Associations of Intact and C-Terminal FGF23 with Inflammatory Markers in Older Patients Affected by Advanced Chronic Kidney Disease.

Background: In patients with chronic kidney disease (CKD), Fibroblast Growth Factor 23 (FGF23) is markedly increased and has been proposed to interact with systemic inflammation. Methods: In this cross-sectional study, we evaluated the correlations of intact FGF23, c-terminal FGF23, and the FGF23 ratio (c-terminal to intact) with some inflammatory cytokines in 111 elderly patients with advanced CKD not yet in dialysis. Results: Estimated glomerular filtration rate (eGFR) was inversely correlated with intact FGF23 and c-terminal FGF23, as well as with interleukin 6 (IL-6), tumor necrosis factor alpha (TNFα), and monocyte chemoattractant protein-1 (MCP-1). Intact FGF23 levels were directly correlated with IL-6 (r = 0.403; p < 0.001) and TNFα (r = 0.401; p < 0.001) while c-terminal FGF23 was directly correlated with MCP-1 (r = 0.264; p = 0.005). The FGF23 ratio was, instead, inversely correlated with IL-6 (r = -0.326; p < 0.001). Multivariate analysis revealed that intact FGF23 was directly associated with TNFα [B = 0.012 (95% CI 0.006, 0.019); p = 0.003] and c-terminal FGF23 was directly associated with MCP-1 [B = 0.001 (95% CI 0.000, 0.002); p = 0.038], while the FGF23 ratio was inversely correlated with IL-6 [B = -0.028 (95% CI -0.047, -0.010); p = 0.002]. Conclusions: Our data demonstrate that, in CKD patients, intact FGF23 and the metabolites deriving from its proteolytic cleavage are differently associated with some inflammatory pathways. In particular, intact FGF23 is mainly associated with IL-6 and TNFα, c-terminal FGF23 with MCP-1, and the FGF23 ratio with IL6.

Nutritional Strategies to Prevent Muscle Loss and Sarcopenia in Chronic Kidney Disease: What Do We Currently Know?

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.

Accelerated AGEing: The Impact of Advanced Glycation End Products on the Prognosis of Chronic Kidney Disease.

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.

Association of Autofluorescent Advanced Glycation End Products (AGEs) with Frailty Components in Chronic Kidney Disease (CKD): Data from a Single-Center Cohort Study.

BACKGROUND: Chronic kidney disease (CKD) is characterized by an overproduction and accumulation of advanced glycation end products (AGEs). Because AGEs may play a role in the development of malnutrition and sarcopenia, two essential components of frailty, we evaluated whether they may also contribute to the onset of frailty in CKD patients. METHODS: We performed a cross-sectional analysis of 117 patients. AGEs were quantified using a fluorescence spectrophotometer and soluble receptor for AGE (sRAGE) isoforms by ELISA. We defined frailty according to the frailty phenotype (FP) proposed by Fried. RESULTS: The average age of patients was 80 ± 11 years, 70% were male, and the mean eGFR was 25 + 11 mL/min/1.73m2. Frailty was diagnosed in 51 patients, and 40 patients were classified as pre-frail. AGEs and RAGE isoforms seem not to correlate with overall frailty. Instead, AGEs were associated with specific frailty domains, inversely associated with BMI (R = -0.22, p = 0.016) and directly associated with gait test time (R = 0.17, p = 0.049). AGEs were also associated with involuntary weight loss (OR 1.84 p = 0.027), independent of age and sex. CONCLUSIONS: AGEs are associated with some pivotal components of the frailty phenotype, although they are not associated with frailty overall.

MCP1 Could Mediate FGF23 and Omega 6/Omega 3 Correlation Inversion in CKD.

