Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers

Kidney disease represents a serious global health problem. One of the main concerns is its late diagnosis, only feasible in a progressed disease state. The lack of a clinical manifestation in the early stages and the fact that the commonly measured parameters of renal function are markedly reduced only during advanced stages of the disease are the main cause. Changes at the molecular level of the kidney tissue occur even before nitrogenous substances, such as creatinine and urea, start to accumulate in the blood. Renal proximal tubules contain a large number of mitochondria and are critical for the energy-demanding process of reabsorption of water and solutes. Mitochondria are the largest producers of oxygen radicals, which, in turn, increase the susceptibility of kidneys to oxidative stress-induced damage. Free radicals and prooxidants produced during acute or chronic kidney injury may further aggravate the course of the disease and play a role in the pathogenesis of subsequent complications. Prevention might be the solution in CKD, but patients are often reluctant to undergo preventive examinations. Noninvasive markers and the possibility to obtain samples at home might help to increase compliance. This review will provide an overview of the possible uses of markers of oxidative status in noninvasive biofluids in patients with renal disease.publishedVersio

Association between metabolically healthy central obesity in women and levels of soluble receptor for advanced glycation end products, soluble vascular adhesion protein-1, and the activity of semicarbazide-sensitive amine oxidase

Aim To determine the levels of circulating soluble receptor for advanced glycation end products (sRAGE), as a biomarker of risk of metabolic syndrome and cardiovascular disease development in centrally obese (CO) women considered metabolically healthy (COH) in comparison with those metabolically unhealthy (COU). Methods 47 lean healthy, 17 COH (presenting waist-toheight ratio ≥0.5 but not elevated blood pressure, atherogenic lipid profile, and insulin resistance), and 50 COU (CO presenting ≥2 risk factors) women aged 40-45 years were included. Anthropometric characteristics, blood chemistry and hematology data, adipokines, markers of inflammation, sRAGE, soluble vascular adhesion protein-1 (sVAP-1), and the activity of semicarbazide sensitive amine oxidase (SSAO) were determined. Results Central obesity associated with low sRAGE levels (lean healthy: 1503 ± 633 pg/mL; COH: 1103 ± 339 pg/mL, P < 0.05; COU: 1106 ± 367 ng/mL, P < 0.0.1), hyperleptinemia, and elevated markers of inflammation irrespective of the presence or absence of cardiometabolic risk factors. COU women presented high adiponectin levels. SVAP-1 concentrations and the activity of SSAO were similar in all 3 groups. Conclusion COH women present abnormalities in nonstandard markers of cardiometabolic risk (sRAGE, leptin, high sensitive C-reactive protein), supporting the view that there is no healthy pattern of obesity. The clinical impact of our findings for future prognosis of metabolically healthy obese subjects remains to be elucidated in longitudinal studies

Prenatal dietary load of Maillard reaction products combined with postnatal Coca-Cola drinking affects metabolic status of female Wistar rats.

AIM: To assess the impact of prenatal exposure to Maillard reaction products (MRPs) -rich diet and postnatal Coca-Cola consumption on metabolic status of female rats. Diet rich in MRPs and consumption of saccharose/fructose sweetened soft drinks is presumed to impose increased risk of development of cardiometabolic afflictions, such as obesity or insulin resistance. METHODS: At the first day of pregnancy, 9 female Wistar rats were randomized into two groups, pair-fed either with standard rat chow (MRP-) or MRPs-rich diet (MRP+). Offspring from each group of mothers was divided into two groups and given either water (Cola-) or Coca-Cola (Cola+) for drinking ad libitum for 18 days. Oral glucose tolerance test was performed, and circulating markers of inflammation, oxidative stress, glucose and lipid metabolism were assessed. RESULTS: MRP+ groups had higher weight gain, significantly so in the MRP+/Cola- vs MRP-/Cola-. Both prenatal and postnatal intervention increased carboxymethyllysine levels and semicarbazide-sensitive amine oxidase activity, both significantly higher in MRP+/Cola + than in MRP-/Cola-. Total antioxidant capacity was lower in MRP+ groups, with significant decrease in MRP+/Cola + vs MRP-/Cola+. Rats drinking Coca-Cola had higher insulin, homeostatic model assessment of insulin resistance, heart rate, advanced oxidation of protein products, triacylglycerols, and oxidative stress markers measured as thiobarbituric acid reactive substances compared to rats drinking water, with no visible effect of MRPs-rich diet. CONCLUSION: Metabolic status of rats was affected both by prenatal and postnatal dietary intervention. Our results suggest that combined effect of prenatal MRPs load and postnatal Coca-Cola drinking may play a role in development of metabolic disorders in later life

