Nutritional Management of Chronic Kidney Disease Kalantar-Zadeh, Kamyar; Fouque, Denis
New England journal of medicine/The New England journal of medicine,
11/2017, Letnik:
377, Številka:
18
Journal Article
Background
Weight loss and homeostatic disturbances of both energy and protein balances are characteristics of several illnesses including cancer, heart failure, and chronic kidney disease (CKD). ...Different definitions have been used to describe this deleterious process. The term protein‐energy wasting (PEW) has been proposed for CKD patients by the International Society of Renal Nutrition and Metabolism.
Methods
We searched the publication in Medline from February 2008 to September 2018 using PEW or cachexia in their title.
Results
Since its inception, the term PEW has been exceptionally successful, highlighted by 327 original publications referenced in PubMed over 10 years. Using this classification, several studies have confirmed that PEW is among the strongest predictors of mortality in CKD patients hazard ratio of 3.03; confidence interval of 1.69–5.26 in 1068 haemodialysis patients and 1.40 (1.04–1.89) in 1487 non‐dialysed patients across PEW stages 0 to 4. Based on this classification, prevalence of PEW is 28% to 54% among 16 434 adults undergoing maintenance dialysis. PEW prevalence increases when renal function declines, that is, from <2% in CKD stages 1–2 to 11–54% in CKD stages 3–5. A more general definition of cachexia for all chronic diseases proposed by the Society on Sarcopenia, Cachexia and Wasting Disorders was also published concurrently. In the CKD area, we found 180 publications using ‘cachexia’ underlining that some confusion or overlap may exist. The definitions of PEW and cachexia are somewhat similar, and the main difference is that a loss of body weight >5% is a mandatory criterion for cachexia but supportive for PEW.
Conclusions
The recent understanding of cachexia physiopathology during CKD progression suggests that PEW and cachexia are closely related and that PEW corresponds the initial state of a continuous process that leads to cachexia, implicating the same metabolic pathways as in other chronic diseases. Despite the success of the definition of PEW, using a more uniform term such as ‘kidney disease cachexia’ could be more helpful to design future research through collaborative groups of researchers with focus on cachexia.
Summary Patients with chronic kidney failure—defined as a glomerular filtration rate persistently below 15 mL/min per 1·73 m2 —have an unacceptably high mortality rate. In developing countries, ...mortality results primarily from an absence of access to renal replacement therapy. Additionally, cardiovascular and non-cardiovascular mortality are several times higher in patients on dialysis or post-renal transplantation than in the general population. Mortality of patients on renal replacement therapy is affected by a combination of socioeconomic factors, pre-existing medical disorders, renal replacement treatment modalities, and kidney failure itself. Characterisation of the key pathophysiological contributors to increased mortality and cardiorenal risk staging systems are needed for the rational design of clinical trials aimed at decreasing mortality. Policy changes to improve access to renal replacement therapy should be combined with research into low-cost renal replacement therapy and optimum clinical care, which should include multifaceted approaches simultaneously targeting several of the putative contributors to increased mortality.
For more than fifty years, low protein diets have been proposed to patients with kidney failure. However, the effects of these diets in preventing severe kidney failure and the need for maintenance ...dialysis have not been resolved.
To determine the efficacy of low protein diets in delaying the need to start maintenance dialysis.
Cochrane Renal Group studies register, the Cochrane Central Register of Controlled studies, MEDLINE, and EMBASE. Congress abstracts (American Society of Nephrology since 1990, European Dialysis Transplant Association since 1985, International Society of Nephrology since 1987). Direct contacts with investigators.
Randomised studies comparing two different levels of protein intake in adult patients suffering from moderate to severe kidney failure, followed for at least one year.
Two authors independently selected studies and extracted data. Statistical analyses were performed using the random effects model and the results expressed as risk ratio (RR) for dichotomous outcomes with 95% confidence intervals (CI). Collection of the number of "renal deaths" defined as the need for starting dialysis, the death of a patient or a kidney transplant during the study.
Ten studies were identified from over 40 studies. A total of 2000 patients were analysed, 1002 had received reduced protein intake and 998 a higher protein intake. There were 281 renal deaths recorded, 113 in the low protein diet and 168 in the higher protein diet group (RR 0.68, 95% CI 0.55 to 0.84, P = 0.0002). To avoid one renal death, 2 to 56 patients need to be treated with a low protein diet during one year.
