Alice Sabatino

Alterations of intestinal barrier and microbiota in chronic kidney disease

Recent studies have highlighted the close relationship between the kidney and the gastrointestinal (GI) tract--frequently referred to as the kidney--gut axis--in patients with chronic kidney disease (CKD). In this regard, two important pathophysiological concepts have evolved: (i) production and accumulation of toxic end-products derived from increased bacterial fermentation of protein and other nitrogen-containing substances in the GI tract, (ii) translocation of endotoxins and live bacteria from gut lumen into the bloodstream, due to damage of the intestinal epithelial barrier and quantitative/qualitative alterations of the intestinal microbiota associated with the uraemic milieu. In both cases, these gut-centred alterations may have relevant systemic consequences in CKD patients, since they are able to trigger chronic inflammation, increase cardiovascular risk and worsen uraemic toxicity. The present review is thus focused on the kidney-gut axis in CKD, with special attention to the alterations of the intestinal barrier and the local microbiota (i.e. the collection of microorganisms living in a symbiotic coexistence with their host in the intestinal lumen) and their relationships to inflammation and uraemic toxicity in CKD. Moreover, we will summarize the most important clinical data suggesting the potential for nutritional modulation of gut-related inflammation and intestinal production of noxious by-products contributing to uraemic toxicity in CKD patients.

Intestinal Microbiota in Type 2 Diabetes and Chronic Kidney Disease

Purpose of the ReviewDiabetes mellitus is a major cause of kidney disease [chronic kidney disease (CKD) and end-stage renal disease (ESRD)] and are both characterized by an increased risk of cardiovascular events. Diabetes and kidney disease are also commonly associated with a chronic inflammatory state, which is now considered a non-traditional risk factor for atherosclerosis. In the case of type 2 diabetes mellitus (T2DM), inflammation is mainly a consequence of visceral obesity, while in the case of CKD or ESRD patients on dialysis, inflammation is caused by multiple factors, classically grouped as dialysis-related and non-dialysis-related. More recently, a key role has been credited to the intestinal microbiota in the pathogenesis of chronic inflammation present in both disease states. While many recent data on the intestinal microbiota and its relationship to chronic inflammation are available for CKD patients, very little is known regarding T2DM and patients with diabetic nephropathy. The aim of this review is to summarize and discuss the main pathophysiological issues of intestinal microbiota in patients with T2DM and CKD/ESRD.Recent FindingsThe presence of intestinal dysbiosis, along with increased intestinal permeability and high circulating levels of lipopolysaccharides, a condition known as “endotoxemia,” characterize T2DM, CKD, and ESRD on dialysis. The hallmark of intestinal dysbiosis is a reduction of saccharolytic microbes mainly producing short-chain fatty acids (SCFA) and, in the case of CKD/ESRD, an increase in proteolytic microbes that produce different substances possibly related to uremic toxicity.SummaryDysbiosis is associated with endotoxemia and chronic inflammation, with disruption of the intestinal barrier and depletion of beneficial bacteria producing SCFAs. T2DM and CKD/ESRD, whose coexistence is increasingly found in clinical practice, share similar negative effects on both intestinal microbiota and function. More studies are needed to characterize specific alterations of the intestinal microbiota in diabetic nephropathy and to assess possible effects of probiotic and prebiotic treatments in this setting.

Protein-energy wasting and nutritional supplementation in patients with end-stage renal disease on hemodialysis.

BACKGROUND & AIMS Protein-Energy Wasting (PEW) is the depletion of protein/energy stores observed in the most advanced stages of Chronic Kidney Disease (CKD). PEW is highly prevalent among patients on chronic dialysis, and is associated with adverse clinical outcomes, high morbidity/mortality rates and increased healthcare costs. This narrative review was aimed at exploring the pathophysiology of PEW in end-stage renal disease (ESRD) on hemodialysis. The main aspects of nutritional status evaluation, intervention and monitoring in this clinical setting were described, as well as the current approaches for the prevention and treatment of ESRD-related PEW. METHODS An exhaustive literature search was performed, in order to identify the relevant studies describing the epidemiology, pathogenesis, nutritional intervention and outcome of PEW in ESRD on hemodialysis. RESULTS AND CONCLUSION The pathogenesis of PEW is multifactorial. Loss of appetite, reduced intake of nutrients and altered lean body mass anabolism/catabolism play a key role. Nutritional approach to PEW should be based on a careful and periodic assessment of nutritional status and on timely dietary counseling. When protein and energy intakes are reduced, nutritional supplementation by means of specific oral formulations administered during the hemodialysis session may be the first-step intervention, and represents a valid nutritional approach to PEW prevention and treatment since it is easy, effective and safe. Omega-3 fatty acids and fibers, now included in commercially available preparations for renal patients, could lend relevant added value to macronutrient supplementation. When oral supplementation fails, intradialytic parenteral nutrition can be implemented in selected patients.

