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A special issue of Nutrients (ISSN 2072-6643). This special issue belongs to the section "Clinical Nutrition".

Deadline for manuscript submissions: closed (15 April 2021) | Viewed by 80391

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Special Issue Editor

Prof. Dr. Piergiorgio Messa

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Guest Editor

1. Nephrol Unit, University of Milan, Via Commenda 15, I-20122 Milan, Italy
2. Fdn IRCCS Ca Granda Osped Maggiore Policlin Milan, Nephrol Dialysis & Renal Transplant Unit, Via Commenda 15, I-20122 Milan, Italy
Interests: chronic kidney disease; renal transplantation; nutrition; low protein diet; micronutrients
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Special Issue Information

Dear Colleagues,

Medical literature offers strong evidence that dietary habits are associated with the development and possibly the progression of chronic kidney disease (CKD). Therefore, the guidelines of many scientific societies suggest prescribing a low-protein diet to avoid the metabolic consequences of advanced CKD and to slow its progression to end-stage renal disease.

However, there are still some uncertainties regarding the stage of CKD at which starting to restrict protein consumption and whether it is worth-prescribing a progressive restriction that parallels the reduction of the glomerular filtration rate.

Consequently, there are no clear indications about the degree of restriction to adopt in the various stages of CKD (low- vs very-low-protein diet) as well as about possible differences in the quality of protein intake (vegetal or animal origin).

Furthermore, although a hypoproteic diet should not be prescribed in malnourished individuals, there is a substantial lack of information regarding the effect of protein restriction with respect to the onset of malnutrition and sarcopenia in selected categories of patients at risk of malnutrition (i.e., older and frailer individuals). In fact, these individuals have been excluded by most interventional and observational trials. However, since the frail phenotype is present in almost half of elderly CKD patients, the indication for an appropriate dietary prescription in this cohort is a matter of utmost importance.

Another topic that deserves to be explored is the lack of a unanimous definition of malnutrition in the CKD population. In fact, the coexistence of different definitions and clinical scores, validated for the different stages of CKD, is preventing the collection of accurate information on the epidemiology of this phenomenon and generates confusion respect to the nutritional outcomes of patients enrolled in clinical and observational trials.

Another source of confusion derives from the numerous areas of overlap between the current definitions of sarcopenia, malnutrition, and protein-energy wasting syndrome among CKD patients. Although the guidelines strongly indicate to prescribe a low-protein diet in well-nourished patients with advanced CKD, the same guidelines give limited relevance to the intake of the various micronutrients. In fact, although they report the suggested daily intake of microelements, there are no indications about the opportunity of their periodical monitoring and about the necessity of supplementing these nutrients at the different stages of CKD.

Finally, there are a number of unanswered issues in the field of dietary prescription in renal transplanted patients. In fact, it would be very relevant to have an accurate estimation of their nutritional status as well as to explore which nutritional intervention could help to maintain an optimal nutritional status and possibly to prevent or delay the metabolic complications of immunosuppressive therapy.

This Special Issue of Nutrients will address topics, including those mentioned here, that are of the utmost relevance for nutritional evaluation and dietary prescription in patients with various stages of CKD.

Prof. Piergiorgio Messa
Guest Editor

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Keywords

Chronic kidney disease
Renal transplantation
Nutrition
Low-protein diet
Micronutrients

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Published Papers (11 papers)

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Editorial

Jump to: Research, Review

4 pages, 182 KiB

Open AccessEditorial

Renal Nutrition and Metabolism

by Piergiorgio Messa

Nutrients 2022, 14(9), 1959; https://doi.org/10.3390/nu14091959 - 7 May 2022

Viewed by 2419

Abstract

Since the dawn of nephrology, dietary intervention has been one of the cornerstones of therapeutic intervention, used by nephrologists in an attempt to reduce the symptoms and metabolic complications that characterize chronic kidney disease (CKD) and, possibly, to stop its evolution [...] Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

