The mechanism underlying podocyte dysfunction in minimal change disease (MCD) remains unknown. This study aimed to shed light on the potential pathophysiology of MCD using glomerular proteomic analysis. Shotgun proteomics using label-free quantitative mass spectrometry was performed on formalin-fixed, paraffin-embedded (FFPE) renal biopsies from two groups of samples: control (CTR) and MCD. Glomeruli were excised from FFPE renal biopsies using laser capture microdissection (LCM), and a single-pot solid-phase-enhanced sample preparation (SP3) digestion method was used to improve yield and protein identifications. Principal component analysis (PCA) revealed a distinct separation between the CTR and MCD groups. Forty-eight proteins with different abundance between the two groups (p-value ≤ 0.05 and |FC| ≥ 1.5) were identified. These may represent differences in podocyte structure, as well as changes in endothelial or mesangial cells and extracellular matrix, and some were indeed found in several of these structures. However, most differentially expressed proteins were linked to the podocyte cytoskeleton and its dynamics. Some of these proteins are known to be involved in focal adhesion (NID1 and ITGA3) or slit diaphragm signaling (ANXA2, TJP1 and MYO1C), while others are structural components of the actin and microtubule cytoskeleton of podocytes (ACTR3 and NES). This study suggests the potential of mass spectrometry-based shotgun proteomic analysis with LCM glomeruli to yield valuable insights into the pathogenesis of podocytopathies like MCD. The most significantly dysregulated proteins in MCD could be attributable to cytoskeleton dysfunction or may be a compensatory response to cytoskeleton malfunction caused by various triggers.

Background/Objectives: In hemodialysis (HD), inflammatory biomarkers are discussed as prognostic markers for survival and cardiovascular events (CVEs). The results of the studies are not uniform and there are particularities related to population groups and comorbidities. In addition, it is known that inflammation determines protein malnutrition and less about the effect of adipose tissue on inflammation in HD. This study investigates the relationship between inflammatory molecules and nutritional biomarkers, and CVE and survival in HD patients. Methods: We included, in an observational, longitudinal study, 65 patients with chronic HD (53 without diabetes and 22 smokers), with a mean age of 60.1 ± 12.4 years. High-sensitivity C-reactive protein (hs-CRP), interleukin 1 beta, tumor necrosis factor alpha (TNF-alpha), interleukin 6, soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK), soluble CD163 (sCD163), and fibroblast growth factor 21 were determined. We recorded survival and cardiovascular events for 60 months. Univariate and multivariate analyses were performed. Results: Hs-CRP was significantly associated with survival (p = 0.014) in the total group. In smokers and former smokers, TNF-α lower than 368.34 pg/mL was associated with better survival. In multivariate analysis, hs-CRP was correlated with adipose tissue biomarkers (p = 0.006), and sCD163 was correlated with total and LDL cholesterol (p = 0.002). In addition, in univariate analysis, sTWEAK was correlated with serum albumin (p = 0.026, r = −0.30). In conclusion, in HD patients, hs-CRP was significantly associated with survival, and low TNF-alpha values in smokers and former smokers were linked to better survival. Hs-CRP was also correlated with adipose tissue biomarkers, CD163 was correlated with total and LDL cholesterol, and albumin was inversely associated with sTWEAK. The relation between inflammatory molecules and adipose tissue biomarkers was less identified in HD patients until now.

Podocyte injury plays a central role in both focal segmental glomerulosclerosis (FSGS) and minimal change disease (MCD). Pathogenic mechanisms are diverse and incompletely understood, partially overlap between FSGS and MCD, and are not reflected by kidney biopsy. In order to optimize the current variable response to treatment, personalized management should rely on pathogenesis. One promising approach involves identifying biomarkers associated with specific pathogenic pathways. With the advancement of technology, proteomic studies could be a valuable tool to improve knowledge in this area and define valid biomarkers, as they have in other areas of glomerular disease. This work attempts to cover and discuss the main mechanisms of podocyte injury, followed by a review of the recent literature on proteomic biomarker studies in podocytopathies. Most of these studies have been conducted on biofluids, while tissue proteomic studies applied to podocytopathies remain limited. While we recognize the importance of non-invasive biofluid biomarkers, we propose a sequential approach for their development: tissue proteomics could first identify proteins with increased expression that may reflect underlying disease mechanisms; subsequently, the validation of these proteins in urine or plasma could pave the way to a diagnostic and prognostic biomarker-based approach.

