The SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic has posed a huge threat to global health because of its rapid spread and various mutant variants. Critical illness occurs in ...the elderly and vulnerable individuals, such as those with chronic kidney disease. The severity of SARS-CoV-2 infection is associated with the severity of chronic kidney disease (CKD)and even kidney transplantation (KT) because of the chronic use of immunosuppressive agents. To develop adaptive immunity against SARS-CoV-2, vaccination against the spike protein is important. Current phase III trials of vaccines against SARS-CoV-2 have not focused on a specific group of individuals, such as patients with CKD or those undergoing dialysis or kidney transplantation. Chronic use of immunosuppressive agents might disturb the immune response to the SARS-CoV-2 spike protein. On the basis of limited evidence, the immune compromised status of CKD patients might decrease neutralizing antibody development after a single dose of a specific vaccine. Boosting dosage more than the protocol might increase the titer of the neutralizing antibody in CKD patients. Further evidence is needed to understand the factors disturbing the immunogenicity of the SARS-CoV-2 vaccine, and CKD patients should receive the recommended dose of the SARS-CoV-2 vaccine due to their relatively immune compromised status.
For patients with chronic kidney disease (CKD), the leading cause of mortality is cardiovascular disease. One of the main novel risk factors is oxidative stress, which occurs when there is ...overproduction of reactive oxygen species (ROS) and/or a reduction in antioxidant defense capacity. Oxidative stress is involved in the progression of renal injury, pathogenesis of atherosclerosis, and exacerbation of disease burden in CKD patients. In addition, uremic- and dialysis-associated factors in these patients further contribute to oxidative stress via a proinflammatory state, including exposure to dialysate endotoxins or the use of bioincompatible hemodialysis dialyzer membranes. Consequences of oxidative stress in CKD patients include atherosclerosis, amyloidosis, and anemia. Strategies to combat oxidative stress include antioxidant therapies such as vitamins C and E or N-acetylcysteine (NAC). While these antioxidant strategies are promising, few interventional studies have examined their effects until now. In light of the disparate experimental and clinical data, large, randomized, long-term studies are required to establish their efficacy and safety in CKD patients.
Background
Volume overload is frequently encountered and is associated with cardiovascular risk factors in patients with chronic kidney disease (CKD). However, the relationship between volume ...overload and adverse outcomes in CKD is not fully understood.
Methods and Results
A prospective cohort of 338 patients with stage 3 to 5 CKD was followed for a median of 2.1 years. The study participants were stratified by the presence or absence of volume overload, defined as an overhydration index assessed by bioimpedance spectroscopy exceeding 7%, the 90th percentile for the healthy population. The primary outcome was the composite of estimated glomerular filtration rate decline ≥50% or end‐stage renal disease. The secondary outcome included a composite of morbidity and mortality from cardiovascular causes. Animal models were used to simulate fluid retention observed in human CKD. We found that patients with volume overload were at a higher risk of the primary and secondary end points in the adjusted Cox models. Furthermore, overhydration appears to be more important than hypertension in predicting an elevated risk. In rats subjected to unilateral nephrectomy and a high‐salt diet, the extracellular water significantly increased. This fluid retention was associated with an increase in blood pressure, proteinuria, renal inflammation with macrophage infiltration and tumor necrosis factor‐α overexpression, glomerular sclerosis, and cardiac fibrosis. Diuretic treatment with indapamide attenuated these changes, suggesting that fluid retention might play a role in the development of adverse outcomes.
Conclusions
Volume overload contributes to CKD progression and cardiovascular diseases. Further research is warranted to clarify whether the correction of volume overload would improve outcomes for CKD patients.
