Protein-energy wasting and sarcopenia in CKD

Protein-energy wasting (PEW) and sarcopenia are closely related conditions that significantly impact patients with CKD, increasing susceptibility to infections, cardiovascular events and mortality. PEW involves the loss of body protein and energy stores, while sarcopenia refers to the progressive loss of muscle mass and strength, particularly common in patients with CKD on dialysis. Both conditions worsen CKD progression and patient outcomes.

Adequate protein intake is crucial in managing PEW and sarcopenia, as it helps to maintain muscle mass, prevent deficiencies and improve overall health. Effective strategies include optimising protein intake, caloric consumption and the use of oral nutritional supplements when needed^{(Reference Aparicio, Chauveau, Vaĺ, De Précigout, Précigout and Bouchet10–Reference Anderson, Gilbert and Elia13)}. Duarte et al. (2024) highlighted that sarcopenia affects 24·5% of patients with CKD globally, with heightened risk among dialysis patients^{(Reference Duarte, Almeida, Neri, Oliveira, Wilkinson and Ribeiro14)}. In addition, Massini et al. (2023) demonstrated that high-protein diets and essential-amino-acid supplementation significantly improve muscle outcomes, underscoring the importance of tailored dietary interventions^{(Reference Massini, Caldiroli, Molinari, Maria, Carminati and Castellano15)}.

Given the overlap between these conditions, a personalised nutritional approach is essential. Interventions should prioritise maintaining muscle mass and ensuring overall nutritional adequacy. For a more detailed discussion on personalised nutrition strategies, refer to the dedicated section.

Comparison of dietary strategies in CKD

To provide a structured overview of various dietary approaches in CKD, Table 1 summarises the strengths, weaknesses, applicable populations and potential risks of low-protein diet (LPD), very-low-protein diet (VLPD), plant-based diet (PBD) and high-protein diet (HPD).

Table 1.

Comparative analysis of dietary strategies in CKD

Positive outcomes of low-protein and very-low-protein diets

Numerous studies and meta-analyses support the beneficial effects of LPD and VLPD in CKD management, as outlined in Table 2. Foundational research by Maschio et al. (1982) and Ihle et al. (1989) demonstrated that these diets can significantly slow the decline in renal function, establishing the importance of protein restriction in CKD management^{(Reference Maschio, Oldrizzi, Tessitore, D’Angelo, Valvo and Lupo16,Reference Ihle, Becker, Whitworth, Charlwood and Kincaid-Smith17)} . Further evidence by Garneata et al. (2016) highlighted the effectiveness of a ketoanalogue-supplemented VLPD in reducing CKD progression, particularly when dietary interventions are tailored to individual patient needs^{(Reference Garneata, Stancu, Dragomir, Stefan and Mircescu18)}.

Table 2.

RCT on protein intake in CKD: positive outcomes

Recent meta-analyses continue to validate the efficacy of these dietary approaches. Li et al. (2021) found that restricting protein intake to below 0·8 g/kg/d in LPDs effectively slows CKD progression, especially in patients with early-stage CKD^{(Reference Li, Wen, Wang, Li, Lin and Qi19)}. Similarly, Chewcharat et al. (2020) reported that LPD reduce the rate of GFR decline and proteinuria in non-diabetic patients with CKD, reinforcing the role of protein restriction as a cornerstone in CKD management^{(Reference Chewcharat, Takkavatakarn, Wongrattanagorn, Panrong, Kittiskulnam and Eiam-Ong20)}.

Despite these positive findings, the long-term sustainability of LPD and VLPD, along with patient adherence, remains a challenge. Variability in patient responses underscores the need for personalised dietary strategies, which are addressed in detail in the section on personalised nutrition.

High-protein diets

HPD have traditionally been viewed as risky for individuals with CKD owing to their potential to exacerbate kidney damage through mechanisms such as increased intraglomerular pressure and glomerular hyperfiltration. Studies by Friedman (2004) and Kalantar-Zadeh et al. (2020) highlighted these risks, particularly in relation to animal protein, which can accelerate CKD progression by causing intraglomerular hypertension and proteinuria^{(Reference Friedman42,Reference Kalantar-Zadeh, Kramer and Fouque43)} .