Reducing protein intake in patients with chronic kidney disease reduces the occurrence of renal death by 32% as compared with higher or unrestricted protein intake. The optimal level of protein intake cannot be confirmed from these studies.
Regardless of the primary disease responsible for kidney failure, patients suffering from chronic kidney disease (CKD) have in common multiple impairments of both the innate and adaptive immune ...systems, the pathophysiology of which has long remained enigmatic. CKD-associated immune dysfunction includes chronic low-grade activation of monocytes and neutrophils, which induces endothelial damage and increases cardiovascular risk. Although innate immune effectors are activated during CKD, their anti-bacterial capacity is impaired, leading to increased susceptibility to extracellular bacterial infections. Finally, CKD patients are also characterized by profound alterations of cellular and humoral adaptive immune responses, which account for an increased risk for malignancies and viral infections. This review summarizes the recent emerging data that link the pathophysiology of CKD-associated immune dysfunctions with the accumulation of microbiota-derived metabolites, including indoxyl sulfate and p-cresyl sulfate, the two best characterized protein-bound uremic retention solutes.
Abstract
Diabetes, hypertension and cardiovascular disease have been listed as risk factors for severe coronavirus disease 2019 (COVID-19) since the first report of the disease in January 2020. ...However, this report did not mention chronic kidney disease (CKD) nor did it provide information on the relevance of estimated glomerular filtration rate (eGFR) or albuminuria. As the disease spread across the globe, information on larger populations with greater granularity on risk factors emerged. The recently published OpenSAFELY project analysed factors associated with COVID-19 death in 17 million patients. The picture that arose differs significantly from initial reports. For example, hypertension is not an independent risk factor for COVID-19 death adjusted hazard ratio (aHR) 0.89, but renal disease very much is. Dialysis (aHR 3.69), organ transplantation (aHR 3.53) and CKD (aHR 2.52 for patients with eGFR <30 mL/min/1.73 m2) represent three of the four comorbidities associated with the highest mortality risk from COVID-19. The risk associated with CKD Stages 4 and 5 is higher than the risk associated with diabetes mellitus (aHR range 1.31–1.95, depending upon glycaemic control) or chronic heart disease (aHR 1.17). In another recent publication, the Global Burden of Disease collaboration identified that worldwide, CKD is the most prevalent risk factor for severe COVID-19. Moreover, the distribution of risk factors for COVID-19 mortality appears to be different in patients with CKD when compared with the general population. The high prevalence of CKD in combination with the elevated risk of mortality from COVID-19 in CKD necessitates urgent action for this group of patients. This article defines essential action points (summarized in Box 1), among which is advocating the inclusion of CKD patients in clinical trials testing the efficacy of drugs and vaccines to prevent severe COVID-19.
Protein energy wasting (PEW) is common in patients with chronic kidney disease (CKD) and is associated with adverse clinical outcomes, especially in individuals receiving maintenance dialysis ...therapy. A multitude of factors can affect the nutritional and metabolic status of CKD patients requiring a combination of therapeutic maneuvers to prevent or reverse protein and energy depletion. These include optimizing dietary nutrient intake, appropriate treatment of metabolic disturbances such as metabolic acidosis, systemic inflammation, and hormonal deficiencies, and prescribing optimized dialytic regimens. In patients where oral dietary intake from regular meals cannot maintain adequate nutritional status, nutritional supplementation, administered orally, enterally, or parenterally, is shown to be effective in replenishing protein and energy stores. In clinical practice, the advantages of oral nutritional supplements include proven efficacy, safety, and compliance. Anabolic strategies such as anabolic steroids, growth hormone, and exercise, in combination with nutritional supplementation or alone, have been shown to improve protein stores and represent potential additional approaches for the treatment of PEW. Appetite stimulants, anti-inflammatory interventions, and newer anabolic agents are emerging as novel therapies. While numerous epidemiological data suggest that an improvement in biomarkers of nutritional status is associated with improved survival, there are no large randomized clinical trials that have tested the effectiveness of nutritional interventions on mortality and morbidity.