High-dose intravenous iron supplementation is associated with adverse cardiovascular outcomes in patients with CKD, but the underlying mechanism is unknown. Our study investigated the causative role ...of iron sucrose in leukocyte-endothelium interactions, an index of early atherogenesis, and subsequent atherosclerosis in the mouse remnant kidney model. We found that expression levels of intracellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and adhesion of U937 cells increased in iron-treated human aortic endothelial cells through upregulated NADPH oxidase (NOx) and NF-κB signaling. We then measured mononuclear-endothelial adhesion and atherosclerotic lesions of the proximal aorta in male C57BL/6 mice with subtotal nephrectomy, male apolipoprotein E-deficient (ApoE(-/-)) mice with uninephrectomy, and sham-operated mice subjected to saline or parenteral iron loading. Iron sucrose significantly increased tissue superoxide production, expression of tissue cell adhesion molecules, and endothelial adhesiveness in mice with subtotal nephrectomy. Moreover, iron sucrose exacerbated atherosclerosis in the aorta of ApoE(-/-) mice with uninephrectomy. In patients with CKD, intravenous iron sucrose increased circulating mononuclear superoxide production, expression of soluble adhesion molecules, and mononuclear-endothelial adhesion compared with healthy subjects or untreated patients. In summary, iron sucrose aggravated endothelial dysfunction through NOx/NF-κB/CAM signaling, increased mononuclear-endothelial adhesion, and exacerbated atherosclerosis in mice with remnant kidneys. These results suggest a novel causative role for therapeutic iron in cardiovascular complications in patients with CKD.
Folic acid exerts both anti-inflammatory and antifibrotic effects. Glycine N-methyltransferase (GNMT), the major folic acid-binding protein in the liver, is a crucial enzyme that regulates the ...cellular methylation process by maintaining S-adenosylmethionine levels. However, as yet neither the therapeutic effects of folic acid in renal fibrosis nor whether GNMT is involved in these folic acid-associated mechanisms has been investigated. First, the expression of GNMT was examined in human kidneys with or without obstructive nephropathy. Later, wild-type and
knockout (
) mice were subjected to unilateral ureteral obstruction (UUO) and then treated with either folic acid or vehicle for 14 days. Renal tubular injury, inflammation, fibrosis, and autophagy were evaluated by histological analysis and Western blotting. We observed increased expression of GNMT in humans with obstructive nephropathy. Furthermore, UUO significantly increased the expression of GNMT in mice; in addition, it caused renal injury as well as the development of both hydronephrosis and tubular injury. These were all alleviated by folic acid treatment. In contrast,
mice exhibited exacerbated UUO-induced renal injury, but the protective effect of folic acid was not observed in
mice. We propose a novel role for folic acid in the treatment of renal fibrosis, which indicates that GNMT may be a therapeutic target.
Hyperuricemia is a well-known risk factor for chronic kidney disease (CKD). Little is known about whether a vegetarian diet is associated with a lower risk of CKD in patients with hyperuricemia. From ...5 September 2005, to 31 December 2016, we retrospectively included clinically stable patients with hyperuricemia who received health check-ups at Taipei Tzu Chi Hospital. All participants completed a dietary habits questionnaire to determine whether they were omnivorous, lacto-ovo vegetarian, or vegan. CKD was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m
or the presence of proteinuria. A total of 3618 patients with hyperuricemia were recruited for this cross-sectional study, consisting of 225 vegans, 509 lacto-ovo vegetarians, and 2884 omnivores. After adjusting for age and sex, vegans had a significantly lower odds ratio (OR) of CKD than omnivores (OR, 0.62;
0.006). The OR of CKD remained significantly lower in vegans after adjusting for additional confounders (OR, 0.69;
0.04). Additionally, age (per year OR, 1.06;
< 0.001), diabetes mellitus (OR, 2.12;
< 0.001), hypertension (OR, 1.73;
< 0.001), obesity (OR, 1.24;
= 0.02), smoking (OR, 2.05;
< 0.001), and very high uric acid levels (OR, 2.08;
< 0.001) were independent risk factors for CKD in patients with hyperuricemia. Moreover, structural equation modeling revealed that a vegan diet was associated with a lower OR of CKD (OR, 0.69;
< 0.05). A vegan diet is associated with a 31% lower risk of CKD in patients with hyperuricemia. A vegan diet may be beneficial in reducing the occurrence of CKD in patients with hyperuricemia.