However, recent research suggests that the impact of protein intake may vary depending on the population. Kubo et al. (2023) found that, in a Japanese population initially free from CKD, higher total and animal protein intake, particularly from seafood, was associated with a lower risk of developing CKD^{(Reference Kubo, Imano, Muraki, Kitamura, Noda and Cui44)}. This finding indicates that HPD might have protective effects in certain populations, such as older adults with mild-to-moderate CKD, challenging the traditional view that protein restriction is universally beneficial.

Given the variability in patient responses to HPD, personalised assessments are essential to determine their appropriateness on an individual basis, considering factors such as CKD stage, comorbidities and the source of protein. For a more in-depth discussion, refer to the section on personalised nutrition.

Plant-based diets

PBD have gained significant attention for their potential benefits in managing CKD, primarily due to their lower phosphorus content and favourable metabolic effects. Plant proteins generally have lower phosphorus bioavailability compared with animal proteins, which is particularly beneficial for patients with CKD who have hyperphosphataemia^{(Reference Garneata, Stancu, Dragomir, Stefan and Mircescu18,Reference Moe, Zidehsarai, Chambers, Jackman, Radcliffe and Trevino36)} . Garneata et al. (2016) demonstrated that a low-protein PBD can slow CKD progression by reducing phosphorus bioavailability and improving renal outcomes^{(Reference Garneata, Stancu, Dragomir, Stefan and Mircescu18)}.

In addition to lowering phosphorus levels, PBD are associated with reduced inflammation and improved gut microbiome composition, both of which play crucial roles in slowing CKD progression^{(Reference Gutiérrez, Muntner, Rizk, McClellan, Warnock and Newby4)}. However, ensuring adequate protein intake from plant sources can be challenging, particularly for older adults at risk of malnutrition, necessitating careful dietary planning and supplementation^{(Reference Piccoli, Cederholm, Avesani, Bakker, Bellizzi and Cuerda5)}.

Inconclusive evidence on low-protein diets

While many studies highlight the benefits of LPD in CKD management, some research presents inconclusive or conflicting evidence. Williams et al. (2020) conducted an RCT that found no significant difference in CKD progression between patients on an LPD and those on a standard protein diet, suggesting that variability in patient adherence, baseline kidney function and the short follow-up period could explain the lack of observed benefits^{(Reference Williams, Stevens, Fass, Irons and Bone45)}.

Similarly, a meta-analysis by Fouque et al. (2009) indicated that, although LPD may delay the need for dialysis, their effects on overall survival and quality of life remain uncertain. The analysis highlighted the heterogeneity of study designs, patient populations and protein intake levels as contributors to these mixed results^{(Reference Fouque and Laville7)}. Klahr et al. (1994) also reported that LPD did not significantly slow CKD progression in patients with moderate renal insufficiency, noting that the benefits of protein restriction were modest and varied based on disease severity and patient adherence^{(Reference Klahr, Levey, Beck, Caggiula, Hunsicker and Kusek46)}.

These studies underscore the complexity of dietary management in CKD, suggesting that, while LPD may benefit some patients, they may not offer universal advantages. Individual variability, comorbidities and challenges in maintaining dietary adherence likely play significant roles in these outcomes (Table 3). The conflicting evidence does not negate the potential benefits of LPD but highlights the need for further research, particularly long-term, large-scale RCT, to clarify their role in CKD management. In addition, exploring the mechanisms by which LPD benefit certain subgroups of patients with CKD while offering limited effects to others is crucial.

Table 3.

Randomised controlled trials on protein intake in CKD: mixed or inconclusive findings

Dietary considerations for special populations: elderly patients and ethnic groups

Personalised nutrition

Personalised nutrition is crucial in CKD management owing to the variability in patient needs across different CKD stages, comorbidities and nutritional statuses. Individualised dietary plans improve adherence and outcomes, particularly in elderly patients with CKD, who may require tailored strategies balancing renal protection with nutritional adequacy^{(Reference Torreggiani, Fois, Moio, Chatrenet, Mazé and Lippi63,Reference Villain, Wagner and Koppe64)} .

