scholarly journals The importance of polymorphisms of regulatory and catalytic antioxidant proteins in chronic kidney disease

2021 ◽  
Vol 72 (1) ◽  
pp. 25-33
Author(s):  
Đurđa Jerotić ◽  
Marija Matić ◽  
Lana McClements

Both excessive production of reactive oxygen species (ROS) and impaired antioxidant function are found in patients with chronic kidney disease (CKD). Therefore, individual susceptibility towards CKD can be induced by functional variations of genes encoding antioxidant regulatory (nuclear factor erythroid 2 - related factor 2 (Nrf2)) and catalytic (superoxide dismutase (SOD2) and glutathione peroxidase (GPX1)) proteins. Several types of single nucleotide polymorphisms (SNPs) have been found within the genes encoding these proteins, with Nrf2 (-617C/A), SOD2 (Ala16Val) and GPX1 (Pro198Leu) conferring impaired catalytic activity. The most unexplored gene polymorphism in CKD susceptibility, progression and survival, with only two original studies published, is the Nrf2 (-617C/A) polymorphism. The results of these studies showed that there was no individual impact of this polymorphism on the susceptibility towards end stage renal disease (ESRD) development, oxidative phenotype and mortality. However, Nrf2 had a significant role in ESRD risk and survival, when combined with other antioxidant genes. The results regarding the impact of SOD2 (Ala16Val) and GPX1 (Pro198Leu) polymorphisms on either CKD or ESRD are still inconclusive. Namely, some studies showed that patients having variant SOD2 (Val) or GPX1 (Leu) allele were at increased risk of CKD development and progression, while other studies reported only weak or no association between these polymorphisms and CKD. Surprisingly, the only study that reported an association of GPX1 polymorphism with overall/cardiovascular survival in ESRD patients showed a significant impact of low activity GPX1 (Leu/Leu) genotype on better survival. In this review, we comprehensively and critically appraise the literature on these polymorphisms related to oxidative stress in CKD patients, in order to identify gaps and provide recommendations for further clinical research and translation. New developments in the field of antioxidant polymorphisms in CKD patients could lead to better stratification of CKD patients, based on a prognostic antioxidant gene panel, and provide a more personalised medicine approach for the need of antioxidant therapy in these patients.

2018 ◽  
Vol 108 (5) ◽  
pp. 1145-1153 ◽  
Author(s):  
Ting-Yun Lin ◽  
Jia-Sin Liu ◽  
Szu-Chun Hung

ABSTRACT Background Obesity is a risk factor for de novo chronic kidney disease (CKD) in the general population. Obesity has been increasingly prevalent in patients with CKD and may lead to further progression of pre-existing CKD. However, whether obesity is associated with the development of end-stage renal disease (ESRD) in patients with CKD is not well understood. Objective We investigated the impact of obesity on ESRD (needing chronic dialysis treatment or pre-emptive renal transplantation) or all-cause mortality in patients with moderate to advanced CKD. Design A total of 322 patients with stages 3–5 CKD who were not yet on dialysis were prospectively followed for a median of 4.9 y. Obesity was defined by body mass index (BMI, in kg/m2) ≥30 or body fat percentage (BF%) >25% in men and >35% in women. BF% was assessed with the use of the Body Composition Monitor, a multifrequency bioimpedance spectroscopy device. Results In total, 100 participants progressed to ESRD and 39 participants died. Obesity, whether defined by BMI or BF%, was not associated with a significantly increased risk of ESRD in Cox proportional hazards models that adjusted for age, sex, diabetes mellitus, cardiovascular disease, estimated glomerular filtration rate, urine protein:creatinine ratio, high-sensitivity C-reactive protein, and use of renin-angiotensin-aldosterone system inhibitors or statins, accounting for the competing risk for mortality (subdistribution HR: 1.15; 95% CI: 0.62, 2.14 for BMI-defined obesity and subdistribution HR: 0.84, 95% CI: 0.54, 1.29 for BF%-defined obesity, respectively). Results were similar when BMI and BF% were analyzed as continuous or time-dependent variables. Whereas higher BMI was protective, higher BF% appeared to be associated with increased all-cause mortality. Conclusions Obesity did not confer an increased risk of ESRD in patients with moderate to advanced CKD. This trial was registered at http://www.clinicaltrials.gov as NCT03285074.


