Diuretic Resistance in Cardio-Nephrology: Role of Pharmacokinetics, Hypochloremia, and Kidney Remodeling

Background: Diuretic resistance is among the most challenging problems that the cardio-nephrologist must address in daily clinical practice, with a considerable burden on hospital admissions and health care costs. Indeed, loop diuretics are the first-line therapy to overcome fluid overload in heart failure patients. The pathophysiological mechanisms of fluid and sodium retention are complex and depend on several neuro-hormonal signals mainly acting on sodium reabsorption along the renal tubule. Consequently, doses and administration modalities of diuretics must be carefully tailored to patients in order to overcome under- or overtreatment. The frequent and tricky development of diuretic resistance depends in part on post-diuretic sodium retention, reduced tubular secretion of the drug, and reduced sodium/chloride sensing. Sodium and chloride depletions have been recently shown to be major factors mediating these processes. Aquaretics and high-saline infusions have been recently suggested in cases of hyponatremic conditions. This review discusses the limitations and strengths of these approaches. Summary: Long-term diuretic use may lead to diuretic resistance in cardio-renal syndromes. To overcome this complication intravenous administration of loop diuretics and a combination of different diuretic classes have been proposed. In the presence of hyponatremia, high-saline solutions in addition to loop diuretics might be beneficial, whereas aquaretics require caution to avoid overcorrection. Key Messages: Diuretic resistance is a central theme for cardio-renal syndromes. Hyponatremia and hypochloremia may be part of the mechanisms for diuretic resistance. Aquaretics and high-saline solutions have been proposed as possible new therapeutic solutions

Peritoneal dialysis in older adults: evaluation of clinical, nutritional, metabolic outcomes, and quality of life

The number of older adults requiring dialysis is increasing worldwide, whereas the use of peritoneal dialysis (PD) in this population is lower respect to younger patients, despite the theoretical advantages of PD respect to hemodialysis. This is most likely due to the concern that older patients may not be able to correctly and safely manage PD. We aimed to prospectively compare clinical, nutritional and metabolic outcomes and measures of quality of life between younger (<65years old) and older (≥65years old) patients on PD. PD patients were enrolled and divided into 2 groups according to age (Group A < 65 years, Group B ≥ 65 years). Clinical and instrumental parameters, and quality of life were evaluated at baseline (start of PD) (T0) and at 24 months (T1). Technique survival, mortality, total number of hospitalizations, and the index of peritonitis (episodes of peritonitis/month) were also evaluated. Fifty-one patients starting PD were enrolled. Group A included 22 patients (48.7±8.3 years), and Group B consisted of 29 patients (74.1 ± 6.4 years). At baseline, the 2 groups showed no differences in cognitive status, whereas Group A showed higher total cholesterol (p=0.03), LDL (p=0.03), and triglycerides (p=0.03) levels and lower body mass index (p=0.02) and carotid intima media thickness (p<0.0001) with respect to Group B. At T1 Group B showed, compared to baseline, a significant reduction in albumin (p<0.0001) and phosphorus (p=0.045) levels, while no significant differences on body composition, technique survival, total number of hospitalizations, index of peritonitis and quality of life indices were observed. Our data do not show clinically relevant barriers to use PD in older adult patients, supporting its use in this population. Nutritional and metabolic parameters should be carefully monitored in older PD patients

Fatigue in Patients on Chronic Hemodialysis: The Role of Indoleamine 2,3-Dioxygenase (IDO) Activity, Interleukin-6, and Muscularity

Fatigue is a frequent symptom in hemodialysis (HD), and the indolamine-2,3-dioxygenase (IDO) metabolic trap has been hypothesized in the pathogenesis of fatigue. The association between IDO activity according to fatigue and its relationship with muscle mass and function in HD patients was verified. Chronic HD patients were considered, and fatigue was assessed. The plasma kynurenines and tryptophan ratio (Kyn/Trp), as surrogate of IDO activity, and interleukin (IL)-6 were measured. Muscularity was assessed by BIA and muscle strength by hand-grip dynamometer. 50 HD patients were enrolled, and fatigue was present in 24% of the cohort. Patients with fatigue showed higher Kyn/Trp (p = 0.005), were older (p = 0.007), and IL-6 levels resulted higher than in non-fatigue patients (p < 0.001). HD patients with fatigue showed lower intracellular water (surrogate of muscle mass) (p < 0.001), as well as lower hand grip strength (p = 0.02). The Kyn/Trp ratio positively correlated with IL-6 and ECW/ICW (p = 0.004 and p = 0.014). By logistic regression analysis, higher ICW/h(2) was associated with lower odds of fatigue (OR, 0.10; 95% CI, 0.01 to 0.73). In conclusion, our cohort fatigue was associated with a higher Kyn/Trp ratio, indicating a modulation of IDO activity. The Kyn/Trp ratio correlated with IL-6, suggesting a potential role of IDO and inflammation in inducing fatigue and changes in muscularity

