In patients with chronic kidney disease (CKD), sarcopenia can be determined by a wide spectrum of risk factors. We evaluated the association of sarcopenia with nutritional, behavioral and ...inflammatory patterns in older patients with advanced CKD.
we cross-sectionally evaluated 113 patients with CKD stages 3b-5. Sarcopenia was defined according to the EWGSOP2 criteria. We assessed: anthropometry, bioelectrical impedance analysis, physical, and psychological performance. Nutritional status was assessed using the Malnutrition Inflammation Score (MIS) and by verifying the eventual presence Protein Energy Wasting syndrome (PEW). Systemic inflammation was assessed by dosing: CRP, IL6, TNFα, MCP1, IL10, IL17, fetuin, IL12.
24% of patients were sarcopenic. Sarcopenic individuals had lower creatinine clearance (18 ± 11 vs. 23 ± 19 mL/min;
= 0.0087) as well as lower BMI (24.8 ± 3.0 vs. 28.4 ± 5.5 Kg/m
;
< 0.0001) and a lower FTI (11.6 ± 3.9 vs. 14.4 ± 5.1 kg/m
,
= 0.023). Sarcopenic persons had higher prevalence of PEW (52 vs. 20%,
< 0.0001) and a tendency to have higher MIS (6.6 ± 6.5 vs. 4.5 ± 4.0,
= 0.09); however, they did not show any difference in systemic inflammation compared to non-sarcopenic individuals.
CKD sarcopenic patients were more malnourished than non-sarcopenic ones, but the two groups did not show any difference in systemic inflammation.
Carbon nanomaterials offer excellent prospects as therapeutic agents, and among them, graphene quantum dots (GQDs) have gained considerable interest thanks to their aqueous solubility and intrinsic ...fluorescence, which enable their possible use in theranostic approaches, if their biocompatibility and favorable pharmacokinetic are confirmed. We prepared ultra-small GQDs using an alternative, reproducible, top-down synthesis starting from graphene oxide with a nearly 100% conversion. The materials were tested to assess their safety, demonstrating good biocompatibility and ability in passing the ultrafiltration barrier using an
in vitro
model. This leads to renal excretion without affecting the kidneys. Moreover, we studied the GQDs
in vivo
biodistribution confirming their efficient renal clearance, and we demonstrated that the internalization mechanism into podocytes is caveolae-mediated. Therefore, considering the reported characteristics, it appears possible to vehiculate compounds to kidneys by means of GQDs, overcoming problems related to lysosomal degradation.
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 m
, 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
and
families and of
,
,
,
and
genera. They had a lower abundance of the
and
families and of
and
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.
The glomerular filtration barrier (GFB), composed of endothelial cells, glomerular basement membrane, and podocytes, is a unique structure for filtering blood while detaining plasma proteins ...according to size and charge selectivity. Structurally, the fenestrated endothelial cells, which align the capillary loops, are in close proximity to mesangial cells. Podocytes are connected by specialized intercellular junctions known as slit diaphragms and are separated from the endothelial compartment by the glomerular basement membrane. Podocyte-endothelial cell communication or crosstalk is required for the development and maintenance of an efficient filtration process in physiological conditions. In pathological situations, communication also has an essential role in promoting or delaying disease progression. Podocytes and endothelial cells can secrete signaling molecules, which act as crosstalk effectors and, through binding to their target receptors, can trigger bidirectional paracrine or autocrine signal transduction. Moreover, the emerging evidence of extracellular vesicles derived from various cell types engaging in cell communication has also been reported. In this review, we summarize the principal pathways involved in the development and maintenance of the GFB and the progression of kidney disease, particularly in kidney transplantation.
Background Protein restriction has been extended to stage 3 chronic kidney disease (CKD) regardless of age in the latest K-DOQI guidelines for the dietary management of patients with CKD. However, in ...elderly CKD patients there is a tendency to a spontaneous reduction in protein and energy intake that may impair the overall nutritional status. The aim of our study is to assess whether there are differences in malnutrition, exercise capacity and inflammatory status in elderly CKD patients with spontaneously low protein intake (sLPI) compared with patients with normal protein intake (NPI). Methods We performed a cross-sectional analysis of 123 incident patients. Malnutrition was assessed using Malnutrition Inflammation Score (MIS) and serum markers; As for physical performance, we used Short Physical Performance Battery (SPPB) and handgrip strength. Results We found that in older patients with advanced CKD, as many as 68% had low spontaneous protein intake, and they were more malnourished evaluated with MIS (25% vs. 10%, p = 0.033), protein-energy wasting (PEW) (43% vs. 14%, p = 0.002) and nPCR (0.630.51–0.69 vs. 0.950.87–1.1, p < 0.0001). They also had worse body composition, in terms of lower mid-arm muscular circumference (MAMC), fat tissue index (FTI) and higher overhydration (OH). sLPI patients also had higher levels of IL6 (4.62.9–8.9 vs. 2.80.8–5.1, p = 0.002). Moreover, sLPI patients were frailer (33% vs. 24%, p = 0.037) and had poorer physical performance especially when assessed with (SPPB) (75–9 vs. 97–10, p = 0.004) and gait test time (6.08 + 2 vs. 7.22 + 2.7, p = 0.04). sLPI was associated with lower physical performance SPPB OR, 0.79 (0.46–0.97), p = 0.046 and malnutrition MIS 1.6 (1.05–3.5), p = 0.041 independently from patients’ age and eGFR. Conclusion We found that in older patients with advanced CKD, up to 68% had low spontaneous protein intake and were frailer, more malnourished and with lower physical performance. These findings emphasize the importance of assessing patients’ needs, and personalized approaches with individual risk–benefit assessments should be sought. To achieve the best possible outcomes, targeted interventions should use all available tools.