Chronic kidney disease (CKD) and its complications are major global public health issues. Vegetarian diets are associated with a more favorable profile of metabolic risk factors and lower blood ...pressure, but the protective effect in CKD is still unknown. We aim to assess the association between vegetarian diets and CKD. A cross-sectional study was based on subjects who received physical checkups at the Taipei Tzu Chi Hospital from 5 September 2005, to 31 December 2016. All subjects completed a questionnaire to assess their demographics, medical history, diet pattern, and lifestyles. The diet patterns were categorized into vegan, ovo-lacto vegetarian, or omnivore. CKD was defined as an estimated GFR <60 mL/min/1.73 m² or the presence of proteinuria. We evaluated the association between vegetarian diets and CKD prevalence by using multivariate analysis. Our study recruited 55,113 subjects. CKD was significantly less common in the vegan group compared with the omnivore group (vegan 14.8%, ovo-lacto vegetarians 20%, and omnivores 16.2%,
< 0.001). The multivariable logistic regression analysis revealed that vegetarian diets including vegan and ovo-lacto vegetarian diets were possible protective factors odds ratios = 0.87 (0.77⁻0.99),
= 0.041; 0.84 (0.78⁻0.90),
< 0.001. Our study showed a strong negative association between vegetarian diets and prevalence of CKD. If such associations are causal, vegetarian diets could be helpful in reducing the occurrence of CKD.
Uremic toxins (UTs) are mainly produced by protein metabolized by the intestinal microbiota and converted in the liver or by mitochondria or other enzymes. The accumulation of UTs can damage the ...intestinal barrier integrity and cause vascular damage and progressive kidney damage. Together, these factors lead to metabolic imbalances, which in turn increase oxidative stress and inflammation and then produce uremia that affects many organs and causes diseases including renal fibrosis, vascular disease, and renal osteodystrophy. This article is based on the theory of the intestinal-renal axis, from bench to bedside, and it discusses nonextracorporeal therapies for UTs, which are classified into three categories: medication, diet and supplement therapy, and complementary and alternative medicine (CAM) and other therapies. The effects of medications such as AST-120 and meclofenamate are described. Diet and supplement therapies include plant-based diet, very low-protein diet, probiotics, prebiotics, synbiotics, and nutraceuticals. The research status of Chinese herbal medicine is discussed for CAM and other therapies. This review can provide some treatment recommendations for the reduction of UTs in patients with chronic kidney disease.
The association between intravenous (IV) iron administration and outcomes in hemodialysis (HD) patients is still debated. Therefore, this study was aimed to assess the relationship between the IV ...administration of ferric chloride hexahydrate (Atofen®) and cardiovascular (CV) outcome and the interaction between iron-induced oxidative stress and endothelial dysfunction in chronic HD patients.
A cohort of 1239 chronic HD patients was recruited. In a follow-up of 12 months, Kaplan-Meier survival curves showed that higher doses of IV Atofen associated with higher risks for CV events and deaths in HD patients. In multivariate Cox models, compared to no iron supplementation, IV Atofen administration was an independent predictor for CV events and overall mortality. However, the nature of the observational cohort study possibly bears selection bias. We further found that IV Atofen enhanced the superoxide production of mononuclear cells (MNCs), the levels of circulating soluble adhesion molecules, and the adhesion of MNCs to human aortic endothelial cells (HAECs). In vitro experiments showed that Atofen increased the expression of intracellular cell adhesion molecule-1 and vascular cell adhesion molecule-1 in HAECs and aggravated the endothelial adhesiveness in a dose-dependent manner. These iron-induced changes were significantly attenuated by the co-treatment of HAECs with N-acetylcysteine and inhibitors of NADPH oxidase, nuclear factor κB, and activator protein-1.
A cumulative dose of IV Atofen >800 mg within 6 months was associated with an adverse CV outcome and a higher mortality among chronic HD patients. The detrimental effects of IV iron supplementation were partly due to the increased oxidative stress and induction of MNC adhesion to endothelial cells, a pivotal index of early atherogenesis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
PDF