Author(s):  
Amit N Vora ◽  
Maggie A Stanislawski ◽  
John S Rumsfeld ◽  
Thomas M Maddox ◽  
Mladen Vidovich ◽  
...  

Background: Patients with chronic kidney disease (CKD) are at increased risk of bleeding and transfusion after cardiac catheterization. Whether rates of these complications or progression to new dialysis are increased in this high-risk population undergoing transradial (TR) access compared to transfemoral (TF) access is unknown. Methods: From the Veterans Affairs Clinical Assessment, Reporting, and Tracking (CART) Program between 10/2007-09/2012 we identified 40,160 CKD patients undergoing cardiac catheterization with baseline glomerular filtration rate (GFR) ≤ 60 ml/min. We used multivariable Cox modeling to determine the independent association between TR access and post-procedure transfusion as well as progression to new dialysis using TF as the reference. Results: Overall, 3,828 (9.5%) of CKD patients underwent TR access and tended to be slightly younger but overall had similar rates of CKD severity compared with TF patients (GFR 45-60 ml/min: 77.0% vs. 77.0%; GFR 30-44 ml/min: 19.7% vs. 19.3%; GFR 15-29 ml/min: 3.3% vs. 3.7%, p=0.35). TR patients had longer fluoroscopy times (8.1 vs 6.9 minutes, p=<0.0001) but decreased contrast use (90.0 vs 100.0 ml, p=<0.0001). Among the 31,692 patients with a full year of follow-up, 42 (1.7%) of TR patients and 545 (1.9%) of TF patients progressed to new dialysis within 1 year (p=0.64). However, only 33 (0.9%) of TR patients compared with 570 TF patients (1.6%) needed post-procedure blood transfusion (p=0.0006). After multivariable adjustment, there was no significant difference in progression to ESRD between TR and TF patients but TR was associated with a significant decrease in transfusion (Figure). Conclusion: Among CKD patients undergoing cardiac catheterization in the VA health system, TR access is associated with a decreased risk for post-procedure transfusion compared with TF access. There was no significant difference between the two approaches with respect to progression to ESRD. These data suggest that TR is a reasonable option for patients with any level of CKD undergoing cardiac catheterization.


Nutrients ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 1945 ◽  
Author(s):  
Dina Tallman ◽  
Sharmela Sahathevan ◽  
Tilakavati Karupaiah ◽  
Pramod Khosla

Patients with chronic kidney disease (CKD) are often instructed to adhere to a renal-specific diet depending on the severity and stage of their kidney disease. The prescribed diet may limit certain nutrients, such as phosphorus and potassium, or encourage the consumption of others, such as high biological value (HBV) proteins. Eggs are an inexpensive, easily available and high-quality source of protein, as well as a rich source of leucine, an essential amino acid that plays a role in muscle protein synthesis. However, egg yolk is a concentrated source of both phosphorus and the trimethylamine N-oxide precursor, choline, both of which may have potentially harmful effects in CKD. The yolk is also an abundant source of cholesterol which has been extensively studied for its effects on lipoprotein cholesterol and the risk of cardiovascular disease. Efforts to reduce dietary cholesterol to manage dyslipidemia in dialysis patients (already following a renal diet) have not been shown to offer additional benefit. There is a paucity of data regarding the impact of egg consumption on lipid profiles of CKD patients. Additionally, egg consumption has not been associated with the risk of developing CKD based on epidemiological studies. The egg yolk also contains bioactive compounds, including lutein, zeaxanthin, and vitamin D, which may confer health benefits in CKD patients. Here we review research on egg intake and CKD, discuss both potential contraindications and favorable effects of egg consumption, and describe the need for further research examining egg intake and outcomes in the CKD and end-stage renal disease population.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M Burnier ◽  
L R Ruilope ◽  
G B Bader ◽  
S D Durg ◽  
P B Brunel