Fibroblast growth factor 23 (FGF23) concentrations rise after the early stages of chronic kidney disease (CKD). FGF23 is involved in inflammatory reactions closely associated with an incremented risk of cardiovascular disease (CVD). There is growing evidence that omega-6 (n-6) and n-3 polyunsaturated fatty acids (PUFA) can modulate inflammation through several mediators producing an opposite effect on cardiovascular (CV) risks. In this study, we explore whether there is any correlation between PUFA, FGF23, and inflammation in CKD patients. We evaluated, cross-sectionally, 56 patients at different stages of CKD. Monocyte chemoattractant protein 1 (MCP1), and intact and c-terminal FGF23 (iFGF23, cFGF23) were quantified by the ELISA, and the fatty acids (FA) profile was analyzed by gas chromatography. Concurrently with an eGFR decrease (p < 0.01) and an MCP1 increase (p = 0.031), we observed an inversion of the correlation between FGF23 and the n-6/n-3 ratio. This last correlation was inversed in CKD stage 3 (r2 (−) 0.502 p = 0.029) and direct in stage 5 (r2 0.657 p = 0.020). The increase in MCP1 seems to trigger events in the inversion of the correlation between FGF23 and the n-6/n-3 PUFA ratio. This result strongly encourages future studies on basal pathways, on possible pharmacological interventions, and on managing kidney transplant patients treated with immunosuppressive therapy.

Frailty in kidney transplantation: a review on its evaluation, variation and long-term impact.

The problem of frailty in kidney transplantation is an increasingly discussed topic in the transplant field, partially also generated by the multiple comorbidities by which these patients are affected. The criteria currently used to establish the presence and degree of frailty can be rapidly assessed in clinical practice, even in patients with chronic kidney disease (CKD). The main objectives of this work are: (i) to describe the method of evaluation and the impact that frailty has in patients affected by CKD, (ii) to explore how frailty should be studied in the pre-transplant evaluation, (iii) how frailty changes after a transplant and (iv) the impact frailty has over the long term on the survival of renal transplant patients.

Can Mediterranean Diet Have a Positive Impact on Kidney Health? A Pending Answer to a Long-Time Question.

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.

Association between Advanced Glycation End-Products and Sarcopenia in Patients with Chronic Kidney Disease.

BACKGROUND: In patients with chronic kidney disease (CKD), there is an overproduction and accumulation of advanced glycation end-products (AGEs). Since AGEs may have detrimental effects on muscular trophism and performance, we evaluated whether they may contribute to the onset of sarcopenia in CKD patients. METHODS: We enrolled 117 patients. The AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer and soluble receptor for AGE (sRAGE) isoforms by ELISA. As for the sarcopenia definition, we used the European Working Group on Sarcopenia in Older People (EWGSOP2) criteria. RESULTS: The average age was 80 ± 11 years, 70% were males, and the mean eGFR was 25 + 11 mL/min/1.73 m2. Sarcopenia was diagnosed in 26 patients (with a prevalence of 22%). The sarcopenic patients had higher levels of circulating AGEs (3405 ± 951 vs. 2912 ± 722 A.U., p = 0.005). AGEs were higher in subjects with a lower midarm muscle circumference (MAMC) (3322 ± 919 vs. 2883 ± 700 A.U., respectively; p = 0.005) and were directly correlated with the gait test time (r = 0.180, p = 0.049). The total sRAGE and its different isoforms (esRAGE and cRAGE) did not differ in patients with or without sarcopenia. CONCLUSIONS: In older CKD patients, AGEs, but not sRAGE, are associated with the presence of sarcopenia. Therefore, AGEs may contribute to the complex pathophysiology leading to the development of sarcopenia in CKD patients.

In Patients with Chronic Kidney Disease Advanced Glycation End-Products Receptors Isoforms (sRAGE and esRAGE) Are Associated with Malnutrition.

