = 3.25 [95% CI = 1.29-8.13]). CONCLUSION Malnutrition according to the GLIM criteria was highly prevalent in patients with CKD and was associated with a threefold increased risk of hospitalizations during the first year on the waiting list; these associations remained significant after adjusting for age, frailty status, handgrip strength, and comorbidities.
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Anything New in the Treatment of Obesity in Obese Patients with CKD?
Sandino, J, Cordero Garcia-Galán, L, Aubert Girbal, L, Praga, M, Pascual, J, Morales, E
Nephron. 2022;(6):616-623
Abstract
Treatment for obesity in patients with CKD englobes a wide range of options, from lifestyle modification to bariatric surgery. Weight loss improves metabolic parameters and stimulates changes in renal function that lead to improvement of glomerular hyperfiltration. The most common clinical presentation is a slowly increasing non-nephrotic proteinuria that is followed by a progressive decline of kidney function. The use of multitarget therapies, with appropriate dietary education, emerging diets, the use of new RAAS blocking agents, the combination of iSGLT2 or GLP-1 agonists, as well as bariatric surgery, may play a key role in finally achieving the desired nephroprotection in this CKD population. New therapeutic agents and novel biomarkers, such as adipocyte cytokines, are needed to monitor and mitigate progression to end-stage renal disease. The emerging "lipidomics" and the role of nonalcoholic fatty liver are relevant research lines.
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Corrigendum: Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study.
Pérez-Sáez, MJ, Uffing, A, Leon, J, Murakami, N, Watanabe, A, Borges, TJ, Sabbisetti, VS, Cureton, P, Kenyon, V, Keating, L, et al
Frontiers in immunology. 2021;:798560
Abstract
[This corrects the article DOI: 10.3389/fimmu.2021.624821.].
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Mortality in Hemodialysis Patients with COVID-19, the Effect of Paricalcitol or Calcimimetics.
Arenas Jimenez, MD, González-Parra, E, Riera, M, Rincón Bello, A, López-Herradón, A, Cao, H, Hurtado, S, Collado, S, Ribera, L, Barbosa, F, et al
Nutrients. 2021;(8)
Abstract
BACKGROUND In COVID-19 patients, low serum vitamin D (VD) levels have been associated with severe acute respiratory failure and poor prognosis. In regular hemodialysis (HD) patients, there is VD deficiency and markedly reduced calcitriol levels, which may predispose them to worse outcomes of COVID-19 infection. Some hemodialysis patients receive treatment with drugs for secondary hyperparathyroidism, which have well known pleiotropic effects beyond mineral metabolism. The aim of this study was to evaluate the impact of VD status and the administration of active vitamin D medications, used to treat secondary hyperparathyroidism, on survival in a cohort of COVID-19 positive HD patients. METHODS A cross-sectional retrospective observational study was conducted from 12 March to 21 May 2020 in 288 HD patients with positive PCR for SARS-CoV2. Patients were from 52 different centers in Spain. RESULTS The percent of HD patients with COVID-19 was 6.1% (288 out of 4743). Mortality rate was 28.4% (81/285). Three patients were lost to follow-up. Serum 25(OH)D (calcidiol) level was 17.1 [10.6-27.5] ng/mL and was not significantly associated to mortality (OR 0.99 (0.97-1.01), p = 0.4). Patients receiving active vitamin D medications (16/94 (17%) vs. 65/191(34%), p = 0.003), including calcimimetics (4/49 (8.2%) vs. 77/236 (32.6%), p = 0.001), paricalcitol or calcimimetics (19/117 (16.2%) vs. 62/168 (36.9%); p < 0.001), and also those on both paricalcitol and calcimimetics, to treat secondary hyperparathyroidism (SHPTH) (1/26 (3.8%) vs. 80/259 (30.9%), p < 0.001) showed a lower mortality rate than patients receiving no treatment with either drug. Multivariate Cox regression analysis confirmed this increased survival. CONCLUSIONS Our findings suggest that the use of paricalcitol, calcimimetics or the combination of both, seem to be associated with the improvement of survival in HD patients with COVID-19. No correlation was found between serum VD levels and prognosis or outcomes in HD patients with COVID-19. Prospective studies and clinical trials are needed to support these findings.