Abstract Background Blood pressure (BP) control is critical in delaying the progression of chronic kidney disease (CKD), which otherwise results in an increased risk of cardiovascular morbidity and mortality. Angiotensin II receptor blockers (ARBs) or angiotensin-converting enzyme inhibitors, are recommended by several guidelines as first-line treatment for patients with hypertension and CKD. Purpose We reviewed and analysed the effect of ARB treatment on BP and renal outcomes (estimated glomerular filtration rate (eGFR), serum creatinine (SCr), creatinine clearance (CrCl) or proteinuria) in patients with hypertension and CKD with or without diabetes, including large clinical trials such as RENAAL and IDNT. Methods MEDLINE, EMBASE, and BIOSIS databases were searched for literature from the earliest available date to July 2017. Randomised (parallel-group) controlled trials of ≥8 weeks assessed the impact of ARBs on systolic/diastolic BP (SBP/DBP), eGFR, SCr, CrCl or proteinuria were included in the analysis. Meta-analysis (post- versus pre-treatment) and meta-regression were conducted in R-statistical software (v3.4.1) using meta- and metafor-packages. Mean difference (MD, generic inverse variance) with 95% confidence intervals (CIs) was used to pool data for an outcome in a single forest plot. The risk of bias (quality) of included studies was assessed by the six items of the Cochrane instrument. Results Of the 165 articles assessed for eligibility, 24 studies were included in the analysis (19 evaluated ARBs as monotherapy, 4 evaluated ARBs in combination with other antihypertensives and 1 evaluated ARBs both as mono- and combination therapy). Treatment with ARBs as monotherapy for ≥8 weeks to <1 year significantly reduced mean office SBP (MD, −12.60 mmHg; 95% CI, −18.53 to −6.67)/DBP (−6.52 mmHg; −11.27 to −1.77) (p<0.01). BP reduction was also significant (p<0.01) with ARB monotherapy for ≥1 year SBP (−14.84 mmHg; −17.82 to −11.85)/DBP (−10.27 mmHg; −12.26 to −8.27). ARBs also significantly reduced SBP/DBP when combined with other antihypertensive treatments for ≥8 weeks to <1 year as well as for ≥1 year (Figure). Moreover, ARBs induced significant reductions (p<0.01) in proteinuria (≥8 weeks to <1 year [MD, −0.6 g/L; 95% CI, −0.93 to −0.26; ≥1 year [−0.9 g/L; −1.22 to −0.59]), but no significant changes in eGFR, CrCl or SCr levels. The beneficial effect of ARBs was maintained overtime with no significant additional impact on SBP change (estimate: 0.025; 95% CI, –0.14 to 0.19) or eGFR (estimate: 0.068; 95% CI, −0.14 to 0.28; p=0.53). The overall risk of bias was judged to be low. Effect of ARBs on blood pressure changes Conclusion Treatment with ARBs effectively and sustainably lowered BP and proteinuria with no significant change in eGFR in patients with hypertension and CKD with or without diabetes.


2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Ifeoma I. Ulasi ◽  
Chinwuba K. Ijoma

Background. The magnitude of the problem of chronic kidney disease (CKD) is enormous, and the prevalence keeps rising. To highlight the burden of CKD in developing countries, the authors looked at end-stage renal disease (ESRD) patients seen at the University of Nigeria Teaching Hospital (UNTH), Enugu, South-East Nigeria.Method. ESRD patients seen from 01/05/1990 to 31/12/2003 were recruited. Records from A&E Department, medical-out-patients, wards and dialysis unit were used.Results. A total of 1001 male versus 537 female patients were reviewed. About 593 male versus 315 female patients had haemodialysis. The mean age was years and 86.5% were <60 years. Primary renal disease could not be determined in 51.6% while hypertension and glomerulonephritis accounted for −17.2% and 14.6%, respectively. Death from renal causes constituted 22.03% of medical deaths.Conclusion. The prognosis for CKD patients in Nigeria is abysmal. Only few patients had renal-replacement-therapy (RRT). The prohibitive cost precludes many patients. This underscores the need for preventive measures to reduce the impact of CKD in the society.