A structured approach to personalised nutrition helps to optimise dietary interventions while addressing individual patient variability. The following factors play a critical role in developing a personalised diet plan:

Key factors influencing a personalised diet plan include:

• Age: Older adults face a higher risk of sarcopenia and malnutrition, necessitating adequate protein intake, while younger patients may tolerate stricter protein restrictions.

• Sex: Men generally require more protein owing to greater muscle mass, while women may need phosphorus and calcium adjustments to prevent osteoporosis.

• Lifestyle and activity level: Sedentary patients require fewer calories, whereas active individuals may need increased energy and plant-based protein intake.

• Comorbidities: Diabetic patients with CKD need careful carbohydrate management, while hypertensive patients benefit from sodium reduction and potassium monitoring.

• Cultural preferences: Adapting dietary recommendations to cultural food habits (e.g. Mediterranean or Asian diets) enhances adherence.

Regular dietary assessments, incorporating biochemical monitoring (e.g. serum albumin, eGFR and proteinuria levels) and mobile health applications are essential for tracking adherence and optimising interventions.

Maintaining nutritional balance is especially important in diabetic nephropathy. While severe protein restriction may increase malnutrition risk, moderate protein intake improves metabolic control and may slow disease progression in elderly diabetic patients with CKD^{(Reference Giordano, Ciarambino, Castellino, Cataliotti, Malatino and Ferrara39,Reference Meloni, Morosetti, Suraci, Pennafina, Tozzo and Taccone-Gallucci65)} . Emerging evidence also suggests that higher protein intake benefits certain elderly CKD populations, challenging traditional guidelines^{(Reference Carballo-Casla, Carla, Beridze, Ortolá and García-Esquinas66)}.

Since patients with CKD respond differently to protein restriction, ongoing dietary monitoring and adjustments are essential. A multidisciplinary approach, considering age, genetics and comorbidities, ensures that dietary plans remain effective despite resource limitations^{(Reference Dussol, Iovanna, Raccah, Darmon, Morange and Vague51,Reference Menon, Kopple, Wang, Beck, Collins and Kusek55)} . In addition, sustainable, plant-based dietary practices benefit both CKD management and broader public health goals^{(Reference Cai, Duan, Dekker, Carrero, Avesani and Bakker67,Reference D’Alessandro, Piccoli, Calella, Brunori, Pasticci and Egidi68)} .

Need for standardised diagnostic criteria and long-term RCT

One significant gap in the literature is the lack of standardised diagnostic criteria for PEW and dietary management in patients with CKD. Uniform definitions and diagnostic protocols are essential for enabling better comparison and interpretation of research findings. Carrero et al. (2018) and Gonzalez et al. (2022) emphasise the variability in reported PEW prevalence due to inconsistent definitions and assessment tools, underscoring the need for standardised criteria to accurately assess PEW prevalence and impact^{(Reference Carrero, Thomas, Nagy, Arogundade, Avesani and Chan69,Reference Gonzalez, Lozano and Solano93)} . Oosterwijk et al. (2022) also highlight the importance of uniform diagnostic standards to enhance the comparability of research outcomes and clinical practices^{(Reference Oosterwijk, Navis, Bakker and Laverman94)}. Establishing clear diagnostic guidelines would allow more targeted interventions, ultimately improving patient outcomes^{(Reference Bagros, Malvy, Maingourd, Pengloan and Nivet47,Reference Bellizzi, Signoriello, Minutolo, Di Iorio, Nazzaro and Garofalo57)} .