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5.
Calcifediol Treatment and COVID-19-Related Outcomes.
Nogues, X, Ovejero, D, Pineda-Moncusí, M, Bouillon, R, Arenas, D, Pascual, J, Ribes, A, Guerri-Fernandez, R, Villar-Garcia, J, Rial, A, et al
The Journal of clinical endocrinology and metabolism. 2021;(10):e4017-e4027
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Abstract
CONTEXT COVID-19 is a major health problem because of saturation of intensive care units (ICU) and mortality. Vitamin D has emerged as a potential treatment able to reduce the disease severity. OBJECTIVE This work aims to elucidate the effect of 25(OH)D3 (calcifediol) treatment on COVID-19-related outcomes. METHODS This observational cohort study was conducted from March to May 2020, among patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 patients with COVID-19 were included; 92 were excluded because of previous calcifediol intake. Of the remaining 838, a total of 447 received calcifediol (532 μg on day 1 plus 266 μg on days 3, 7, 15, and 30), whereas 391 were not treated at the time of hospital admission (intention-to-treat). Of the latter, 53 patients were treated later during ICU admission and were allocated in the treated group in a second analysis. In healthy individuals, calcifediol is about 3.2-fold more potent on a weight basis than cholecalciferol. Main outcome measures were ICU admission and mortality. RESULTS ICU assistance was required by 102 (12.2%) participants. Out of 447 patients treated with calcifediol at admission, 20 (4.5%) required the ICU, compared to 82 (21%) out of 391 nontreated (P < .001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, sex, linearized 25-hydroxyvitamin D levels at baseline, and comorbidities showed that treated patients had a reduced risk of requiring the ICU (odds ratio [OR] 0.13; 95% CI 0.07-0.23). Overall mortality was 10%. In the intention-to-treat analysis, 21 (4.7%) out of 447 patients treated with calcifediol at admission died compared to 62 patients (15.9%) out of 391 nontreated (P = .001). Adjusted results showed a reduced mortality risk with an OR of 0.21 (95% CI, 0.10-0.43). In the second analysis, the obtained OR was 0.52 (95% CI, 0.27-0.99). CONCLUSION In patients hospitalized with COVID-19, calcifediol treatment significantly reduced ICU admission and mortality.
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The FRAILMar Study Protocol: Frailty in Patients With Advanced Chronic Kidney Disease Awaiting Kidney Transplantation. A Randomized Clinical Trial of Multimodal Prehabilitation.
Pérez-Sáez, MJ, Morgado-Pérez, A, Faura, A, Muñoz-Redondo, E, Gárriz, M, Muns, MD, Nogués, X, Marco, E, Pascual, J
Frontiers in medicine. 2021;:675049
Abstract
Introduction: Frailty is very frequent among patients with chronic kidney disease (CKD) who are awaiting deceased donor kidney transplantation (KT), and transplant outcomes are worsened in those frail recipients. Frailty and poor fitness powerfully predict mortality, kidney graft survival, and healthcare utilization after KT. Intervention is essential to improve survival and quality of life for frail CKD patients, regardless of their age. Studies of post-transplant physical therapy intervention have been met with limited success, in large part due to high dropout rates. A pre-transplant clinical framework for multimodal prehabilitation interventions including physical therapy, nutritional measures, and psychological support scheduled during the KT waiting list period may improve patient retention and compliance, better mitigate the effects of frailty and poor fitness after KT, and improve main outcomes in frail CKD patients. Main Objective: To study the effectiveness, feasibility, and safety of multimodal prehabilitation (exercise, nutritional plans, psychological advice) in KT candidates. Methods: Randomized controlled clinical trial in 38 frail and 76 non-frail KT candidates. The prehabilitation program will consist of physical exercise (24 sessions, 8 weeks), nutritional supplementation, and psychological advice. The primary endpoint will be a composite achievement of clinical and functional main outcomes in frail and non-frail KT candidates at 90 days post-transplantation. Secondary outcomes include changes in exercise capacity, physical activity, gait speed, respiratory and peripheral muscle strength, muscle size, body composition, performance in activities of daily living (basic and instrumental), anxiety and depression symptoms, and health-related quality of life. Feasibility of the intervention will be also analyzed. Expected Results: Multimodal prehabilitation is a feasible and effective intervention to decrease bad outcomes at 90 days post-KT by 25 and 12.5% in frail and non-frail patients, respectively. Clinical Trial Registration: clinicaltrials.gov (NCT04701398), date: 2021, January 8th (Protocol version: Frailmar_vers2).