2018 ◽  
Vol 34 (8) ◽  
pp. 1354-1360 ◽  
Author(s):  
Ping-Fang Chiu ◽  
Chin-Hua Chang ◽  
Chia-Lin Wu ◽  
Teng-Hsiang Chang ◽  
Chun-Chieh Tsai ◽  
...  

Abstract Background Numerous studies have shown that exposure to air pollution, especially particulate matter (PM) with a diameter <2.5 μm (PM2.5), was associated with various diseases. We tried to determine the impact of PM2.5 and other weather factors on acute lung edema in patients with Stage 5 nondialysis chronic kidney disease (CKD Stage 5-ND). Methods In total, 317 CKD Stage 5-ND (estimated glomerular filtration rate 6.79 ± 4.56 mL/min) patients residing in central Taiwan who developed acute lung edema and initiated long-term dialysis were included in this case-crossover study. Pearson’s correlation test was used to examine the relationship of acute lung edema cases with PM2.5 levels and ambient temperature separately. Results The average PM2.5 level within the 7-day period correlated with acute lung edema incidence in the fall [adjusted odds ratio (OR) 3.23, P = 0.047] and winter (adjusted OR 1.99, P < 0.001). In winter, even a 3-day exposure to PM2.5 was associated with increased risk (adjusted OR 1.55, P < 0.001). The average temperatures within 3 days in spring and summer were correlated positively with the risk (adjusted OR 2.77 P < 0.001 and adjusted OR 2.72, P < 0.001, respectively). In the fall and winter, temperatures were correlated negatively with the risk (adjusted OR 0.36, P < 0.001 and adjusted OR 0.54, P < 0.001, respectively). Conclusions A high PM2.5 level was associated with an increased risk of acute lung edema. High ambient temperature in hot seasons and low ambient temperature in cold seasons were also associated with increased risk. It is essential to educate these patients to avoid areas with severe air pollution and extreme ambient temperature.


2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Sol Carriazo ◽  
Maria Dolores Sanchez-Nino ◽  
Maria Vanessa Perez Gomez ◽  
Laura Castañeda-Infante ◽  
Catalina Martin ◽  
...  

Abstract Background and Aims Chronic kidney disease (CKD) is the most common risk factor for lethal COVID19 and the risk factor that most increases the risk of death of COVID19 patients. Additionally, acute kidney injury (AKI) is frequent in COVID19 and AKI increases the risk of death. However, the underlying cellular and molecular mechanisms of such increased risk are unclear. SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) are required for and/or regulate (in a positive or negative manner) coronary cell entry and/or viral replication. We have now studied changes in the expression of genes encoding for SCARF in the context of acute and chronic kidney disease. Method Data mining of in-house (experimental models of AKI -folic acid nephropathy- and CKD -Unilateral ureteral obstruction- in mice) and publicly available databases (Nephroseq, published single cell transcriptomics studies) of kidney tissue transcriptomics as well as the Protein Atlas database. Results Out of 28 SCARF genes identified by Singh et al (Cell Reports 2020), 26 were represented in the experimental AKI database. Of them 7 (27%) were differentially expressed during AKI (FDR &lt;0.05), 4 of them upregulated and 3 downregulated (Figure 1.A). Additionally, 27 were represented in the experimental CKD database. Of them 17 (63%) were differentially expressed during experimental CKD, 6 of them upregulated and 11 downregulated (Figure 1.B). Two genes were consistently upregulated (Ctsl and Ifitm3) and two consistently downregulated (Tmprss2 and Top3b) in both experimental AKI and CKD (Figure 1.A and B). They encode cathepsin L, interferon induced transmembrane protein 3, transmembrane serine protease 2, DNA topoisomerase III beta, respectively. Single cell transcriptomics databases localized Ctsl expression mainly to podocytes and tubular cells while protein atlas showed clear tubular staining. The main site of Ifitm3 was endothelium in both datasets and it was also localized to leukocytes by single cell transcriptomics. Tmprss2 was mainly localized to tubular cells in both datasets while Top3b was widely expressed in parenchymal renal cells, endothelium and leucocytes in single cell transcriptomics. Increased kidney expression of Ifitm3 and decreased expression of Tmprss2 and Top3b were confirmed in diverse CKD datasets in Nephroseq. Conclusion Both AKI and CKD are associated with differential expression of SCARF genes in kidney tissue, the impact of CKD appearing to be larger. Characterization of these changes and their functional impact in kidney tissue and beyond the kidneys may provide clues to the increased risk of severe or lethal COVID19 in kidney disease patients. Kidney SCARF gene expression


