The role of exercise training on cardiovascular risk factors and heart disease in patients with chronic kidney disease G3-G5 and G5D: A Clinical Consensus Statement of the European Association of Preventive Cardiology (EAPC) of the ESC and the European Association of Rehabilitation in Chronic Kidney Disease (EURORECKD).

Cardiovascular (CV) morbidity and mortality is high in patients with chronic kidney disease (CKD). Most patients reveal a high prevalence of CV risk factors such as diabetes or arterial hypertension and many have manifest cardiovascular disease (CVD), such as coronary artery disease and chronic heart failure with an increased risk of clinical events including sudden cardiac death. Diabetes mellitus and hypertension contribute to the development of CKD and the prevalence of CKD is in the range of 20%-65% in diabetic and 30%-50% in hypertensive patients. Therefore, prevention and optimal treatment of CV risk factors and comorbidities are key strategies to reduce CV risk and improve survival in CKD. Beyond common CV risk factors, patients with CKD are often physically inactive and have low physical function leading to subsequent frailty with muscle fatigue and weakness, sarcopenia and increased risk of falling. Consequently, the economic health burden of CKD is high, requiring feasible strategies to counteract this vicious cycle. Regular physical activity and exercise training have been shown to be effective in improving risk factors, reducing CVD and reducing frailty and falls. Nonetheless, combining exercise training and a healthy lifestyle with pharmacological treatment is not frequently applied in clinical practice. For that reason, this Clinical Consensus Statement reviews the current literature and provides evidence-based data regarding the role of exercise training in reducing CV and overall burden in patients with CKD. The aim is to increase awareness among cardiologists, nephrologists, and health care professionals of the potential of exercise therapy in order to encourage implementation of exercise training in clinical practice, eventually reducing CV risk and disease, as well as reducing frailty in patients with CKD G3 to G5D.

Physical activity and exercise programs for kidney patients: an Italian survey of nephrology centres.

BACKGROUND: Data on exercise activities in place, and on the interest for developing them in Nephrology Services in Italy is limited. To address this gap, we carried out this cross-sectional study to investigate the status of physical activity and exercise programs available in Italian Nephrology Centres. Additionally, research priorities on this topic were examined. METHODS: We developed a 14-item electronic survey, which consisted of multiple-choice questions covering exercise training programs, physical assessment, barriers to exercise practice and to exercise programs, exercise and physical activity counselling practices, perceived exercise benefits, literature evidence, and research priorities. Data on the characteristics of the centres were also collected. RESULTS: Sixty-two responses from Italian nephrology centres were collected. Ninety-three percent of the respondents were aware of the scientific evidence supporting the benefits of regular exercise programs for chronic kidney disease (CKD) patients. Additionally, in 75% of centres the nephrologists believed that physical activity counselling should be performed by the nephrologists. However, only 26% of centres provided exercise programs, mainly for dialysis patients, and 63% never or infrequently assessed physical activity in the context of patient management. Eighty-nine percent of centres reported barriers to implementing exercise programs, including lack of funding, institutional disinterest, patient refusal, and negative attitudes of the healthcare personnel. Forty-six research priorities related to exercise in CKD patients were suggested, with the majority focusing on impact of exercise programs and physical activity on cardiovascular, nutritional, and psychosocial outcomes. CONCLUSION: This survey highlights the limited availability of exercise programs and physical activity evaluation in clinical practice in Italian Nephrology Centres. However, the survey also revealed a strong interest for counselling CKD patients on physical activity and implementing exercise prescriptions and interventions.

ABCs of hemodiafiltration prescription: The Pisa style.

In end-stage kidney disease patients, hemodiafiltration, a mixed diffusive-convective technique, has shown beneficial effects in terms of improvement of anemia, inflammation, mineral bone disorders, malnutrition and cardiovascular stability. Greater convective volume exchange was also associated with improved overall and cardiovascular survival. However, absolute target threshold volume would be difficult to define and achieve in daily clinical practice, mainly because of differences in patient size. Convective volumes standardized for body surface area would appear to be the simplest approach in clinical practice. Several factors can affect achievement of optimal convective volume, with vascular access being the main limiting factor. Based on our own clinical experience, hemodiafiltration is a more effective and preferable dialysis technique but only when a target convective volume greater than 20 L can be achieved. Conversely, standard high flux hemodialysis or expanded hemodialysis may be helpful and valuable alternative dialysis techniques.

RAASi Therapy Attenuates the Association between 24-h Urinary Potassium Excretion and Dietary Potassium Intake in CKD Patients.

