Association Between Weight Loss Before Deceased Donor Kidney Transplantation and Posttransplantation Outcomes.

RATIONALE & OBJECTIVE: There is debate on whether weight loss, a hallmark of frailty, signals higher risk for adverse outcomes among recipients of deceased donor kidney transplantation (DDKT). STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Using national Organ Procurement and Transplantation Network data, we included all DDKT recipients in the United States between December 4, 2004, and December 3, 2014, who were adults (aged ≥ 18 years) when listed for DDKT. EXPOSURES: Relative pre-DDKT weight change as a continuous predictor and categorized as <5% weight change from listing to DDKT, ≥5% to <10% weight loss, ≥10% weight loss, ≥5% to <10% weight gain, and ≥10% weight gain. OUTCOMES: We examined 3 post-DDKT outcomes: (1) transplant hospitalization length of stay (LOS) in days, (2) all-cause graft failure, and (3) mortality. ANALYTIC APPROACH: Unadjusted fractional polynomial methods, multivariable log-gamma models, and multivariable Cox proportional hazards models. RESULTS: Among 94,465 recipients of DDKT, median pre-DDKT weight change was 0 (interquartile range, -3.5 to +3.9) kg. There were nonlinear unadjusted associations between relative pre-DDKT weight loss and longer transplant hospitalization LOS, higher all-cause graft loss, and higher mortality. Compared with recipients with <5% pre-DDKT weight change (n = 49,366; 52%), recipients who lost ≥10% of their listing weight (n = 10,614; 11%) had 0.66 (95% CI, 0.23-1.09) days longer average transplant hospitalization LOS (P = 0.003), 1.11-fold higher graft loss (adjusted HR [aHR], 1.11; 95% CI, 1.06-1.17; P < 0.001), and 1.18-fold higher mortality (aHR, 1.18; 95% CI, 1.11-1.25; P < 0.001) independent of recipient, donor, and transplant factors. Pre-DDKT dialysis exposure, listing body mass index category, and waiting time modified the association of pre-DDKT weight change with hospital LOS (interaction P < 0.10), but not with all-cause graft loss and mortality. LIMITATIONS: Unmeasured confounders and inability to identify volitional weight change. Also, the higher significance level set to increase the power of detecting interactions with the fixed sample size may have resulted in increased risk for type 1 error. CONCLUSIONS: DDKT recipients with ≥10% pre-DDKT weight loss are at increased risk for adverse outcomes and may benefit from augmented support post-DDKT.

Exacerbated oxidative stress in the fasting liver according to fuel partitioning.

Complete starvation may prove lethal due to excessive loss of body proteins. However, it is still not completely understood whether responses to food deprivation are time-dependently induced or triggered in relation with the successive phases of protein sparing and wasting that characterize prolonged fasting. As the liver has a wide range of vital functions, we examined the hepatic regulatory mechanisms elicited during prolonged fasting. We showed that fasting-induced transcriptome/proteome changes occur in close relation with fuel partitioning, independently of ATP levels. Omics data suggesting a worsening of oxidative stress during the proteolytic stage of fasting were further validated using biochemical assays. Low levels of antioxidant factors were indeed paralleled by their decreased activity that could be impaired by low NADPH levels. Oxidative damage to lipids and proteins was accordingly increased only during late fasting. At this stage, the gene/protein expression of several chaperones was also repressed. Together with the impairment of metabolic achievements, a vicious cycle involving protein misfolding and oxidative stress could jeopardize liver function when the proteolytic stage of fasting is reached. Thus, monitoring of liver impairments should help to better manage or treat catabolic and/or oxidative stress conditions, such as ageing and degeneration.

A Yet Unrecognized Cause of Unusually High Levothyroxine Replacement Dose: Protein-Losing Enteropathy.