Barriers to Physical Activity in Chronic Hemodialysis Patients: A Single-Center Pilot Study in an Italian Dialysis Facility

Background/Aims: In patients on chronic dialysis a sedentary lifestyle is a strong, yet potentially modifiable, predictor of mortality. The present single-center pilot study evaluated social, psychological and clinical barriers that may hinder physical activity in this population. Methods: We explored the association between barriers to physical activity and sedentarism in adult patients at a chronic dialysis facility in Parma, Italy. We used different questionnaries exploring participation in physical activity, physical functioning, patient attitudes and preferences, and barriers to physical activity perceived by either patients or dialysis doctors and nurses. Results: We enrolled 104 patients, (67 males, 65%), mean age 69 years (79% of patients older than 60 years); median dialysis vintage 60 months (range 8-440); mean Charlson score 5.55, ADL (Activities of Daily Living) score 5.5. Ninety-two participants (88.5%) reported at least one barrier to physical activity. At multivariable analysis, after adjusting for age and sex, feeling to have too many medical problems (OR 2.99, 95% CI 1.27 to 7.07; P=0.012), chest pain (OR 10.78, 95% CI 1.28 to 90.28; P=0.029) and sadness (OR 2.59, 95% CI 1.10 to 6.09; P=0.030) were independently associated with physical inactivity. Lack of time for exercise counseling and the firm belief about low compliance/interest by the patients toward exercise were the most frequent barriers reported by doctors and nurses. Conclusion: We identified a number of patient-related and health personnel-related barriers to physical activity in patients on chronic dialysis. Solutions for these barriers should be addressed in future studies aimed at increasing the level of physical activity in this population.

Intradialytic parenteral nutrition in end-stage renal disease: Practical aspects, indications and limits

Protein-energy malnutrition (PEW) is highly prevalent in patients with end-stage renal disease (ESRD) and is associated with a significant increase of the already high mortality and morbidity risk typical of this clinical setting. Since a key mechanism of PEW in ESRD is inadequate nutrient intake, oral nutritional supplements are extensively employed, and have been demonstrated to be highly effective in PEW prevention and treatment. Intradialytic parenteral nutrition (IDPN), i.e. the administration of nutrients through the extracorporeal circuit during hemodialysis, has also been proposed as a modality of nutritional support for patients with ESRD. However, even though metabolic/nutritional status is improved by this nutritional approach, the evidence linking IDPN to decreased hospitalization rate and lower mortality risk is still scant. The aim of the present paper is to review the role of IDPN as a modality of nutritional supplementation for ESRD patients on hemodialysis. To this end, quantitative and qualitative aspects, practical management, the indications, and limits of IDPN are discussed. On the basis of the available evidence, it is suggested that IDPN is a safe and efficacious modality of nutritional support in ESRD, and could represent an adjunctive strategy for patients with reduced spontaneous dietary intake when intensive dietetic counseling and oral supplementation have failed.

Diet and enteral nutrition in patients with chronic kidney disease not on dialysis: a review focusing on fat, fiber and protein intake

The clinical data available on dietary requirements of patients with chronic kidney disease (CKD) not on dialysis are limited and largely inconclusive in terms of the renal, cardiovascular and nutritional outcomes achievable through dietary modifications. Restriction of protein intake during the early stages of CKD may in fact slow its progression, but at the same time this approach may also lead to protein-energy wasting, if energy intake is not adequate and properly monitored. Unfortunately, compliance to dietary recommendations is traditionally low in this patient population. A switch from saturated to mono- and polyunsaturated fats is generally recognized as advantageous for cardiac health; however, the benefits in term of renal function are largely unknown. Similarly, the association between dietary fiber intake and kidney disease is largely unknown. In fact, while there is evidence on the positive health effects of dietary fibers in the general population, nutritional guidelines for CKD lack formal recommendations concerning fiber intake. This paper reviews data and evidence from clinical trials and meta-analyses on renal and cardiovascular outcomes related to modifications in protein, fat and fiber intake. Suggestions for maintaining nutritional status through patient-oriented dietary patterns and enteral supplementation in CKD patients on conservative therapy are also presented.

Correction: Interaction of healthcare staff’s attitude with barriers to physical activity in hemodialysis patients: A quantitative assessment