Association between growth differentiation factor-15 (GDF-15) serum levels, anorexia and low muscle mass among cancer patients

The pathophysiology of cancer anorexia is complex and serum biomarkers, including growth and differentiation factor(s) (GDF), may be modulated. We explored the association(s) between GDF-15 serum levels and anorexia and, secondarily, with low muscle mass and body weight loss in cancer patients. We considered gastrointestinal and lung cancer patients (CP) and healthy BMI-matched controls. The FAACT-questionnaire was administered to diagnose anorexia and we calculated the L3-SMI by CT scan to assess low muscularity, setting their cutoff values at the lowest tertile. GDF-15 serum levels were assessed by ELISA. We enrolled 59 CP and 30 controls; among CP, 25 were affected by gastrointestinal and 34 by lung cancer. Anorexia was present in 36% of CP. Gastrointestinal CP resulted more anorexic compared to lung CP (p = 0.0067). Low muscle mass was present in 33.9% of CP and L3-SMI was lower in gastrointestinal compared to lung CP (p = 0.049). The GDF-15 levels were higher in CP vs. controls (p = 0.00016), as well as in anorexic vs. non-anorexic CP (p = 0.005) and vs. controls (p < 0.0001). Gastrointestinal CP showed higher GDF-15 levels vs. lung CP (p = 0.0004). No difference was found in GDF-15 between CP with low muscle mass and those with moderate/high muscularity and between patients with body weight loss and those with stable weight. Our data support the involvement of GDF-15 in the pathogenesis of cancer anorexia. The mechanisms of action of GDF-15 in cancer should be further clarified also regarding the changes in muscularity

Nutrition support for treating cancer-associated weight loss: an update

PURPOSE OF REVIEW: Patients with cancer present high risk for involuntary body weight loss and reduced food intake, which, contributing to progressive tissue wasting and affecting the nutritional status, are often under-estimated in the clinical practice. In this article, we aimed at focusing on cancer-associated weight loss and investigating recent evidences on the indications of nutritional interventions to treat this condition.RECENT FINDINGS: During the last few years, increased emphasis has been addressed on the mechanisms underlying body weight loss in cancer that can be induced by either cancer metabolism and inflammation, either several side-effects of the anticancer treatments. This led to consider clinical parameters, such as BMI, body weight change and food intake, and their modification overtime, in predicting patient's overall survival. In this light, nutritional support has to be considered to maintain or restore nutritional status, improve tolerance to oncological therapies, and ameliorate physical performance and quality of life.SUMMARY: Increased awareness on weight loss in cancer patients and on cancer cachexia is needed to carry out a nutritional assessment at an early stage of cancer journey and to establish its management and nutritional support to obtain advantages in terms of treatment tolerance and clinical outcomes

Foods and their components promoting gastrointestinal cancer

Purpose of review Cancer represents one of the most feared diseases. Despite an increasing number of available scientific data, most people remain unaware of those basic dietary and healthy lifestyle measures, which might reduce their risk to develop cancer. Environmental factors, diet, and lifestyle play a crucial role in the development of several different neoplastic diseases, particularly gastrointestinal cancer. In this article, we aimed at focusing on foods and their components able to increase gastrointestinal cancer risk. Recent findings During the last few years, major emphasis has been addressed on the relation between red meat and gastrointestinal cancer. Many potential mechanisms linked red meat consumption and cancer risk, including heterocyclic amines, polycyclic aromatic hydrocarbons, N-nitroso compounds, and heme iron. Other chemical substances, contaminating food, such as acrylamide, showed gastrointestinal carcinogenic properties. Summary Correct diet and lifestyle are clinically relevant strategies in preventing gastrointestinal cancer. In the fight against cancer, nutritional educative intervention programs are necessary to spread the knowledge on healthy eating and appropriate nutrition to reduce cancer risk. © 2016 Wolters Kluwer Health, Inc

Omega-3 Polyunsaturated Fatty Acids in Critical Illness: Anti-Inflammatory, Proresolving, or Both?

Prognosis and outcomes of critically ill patients are strictly related with inflammatory status. Inflammation involves a multitude of interactions between different cell types and chemical mediators. Omega-3 polyunsaturated fatty acids (PUFAs), mainly represented by eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are able to inhibit different pathways including leukocyte chemotaxis, adhesion molecule expression and interactions, and production of inflammatory cytokines, through the action of specialized proresolving mediators (SPMs). SPMs from omega-6 fatty acids, such as lipoxins, and from omega-3 fatty acids such as resolvins, protectins, and maresins, act in reducing/resolving the inflammatory process in critical diseases, stimulating the phases of resolution of inflammation. In this light, the resolution of inflammation is nowadays considered as an active process, instead of a passive process. In critical illness, SPMs regulate the excessive posttrauma inflammatory response, protecting organs from damage. This review focuses on the role of omega-3 PUFAs as pharma nutrition agents in acute inflammatory conditions, highlighting their effects as anti-inflammatory or proresolving agents