Research

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13 pages, 1088 KiB

Open AccessArticle

Current Management of Hyperkalemia in Non-Dialysis CKD: Longitudinal Study of Patients Receiving Stable Nephrology Care

by Silvio Borrelli, Luca De Nicola, Roberto Minutolo, Giuseppe Conte, Paolo Chiodini, Adamasco Cupisti, Domenico Santoro, Vincenzo Calabrese, Domenico Giannese, Carlo Garofalo, Michele Provenzano, Vincenzo Bellizzi, Luca Apicella, Giorgina Barbara Piccoli, Massimo Torreggiani and Biagio Raffaele Di Iorio

Nutrients 2021, 13(3), 942; https://doi.org/10.3390/nu13030942 - 15 Mar 2021

Cited by 13 | Viewed by 4259

Abstract

Background: No study has explored the limitations of current long-term management of hyperkalemia (HK) in outpatient CKD clinics. Methods: We evaluated the association between current therapeutic options and control of serum K (sK) during 12-month follow up in ND-CKD patients stratified in four groups by HK (sK ≥ 5.0 mEq/L) at baseline and month 12: Absent (no-no), Resolving (yes-no), New Onset (no-yes), Persistent (yes-yes). Results: We studied 562 patients (age 66.2 ± 14.5 y; 61% males; eGFR 39.8 ± 21.8 mL/min/1.73 m², RAASI 76.2%). HK was “absent” in 50.7%, “resolving” in 15.6%, “new onset” in 16.6%, and “persistent” in 17.1%. Twenty-four hour urinary measurements testified adherence to nutritional recommendations in the four groups at either visit. We detected increased prescription from baseline to month 12 of bicarbonate supplements (from 5.0 to 14.1%, p < 0.0001), K-binders (from 2.0 to 7.7%, p < 0.0001), and non-K sparing diuretics (from 34.3 to 41.5%, p < 0.001); these changes were consistent across groups. Similar results were obtained when using higher sK level (≥5.5 mEq/L) to stratify patients. Mixed-effects regression analysis showed that higher sK over time was associated with eGFR < 60, diabetes, lower serum bicarbonate, lower use of non-K sparing diuretics, bicarbonate supplementation, and K-binder use. Treatment-by-time interaction showed that sK decreased in HK patients given bicarbonate (p = 0.003) and K-binders (p = 0.005). Conclusions: This observational study discloses that one-third of ND-CKD patients under nephrology care remain with or develop HK during a 12-month period despite low K intake and increased use of sK-lowering drugs. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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14 pages, 1459 KiB

Open AccessArticle

Ready to Change: Attitudes of an Elderly CKD Stage 3–5 Population towards Testing Protein-Free Food

by Elisa Longhitano, Tiziana Trabace, Antioco Fois, Antoine Chatrenet, Maria Rita Moio, Francoise Lippi, Jerome Vigreux, Coralie Beaumont, Domenico Santoro, Massimo Torreggiani and Giorgina Barbara Piccoli

Nutrients 2020, 12(11), 3519; https://doi.org/10.3390/nu12113519 - 16 Nov 2020

Cited by 7 | Viewed by 2856

Abstract

The recent Kidney Disease Outcomes Quality Initiative (K-DOQI) guidelines suggest an early start of protein restriction, raising issues on willingness to change dietary habits. The aim of this exploratory real-life study was to report on a test of dietary products (protein-free, not previously available in France) in a large, mainly elderly, chronic kidney disease (CKD) population (220 patients, median age: 77.5 years, Charlson comorbidity index (CCI): seven, malnutrition inflammation score (MIS): five, estimated glomerular filtration rate (eGFR): 26 mL/min), also as a means to tailor further implementation strategies. Forty-nine patients (22.28%) were considered to be poor candidates for the trial (metabolically unstable or with psychological, psychiatric or logistic barriers); of the remaining 171, 80.70% agreed to participate. Patients to whom the diet was not proposed had lower eGFR and higher comorbidity (eGFR 21 vs. 27 p = 0.021; MIS six vs. four p: <0.001). Patients who refused were 10 years older than those who accepted (83 vs. 73 years p < 0.001), with a higher CCI (eight vs. seven p = 0.008) and MIS (five vs. four p = 0.01). In the logistic regression, only age was significantly associated with refusal to participate (Odds ratio (OR): 5.408; 95% CI: 1.894 to 15.447). No difference was found according to low/intermediate/high frequency of weekly use of protein-free food. Our study suggests that most of the patients are ready to test new diet approaches. Only old age correlated with refusal, but frequency of implementation depended on individual preferences, underlying the importance of tailored approaches to improve adherence. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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16 pages, 3942 KiB