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Immunological Impact of a Gluten-Free Dairy-Free Diet in Children With Kidney Disease: A Feasibility Study.
Pérez-Sáez, MJ, Uffing, A, Leon, J, Murakami, N, Watanabe, A, Borges, TJ, Sabbisetti, VS, Cureton, P, Kenyon, V, Keating, L, et al
Frontiers in immunology. 2021;:624821
Abstract
Kidney disease affects 10% of the world population and is associated with increased mortality. Steroid-resistant nephrotic syndrome (SRNS) is a leading cause of end-stage kidney disease in children, often failing standard immunosuppression. Here, we report the results of a prospective study to investigate the immunological impact and safety of a gluten-free and dairy-free (GF/DF) diet in children with SRNS. The study was organized as a four-week summer camp implementing a strict GF/DF diet with prospective collection of blood, urine and stool in addition to whole exome sequencing WES of DNA of participants. Using flow cytometry, proteomic assays and microbiome metagenomics, we show that GF/DF diet had a major anti-inflammatory effect in all participants both at the protein and cellular level with 4-fold increase in T regulatory/T helper 17 cells ratio and the promotion of a favorable regulatory gut microbiota. Overall, GF/DF can have a significant anti-inflammatory effect in children with SRNS and further trials are warranted to investigate this potential dietary intervention in children with SRNS.
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Renal safety outcomes of spironolactone in patients with resistant hypertension.
Galceran, I, Vázquez, S, Durán, X, Outón, S, Pascual, J, Oliveras, A
Nefrologia. 2020;(4):414-420
Abstract
INTRODUCTION Resistant hypertension (RH) is a significant health problem with complex management. The aim of this study was to evaluate the risks and benefits of adding spironolactone to treat RH. MATERIAL AND METHODS In total, 216 patients with RH in whom spironolactone (12.5-25mg daily) was added as an antihypertensive were evaluated. One-hundred and twenty-five (125) were analysed retrospectively and 91 prospectively. Blood pressure (BP) and laboratory parameters (serum creatinine [sCrea], estimated glomerular filtration rate [eGFR] and serum potassium [sK]) were analysed at baseline and at 3-6-12 months after introducing spironolactone. RESULTS A change of systolic/diastolic BP (mean±standard deviation) of -10.9±2.7/-4.3±1.6mmHg at 3 months and -13.6±2.8/-6.0±1.6mmHg at 12 months; p<0.001 was observed. These values were confirmed with ambulatory-BP monitoring at 12 months. At 3 months, an increase in sCrea of 0.10±0.04mg/dl, a decrease in eGFR of -5.4±1.9ml/min/1.73m2 and an increase in sK of 0.3±0.1mmol/l; p<0.001 was observed for all cases. These changes were maintained after 12 months. There were no significant differences in changes of BP, sCrea, eGFR and sK between 3 and 12 months. Results of the retrospective and prospective cohorts separately were superimposable. In the prospective cohort, spironolactone was withdrawn in 9 patients (9.9%) because of adverse effects. CONCLUSIONS After 3 months with spironolactone, a decrease in BP associated with a decrease in the eGFR and an increase in sCrea and sK was observed. These changes were maintained at 12 months. Spironolactone is an effective and safe treatment for RH in patients with baseline eGFR ≥30ml/min/1.73m2.