Traditional dietary recommendations for patients with chronic kidney disease (CKD) focus on the quantity of nutrients consumed. Without appropriate dietary counselling, these restrictions can result ...in a low intake of fruits and vegetables and a lack of diversity in the diet. Plant nutrients and plant-based diets could have beneficial effects in patients with CKD: increased fibre intake shifts the gut microbiota towards reduced production of uraemic toxins; plant fats, particularly olive oil, have anti-atherogenic effects; plant anions might mitigate metabolic acidosis and slow CKD progression; and as plant phosphorus has a lower bioavailability than animal phosphorus, plant-based diets might enable better control of hyperphosphataemia. Current evidence suggests that promoting the adoption of plant-based diets has few risks but potential benefits for the primary prevention of CKD, as well as for delaying progression in patients with CKD G3-5. These diets might also help to manage and prevent some of the symptoms and metabolic complications of CKD. We suggest that restriction of plant foods as a strategy to prevent hyperkalaemia or undernutrition should be individualized to avoid depriving patients with CKD of these potential beneficial effects of plant-based diets. However, research is needed to address knowledge gaps, particularly regarding the relevance and extent of diet-induced hyperkalaemia in patients undergoing dialysis.
Sclerostin, a bone antianabolic peptide involved in osteoporosis, is elevated in patients undergoing maintenance dialysis. However, there are no data for patients with early CKD.
Between January and ...July 2010, serum sclerostin and GFR (calculated by inulin clearance) were measured in 90 patients with CKD. Fasting blood samples were also drawn for determination of calcium, phosphorus, parathyroid hormone, bone alkaline phosphatase, and 25-OH vitamin D.
Median GFR was 66.5 (interquartile range, 40.0-88.3) ml/min per 1.73 m(2). Median sclerostin level was 53.5 (interquartile range, 37.5-77.2) pmol/L, was higher in patients with a GFR <60 ml/min per 1.73 m(2), and was highest in those with ESRD. Sclerostin levels were significantly more elevated in men than women (P<0.05). An inverse relationship was found between sclerostin and GFR (r=-0.58; P<0.001), and a positive correlation was seen with age (r=0.34; P<0.01) and serum phosphate (r=0.26; P=0.02). In multiple regression analyses, GFR, sex, and serum phosphate were the only variables associated with serum sclerostin (P<0.001). Age lost its relationship with sclerostin level.
This is the first study reporting higher serum sclerostin levels starting at CKD stage III. GFR, sex, and serum phosphate were the only measures associated with sclerostin level, suggesting that the effect of age reported in the literature might instead be attributable to the altered renal function in the elderly. Correcting the serum phosphorus level may be associated with lower sclerostin levels.
Diet is a key component of care during chronic kidney disease (CKD). Nutritional interventions, and, specifically, a restricted protein diet has been under debate for decades. In order to reduce the ...risk of nutritional disorders in very-low protein diets (VLDP), supplementation by nitrogen-free ketoacid analogues (KAs) have been proposed. The aim of this review is to summarize the potential effects of this dietary therapy on renal function, uremic toxins levels, and nutritional and metabolic parameters and propose future directions. The purpose of this paper is also to select all experimental and randomized clinical studies (RCTs) that have compared VLDP + KA to normal diet or/and low protein diet (LPD). We reviewed the SCOPUS, WEB of SCIENCES, CENTRAL, and PUBMED databases from their inception to 1 January, 2019. Following duplicate removal and application of exclusion criteria, 23 RCTs and 12 experimental studies were included. LPD/VLPD + KAs appear nutritionally safe even if how muscle protein metabolism adapts to an LPD/VLPD + KAs is still largely unknown. VLPD + KAs seem to reduce uremic toxins production but the impact on intestinal microbiota remains unexplored. All studies observed a reduction of acidosis, phosphorus, and possibly sodium intake, while still providing adequate calcium intake. The impact of this diet on carbohydrate and bone parameters are only preliminary and need to be confirmed with RCTs. The Modification of Diet in Renal Disease study, the largest RCTs, failed to demonstrate a benefit in the primary outcome of the decline rate for the glomerular filtration rate. However, the design of this study was challenged and data were subsequently reanalyzed. However, when adherent patients were selected, with a rapid rate of progression and a long-term follow up, more recent meta-analysis and RCTs suggest that these diets can reduce the loss of the glomerular filtration rate in addition to the beneficial effects of renin-angiotensin-aldosterone system (RAAS) inhibitors. The current evidence suggests that KAs supplemented LPD diets should be included as part of the clinical recommendations for both the nutritional prevention and metabolic management of CKD. More research is needed to examine the effectiveness of KAs especially on uremic toxins. A reflection about the dose and composition of the KAs supplement, the cost-effective features, and their indication to reduce the frequency of dialysis needs to be completed.
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