Open AccessArticle

Compositional and Functional Adaptations of Intestinal Microbiota and Related Metabolites in CKD Patients Receiving Dietary Protein Restriction

by I-Wen Wu, Chin-Chan Lee, Heng-Jung Hsu, Chiao-Yin Sun, Yuen-Chan Chen, Kai-Jie Yang, Chi-Wei Yang, Wen-Hun Chung, Hsin-Chih Lai, Lun-Ching Chang and Shih-Chi Su

Nutrients 2020, 12(9), 2799; https://doi.org/10.3390/nu12092799 - 12 Sep 2020

Cited by 31 | Viewed by 4374

Abstract

The relationship between change of gut microbiota and host serum metabolomics associated with low protein diet (LPD) has been unraveled incompletely in CKD patients. Fecal 16S rRNA gene sequencing and serum metabolomics profiling were performed. We reported significant changes in the β-diversity of gut microbiota in CKD patients having LPD (CKD-LPD, n = 16). We identified 19 genera and 12 species with significant differences in their relative abundance among CKD-LPD patients compared to patients receiving normal protein diet (CKD-NPD, n = 27) or non-CKD controls (n = 34), respectively. CKD-LPD had a significant decrease in the abundance of many butyrate-producing bacteria (family Lachnospiraceae and Bacteroidaceae) associated with enrichment of functional module of butanoate metabolism, leading to concomitant reduction in serum levels of SCFA (acetic, heptanoic and nonanoic acid). A secondary bile acid, glyco λ-muricholic acid, was significantly increased in CKD-LPD patients. Serum levels of indoxyl sulfate and p-cresyl sulfate did not differ among groups. The relationship between abundances of microbes and metabolites remained significant in subset of resampling subjects of comparable characteristics. Enrichment of bacterial gene markers related to D-alanine, ketone bodies and glutathione metabolism was noted in CKD-LPD patients. Our analyses reveal signatures and functions of gut microbiota to adapt dietary protein restriction in renal patients. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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11 pages, 922 KiB

Open AccessArticle

Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet

by Yi-Chun Wang, Shu-Hui Juan, Chu-Lin Chou, Tsung-Cheng Hsieh, Jung-Lun Wu and Te-Chao Fang

Nutrients 2020, 12(9), 2708; https://doi.org/10.3390/nu12092708 - 4 Sep 2020

Cited by 10 | Viewed by 5250

Abstract

The effects of ketoanalogues (KA) supplementation on mortality and progression to dialysis in patients with pre-dialysis stage 5 chronic kidney disease (CKD) receiving a low-protein diet (LPD) remain ambiguous. From Taiwan’s National Health Insurance Research Database during 1996–2011, 165 patients with pre-dialysis CKD on an LPD (0.6 g/kg/day) with KA supplementation were matched with 165 patients with pre-dialysis CKD on an LPD without KA supplementation. Of the 165 patients with advanced CKD receiving KA supplementation, 34 (20.6%) died, and 124 (75.2%) underwent long-term dialysis during the study period. There was no significant difference in mortality between the KA-user group and the KA-nonuser group (adjusted hazard ratio [HR], 1.41; 95% confidence interval [CI], 0.68–2.93; p = 0.355). KA supplementation significantly increased long-term dialysis risk (adjusted HR, 1.41; 95% CI, 1.04–1.90; p = 0.025) and combined outcome risk (defined as long-term dialysis and death; adjusted HR, 1.37; 95% CI, 1.02–1.83; p = 0.034). KA supplementation also increased long-term dialysis risk (adjusted HR, 1.49; 95% CI, 1.00–2.20; p = 0.048) in the subgroup of pre-dialysis patients with diabetes mellitus (DM), but not in those patients without DM. In conclusion, KA supplementation might increase long-term dialysis risk in patients with advanced CKD receiving an LPD, but it did not increase mortality. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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18 pages, 644 KiB