BACKGROUND: in patients with chronic kidney disease (CKD), the inflammatory and pro-oxidant milieu may contribute to malnutrition development. In this study, we investigated the relationship between inflammation, advanced glycation end-products (AGEs), and their receptors (RAGEs) with malnutrition in CKD patients. METHODS: we evaluated 117 patients. AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer, soluble RAGEs isoforms, and inflammatory interleukins by ELISA. Malnutrition was assessed by a malnutrition inflammation score. RESULTS: mean age was 80 ± +11 years, eGFR was 25 ± +11 mL/min/1.73 m2 and BMI was 28 ± 5 Kg/m2. Malnourished individuals were older, had lower estimated protein intake (nPCR 0.65 ± 0.2 vs. 0.8 ± 0.2 vs. 0.8 ± 0.3, p = 0.01), higher C reactive protein (CRP 0.6 ± 1 vs. 0.6 ± 0.7 vs. 0.17 ± 0.13, p = 0.02) and tumor necrosis factor α (TNF α 14.7 ± 8.7 vs. 15.6 ± 8 vs. 11.8 ± 5.8, p = 0.029). Malnourished patients had higher sRAGE (2813 ± 1477 vs. 2158 ± 1236 vs. 2314 ± 1115, p = 0.035) and esRAGE (648 [408-1049] vs. 476 [355-680] vs. 545 [380-730] p = 0.033). In the multivariate analysis, only sRAGE maintained its association with malnutrition (p = 0.02) independently of aging and inflammation. CONCLUSIONS: in CKD patients, RAGEs isoforms, but not AGEs, are associated with malnutrition, irrespective of systemic inflammation, aging, and renal function.

AGEs and sRAGE Variations at Different Timepoints in Patients with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) are affected by enhanced oxidative stress and chronic inflammation, and these factors may contribute to increase advanced glycation end-products (AGEs). In this study we quantified AGEs and soluble receptors for AGE (sRAGE) isoforms and evaluated the association between their variations and eGFR at baseline and after 12 months. We evaluated 64 patients. AGEs were quantified by fluorescence intensity using a fluorescence spectrophotometer, and sRAGE by ELISA. Median age was 81 years, male patients accounted for 70%, 63% were diabetic, and eGFR was 27 ± 10 mL/min/1.73 m2. At follow up, sRAGE isoforms underwent a significant decrement (1679 [1393;2038] vs. 1442 [1117;2102], p < 0.0001), while AGEs/sRAGE ratios were increased (1.77 ± 0.92 vs. 2.24 ± 1.34, p = 0.004). Although AGEs and AGEs/sRAGE ratios were inversely related with eGFR, their basal values as well their variations did not show a significant association with eGFR changes. In a cohort of patients with a stable clinical condition at 1 year follow-up, AGEs/sRAGE was associated with renal function. The lack of association with eGFR suggests that other factors can influence its increase. In conclusion, AGEs/sRAGE can be an additional risk factor for CKD progression over a longer time, but its role as a prognostic tool needs further investigation.

Association of Sarcopenia and Gut Microbiota Composition in Older Patients with Advanced Chronic Kidney Disease, Investigation of the Interactions with Uremic Toxins, Inflammation and Oxidative Stress.

Sarcopenia is a prevalent condition in chronic kidney disease (CKD). We determined gut microbiota (gMB) composition in CKD patients with or without sarcopenia. Furthermore, we investigated whether in these patients, there was any association between gMB, uremic toxins, inflammation and oxidative stress. We analyzed gMB composition, uremic toxins (indoxyl sulphate and p-cresyl sulphate), inflammatory cytokines (interleukin 10, tumor necrosis factor α, interleukin 6, interleukin 17, interleukin 12 p70, monocyte chemoattractant protein-1 and fetuin-A) and oxidative stress (malondialdehyde) of 64 elderly CKD patients (10 < eGFR < 45 mL/min/1.73 m2, not on dialysis) categorized as sarcopenic and not-sarcopenic. Sarcopenia was defined according to European Working Group on Sarcopenia in Older People 2 criteria. Sarcopenic patients had a greater abundance of the Micrococcaceae and Verrucomicrobiaceae families and of Megasphaera, Rothia, Veillonella, Akkermansia and Coprobacillus genera. They had a lower abundance of the Gemellaceae and Veillonellaceae families and of Acidaminococcus and Gemella genera. GMB was associated with uremic toxins, inflammatory cytokines and MDA. However, uremic toxins, inflammatory cytokines and MDA were not different in sarcopenic compared with not-sarcopenic individuals, except for interleukin 10, which was higher in not-sarcopenic patients. In older CKD patients, gMB was different in sarcopenic than in not-sarcopenic ones. Several bacterial families and genera were associated with uremic toxins and inflammatory cytokines, although none of these latter substantially different in sarcopenic versus not-sarcopenic patients.

