scholarly journals Role of GDF-15, YKL-40 and MMP 9 in patients with end-stage kidney disease: focus on sex-specific associations with vascular outcomes and all-cause mortality

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Agne Laucyte-Cibulskiene ◽  
Liam J. Ward ◽  
Thomas Ebert ◽  
Giulia Tosti ◽  
Claudia Tucci ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Gut Microbiota ◽  
Vascular Calcification ◽  
Cardiovascular Complications ◽  
Enzyme Linked Immunosorbent Assay ◽  
End Stage Kidney Disease ◽  
All Cause Mortality ◽  
Novel Biomarkers ◽  
End Stage

Abstract Background Sex differences are underappreciated in the current understanding of cardiovascular disease (CVD) in association with chronic kidney disease (CKD). A hallmark of CKD is vascular aging that is characterised, amongst others, by; systemic inflammation, microbiota disbalance, oxidative stress, and vascular calcification—features linked to atherosclerosis/arteriosclerosis development. Thus, it is the necessary to introduce novel biomarkers related to athero-/arteriosclerotic damage for better assessment of vascular ageing in patients CKD. However, little is known about the relationship between uraemia and novel CVD biomarkers, such as growth differentiation factor-15 (GDF-15), cartilage glycoprotein-39 (YKL-40) and matrix metalloproteinase-9 (MMP-9). Therefore, we hypothesise that there are sex-specific relationships between GDF-15, YKL-40, MMP-9 levels in end-stage kidney disease (ESKD) patients in relation to gut microbiota, vascular calcification, inflammation, comorbidities, and all-cause mortality. Methods ESKD patients, males (n = 151) and females (n = 79), not receiving renal replacement therapy were selected from two ongoing prospective ESKD cohorts. GDF-15, YKL-40 and MMP9 were analysed using enzyme-linked immunosorbent assay kits. Biomarker levels were analysed in the context of gut microbiota-derived trimethylamine N-oxide (TMAO), vascular calcification, inflammatory response, oxidative stress, comorbidities, and all-cause mortality. Results Increased GDF-15 correlated with higher TMAO in females only, and with higher coronary artery calcification and IL-6. In females, diabetes was associated with elevated GDF-15 and MMP-9, whilst males with diabetes only had elevated GDF-15. No associations were found between biomarkers and CVD comorbidity. Deceased males and females had higher GDF-15 concentrations (p = 0.01 and p < 0.001, respectively), meanwhile only YKL-40 was increased in deceased males (p = 0.02). Conclusions In conclusion, in males GDF-15 and YKL-40 were related to vascular calcification, inflammation, and oxidative stress, whilst in females GDF-15 was related to TMAO. Increased levels of YKL-40 and GDF-15 in males, and only GDF-15 in females, were associated with all-cause mortality. Our findings suggest that sex-specific associations of novel CVD biomarkers have a potential to affect development of cardiovascular complications in patients with ESKD.

Alteration of the gut microbiota by vinegar is associated with amelioration of hyperoxaluria-induced kidney injury

2020 ◽  
Vol 11 (3) ◽  
pp. 2639-2653
Author(s):  
Wei Zhu ◽  
Yang Liu ◽  
Xiaolu Duan ◽  
Chenglin Xiao ◽  
Yu Lan ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Gut Microbiota ◽  
Renal Injury ◽  
Kidney Injury ◽  
End Stage Kidney Disease ◽  
End Stage

Hyperoxaluria is well known to cause renal injury and end-stage kidney disease.

scholarly journals Serum Erythroferrone Levels Associate with Mortality and Cardiovascular Events in Hemodialysis and in CKD Patients: A Two Cohorts Study

2019 ◽  
Vol 8 (4) ◽  
pp. 523 ◽  
Author(s):  
Spoto ◽  
Kakkar ◽  
Lo ◽  
Devalaraja ◽  
Pizzini ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Iron Absorption ◽  
Linear Increase ◽  
Enzyme Linked Immunosorbent Assay ◽  
End Stage Kidney Disease ◽  
End Point ◽  
Traditional Risk Factors ◽  
End Stage ◽  
Stage 1 ◽  
The Relationship

Erythroferrone (ERFE) is a hepcidin inhibitor whose synthesis is stimulated by erythropoietin, which increases iron absorption and mobilization. We studied the association between serum ERFE and mortality and non-fatal cardiovascular (CV) events in a cohort of 1123 hemodialysis patients and in a cohort of 745 stage 1–5 chronic kidney disease (CKD) patients. Erythroferrone was measured by a validated enzyme-linked immunosorbent assay (ELISA). In the hemodialysis cohort, serum ERFE associated directly with erythropoiesis stimulating agents (ESA) dose (p < 0.001) and inversely with serum iron and ferritin (p < 0.001). Erythroferrone associated with the combined outcome in an analysis adjusting for traditional risk factors, factors peculiar to end-stage kidney disease, serum ferritin, inflammation, and nutritional status (HR, hazard ratio, (5 ng/mL increase: 1.04, 95% confidence interval, CI: 1.01–1.08, p = 0.005). Furthermore, treatment with ESA modified the relationship between ERFE and the combined end-point in adjusted analyses (p for the effect modification = 0.018). Similarly, in CKD patients there was a linear increase in the risk for the same outcome in adjusted analyses (HR (2 ng/mL increase): 1.04, 95% CI: 1.0–1.07, p = 0.015). Serum ERFE is associated with mortality and CV events in CKD and in HD patients, and treatment by ESA amplifies the risk for this combined end-point in HD patients.