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.
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).
At the end of the study, Malnutrition Inflammation Score was improved in both LP and NP groups (respectively: 3 ± 3 vs. 6 ± 1.5,
= 0.020 and 3 ± 2.5 vs. 6 ± 2,
= 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 m
;
< 0.05), lower serum urea (105 ± 65 vs. 138 ± 30 mg/dl;
< 0.05) and lower parathormone (68 ± 10 vs. 99 ± 61 ng/L;
< 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,
< 0.01 and in NP: 86 (57; 194) vs. 143 (119; 186) pg/ml,
< 0.01; FGF23 c-terminal in LP: 77 (30.3; 112) vs. 111 (63; 384) RU/ml,
< 0.01 and in NP: 142 (56.6; 175) vs. 157 (76.7; 281) RU/ml,
< 0.01.
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.
https://clinicaltrials.gov/ct2/show/NCT05015647, identifier: NCT05015647.
Podocytes possess the complete machinery for glutamatergic signaling, raising the possibility that neuron-like signaling contributes to glomerular function. To test this, we studied mice and cells ...lacking Rab3A, a small GTPase that regulates glutamate exocytosis. In addition, we blocked the glutamate ionotropic N-methyl-d-aspartate receptor (NMDAR) with specific antagonists. In mice, the absence of Rab3A and blockade of NMDAR both associated with an increased urinary albumin/creatinine ratio. In humans, NMDAR blockade, obtained by addition of ketamine to general anesthesia, also had an albuminuric effect. In vitro, Rab3A-null podocytes displayed a dysregulated release of glutamate with higher rates of spontaneous exocytosis, explained by a reduction in Rab3A effectors resulting in freedom of vesicles from the actin cytoskeleton. In addition, NMDAR antagonism led to profound cytoskeletal remodeling and redistribution of nephrin in cultured podocytes; the addition of the agonist NMDA reversed these changes. In summary, these results suggest that glutamatergic signaling driven by podocytes contributes to the integrity of the glomerular filtration barrier and that derangements in this signaling may lead to proteinuric renal diseases.
Irinotecan (CTP-11) is one of the standard therapies for colorectal cancer (CRC). CTP-11 is enzymatically converted to the hydrophobic 7-ethyl-10-hydroxycamptothecin (SN38), a one hundred-fold more ...active metabolite. Conjugation of hydrophobic anticancer drugs to nanomaterials is a strategy to improve their solubility, efficacy, and selectivity. Carbon dots (CDs) have garnered interest for their small sizes (<10 nm), low toxicity, high water solubility, and bright fluorescence. This paper describes the use of CDs to improve drug vehiculation, stability, and chemotherapeutic efficiency of SN38 through a direct intracellular uptake in CRC. The covalent conjugation of SN38 to CDs via a carbamate bond provides a CD-SN38 hybrid material for slow, sustained, and pH-responsive drug release. CD-SN38 successfully penetrates the CRC cells with a release in the nucleus affecting first the cell cycle and then the cytoskeleton. Moreover, CD-SN38 leads to a deregulation of the extracellular matrix (ECM), one of the major components of the cancer niche considered a possible target therapy for reducing the cancer progression. This work shows the combined therapeutic and imaging potential of CD-based hybrid materials for the treatment of CRC. Future efforts for targeted therapy of chronic diseases characterized by altered ECM deposition, such as chronic kidney disease and chronic allograft nephropathy in kidney transplant patients are envisaged.
Image 1
Background/Aims The research of genes implicated in kidney glomerular function, eliciting cell fate program, is always at the forefront in nephrological studies. Several neurological molecules have ...been recently the object of study not only for their involvement in the central nervous system differentiation but also for their importance in the functionality of other organs and for mature phenotype, as in kidney. NeuroD, in CNS, is related to two functional roles, the early survival and the differentiation. The aim of our study was to ascertain the presence of NeuroD transcription factor in glomeruli and to understand which targets and mechanisms NeuroD controls. Methods: We used immunofluorescence (IF) studies on both human and mice renal tissues and on cultured podocytes to describe NeuroD distribution; then we investigated NeuroD binding to the nephrin promoter region in cultured podocytes by chromatin-immuno-precipitation (ChIP) assay. The overexpression of NeuroD in podocytes was used to establish first its role in nephrin synthesis, evaluated by real-time quantitative (RTq) PCR and western-blot (WB) and successively to determine the recovery of cell morphology after adriamycin injury, measuring foot processes length. Results: We identified NeuroD transcription factor in glomeruli, in the same cells positive for WT1 and synaptopodin, namely podocytes; subsequently we observed a differentiation dependent NeuroD distribution in cultured podocytes, and a consistent link of NeuroD with the Nephrin promoter leading to the regulation of Nephrin translation and transcription. Our data also describes NeuroD expression in cytoplasm as phosphoprotein linked to nephrin and actinin4. Preliminary experiments seem to indicate NeuroD involved in dynamics of cell shape regulation after adriamycin injury. Conclusion: we propose that NeuroD possess in podocytes a dual ability acting in the nucleus as a transcription factor and in cytoplasm stabilizing cell shape.
PDF