Chronic kidney disease (CKD) is a leading condition in terms of prevalence and overall health impact. With the increased life expectancy of the CKD population and the improvement in medical care, controlling musculoskeletal complications remains a tough challenge. Patients with CKD are prone to falls, fractures and sarcopenia, enhancing the risk of death. A multitude of mechanisms contribute to fractures, and treatment is suboptimal; therefore, prevention must stand out as a key step. This review aims to provide an overview of the most relevant data regarding the impact of nutrition on bone disorders and sarcopenia in CKD. The newest relevant studies emphasize that plant protein intake is associated with a lower production of uremic toxins, lower serum phosphorus levels, and stronger bones. We conclude that patients with CKD should adopt specific diets tailored to the presence of osteoporosis, renal osteodystrophy, and muscle wasting. Low-protein diets or plant-dominant diets containing an adequate amount of protein could be better choices for predialysis patients with CKD in order to protect their bones and muscles, whereas in the dialysis population, a higher protein intake could be essential to prevent osteoporosis and sarcopenia. In all patients with CKD, focusing on antioxidant food intake could provide a strong antiaging benefit through ensuring good musculoskeletal health.

Background: As societies rapidly age, the prevalence of mental health disorders and chronic kidney disease (CKD) is simultaneously rising, and data on the link between these conditions remain inconclusive. This study aimed to investigate the associations among cognitive impairment, depression, and kidney involvement in elderly patients. Methods: A cross-sectional analysis was conducted among hospitalized patients aged ≥65 years. Standardized tools such as the geriatric depression scale (GDS) and Montreal Cognitive Assessment (MoCA) were used to assess depression and cognitive impairment, and kidney function was evaluated using eGFR and albuminuria. Bivariate and multivariate logistic regressions were performed to identify associations. Results: The study population consisted of 719 participants with a median age of 80 years. Kidney and mental health issues were highly prevalent: CKD was identified in 59.4%, cognitive impairment in 74%, and depression in 61.9% of patients. Patients with CKD were older and exhibited lower MoCA scores (p = 0.001), higher GDS scores (p = 0.007), reduced albumin (p < 0.001), lower hemoglobin levels (p < 0.001), and elevated C-reactive protein (p < 0.001). Increased albuminuria was associated with poorer cognition (p < 0.001) but showed no correlation with GDS scores. Additionally, worse cognitive scores (p = 0.001) and increased depression symptoms (p < 0.001) were correlated with declining estimated glomerular filtration rate (eGFR). Conclusions: Cognitive impairment and depressive symptoms are highly prevalent among elderly hospitalized patients. Cognitive decline correlates with increased albuminuria and reduced eGFR, while depression worsens with declining kidney function. These findings highlight the complex interplay between renal health and neuropsychiatric conditions in aging populations.

In chronic kidney disease (CKD), various disorders occur that worsen with the progression of CKD. These include increased levels of hormones such as adiponectin, leptin, and prolactin, changes in feedback loops and metabolism, and decreased renal clearance, contributing to significant morbidity and mortality. We conducted a cross-sectional observational study on 157 randomly selected patients with various stages of chronic kidney disease, 29% of whom had diabetes. We recorded clinical and usual laboratory data. We determined muscle mass and adipose tissue mass using bioimpedance. In addition, we measured serum prolactin levels, tumor necrosis factor-alpha (TNF-α), Interleukin 6 (IL-6), and Interleukin-1 beta (IL-1β). N-terminal pro-B-type natriuretic peptide (NT-proBNP) was evaluated as a marker of cardiac function. We evaluated the relation between prolactin, TNF-α, IL-6, IL-1β, and NT-proBNP by bivariate and multivariate analysis. In bivariate analysis, we recorded associations of prolactin with inflammatory markers: TNF-α (r = 0.65, p < 0.001), IL-6 (r = 0.66, p < 0.001), and IL-1β (r = 0.25, p = 0.002). In multivariate analysis we observed that serum prolactin values are associated with IL-1β [median (25th–75th percentile): [−0.001 (−0.001; −0.00003), p = 0.037], muscle mass [−0.03 (−0.04; −0.01), p = 0.003], and NT-proBNP [0.0001 (0.0001; 0.0001)] p < 0.001 In conclusion, in chronic kidney disease, prolactin is associated with inflammatory markers (IL-1β, TNF-α, IL-6), and nutritional status. Additionally, prolactin has been linked to NT-ProBNP, a marker of cardiac function.