Furthermore, there is a critical need for long-term RCT to establish the efficacy and safety of various dietary interventions over extended periods. Jesudason et al. (2013) found no significant differences in renal outcomes between moderate-protein and standard-protein diets, demonstrating the need for more comprehensive studies^{(Reference Jesudason, Pedersen and Clifton56)}. Gonzalez et al. (2022) stress the importance of understanding metabolic pathways and individual patient characteristics in guiding personalised dietary interventions, while Oosterwijk et al. (2022) note that RCT should incorporate individualised patient profiles to tailor dietary interventions more effectively^{(Reference Gonzalez, Lozano and Solano93,Reference Oosterwijk, Navis, Bakker and Laverman94)} . Current RCT often have limitations in duration and sample diversity, which obscure the long-term effects of dietary strategies. Long-term studies could provide valuable insights into the sustained impact of dietary interventions on CKD progression, cardiovascular outcomes and quality of life^{(Reference Bagros, Malvy, Maingourd, Pengloan and Nivet47,Reference Bellizzi, Signoriello, Minutolo, Di Iorio, Nazzaro and Garofalo57)} .

Despite positive findings, many studies have not conclusively proven that LPD universally slow CKD progression. As shown in Table 3, there is considerable variability in patient responses, likely influenced by genetic factors, comorbidities and nutritional status. These mixed results underscore the need for personalised dietary management, as a one-size-fits-all approach may not effectively address the diverse needs of patients with CKD. Future research should focus on identifying subgroups that may benefit most from LPD, developing biomarkers to predict individual responses and integrating dietary interventions with other treatments

Lack of data on specific populations and adherence to dietary interventions

The literature also reveals a lack of data on specific populations, such as paediatric and elderly patients with CKD. While studies such as Giordano et al. (2014) and Dussol et al. (2005) highlight the importance of personalised nutrition, there is limited evidence on how dietary interventions affect different demographic groups. These populations may have unique nutritional needs that require specialised approaches.

Patient adherence to dietary interventions remains a significant challenge, particularly with restrictive diets such as LPD and VLPD. Future research should explore behavioural, psychological and social factors influencing adherence, and develop strategies to support long-term compliance^{(Reference Giordano, Ciarambino, Castellino, Cataliotti, Malatino and Ferrara39,Reference Dussol, Iovanna, Raccah, Darmon, Morange and Vague51)} .

Insufficient evidence on practical implementation of dietary guidelines

Another notable gap is the insufficient evidence on the practical implementation of dietary guidelines in clinical settings. While studies such as Garneata et al. (2016) and Gutiérrez et al. (2014) provide valuable insights into the benefits of plant-based diets, there is limited guidance on how to effectively incorporate these diets into everyday practice^{(Reference Gutiérrez, Muntner, Rizk, McClellan, Warnock and Newby4,Reference Garneata, Stancu, Dragomir, Stefan and Mircescu18)} . Naber and Purohit (2021) highlight the complexities involved in translating dietary recommendations into practice, stressing the need for comprehensive patient education and support systems^{(Reference Naber and Purohit95)}. Further research is needed to develop scalable models for dietary counselling and support that can be integrated into routine CKD management. This implementation requires collaboration among healthcare providers, dietitians and patients to create realistic and sustainable dietary plans. Furthermore, research should explore the role of technology, such as mobile apps and telehealth, in supporting dietary management and adherence^{(Reference Gutiérrez, Muntner, Rizk, McClellan, Warnock and Newby4,Reference Garneata, Stancu, Dragomir, Stefan and Mircescu18)} .

Recommendations for clinicians on managing protein intake in patients with CKD

Clinicians should adopt a personalised approach when managing protein intake in patients with CKD, as one-size-fits-all recommendations may not be optimal. Individualised assessment is crucial for determining the appropriate dietary plan, considering patient-specific factors such as CKD stage, comorbidities and nutritional status. While LPD and VLPD have traditionally been emphasised to slow CKD progression, these diets must be carefully monitored to prevent PEW and ensure adequate nutrition (Bagros et al., 1999; Bellizzi et al., 2022).