Cardiorenal Syndrome in End-Stage Kidney Disease

2015 ◽  
Vol 40 (4) ◽  
pp. 337-343 ◽  
Author(s):  
Kazuhiko Tsuruya ◽  
Masahiro Eriguchi ◽  
Shunsuke Yamada ◽  
Hideki Hirakata ◽  
Takanari Kitazono
Keyword(s):  
Risk Factor ◽  
Kidney Disease ◽  
Chronic Inflammation ◽  
Vascular Calcification ◽  
Fibroblast Growth Factor 23 ◽  
Cardiorenal Syndrome ◽  
End Stage Kidney Disease ◽  
Mineral And Bone Disorder ◽  
End Stage ◽  
Mia Syndrome

Background: Cardiorenal syndrome (CRS) in patients with end-stage kidney disease (ESKD) represents mainly cardiovascular disease (CVD) due to various complications associated with renal dysfunction—defined as type 4 CRS by Ronco et al.—because the effect of cardiac dysfunction on the kidneys does not need to be taken into consideration, unlike in non-dialysis dependent chronic kidney disease (CKD). Summary: Patients with ESKD are often in a state of chronic inflammation due to the upregulation of proinflammatory cytokines. Chronic inflammation leads to malnutrition and consequently to vascular endothelial dysfunction and vascular calcification, which is referred to as malnutrition-inflammation-atherosclerosis (MIA) syndrome and acts as a major risk factor for CVD. Anemia also plays a crucial role in CVD, and individuals with erythropoietin-resistant anemia have a particularly high risk of CVD. However, caution is emphasized because not only anemia itself, but also the overtreatment of anemia with erythropoiesis-stimulating agents aimed at elevating hemoglobin to ≥13 g/dl can also increase the risk of CVD. In CKD-mineral and bone disorder (CKD-MBD), phosphate load triggers the interactions between various factors such as calcium, parathyroid hormone, vitamin D, and fibroblast growth factor 23, promoting vascular calcification and thus becoming a risk factor for CVD. Key Messages: In addition to traditional atherosclerosis risk factors such as hypertension, diabetes, and dyslipidemia, the involvement of MIA syndrome, anemia, and CKD-MBD accompanying CKD have also become a focus for investigation as major players in CRS in patients with ESKD.

The role of bone metabolism regulators sclerotin and osteoprotegerin in the development of cardiovascular complications in the late stages of chronic kidney disease

2021 ◽  
Vol 25 (6) ◽  
pp. 63-70
Author(s):  
F. U. Dzgoeva ◽  
O. V. Remizov ◽  
V. Kh. Botsieva ◽  
N. G. Malakhova ◽  
Z. R. Ikoeva ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Blood Serum ◽  
Bone Metabolism ◽  
Vascular Calcification ◽  
Cardiovascular Complications ◽  
Left Ventricular ◽  
Enzyme Linked Immunosorbent Assay ◽  
Commercial Kits

BACKGROUND. Cardiovascular complications caused by vascular calcification in chronic kidney disease (CKD) are closely related to disorders of bone and mineral metabolism, the mechanisms of which require further study.THE AIM: to clarify the role of the regulatory proteins of bone metabolism of sclerostin and osteoprotegerin in the processes of vascular calcification and the development of cardiovascular complications in CKD.PATIENTS AND METHODS. 110 patients with stage 3-5D CKD (67 men) were examined. Median age is 47.0 (23.0-68.0) years. Osteoprotegerin (OPG), sclerostin, intact parathyroid hormone (IPTG), troponin I in blood serum were determined using commercial kits "Enzyme-linked Immunosorbent Assay Kit for Sclerostin" ("Cloud-Clone Corp.", USA) and commercial kits "ELISA kit" ("Biomedica" (Austria) by enzyme immunoassay (ELISA). Echocardiography with Dopplerography was performed on the device "ALOKA 4000" ("Toshiba", Japan). The left ventricular myocardial mass index (LVMI) and peak systolic blood flow velocity in the aortic arch (Vps, peak systolic velocity) were determined to quantify hemodynamic changes indirectly indicating the state of the aortic vascular wall.RESULTS. Analysis of the ratios of the calculated glomerular filtration rate (EGFR), IMLJ, Vps, OPG, and sclerostin showed that a decrease in excretory kidney function is accompanied by an increase in the concentrations of OPG and sclerostin in the blood serum. At the same time, there is an increase in IMLJ and Vps. During the correlation analysis, it was shown that the level of OPG was positively correlated with the level of sclerostin and negatively with the level of iPTG.CONCLUSION. In our study, we obtained data confirming the interactive interaction between the vascular and bone systems. Morphogenetic proteins-inhibitors of bone metabolism (sclerostin and OPG) play a significant role in the defeat of the cardiovascular system in patients with CKD, as they promotes the development of vascular calcification.