Open AccessArticle

Urinary Excretion of N¹-Methylnicotinamide and N¹-Methyl-2-Pyridone-5-Carboxamide and Mortality in Kidney Transplant Recipients

by Carolien P.J. Deen, Anna van der Veen, António W. Gomes-Neto, Johanna M. Geleijnse, Karin J. Borgonjen-van den Berg, M. Rebecca Heiner-Fokkema, Ido P. Kema and Stephan J.L. Bakker

Nutrients 2020, 12(7), 2059; https://doi.org/10.3390/nu12072059 - 10 Jul 2020

Cited by 11 | Viewed by 3522

Abstract

It is unclear whether niacin nutritional status is a target for improvement of long-term outcome after renal transplantation. The 24-h urinary excretion of N¹-methylnicotinamide (N¹-MN), as a biomarker of niacin status, has previously been shown to be negatively associated with premature mortality in kidney transplant recipients (KTR). However, recent evidence implies higher enzymatic conversion of N¹-MN to N¹-methyl-2-pyridone-5-carboxamide (2Py) in KTR, therefore the need exists for interpretation of both N¹-MN and 2Py excretion for niacin status assessment. We assessed niacin status by means of the 24-h urinary excretion of the sum of N¹-MN and 2Py (N¹-MN + 2Py), and its associations with risk of premature mortality in KTR. N¹-MN + 2Py excretion was measured in a longitudinal cohort of 660 KTR with LS-MS/MS. Prospective associations of N¹-MN + 2Py excretion were investigated with Cox regression analyses. Median N¹-MN + 2Py excretion was 198.3 (155.9–269.4) µmol/day. During follow-up of 5.4 (4.7–6.1) years, 143 KTR died, of whom 40 due to an infectious disease. N¹-MN + 2Py excretion was negatively associated with risk of all-cause mortality (HR 0.61; 95% CI 0.47–0.79; p < 0.001), and infectious mortality specifically (HR 0.47; 95% CI 0.29–0.75; p = 0.002), independent of potential confounders. Secondary analyses showed effect modification of hs-CRP on the negative prospective association of N¹-MN + 2Py excretion, and sensitivity analyses showed negative and independent associations of N¹-MN and 2Py excretion with risk of all-cause mortality separately. These findings add further evidence to niacin status as a target for nutritional strategies for improvement of long-term outcome in KTR. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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13 pages, 509 KiB

Open AccessArticle

Dietary Patterns Based on Estimated Glomerular Filtration Rate and Kidney Function Decline in the General Population: The Lifelines Cohort Study

by Qingqing Cai, Louise H. Dekker, Stephan J. L. Bakker, Martin H. de Borst and Gerjan J. Navis