Association between the uremic toxins indoxyl-sulfate and p-cresyl-sulfate with sarcopenia and malnutrition in elderly patients with advanced chronic kidney disease.

BACKGROUND: in patients with chronic kidney disease (CKD) indoxyl sulfate (IS) and p-cresyl sulfate (PCs) may induce sarcopenia either directly or via systemic inflammation. We evaluated whether IS and PCs were associated with: sarcopenia, systemic inflammation and nutritional status. METHODS: we examined cross sectionally 93 patients with advanced CKD. Sarcopenia was identified according to EWGSOP2 definition. Malnutrition was assessed by Malnutrition Inflammation Score (MIS) and Protein Energy Wasting syndrome (PEW). Inflammatory status was assessed by dosing: CRP, IL6, TNFα, MCP1, IL10, IL17, IL12p70. RESULTS: we did not find any association of sarcopenia with IS and PCs. IS was associated with LogTNFα and LogMCP-1 in the overall cohort (r = 0.30, p = 0.0043; r = 0.22 p = 0.047) and in not sarcopenic patients (r = 0.32, p = 0.0077; r = 0.25, p = 0.041). PCs was associated with LogIL10 and LogIL12p70 in sarcopenic patients (r = 0.58, p = 0.0042; r = 0.52, p = 0.013). IS was higher in patients without PEW (p = 0.029), while PCs was higher in patients with PEW (p = 0.0040). IS and PCs were not different in patients with normal or increased MIS. CONCLUSIONS: IS and PCs were not associated with sarcopenia, although they were both associated with some inflammatory pathways. Notably, we found a positive association of PCs with PEW syndrome.

Associations Between Cholesterol and Fatty Acid Profile on the Severity of Depression in Older Persons With Nondialysis Chronic Kidney Disease.

Depressive symptoms worsen the outcomes of patients affected by chronic kidney disease (CKD). The purpose of the present article is to study the association between serum lipid profile and the severity of depression in patients with CKD. We evaluated 132 older subjects with advanced CKD (stage 3-5, not receiving dialysis) in regular follow-up in a nephrology clinic. Blood samples were collected after an overnight fast. All patients were evaluated with the Geriatric Depression Scale which is comprised of 30 items that assess the severity of depressive symptoms. A backward multivariate regression analysis was performed to study the association between lipid profile and severity of depression. Low-density lipoprotein levels (ß = 2.77, P = .008) and arachidonic acid/linoleic acid ratio (ß = 2.51, P = .015) were found to be significantly associated with severity of depressive symptoms. Change in dietary habits or the use of hypocholesterolemic drugs could potentially prevent depressive symptoms and ameliorate outcome of patients affected by CKD. Data from prospective studies are needed to confirm these preliminary results.

Possible Benefits of a Low Protein Diet in Older Patients With CKD at Risk of Malnutrition: A Pilot Randomized Controlled Trial.