Recent guidelines, such as those from Kidney Disease: Improving Global Outcomes (KDIGO, 2024) and Kidney Disease Outcomes Quality Initiative (KDOQI, 2020), recommend normalising protein intake to 0·8 g/kg/d for the general CKD population, with further restrictions in select cases based on individual patient needs. These guidelines highlight the importance of flexibility and personalisation, particularly to mitigate malnutrition risks while ensuring adequate protein intake^{(96,Reference Alp Ikizler, Burrowes, Byham-Gray, Campbell, Carrero and Chan97)} .

Adherence to LPD remains a significant challenge, as studies, including the modification of diet in renal disease (MDRD) study, have shown that poor adherence can reduce its potential benefits (Levey et al., 1999; Piccoli et al., 2015). Recent evidence from Carballo-Casla et al. (2024) suggests that higher protein intake may benefit specific populations, such as older adults with mild-to-moderate CKD, potentially reducing mortality risk and preserving muscle mass^{(Reference Carballo-Casla, Carla, Beridze, Ortolá and García-Esquinas66)}. This position challenges the traditional focus on protein restriction and highlights the need to integrate insights from both nephrology and geriatric guidelines^{(Reference Isaka98)}. Given these findings, elderly patients with CKD may benefit from moderate-to-higher protein diets tailored to their metabolic needs and comorbidities. In addition, workshops, digital resources and personalised feedback can support ongoing patient education, improving adherence and the practical application of dietary recommendations^{(Reference Giordano, Ciarambino, Castellino, Cataliotti, Malatino and Ferrara39)}.

Clinicians should collaborate closely with dietitians, nephrologists and other healthcare professionals to tailor dietary interventions, ensuring ongoing monitoring and adjustments through regular follow-ups. Addressing patient-specific barriers to adherence, such as education, cultural preferences and access to resources, is essential for enhancing patient engagement and compliance. Culturally sensitive dietary plans and tailored educational resources can significantly improve adherence^{(Reference Oosterwijk, Navis, Bakker and Laverman94)}.

Potential areas for future research

Future research should focus on the long-term effects of dietary protein intake in patients with CKD, particularly regarding higher protein intake in elderly populations. Findings from Carballo-Casla et al. (2024) suggest that traditional dietary guidelines for older adults may need reassessment, especially considering their vulnerability to sarcopenia and frailty^{(Reference Carballo-Casla, Carla, Beridze, Ortolá and García-Esquinas66)}.

The development of personalised nutrition strategies should remain a priority. Research should aim to identify biomarkers that predict individual responses to dietary changes, enhancing adherence and tailoring interventions to specific patient profiles. The integration of technological innovations, such as telehealth and mobile apps, presents an opportunity to improve patient engagement and adherence. These tools offer scalable solutions for routine CKD care, facilitating continuous monitoring and personalised feedback. Further studies are needed to explore the practical implementation of these technologies in diverse clinical settings and their effectiveness in improving patient outcomes

Summary of key guidelines

Implementation in clinical practice

Implementing these guidelines in practice presents challenges, particularly in ensuring patient adherence to dietary recommendations. Bellizzi et al. (2022) highlight the difficulties of maintaining compliance with low-protein diets, emphasising the need for regular follow-up and support^{(Reference Bellizzi, Signoriello, Minutolo, Di Iorio, Nazzaro and Garofalo57)}. To improve adherence, clinicians can utilise digital tools for dietary tracking, implement personalised education programmes and involve family members in dietary planning. Regular follow-up visits remain essential for adjusting dietary plans on the basis of patient progress and feedback, ensuring sustained adherence and optimal CKD management.

Personalised dietary plans are crucial, as individual patient needs vary. Clinicians must balance protein restriction with preventing malnutrition, necessitating careful monitoring of nutritional status and disease progression. A multidisciplinary healthcare team – including dietitians, nephrologists and primary care providers – plays a critical role in providing comprehensive dietary counselling and support.

Finally, the practical implementation of these guidelines requires comprehensive patient education and collaboration between healthcare professionals. Addressing barriers such as cultural preferences, resource availability and access to dietary supplements is essential for ensuring successful implementation.