Nutrients 2020, 12(4), 1099; https://doi.org/10.3390/nu12041099 - 16 Apr 2020

Cited by 12 | Viewed by 3765

Abstract

No specific dietary patterns have been established that are linked with loss of kidney function. We aimed to identify an estimated glomerular filtration rate-based dietary pattern (eGFR-DP) and to evaluate its association with eGFR decline and chronic kidney disease (CKD) incidence in the general population. We included 78,335 participants from the Lifelines cohort in the Northern Netherlands. All participants had an eGFR >60 mL/min/1.73 m² at baseline and completed a second visit five years later. The eGFR-DP was constructed at baseline using a 110-item food frequency questionnaire by reduced rank regression, stratified by sex. Logistic regression was performed to evaluated the association between the eGFR-DP score and either a ≥20% eGFR decline or incident CKD. Among women, eGFR-DP were characterized by high consumption of egg, cheese, and legumes and low consumption of sweets, white meat, and commercially prepared dishes. In men, eGFR-DP were characterized by high consumption of cheese, bread, milk, fruits, vegetables, and beer and low consumption of white and red meat. A higher eGFR-DP score was associated with a lower risk of a ≥20% eGFR decline (OR 4th vs. 1st quartile, women: 0.79 [95% CI: 0.73–0.87]; men: 0.67 [0.59–0.76]). The association between the eGFR-DP score and CKD incidence was lost upon adjustment for baseline eGFR. Our results provide support for dietary interventions to prevent kidney function decline in the general population. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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Review

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16 pages, 555 KiB

Open AccessReview

Influence of Plant and Animal Proteins on Inflammation Markers among Adults with Chronic Kidney Disease: A Systematic Review and Meta-Analysis

by Danielle Francesca Aycart, Sofía Acevedo, Lucía Eguiguren-Jimenez and Jeanette Mary Andrade

Nutrients 2021, 13(5), 1660; https://doi.org/10.3390/nu13051660 - 14 May 2021

Cited by 20 | Viewed by 7514

Abstract

Proteins, especially plant proteins, may reduce inflammation among adults with chronic kidney disease (CKD). This systematic review and meta-analysis were conducted to evaluate the effect protein types (animal or plant) have on inflammation markers (CRP, IL-6, TNF-α) among adults with varying stages of CKD. The Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) was conducted to identify articles from inception until January 2021, utilizing six databases. Controlled trials that compared the effects of different protein types were analyzed using random-effects meta-analysis. Quality assessment and risk of bias of the included articles were assessed by using Cochrane risk of bias instrument and ROBINS-I. Out of the 10 studies that met the criteria, there was a decreasing trend in CRP levels when consuming plant proteins compared to animal proteins among non-dialysis participants. There was a statistically significant decrease when comparing animal proteins to unspecified proteins in CRP levels among dialysis participants [Hedges’ g = 2.11; 95% CI 1.12, 3.11; p ≤ 0.001], favoring unspecified proteins. Furthermore, animal proteins (eggs, red meat) showed increasing trends in CRP levels compared to whey protein isolate. Caution must be considered regarding these results as controlled, non-randomized, trials were included in the analysis, which may have contributed to high risk of bias. Future research should focus on protein types and the impact they have on kidney disease progression and inflammation markers. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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11 pages, 660 KiB

Open AccessReview

Effects of High Glucose and Lipotoxicity on Diabetic Podocytes

by Ran Nakamichi, Kaori Hayashi and Hiroshi Itoh

Nutrients 2021, 13(1), 241; https://doi.org/10.3390/nu13010241 - 15 Jan 2021

Cited by 33 | Viewed by 5317

Abstract

Glomerular podocytes are highly differentiated cells that cover glomerular capillaries from the outside and have a characteristic morphology with numerous foot processes. The formation of slit membranes between the foot processes serves as a final filtration barrier for urine filtration from the blood. Podocyte damage causes disruption of the slit membrane, subsequent proteinuria and finally glomerulosclerosis, which is a common pathway in various types of chronic kidney disease (CKD). In recent years, there has been an increase in diabetes, due to rapid lifestyle changes, which is the main cause of CKD. Therefore, understanding the effect of diabetic status on podocytes is of great importance to establish a strategy for preventing CKD progression. In this review, we summarize altered glucose and lipid metabolism in diabetic podocytes and also discuss the reversibility of the changes in podocyte phenotype. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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17 pages, 1445 KiB

Open AccessReview

Caloric Intake in Renal Patients: Repercussions on Mineral Metabolism

by Angela Vidal, Rafael Ríos, Carmen Pineda, Ignacio López, Ana I. Raya, Escolástico Aguilera-Tejero and Mariano Rodríguez