The aim of this study was to evaluate urinary potassium (K) excretion as a reliable marker of dietary K intake, in a cohort of CKD patients with or without Renin-Angiotensin-Aldosterone System (RAAS) inhibitor therapy. One hundred and thirty-eight consecutive out-patients (51 f and 87 m) aged 60 ± 13 years and affected by CKD stage 3-4, who were metabolically and nutritionally stable, entered the study between November 2021 and October 2022. No difference was observed between patients with (n = 85) or without (n = 53) RAAS inhibitor therapy, regarding dietary intakes, blood biochemistry, and 24-h urine excretion parameters. Considering all patients, urinary K showed a weak relationship with eGFR (r = 0.243, p < 0.01), and with dietary K intake (r = 0.184, p < 0.05). Serum K was not associated with dietary K intake, but an inverse relationship was observed with eGFR (r = -0.269, p < 0.01). When patients were examined depending on whether they were receiving RAAS inhibitor therapy, the weak inverse relationship between serum K and eGFR was maintained in both groups. Conversely, urinary K excretion remained positively associated with dietary K intake only in the no RAAS inhibitor group. In conclusion, 24-h urine K excretion may be used as a surrogate of K intake, but RAAS inhibitor therapy reduces the association between 24-h urine K excretion and dietary K intake in CKD patients.

Nutritional Treatment as a Synergic Intervention to Pharmacological Therapy in CKD Patients.

Nutritional and pharmacological therapies represent the basis for non-dialysis management of CKD patients. Both kinds of treatments have specific and unchangeable features and, in certain cases, they also have a synergic action. For instance, dietary sodium restriction enhances the anti-proteinuric and anti-hypertensive effects of RAAS inhibitors, low protein intake reduces insulin resistance and enhances responsiveness to epoetin therapy, and phosphate restriction cooperates with phosphate binders to reduce the net phosphate intake and its consequences on mineral metabolism. It can also be speculated that a reduction in either protein or salt intake can potentially amplify the anti-proteinuric and reno-protective effects of SGLT2 inhibitors. Therefore, the synergic use of nutritional therapy and medications optimizes CKD treatment. Quality of care management is improved and becomes more effective when compared to either treatment alone, with lower costs and fewer risks of unwanted side effects. This narrative review summarizes the established evidence of the synergistic action carried out by the combination of nutritional and pharmacological treatments, underlying how they are not alternative but complementary in CKD patient care.

Vitamin D and Calcium Supplementation and Urolithiasis: A Controversial and Multifaceted Relationship.

Patients with urolithiasis, and particularly those with hypercalciuria, frequently have a marked reduction of bone mineral content up to the levels of osteoporosis, with a significant increase in bone fracture risk. For these reasons, the indication to prescribe vitamin D and/or calcium supplementations is very frequent in such patients. On the other hand, both calcium supplementation, and even more vitamin D therapy, can worsen the risk of developing urolithiasis by increasing calcium, phosphate, and oxalate urinary excretion. Despite the clinical and practical relevance of this issue, the evidence on this topic is scarce and contradictory. Therefore, some concerns exist about how and whether to prescribe such supplements to a patient with a history of kidney stones. In this narrative review, we resume some pivotal pathophysiological concepts strictly related to the dealt topic, and we draw some considerations and personal opinions on the pros and cons of such prescriptions. Finally, we share with the reader our pragmatic algorithm for handling the urolithiasis risk in patients who have strong indications to be prescribed vitamin D and calcium supplementations.

Nutritional status and the risk of malnutrition in older adults with chronic kidney disease - implications for low protein intake and nutritional care: A critical review endorsed by ERN-ERA and ESPEN.