Background and aim of the study In hemodialysis patients, sedentarism is a potentially modifiable mortality risk factor. We explored whether healthcare staff’s attitude towards exercise interacts with patient-perceived barriers in modifying the level of physical activity in this population. Methods In this prospective, cross-sectional, multicenter study we recruited 608 adult patients and 330 members of the healthcare staff in 16 hemodialysis units in Italy. We assessed patient-perceived barriers to, and healthcare staff’s attitude towards, exercise by specific questionnaires. We fitted multilevel linear models to analyze the relationships of either barriers or staff’s attitude, and their interaction, with a measure of patient self-reported physical activity (the Human Activity Profile–Adjusted Activity Score [HAP-AAS]), adjusting for multiple confounders. We also employed latent class analysis to dichotomize patients into those endorsing or not endorsing barriers. Results Most barriers were negatively associated with the HAP-AAS (adjusted change attributable to a given barrier ranging between -5.1 [“Feeling too old”, 95% Confidence Interval: -9.4 to -0.8] and -15.6 [“Ulcers on legs and feet”, 95%CI: -24.8 to -6.5]. We found a significant interaction between staff’s attitude and barriers (adjusted P values ranging between 0.03 [“I do not believe that it is physician’s or nurse’s role providing advice on exercise to patients on dialysis”] and 0.001 [“I do not often ask patients about exercise”]). A beneficial effect of a proactive staff’s attitude was evident only in patients not endorsing barriers. Conclusions Barriers and non-proactive staff’s attitude reduce physical activity in hemodialysis patients. Patients not endorsing barriers benefit the most from a proactive staff’s attitude.

Efficacy of Nutritional Interventions on Inflammatory Markers in Haemodialysis Patients: A Systematic Review and Limited Meta-Analysis

Low-grade chronic inflammation is prevalent in patients undergoing haemodialysis (HD) treatment and is linked to the development of premature atherosclerosis and mortality. The non-pharmacological approach to treat inflammation in HD patients through nutritional intervention is well cited. We aimed to assess the efficacy of different nutritional interventions at improving inflammatory outcomes in HD patients, based on markers such as C-reactive protein (CRP), interleukin-6 (IL-6), and tumour necrosis factor-α (TNF-α). We searched PubMed, Cochrane Library, and Embase for randomized controlled trials (RCT) published before June 2017. Inclusion criteria included RCTs on adult patients on maintenance HD treatment with duration of nutritional interventions for a minimum 4 weeks. Risk of bias was assessed using the Jadad score. In total, 46 RCTs experimenting different nutritional interventions were included in the review and categorized into polyphenols rich foods, omega-3 fatty acids, antioxidants, vitamin D, fibres, and probiotics. Meta-analyses indicated significant reduction in CRP levels by omega-3 fatty acids (Random model effect: −0.667 mg/L, p < 0.001) and vitamin E (fixed model effect: −0.257 mg/L, p = 0.005). Evidence for other groups of nutritional interventions was inconclusive. In conclusion, our meta-analysis provided evidence that omega-3 fatty acids and vitamin E could improve inflammatory outcomes in HD patients.

Energy and Protein in Critically Ill Patients with AKI: A Prospective, Multicenter Observational Study Using Indirect Calorimetry and Protein Catabolic Rate

The optimal nutritional support in Acute Kidney Injury (AKI) still remains an open issue. The present study was aimed at evaluating the validity of conventional predictive formulas for the calculation of both energy expenditure and protein needs in critically ill patients with AKI. A prospective, multicenter, observational study was conducted on adult patients hospitalized with AKI in three different intensive care units (ICU). Nutrient needs were estimated by different methods: the Guidelines of the European Society of Parenteral and Enteral Nutrition (ESPEN) for both calories and proteins, the Harris-Benedict equation, the Penn-State and Faisy-Fagon equations for energy. Actual energy and protein needs were repeatedly measured by indirect calorimetry (IC) and protein catabolic rate (PCR) until oral nutrition start, hospital discharge or renal function recovery. Forty-two patients with AKI were enrolled, with 130 IC and 123 PCR measurements obtained over 654 days of artificial nutrition. No predictive formula was precise enough, and Bland-Altman plots wide limits of agreement for all equations highlight the potential to under- or overfeed individual patients. Conventional predictive formulas may frequently lead to incorrect energy and protein need estimation. In critically ill patients with AKI an increased risk for under- or overfeeding is likely when nutrient needs are estimated instead of measured.

Nutrients, Nutraceuticals, and Xenobiotics Affecting Renal Health

Chronic kidney disease (CKD) affects 8–16% of the population worldwide. In developed countries, the most important risk factors for CKD are diabetes, hypertension, and obesity, calling into question the importance of educating and acting on lifestyles and nutrition. A balanced diet and supplementation can indeed support the maintenance of a general health status, including preservation of renal function, and can help to manage and curb the main risk factors for renal damage. While the concept of protein and salt restriction in nephrology is historically acknowledged, the role of some nutrients in renal health and the importance of nutrition as a preventative measure for renal care are less known. In this narrative review, we provide an overview of the demonstrated and potential actions of some selected nutrients, nutraceuticals, and xenobiotics on renal health and function. The direct and indirect effects of fiber, protein, fatty acids, curcumin, steviol glycosides, green tea, coffee, nitrates, nitrites, and alcohol on kidney health are reviewed here. In view of functional and personalized nutrition, understanding the renal and systemic effects of dietary components is essential since many chronic conditions, including CKD, are related to systemic dysfunctions such as chronic low-grade inflammation.