Nutrients 2021, 13(1), 18; https://doi.org/10.3390/nu13010018 - 23 Dec 2020

Cited by 2 | Viewed by 4086

Abstract

The aim of this paper is to review current knowledge about how calorie intake influences mineral metabolism focussing on four aspects of major interest for the renal patient: (a) phosphate (P) handling, (b) fibroblast growth factor 23 (FGF23) and calcitriol synthesis and secretion, (c) metabolic bone disease, and (d) vascular calcification (VC). Caloric intake has been shown to modulate P balance in experimental models: high caloric intake promotes P retention, while caloric restriction decreases plasma P concentrations. Synthesis and secretion of the phosphaturic hormone FGF23 is directly influenced by energy intake; a direct correlation between caloric intake and FGF23 plasma concentrations has been shown in animals and humans. Moreover, in vitro, energy availability has been demonstrated to regulate FGF23 synthesis through mechanisms in which the molecular target of rapamycin (mTOR) signalling pathway is involved. Plasma calcitriol concentrations are inversely proportional to caloric intake due to modulation by FGF23 of the enzymes implicated in vitamin D metabolism. The effect of caloric intake on bone is controversial. High caloric intake has been reported to increase bone mass, but the associated changes in adipokines and cytokines may as well be deleterious for bone. Low caloric intake tends to reduce bone mass but also may provide indirect (through modulation of inflammation and insulin regulation) beneficial effects on bone. Finally, while VC has been shown to be exacerbated by diets with high caloric content, the opposite has not been demonstrated with low calorie intake. In conclusion, although prospective studies in humans are needed, when planning caloric intake for a renal patient, it is important to take into consideration the associated changes in mineral metabolism. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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24 pages, 1257 KiB

Open AccessFeature PaperReview

Plant-Dominant Low-Protein Diet for Conservative Management of Chronic Kidney Disease

by Kamyar Kalantar-Zadeh, Shivam Joshi, Rebecca Schlueter, Joanne Cooke, Amanda Brown-Tortorici, Meghan Donnelly, Sherry Schulman, Wei-Ling Lau, Connie M. Rhee, Elani Streja, Ekamol Tantisattamo, Antoney J. Ferrey, Ramy Hanna, Joline L.T. Chen, Shaista Malik, Danh V. Nguyen, Susan T. Crowley and Csaba P. Kovesdy

Nutrients 2020, 12(7), 1931; https://doi.org/10.3390/nu12071931 - 29 Jun 2020

Cited by 161 | Viewed by 33466

Abstract

Chronic kidney disease (CKD) affects >10% of the adult population. Each year, approximately 120,000 Americans develop end-stage kidney disease and initiate dialysis, which is costly and associated with functional impairments, worse health-related quality of life, and high early-mortality rates, exceeding 20% in the first year. Recent declarations by the World Kidney Day and the U.S. Government Executive Order seek to implement strategies that reduce the burden of kidney failure by slowing CKD progression and controlling uremia without dialysis. Pragmatic dietary interventions may have a role in improving CKD outcomes and preventing or delaying dialysis initiation. Evidence suggests that a patient-centered plant-dominant low-protein diet (PLADO) of 0.6–0.8 g/kg/day composed of >50% plant-based sources, administered by dietitians trained in non-dialysis CKD care, is promising and consistent with the precision nutrition. The scientific premise of the PLADO stems from the observations that high protein diets with high meat intake not only result in higher cardiovascular disease risk but also higher CKD incidence and faster CKD progression due to increased intraglomerular pressure and glomerular hyperfiltration. Meat intake increases production of nitrogenous end-products, worsens uremia, and may increase the risk of constipation with resulting hyperkalemia from the typical low fiber intake. A plant-dominant, fiber-rich, low-protein diet may lead to favorable alterations in the gut microbiome, which can modulate uremic toxin generation and slow CKD progression, along with reducing cardiovascular risk. PLADO is a heart-healthy, safe, flexible, and feasible diet that could be the centerpiece of a conservative and preservative CKD-management strategy that challenges the prevailing dialysis-centered paradigm. Full article

(This article belongs to the Special Issue Renal Nutrition and Metabolism)

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