Increased life expectancy is posing unprecedented challenges to healthcare systems worldwide. These include a sharp increase in the prevalence of chronic kidney disease (CKD) and of impaired nutritional status with malnutrition-protein-energy wasting (PEW) that portends worse clinical outcomes, including reduced survival. In older adults with CKD, a nutritional dilemma occurs when indications from geriatric nutritional guidelines to maintain the protein intake above 1.0 g/kg/day to prevent malnutrition need to be adapted to the indications from nephrology guidelines, to reduce protein intake in order to prevent or slow CKD progression and improve metabolic abnormalities. To address these issues, the European Society for Clinical Nutrition and Metabolism (ESPEN) and the European Renal Nutrition group of the European Renal Association (ERN-ERA) have prepared this conjoint critical review paper, whose objective is to summarize key concepts related to prevention and treatment of both CKD progression and impaired nutritional status using dietary approaches, and to provide guidance on how to define optimal protein and energy intake in older adults with differing severity of CKD. Overall, the authors support careful assessment to identify the most urgent clinical challenge and the consequent treatment priority. The presence of malnutrition-protein-energy wasting (PEW) suggests the need to avoid or postpone protein restriction, particularly in the presence of stable kidney function and considering the patient's preferences and quality of life. CKD progression and advanced CKD stage support prioritization of protein restriction in the presence of a good nutritional status. Individual risk-benefit assessment and appropriate nutritional monitoring should guide the decision-making process. Higher awareness of the challenges of nutritional care in older adult patients with CKD is needed to improve care and outcomes. Research is advocated to support evidence-based recommendations, which we still lack for this increasingly large patient subgroup.

Mediterranean Dietary Pattern Adjusted for CKD Patients: The MedRen Diet.

A number of studies in the general population showed that healthy dietary patterns, such as the Mediterranean Diet, can improve or prevent the development of several chronic diseases and are associated with a significant reduction in all-cause and cardiovascular mortality. The Mediterranean diet may also have favorable effects for the prevention of chronic kidney disease (CKD), but no evidence of renoprotection exists in CKD patients. The Mediterranean Renal (MedRen) diet is an adaptation of the Mediterranean diet recommendations comprising a quantitative reduction in the RDA values of protein, salt and phosphate intake for the general population. Hence, MedRen supplies 0.8 g/Kg of protein, 6 g of salt and less than 800 mg of phosphate daily. Obviously, there is a preference for products of plant origin, which contain more alkali, fibers, unsaturated fatty acids than animal-based food. The MedRen diet can be implemented easily in mild-to-moderate stages of CKD with good results, both in terms of adherence to prescriptions and metabolic compensation. In our opinion, it should be the first step of CKD stage 3 nutritional management. This paper describes the features and reports our experience in the implementation of the MedRen diet as an early nutritional approach to CKD.

Diagnosis, Prevalence and Significance of Obesity in a Cohort of CKD Patients.

BACKGROUND: data regarding the association between obesity and morbidity/mortality in patients with chronic kidney disease (CKD) are uncertain and sometimes contradictory. The aims of our study were to determine the associations among different measures of obesity and adiposity, and the risk of all-cause mortality or dialysis entry in stage 3-5 CKD patients. MATERIALS: this observational cohort study included 178 CKD patients followed for a median of 71 months. Biochemistry, anthropometric measures such as body mass index (BMI), waist-to-hip ratio, mid-arm muscle circumference (MAMC) and body composition by bioimpedance analysis were evaluated. RESULTS: we found a weak agreement between BMI and other measures of adiposity. In multivariable regression analysis, all measures of obesity such as BMI, waist circumference and waist-to-height ratio were not associated with dialysis entry and/or mortality. Instead, MAMC was associated with dialysis entry HR 0.82 [95% CI: 0.75-0.89] and high FM% with mortality HR 2.08 [95% CI: 1.04-4.18]. CONCLUSIONS: in our CKD population, lower MAMC was predictive of dialysis commencing, while a higher percentage of fatty mass was a predictor of mortality. Instead, obesity, as defined by BMI, is not associated with dialysis commencing or all-cause mortality.

Kidney Stone Prevention: Is There a Role for Complementary and Alternative Medicine?

Complementary and alternative medicine (CAM) is often implemented in kidney stone patients. It consists of preparations including different ingredients, such as herbs, probiotics, and vitamins, often together with alkali, that are classified within the dietary supplementation category. The majority of dietary supplements claiming to treat or prevent kidney stones contain ingredients with conflicting or no scientific evidence to support their claims. Clinicians should advise stone formers that the effects of most supplements are unknown or unstudied in humans and that the absence of evidence does not imply absence of potential harm. Unfortunately, the CAM preparation consists of a mix of different molecules, often including alkali, with different potential mechanisms of action and, even when favorable results are reported, the role of the single molecules cannot be assessed. Despite all these concerns, CAM products remain quite popular among kidney stone patients. The scarce knowledge in this field prevents one from recommending CAM products in daily clinical practice; only a weak suggestion for their use in kidney stone patients may be reasonable.

Idiopathic Retroperitoneal Fibrosis: What Is the Optimal Clinical Approach for Long-Term Preservation of Renal Function?