scholarly journals Targeting Redox Imbalance as an Approach for Diabetic Kidney Disease

Biomedicines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 40 ◽  
Author(s):  
Keiichiro Matoba ◽  
Yusuke Takeda ◽  
Yosuke Nagai ◽  
Tamotsu Yokota ◽  
Kazunori Utsunomiya ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Public Health Problem ◽  
Cardiovascular Complications ◽  
Current Status ◽  
Diabetic Kidney ◽  
Redox Imbalance ◽  
Stage Renal Disease ◽  
End Stage

Diabetic kidney disease (DKD) is a worldwide public health problem. It is the leading cause of end-stage renal disease and is associated with increased mortality from cardiovascular complications. The tight interactions between redox imbalance and the development of DKD are becoming increasingly evident. Numerous cascades, including the polyol and hexosamine pathways have been implicated in the oxidative stress of diabetes patients. However, the precise molecular mechanism by which oxidative stress affects the progression of DKD remains to be elucidated. Given the limited therapeutic options for DKD, it is essential to understand how oxidants and antioxidants are controlled in diabetes and how oxidative stress impacts the progression of renal damage. This review aims to provide an overview of the current status of knowledge regarding the pathological roles of oxidative stress in DKD. Finally, we summarize recent therapeutic approaches to preventing DKD with a focus on the anti-oxidative effects of newly developed anti-hyperglycemic agents.

scholarly journals Dysfunction of natural killer cells in end-stage kidney disease on hemodialysis

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Kei Nagai
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Nk Cells ◽  
Natural Killer ◽  
Nk Cell ◽  
Cell Number ◽  
Dialysis Patients ◽  
End Stage Kidney Disease ◽  
Activating Receptors ◽  
End Stage

AbstractNatural killer (NK) cells are known to play an important role in defense against infection and tumors. Although there is no clear consensus, most studies have shown that the number and cytotoxicity of NK cells decreases in end-stage kidney disease (ESKD) patients undergoing hemodialysis. Uremic patients chronically suffer from oxidative stress, which could be responsible for downregulation of the activating receptors on NK cells and modulation of ligand expression for activating receptors. Theoretically, the reduced number of NK cells and decreased function might increase susceptibility to viral infections and cancer development in patients with ESKD. There is emerging evidence that NK cell numbers may be an outcome predictor in renal transplantation; however, the clinical significance of NK cell dysfunction in dialysis patients requires clarification. In this review, I describe NK cell number, cytotoxic activity, and activating mechanisms in the context of uremia and oxidative stress, which is anticipated to assist in elucidating the mechanisms underlying immunodeficiency in dialysis patients.

scholarly journals Calciphylaxis in end-stage kidney disease: outcome data from the United Kingdom Calciphylaxis Study

2021 ◽  
Author(s):  
Rajkumar Chinnadurai ◽  
Abby Huckle ◽  
Janet Hegarty ◽  
Philip A Kalra ◽  
Smeeta Sinha
Keyword(s):  
United Kingdom ◽  
Kidney Disease ◽  
Strong Association ◽  
Management Strategies ◽  
Skin Lesions ◽  
Individual Treatment ◽  
End Stage Kidney Disease ◽  
The United Kingdom ◽  
All Cause Mortality ◽  
End Stage

Abstract Background and aims Calciphylaxis is a rare condition associated with very high mortality in patients with end-stage kidney disease. Data from country-based registries have been an invaluable resource for a better understanding of the natural history and management for this condition. This study aimed to investigate the current management strategies and outcomes of patients enrolled in the United Kingdom Calciphylaxis study (UKCS). Methods The study was conducted on 89 patients registered in the UKCS since 2012. The initial analysis included a description of the baseline characteristics, management strategies and outcomes on follow-up until May 2020. Further analysis included a comparison of the mortality outcome of the UKCS patients who were receiving haemodialysis with a propensity score matched cohort of haemodialysis patients from the Chronic Renal Insufficiency Standards Implementation Study- Haemodialysis (CRISIS-HD). Results Median age of the cohort was 59 years, with a predominance of females (61%) and Caucasian (95%) ethnicity. About 54% of the patients were diabetic and 70% were receiving haemodialysis at study entry. The skin lesions were mostly distributed in the lower extremities (48%). Sodium thiosulphate and calcimimetic were the most widely used management strategies. The mortality rate was 72 deaths per hundred patient-years (50 deaths observed in 69.5 patient years). Complete wound healing was noted in 17% and bacteraemia was reported in 26% of patients. In a comparative analysis of the matched haemodialysis patients, the presence of calciphylaxis in 62 patients showed a strong association with all-cause mortality (HR 6.96; p < 0.001), with annual mortality 67% versus 10.2% in haemodialysis patients without calciphylaxis. Conclusions This UK wide study strengthens the evidence that calciphylaxis is a strong and independent risk factor associated with all-cause mortality; no significant benefit was shown with any individual treatment modality. Until further evidence becomes available, a multifaceted approach would be the appropriate treatment strategy in the management of this extremely serious condition. Graphic abstract

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