Author(s):  
Aurea Lima ◽  
Hugo Sousa ◽  
Amanda Nobre ◽  
Ana Luisa Faria ◽  
Manuela Machado

Literature reports that SARS-CoV-2 infection in cancer patients may be associated with higher severity and mortality, nevertheless the knowledge is limited. We aimed to describe patients’ demographic characteristics and COVID-19 disease outcomes in Portuguese cancer patients. We conducted a retrospective study in a cohort of cancer patients diagnosed with COVID-19. A total of 127 individuals were included: 46.5% males and 53.5% females, with a median age of 72 years. Clinicopathological characteristics were used in univariate and multivariable logistic regression analyses to estimate odds ratios for each variable with outcomes adjusting for potential confounders. Our cohort revealed that 84.3% of patients had more than one risk factor for severe disease rather than cancer. In total, 36.2% of patients were admitted to the Department of Internal Medicine, 14.2% developed severe disease, 1.6% required Intensive Care Unit, and mortality was observed in 11.8%. Severe COVID-19 disease was associated with unfit (ECOG PS > 2) patients (p = 0.009; OR = 6.39; 95% CI: 1.60–25.59), chronic kidney disease (p = 0.004; OR = 20.7; 95% CI: 2.64–162.8), immunosuppression (p < 0.001; OR = 10.3; 95% CI: 2.58–41.2), and presence of respiratory symptoms at diagnosis (p = 0.033; OR = 5.05; 95% CI: 1.14–22.4). Increased risk for mortality was associated with unfit patients (p = 0.036; OR = 4.22; 95% CI: 1.10–16.3), cardiac disease (p = 0.003; OR = 8.26; 95% CI: 2.03–33.6) and immunosuppression (p = 0.022; OR = 5.06; 95% CI: 1.27–20.18). Our results demonstrated that unfit and immunosuppressed patients, with chronic kidney disease and cardiac disease, have, respectively, an increased risk for severe disease and mortality related to COVID-19. Hence, this study provides important information on risk factors for severe COVID-19 disease and associated mortality in a Portuguese cancer population.


Toxins ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 82 ◽  
Author(s):  
Sam Hobson ◽  
Samsul Arefin ◽  
Karolina Kublickiene ◽  
Paul Shiels ◽  
Peter Stenvinkel

Together with bone-mineral disorders, premature vascular ageing is a common feature of the uremic phenotype. A detailed understanding of mechanisms involved remains unclear and warrants further research. Available treatment options for end stage renal disease are principally dialysis and organ transplantation, as other treatment alternatives have proven insufficient. Chronic kidney disease (CKD) has been proposed as a model of early vascular and bone ageing, with accumulating evidence supporting the contribution of cellular senescence and the senescence-associated secretory phenotype (SASP) to cardiovascular pathology in CKD. Correspondingly, novel therapies based around the use of senolytic compounds and nuclear factor-erythroid-2-related factor 2 (Nrf2) agonists, have been suggested as attractive novel treatment options. In this review, we detail the contribution of the uremic environment to these processes underpinning ageing and how these relate to vascular health.


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