BACKGROUND: The aim of this study was to investigate the long-term effects of ureteral stenting and the exact timing of stent removal in favor of surgery in patients with idiopathic retroperitoneal fibrosis (IRF). SUMMARY: Medline research terms of "idiopathic retroperitoneal fibrosis" AND " medical therapy" OR "ureteral stenting" OR "surgical treatment" were done. Systematic reviews and observational and clinical studies were analyzed to obtain indication regarding the objective of the study for a narrative review. Ninety-two papers were analyzed. The treatment of IRF includes the monitoring of retroperitoneal fibrotic process spread and the prevention of abdominal organs entrapment. Treatment of ureteral obstruction includes medical therapy and ureteral stenting (US) or percutaneous nephrostomy (PNS) to overcome the worsening of renal function. Up to now, the timing of US or PNS removal is not yet clear, both for the complexity of evaluating the efficacy of the medical therapy and demonstrating the resolution of obstructive nephropathy. Moreover, it is not yet clear if the long-term ureteral stent placement or PNS is able to maintain an efficient renal function. Ureterolysis with a laparoscopic robot-assisted approach is now considered as an ultimate treatment for ureteral obstruction, limiting the progression of kidney impairment and improving the quality of life of patients, although nephrologists are generally abdicant regarding the potential switch toward the surgical approach. KEY MESSAGES: Prospective studies regarding the long-term effects of US on the renal function impairment in patients with IRF should be structured to obtain adequate information on the exact timing for the surgical approach.

Potassium Bioaccessibility in Uncooked and Cooked Plant Foods: Results from a Static In Vitro Digestion Methodology.

Hyperkalemia is a major concern in chronic kidney disease and in end-stage renal disease, representing a predictor of hospitalization and mortality. To prevent and treat hyperkalemia, dietary management is of great clinical interest. Currently, the growing use of plant-based diets causes an increasing concern about potassium load in renal patients. The aim of this study was to assess the bioaccessibility of potassium in vegetables, concerning all aspects of the plants (fruit, flower, root, tuber, leaf and seed) and to what extent different boiling techniques affect potassium content and bioaccessibility of plant-based foods. Bioaccessibility was evaluated by an in vitro digestion methodology, resembling human gastro-intestinal tract. Potassium content was higher in seeds and leaves, despite it not being possible to define a common "rule" according to the type of organ, namely seed, leaf or fruit. Boiling reduced potassium content in all vegetables excluding carrot, zucchini, and cauliflower; boiling starting from cold water contributed to a greater reduction of the potassium content in potato, peas, and beans. Bioaccessibility after in vitro digestion ranged from 12 (peas) to 93% (tomato) regardless of species and organs. Higher bioaccessibility was found in spinach, chicory, zucchini, tomato, kiwi, and cauliflower, and lower bioaccessibility in peas. Potassium from leaf resulted in the highest bioaccessibility after digestion; as a whole potassium bioaccessibility in the fruits and vegetables studied was 67% on average, with differences in relation to the different organs and species. Further, considering the method of boiling to reduce potassium content, these data indicate that the effective potassium load from plant-based foods may be lower than originally expected. This supports the clinical advices to maintain a wide use of plant-based food in the management of renal patients.

Processed Plant-Based Foods for CKD Patients: Good Choice, but Be Aware.

The beneficial effects of vegetarian diets are known in the general population and in patients with chronic kidney disease (CKD). In recent years, the market has developed a number of processed plant-based products because of several factors (lifestyle changes, ethical concerns, and sustainability). The composition in terms of nutrients, ingredients, and additives of 560 products available on the market and on online shopping sites was analyzed to understand the characteristics of these products. Processed plant-based meat substitutes have a higher content of salt (+467%), lipids (+26%), mostly unsaturated, and fiber with respect to regular animal-based ones. Protein content is lower (-40%) in plant-based products with respect to corresponding animal ones. Of the 49 additives on the label (on average 2 per product), 20 contain phosphorus, sodium, potassium, or nitrogen. Several plant-based processed products may contain elevated amounts of salt and additives, which make them not optimal for CKD patients. Although a plant-based diet remains a very important tool for CKD nutritional management, patients should be aware regarding the extra content of sodium and additives in processed plant-based products compared to animal-based processed food.

Interactions between Food and Drugs, and Nutritional Status in Renal Patients: A Narrative Review.