Background/Objective: Large amount of protein wasting such as in nephrotic syndrome is a rare cause of high levothyroxine (LT4) replacement dose requirement. A case has been reported here that demonstrates that protein-losing enteropathy is a novel and yet unrecognized cause of high LT4 replacement dose requirement. Case Report: A 21-year-old man with congenital heart disease was found to have primary hypothyroidism and started LT4 replacement. His weight was approximately 60 kg. Nine months later, while he was taking LT4 100 µg daily, thyroid-stimulating hormone (TSH) level was >200 µIU/mL (normal range, 0.3-4.7 µIU/mL) and free thyroxine level was 0.3 ng/dL (normal range, 0.8-1.7 ng/dL). The patient had excellent medication compliance. LT4 dose was increased to 200 µg daily and then 200 and 300 µg every other day. Two months later, TSH level was 3.1 µIU/mL and free thyroxine level was 1.1 ng/dL. He did not exhibit malabsorption or proteinuria. His albumin levels had been low since the age of 18 years (mostly <2.5 g/dL). Stool α-1-antitrypsin levels and calprotectin levels were elevated on multiple occasions. Protein-losing enteropathy was diagnosed. Discussion: As most circulating LT4 is protein-bound, loss of protein-bound LT4 due to protein-losing enteropathy is the most plausible cause of the large LT4 dose requirement in this case. Conclusion: This case demonstrates that protein-losing enteropathy, through loss of protein-bound thyroxine, is a novel and yet unrecognized cause of high LT4 replacement dose requirement. In patients who require high LT4 dose for unclear reasons, albumin levels should be examined and protein wasting be suspected in those with low albumin levels.

Soporte nutricional en tratamiento sustitutivo renal (hemodiálisis). Revisión y actualización bibliográfica / Nutrition support in renal substitute treatment (hemodialysis) Review and bibliographic update

Resumen Introducción: los pacientes en hemodiálisis (HD) presentan alta prevalencia de desgaste proteico energético (DPE), caracterizado por pérdida simultánea de grasa y de músculo, inflamación y menor supervivencia. La implementación del soporte nutricional (SN) es fundamental en el tratamiento precoz de la malnutrición. El objetivo general de esta revisión fue analizar la evidencia que existe sobre los resultados del SN en pacientes en HD con desnutrición establecida y/o con riesgo de padecerla y como objetivo específico detallar el efecto del SN en relación a parámetros antropométricos, bioquímicos y clínicos en pacientes en HD. Materiales y método: revisión y actualización bibliográfica, no sistemática. Se incluyeron revisiones sistemáticas, metaanálisis y artículos científicos con antigüedad inferior a 10 años de publicación, que estudiaron efectos de nutrición parenteral intradialítica (NPID) y/o suplemento nutricional oral (SNO) en adultos mayores a 18 años en HD, diseño comparativo intra o intersujeto y tiempo de seguimiento mínimo de 3 meses. Se realizaron búsquedas en Google Scholar, PudMed y Medline entre enero de 2018 a enero 2019. Fueron recolectados y analizados 17 estudios, con un total de 31.761 pacientes. Resultados y conclusiones: el asesoramiento nutricional y el SNO son la primera línea para abordar la malnutrición en HD. La implementación precoz del SN en cualquiera de sus formas es una estrategia eficaz que tiene el potencial de mejorar parámetros antropométricos, bioquímicos, calidad de vida y morbimortalidad. La mayoría de los estudios analizados presentan limitantes como pequeño tamaño muestral, heterogeneidad de la población y diversidad en los tiempos de seguimiento. Se requieren más estudios prospectivos y controlados para evaluar los efectos del SN sobre el estado nutricional y la sobrevida de pacientes en HD y para poder verificar la seguridad y eficacia de la intervención nutricional y su impacto en los resultados clínicos.

Abstract Introduction: hemodialysis (HD) patients have a high prevalence of protein energy wasting, characterized by simultaneous loss of fat and muscle, inflammation and reduced survival. The implementation of nutritional support (NS) is essential in the early treatment of malnutrition. The general objective of this review was to analyze the evidence that exists on the results of the nutritional support in HD patients with established malnutrition and / or at risk of suffering it and, as a specific objective, to detail the effect of the nutritional support in relation to anthropometric, biochemical and clinical parameters in HD patients. Materials and method: review and bibliographic update, not systematic. Systematic reviews were included, as well as meta-analyzes and scientific articles less than 10 years old, that studied the effects of Intradialytic Parenteral Nutrition and / or oral nutritional supplements (ONS) in adults over 18 years old in HD, intra or inter-subject comparative design and minimum follow-up of 3 months. Searches on Google Scholar, PudMed and Medline were carried out between January 2018 and January 2019. 17 studies were collected and analyzed, with a total of 31,761 patients. Results and conclusions: nutritional assessment and ONS are the first line to address malnutrition in HD. The quick implementation of NS in any of its forms is an effective strategy that has the potential to improve anthropometric and biochemical parameters, quality of life, and morbidity. Most of the studies analyzed have limitations such as small sample size, heterogeneity of the population and diversity in follow-up times. Further prospective and controlled studies are required to assess the effects of nutritional support on the nutritional status and survival of HD patients and to verify the safety and efficacy of nutritional intervention and its impact on clinical results.