Loss of muscle mass is an extremely frequent complication in patients with chronic kidney disease (CKD). The etiology of muscle loss in CKD is multifactorial and may depend on kidney disease itself, dialysis, the typical chronic low-grade inflammation present in patients with chronic kidney disease, but also metabolic acidosis, insulin resistance, vitamin D deficiency, hormonal imbalances, amino acid loss during dialysis, and reduced dietary intake. All these conditions together increase protein degradation, decrease protein synthesis, and lead to negative protein balance. Aging further exacerbates sarcopenia in CKD patients. Nutritional therapy, such as protein restriction, aims to manage uremic toxins and slow down the progression of CKD. Low-protein diets (LPDs) and very low-protein diets (VLPDs) supplemented with amino acids or ketoacids are commonly prescribed. Energy intake is crucial, with a higher intake associated with maintaining a neutral or positive nitrogen balance. Adequate nutritional and dietary support are fundamental in preventing nutritional inadequacies and, consequently, muscle wasting, which can occur in CKD patients. This review explores the causes of muscle loss in CKD and how it can be influenced by nutritional strategies aimed at improving muscle mass and muscle strength.

Advanced glycation end products (AGEs) are aging products. In chronic kidney disease (CKD), AGEs accumulate due to the increased production, reduced excretion, and the imbalance between oxidant/antioxidant capacities. CKD is therefore a model of aging. The aim of this review is to summarize the present knowledge of AGEs in CKD onset and progression, also focusing on CKD-related disorders (cardiovascular diseases, sarcopenia, and nutritional imbalance) and CKD mortality. The role of AGEs as etiopathogenetic molecules, as well as potential markers of disease progression and/or therapeutic targets, will be discussed.

Background: Healthy ageing relies on maintaining physiological systems, particularly the musculoskeletal system (MKS). After 50, declines in bone density, muscle mass and strength increase the risk of osteoporosis and sarcopenia, leading to frailty, fractures and higher healthcare costs. Osteosarcopenia, combining osteoporosis and sarcopenia, is rising because of the ageing population. Chronic kidney disease (CKD) exacerbates this condition through disruptions in mineral metabolism, hormonal imbalances and inflammation, further compromising musculoskeletal health. Aims: This review examines the pathophysiology of osteosarcopenia associated with CKD, focusing on the role of mineral and hormonal disturbances, chronic inflammation and endocrine dysfunction. It aims to increase clinical awareness and highlight the need for early diagnosis and intervention to mitigate the burden of osteosarcopenia on the quality of life and healthcare systems in ageing CKD populations. Methods: A narrative review of the current literature was conducted, summarising evidence on the mechanisms underlying osteosarcopenia in CKD, including mineral metabolism alterations, inflammatory processes and hormonal imbalances. Results: Osteosarcopenia is a recognised consequence of CKD, contributing to increased morbidity and mortality. The pathophysiology of osteosarcopenia in CKD is multifactorial, involving disruptions in mineral metabolism, inflammation, endocrine dysfunction and physical inactivity. CKD–mineral and bone disorder (CKD‐MBD) leads to alterations in calcium, phosphate, parathyroid hormone (PTH), fibroblast growth factor 23 (FGF‐23) and vitamin D metabolism, resulting in impaired bone mineralisation and increased fracture risk. Simultaneously, CKD accelerates muscle wasting through systemic inflammation, anabolic resistance and metabolic derangements, increasing the risk of sarcopenia. Sarcopenic obesity, inflammaging and hormonal dysregulation further exacerbate bone muscle deterioration. Emerging evidence suggests that osteosarcopenia in CKD is a consequence of interconnected pathophysiological pathways rather than isolated conditions. Diagnosis remains challenging because of overlapping clinical features, necessitating integrated assessment tools. Targeted therapeutic strategies, including mineral metabolism correction, resistance exercise and anabolic interventions, are essential to mitigate osteosarcopenia's progression and improve patient outcomes in CKD. Conclusions: Osteosarcopenia is a growing concern in ageing CKD populations. Early diagnostic strategies and targeted interventions are essential to mitigate the impact of osteosarcopenia on patient outcomes and reduce associated healthcare costs. Increased clinical awareness and research into effective therapies are crucial for improving the quality of life for individuals affected by CKD and osteosarcopenia.

The deposition of antipodocyte autoantibodies in the glomerular subepithelial space induces primary membranous nephropathy (MN), the leading cause of nephrotic syndrome worldwide. Taking advantage of the glomerulus-on-a-chip system, we modeled human primary MN induced by anti-PLA2R antibodies. Here we show that exposure of primary human podocytes expressing PLA2R to MN serum results in IgG deposition and complement activation on their surface, leading to loss of the chip permselectivity to albumin. C3a receptor (C3aR) antagonists as well as C3AR gene silencing in podocytes reduced oxidative stress induced by MN serum and prevented albumin leakage. In contrast, inhibition of the formation of the membrane-attack-complex (MAC), previously thought to play a major role in MN pathogenesis, did not affect permselectivity to albumin. In addition, treatment with a C3aR antagonist effectively prevented proteinuria in a mouse model of MN, substantiating the chip findings. In conclusion, using a combination of pathophysiologically relevant in vitro and in vivo models, we established that C3a/C3aR signaling plays a critical role in complement-mediated MN pathogenesis, indicating an alternative therapeutic target for MN.

Patients affected by chronic kidney disease (CKD) are generally considered to be frailer than those with preserved renal function. We cross-sectionally evaluated the associations between frailty, malnutrition–inflammation syndrome and circulating inflammatory cytokines in 115 older individuals with advanced CKD. As for frailty definition, we adopted Fried’s frailty phenotype (FP), while malnutrition–inflammation syndrome was assessed using the Malnutrition–Inflammation Score (MIS) and circulating inflammatory cytokines (IL-6; TNFα; MCP-1). A total of 48 patients were frail, and mean eGFR was comparable in both frail and non-frail patients (24 ± 10 vs. 25 ± 11 mL/min/1.73 m²; p = 0.63). Frail patients had higher MIS (6 [4–11] vs. 4 [3–5]; p < 0.0001) but cytokine concentrations were comparable in both groups. At multivariate regression, FP was independently associated with MIS, age, gender and pre-albumin but not with cytokines. However, we found some associations between inflammatory cytokines and some specific frailty criteria: weight loss and slowness were associated with MCP-1 (respectively p = 0.049 and p < 0.0001) and weakness with IL-6 (p = 0.005); in conclusion, in older patients with advanced CKD, frailty is strictly associated with malnutrition–inflammation syndrome but not with circulating inflammatory cytokines.

Dietary studies conducted in chronic kidney disease (CKD) patients were focused on the quantities of single nutrients, however it is possible that the excessive attention put on the restriction of proteins, sodium, potassium and phosphorus may compromise the overall quality of the diet in terms of micronutrients and palatability. Instead, concentrating on the nutritional quality healthy dietary patterns, may provide a better approach to improve nutritional prescriptions in CKD patients. All these dietary regimens share common features as reduced content of red meat, salt and saturated fatty acids, and higher fiber content, but may differ in terms of single nutrients consumption. In particular, Mediterranean Diet (Med Diet) has been associated with reduced incidence of diabetes, cardiovascular diseases and obesity, all conditions that are also strictly related to CKD. Given its low content of animal proteins and high contents of fiber it is possible that Med Diet may exert also positive effects on CKD as well as on its metabolic complications. In this review we summarize the role of Med Diet in primary prevention of CKD and on its progression.