Drugs and food interact mutually: drugs may affect the nutritional status of the body, acting on senses, appetite, resting energy expenditure, and food intake; conversely, food or one of its components may affect bioavailability and half-life, circulating plasma concentrations of drugs resulting in an increased risk of toxicity and its adverse effects, or therapeutic failure. Therefore, the knowledge of these possible interactions is fundamental for the implementation of a nutritional treatment in the presence of a pharmacological therapy. This is the case of chronic kidney disease (CKD), for which the medication burden could be a problem, and nutritional therapy plays an important role in the patient's treatment. The aim of this paper was to review the interactions that take place between drugs and foods that can potentially be used in renal patients, and the changes in nutritional status induced by drugs. A proper definition of the amount of food/nutrient intake, an adequate definition of the timing of meal consumption, and a proper adjustment of the drug dosing schedule may avoid these interactions, safeguarding the quality of life of the patients and guaranteeing the effectiveness of drug therapy. Hence, a close collaboration between the nephrologist, the renal dietitian, and the patient is crucial. Dietitians should consider that food may interact with drugs and that drugs may affect nutritional status, in order to provide the patient with proper dietary suggestions, and to allow the maximum effectiveness and safety of drug therapy, while preserving/correcting the nutritional status.

Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial.

BACKGROUND: Vitamin D deficiency is associated with increased risks of mortality in people with chronic kidney disease. The benefits and harm of vitamin D supplementation on cardiovascular outcomes and mortality are unknown. We aimed to assess the effectiveness of calcifediol in reducing mortality in patients with vitamin D insufficiency on hemodialysis compared to no additional therapy. METHODS: A phase III, multicenter, randomized, open-label trial was conducted including 284 adults with vitamin D insufficiency undergoing hemodialysis who were randomly assigned to receive oral calcifediol or standard care for 24 months. RESULTS: Two hundred eighty-four participants were enrolled (143 assigned to the calcifediol group and 141 to the no additional therapy group). The primary outcome (mortality) occurred in 34 and 31 participants in the calcifediol and control group, respectively [hazard ratio (HR) 1.03; 95% confidence interval (CI) 0.63-1.67]. Calcifediol had no detectable effects on cardiovascular death (HR 1.06; 95% CI 0.41-2.74), non-cardiovascular death (HR 1.13; 95% CI 0.62-2.04), nonfatal myocardial infarction (HR 0.20; 95% CI 0.02-1.67) or nonfatal stroke (HR could not be estimated). The incidence of hypercalcemia and hyperphosphatemia was similar between groups. None of the participants underwent parathyroidectomy. CONCLUSIONS: In adults treated with hemodialysis and who had vitamin D insufficiency, calcifediol supplementation for 24 months had inconclusive effects on mortality and cardiovascular outcomes. TRIAL REGISTRATION NUMBER: NCT01457001.

Energy Requirement for Elderly CKD Patients.

The correct management of energy intake is crucial in CKD (chronic kidney disease) patients to limit the risk of protein energy wasting especially during low-protein regimes, but also to prevent overweight/obesity. The aim of this study was to assess the energy requirement of older CKD patients using objective measurements. This cross-sectional study enrolled 67 patients (aged 60-86 years) with CKD stages 3-5 not on dialysis, all of whom were metabolically and nutritionally stable. All patients underwent indirect calorimetry and measurement of daily physical activity level expressed by the average daily Metabolic Equivalent Task, using an accelerometer, in order to measure total energy expenditure (mTEE). Estimated TEE (eTEE) was derived from predictive equations for resting energy expenditure and physical activity levels coefficients. The mTEE were lower than eTEE-based on Harris-Benedict or Schofield or Mifflin equations (1689 ± 523 vs. 2320 ± 434 or 2357 ± 410 or 2237 ± 375 Kcal, p < 0.001, respectively). On average mTEE was 36.5% lower than eTEE. When eTEE was recalculated using ideal body weight the gap between mTEE and eTEE was reduced to 26.3%. A high prevalence of a sedentary lifestyle and reduced physical capabilities were also detected. In conclusion, our data support the energy intake of 25-35 Kcal/Kg/d recently proposed by the NKF-KDOQI (National Kidney Foundation-Kidney Disease Improving Quality Initiative) guidelines on nutritional treatment of CKD, which seem to be more adequate and applicable than that of previous guidelines (30-35 Kcal/Kg/d) in elderly stable CKD patients with a sedentary lifestyle. According to our findings we believe that an energy intake even lower than 25 Kcal/Kg/d may be adequate in metabolically stable, elderly CKD patients with a sedentary lifestyle.

First World Consensus Conference on pancreas transplantation: Part II - recommendations.

The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.