BACKGROUND: Current guidelines do not clarify whether older patients with advanced chronic kidney disease (CKD) may benefit of low protein (LP) diet if they are at risk of malnutrition. We compared the effects of normocalorie/normoprotein (NP) and normocalorie/LP diet on nutritional status and metabolic complications related to the progression of kidney damage in these patients. METHODS: This pilot study had an open-label randomized-controlled design (ClinicalTrials.gov Id: NCT05015647). Thirty-five patients were treated for 6 months with two different diets (LP = 17) and (NP = 18). Malnutrition was assessed by the Malnutrition Inflammation Score and International Society of Renal Nutrition and Metabolism criteria. Renal function was assessed by creatinine and cystatin-C-based estimated glomerular filtration rate (eGFR). RESULTS: At the end of the study, Malnutrition Inflammation Score was improved in both LP and NP groups (respectively: 3 ± 3 vs. 6 ± 1.5, p = 0.020 and 3 ± 2.5 vs. 6 ± 2, p = 0.012), prevalence of protein energy wasting syndrome decreased only in LP. LP group had higher eGFRcys-C (17 ± 6 vs. 12 ± 4 ml/min/1.73 m2; p < 0.05), lower serum urea (105 ± 65 vs. 138 ± 30 mg/dl; p < 0.05) and lower parathormone (68 ± 10 vs. 99 ± 61 ng/L; p < 0.05) than NP. Serum and urinary phosphorous did not change while fibroblast growth factor 23 (FGF23)-intact and FGF23 c-terminal increased in both groups [FGF23-intact in LP: 70 (48; 98) vs. 126 (90; 410) pg/ml, p < 0.01 and in NP: 86 (57; 194) vs. 143 (119; 186) pg/ml, p < 0.01; FGF23 c-terminal in LP: 77 (30.3; 112) vs. 111 (63; 384) RU/ml, p < 0.01 and in NP: 142 (56.6; 175) vs. 157 (76.7; 281) RU/ml, p < 0.01]. CONCLUSIONS: LP diet has a favorable impact on nutritional status as much as NP diet with possible greater benefits on the progression of kidney disease and some of its metabolic complications. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT05015647, identifier: NCT05015647.

Advanced Glycation End Products (AGE) and Soluble Forms of AGE Receptor: Emerging Role as Mortality Risk Factors in CKD.

Advanced glycation end-products (AGE) can promote chronic kidney disease (CKD) progression and CKD-related morbidities. The soluble receptor for AGE (sRAGE) is a potential biomarker of inflammation and oxidative stress. Here, we explored the role of AGE, glycated albumin, sRAGE and its different forms, cRAGE and esRAGE, as prognostic factors for mortality in 111 advanced CKD patients. The median follow-up time was 39 months. AGE were quantified by fluorescence, sRAGE and its forms by ELISA. Malnutrition was screened by the Malnutrition Inflammation Score (MIS). The Cox proportional hazards regression model was used to assess the association of variables with all-cause mortality. Mean levels of sRAGE, esRAGE and cRAGE were 2318 ± 1224, 649 ± 454 and 1669 ± 901 pg/mL. The mean value of cRAGE/esRAGE was 2.82 ± 0.96. AGE were 3026 ± 766 AU and MIS 6.0 ± 4.7. eGFR correlated negatively with AGE, sRAGE, esRAGE and cRAGE, but not with cRAGE/esRAGE. Twenty-eight patients died. No difference was observed between diabetic and non-diabetic patients. Starting dialysis was not associated with enhanced risk of death. AGE, esRAGE and cRAGE/esRAGE were independently associated with all-cause mortality. AGE, esRAGE and cRAGE/esRAGE may help to stratify overall mortality risk. Implementing the clinical evaluation of CKD patients by quantifying these biomarkers can help to improve patient outcomes.

Frailty phenotype and multi-domain impairments in older patients with chronic kidney disease.

BACKGROUND: Older subjects with chronic kidney disease (CKD) are often affected by multiple geriatric impairments that may benefit from a comprehensive geriatric assessment (CGA). However, ordinary execution of CGA in all these individuals would be unaffordable. We evaluated if Frailty Phenotype (FP) could identify older CKD-patients that may benefit the most from a CGA. METHODS: We evaluated 112 CKD patients not yet on dialysis (age ≥ 65 years, eGFR < 45 ml/min). FP was defined according to the criteria proposed by Fried and co-authors. CGA evaluated four domains (nutrition, physical performance, cognition and depression). Malnutrition was defined in accordance to Malnutrition-Inflammation Score (MIS) and/or by the presence of Protein Energy Wasting syndrome (PEW). Physical performance was evaluated using Short Physical Performance Battery (SPPB) and handgrip strength. Cognitive status was assessed by using Mini Mental State Examination (MMSE) and Clock Drawing Test. Mood was investigated with Geriatric Depression Scale (GDS). RESULTS: Average age of our cohort was 80 ± 6 years and mean eGFR 24 ± 11 ml/min/1.73 m2. Prevalence of frailty was 45%. Frail patients (F-CKD) had higher prevalence of malnutrition (58 vs 29%, p = 0.0005), physical impairment (100% vs 78%; p < 0.0001), cognitive dysfunction (83% vs 37%; p < 0.0001) and depression (50% vs 21%; p < 0.001) compared to robust ones (NF-CKD). Moreover, F-CKD patients had higher probability to have > 2 impaired domains (83% sensitivity and 76% specificity) respect to NF-CKD individuals. CONCLUSIONS: FP is a reliable screening tool to identify older CKD-patients that may benefit from a CGA.