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Changes in Central 24-h Ambulatory Blood Pressure and Hemodynamics 12 Months After Bariatric Surgery: the BARIHTA Study.
Oliveras, A, Goday, A, Sans, L, Arias, CE, Vazquez, S, Benaiges, D, Ramon, JM, Pascual, J
Obesity surgery. 2020;(1):195-205
Abstract
BACKGROUND Weight loss is associated to blood pressure (BP) reduction in obese patients. There is no information on central 24-h BP changes after bariatric surgery (BS). METHODS AND RESULTS In this study, we analyzed changes in 24-h BP 12 months following BS, with intermediate evaluations at 1, 3, and 6 months, in severely obese adults. The primary endpoint was aortic (central) 24-h systolic BP changes. Circadian BP patterns and hypertension resolution were also assessed. As secondary endpoints, we analyze changes in central 24-h diastolic BP as well as in all office and ambulatory peripheral BP parameters. Obese adults scheduled for BS as routine clinical care were recruited. We included 62 patients (39% with hypertension, 77% women, body mass index, 42.6 ± 5.5 kg/m2). Reduction in body weight was mean (IQR) 30.5% (26.2-34.4) 1 year after BS. Mean (95% CI) change in central 24-h systolic BP was - 3.1 mmHg (- 5.5 to - 0.7), p = 0.01 after adjustment for age, sex, and baseline hypertensive status. BP parameter changes were different between normotensives and hypertensives. Mean (95% CI) change in central 24-h systolic BP was - 5.2 mmHg (- 7.7 to - 2.7), p < 0.001, in normotensives and - 0.5 mmHg (- 5.1 to 4.0), p = 0.818, in hypertensives. There was a remission of hypertension in 48% of patients. Most patients had a reduced dipping pattern, similarly at baseline and 12 months after BS. CONCLUSIONS Among patients with severe obesity, there was a substantial central 24-h systolic BP decrease 12 months following BS. Importantly, this change was observed in those patients with normal BP at baseline. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT03115502.
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Atherosclerosis in Chronic Kidney Disease: More, Less, or Just Different?
Valdivielso, JM, Rodríguez-Puyol, D, Pascual, J, Barrios, C, Bermúdez-López, M, Sánchez-Niño, MD, Pérez-Fernández, M, Ortiz, A
Arteriosclerosis, thrombosis, and vascular biology. 2019;(10):1938-1966
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Abstract
Patients with chronic kidney disease (CKD) are at an increased risk of premature mortality, mainly from cardiovascular causes. The association between CKD on hemodialysis and accelerated atherosclerosis was described >40 years ago. However, more recently, it has been suggested that the increase in atherosclerosis risk is actually observed in early CKD stages, remaining stable thereafter. In this regard, interventions targeting the pathogenesis of atherosclerosis, such as statins, successful in the general population, have failed to benefit patients with very advanced CKD. This raises the issue of the relative contribution of atherosclerosis versus other forms of cardiovascular injury such as arteriosclerosis or myocardial injury to the increased cardiovascular risk in CKD. In this review, the pathophysiogical contributors to atherosclerosis in CKD that are shared with the general population, or specific to CKD, are discussed. The NEFRONA study (Observatorio Nacional de Atherosclerosis en NEFrologia) prospectively assessed the prevalence and progression of subclinical atherosclerosis (plaque in vascular ultrasound), confirming an increased prevalence of atherosclerosis in patients with moderate CKD. However, the adjusted odds ratio for subclinical atherosclerosis increased with CKD stage, suggesting a contribution of CKD itself to subclinical atherosclerosis. Progression of atherosclerosis was closely related to CKD progression as well as to the baseline presence of atheroma plaque, and to higher phosphate, uric acid, and ferritin and lower 25(OH) vitamin D levels. These insights may help design future clinical trials of stratified personalized medicine targeting atherosclerosis in patients with CKD. Future primary prevention trials should enroll patients with evidence of subclinical atherosclerosis and should provide a comprehensive control of all known risk factors in addition to testing any additional intervention or placebo.