Gut microbiota composition and frailty in elderly patients with Chronic Kidney Disease.

BACKGROUND: Frailty is common in older patients affected by chronic kidney disease (CKD). Since gut microbiota (gMB) may contribute to frailty, we explored possible associations between gMB and frailty in CKD. METHODS: We studied 64 CKD patients (stage 3b-4), categorized as frail (F, 38) and not frail (NF, 26) according to Fried criteria, and 15 controls (C), all older than 65 years. In CKD we assessed serum C-reactive protein, blood neutrophil/lymphocyte ratio, Malnutrition-inflammation Score (MIS); gMB was studied by denaturing gel gradient electrophoresis (DGGE), high-throughput sequencing (16S r-RNA gene), and quantitative real-time PCR (RT-PCR). RESULTS: No differences in alpha diversity between CKD and C and between F and NF patients emerged, but high-throughput sequencing showed significantly higher abundance of potentially noxious bacteria (Citrobacter, Coprobacillus, etc) and lower abundance of saccharolytic and butyrate-producing bacteria (Prevotella spp., Faecalibacterium prausnitzii, Roseburia spp.), in CKD respect to C. Mogibacteriaceae family and Oscillospira genus abundance was positively related to inflammatory indices in the whole CKD cohort, while that of Akkermansia, Ruminococcus and Eubacterium genera was negatively related. Compared with NF, in F there was a higher abundance of some bacteria (Mogibacteriacee, Coriobacteriacee, Eggerthella, etc), many of which have been described as more abundant in other diseases. CONCLUSIONS: These results suggest that inflammation and frailty could be associated to gMB modifications in CKD.

Malnutrition and inflammation are associated with severity of depressive and cognitive symptoms of old patients affected by chronic kidney disease.

OBJECTIVE: Chronic kidney disease (CKD) is a disabling condition associated with different medical comorbidities including depression and cognitive impairment. We investigated the association between malnutrition, inflammation and depressive/cognitive symptoms in elderly subjects with advanced CKD. METHODS: We evaluated cross-sectionally 132 elderly subjects (age ≥65 years) with advanced CKD (stage 4-5, non-dialytic-ND) in regular follow up at the outpatient clinic of nephrology. Blood and urinary samples were collected after an overnight fast. All patients were evaluated by Geriatric Depression Scale (GDS)-30 items for severity of depressive symptoms, Mini Mental State Examination (MMSE) and the Clock Drawing Test (CDT) for cognition. Nutritional status was assessed by Malnutrition Inflammation Score (MIS). Different linear regression models were performed to study the association between clinical variables, diet and inflammatory parameters with the above mentioned rating scale scores. A final linear regression model with only previous statistically significant variables was performed for GDS scores. RESULTS: Our cohort consisted of 95 males and 37 females with a mean age of 78 ±â€¯7. Female gender (B = 3.20, p < .01), higher MIS (B = 0.29, p = .02) and higher IL-12p70 serum levels (pg/mL) (B = 0.37, p = .03) were associated with severity of depressive symptoms. MIS was associated with the severity of cognitive impairment as assessed by MMSE (B = -0.19, p < .01) and CDT (B = 0.10, p = .03). CONCLUSION: In elderly subjects affected by CKD the severity of depressive symptoms and cognitive impairment is associated with specific inflammatory and nutritional parameters. These results have to be considered as preliminary and need replication by further studies.