Oxidative Stress in the Pathophysiology of Kidney Disease: Implications for Noninvasive Monitoring and Identification of Biomarkers

Kidney disease represents a serious global health problem. One of the main concerns is its late diagnosis, only feasible in a progressed disease state. The lack of a clinical manifestation in the early stages and the fact that the commonly measured parameters of renal function are markedly reduced only during advanced stages of the disease are the main cause. Changes at the molecular level of the kidney tissue occur even before nitrogenous substances, such as creatinine and urea, start to accumulate in the blood. Renal proximal tubules contain a large number of mitochondria and are critical for the energy-demanding process of reabsorption of water and solutes. Mitochondria are the largest producers of oxygen radicals, which, in turn, increase the susceptibility of kidneys to oxidative stress-induced damage. Free radicals and prooxidants produced during acute or chronic kidney injury may further aggravate the course of the disease and play a role in the pathogenesis of subsequent complications. Prevention might be the solution in CKD, but patients are often reluctant to undergo preventive examinations. Noninvasive markers and the possibility to obtain samples at home might help to increase compliance. This review will provide an overview of the possible uses of markers of oxidative status in noninvasive biofluids in patients with renal disease

Presence of Cardiometabolic Risk Factors Is Not Associated with Microalbuminuria in 14-to-20-Years Old Slovak Adolescents: A Cross-Sectional, Population Study

<div><p>Introduction</p><p>In adults, microalbuminuria indicates generalized endothelial dysfunction, and is an independent risk factor for cardiovascular and all cause mortality. Slovak adults present one of the highest cardiovascular mortality rates in Europe. Thus Slovak adolescents are on a high-risk to develop cardiovascular afflictions early, and screening for microalbuminuria might be useful in early assessment of their cardiovascular risk. We aimed to study the prevalence of microalbuminuria in Slovak adolescents, and the association of urinary albumin-to-creatinine ratio (ACR) to cardiovascular risk factors.</p><p>Subjects and methods</p><p>Anthropometric data, blood pressure, blood count, glucose homeostasis, lipid profile, renal function, inflammatory status, concentrations of homocysteine and uric acid were determined and associated with ACR in 2 666 adolescents (49.4% boys, 51.6% girls) aged 14-to-20 years. Microalbuminuria was classified as ACR 2.5–25.0 mg/mmol in boys and 3.5–35.0 mg/mmol in girls.</p><p>Results</p><p>Prevalence of microalbuminuria in both genders reached 3.3%, and did not differ significantly between lean and centrally obese subjects. Girls presented higher ACR than boys (normoalbuminuric: 0.6±0.5 mg/mmol vs. 0.5±0.4 mg/mmol, p0.001; microalbuminuric: 9.3±7.3 mg/mmol vs. 5.0±3.8 mg/mmol; p0.001). Microalbuminuric adolescents and those presenting normoalbuminuria within the upper ACR quartile were slimmer than their normoalbuminuric counterparts or adolescents with normoalbuminuria within the lower quartile, respectively. No association between microalbuminuria and cardiovascular risk markers was revealed.</p><p>Conclusion</p><p>Results obtained in this study do not support our assumption that ACR associates with cardiometabolic risk factors in apparently healthy adolescents. Follow-up studies until adulthood are needed to estimate the potential cardiometabolic risk of apparently healthy microalbuminuric adolescents.</p></div

Score scatter plot from OPLS-DA model of normoalbuminuric (NA, green circles) and microalbuminuric (MA, red circles) boys.

<p>Scores are orthogonal (= completely independent from each other), representing new variables summarizing the input of all determined variables (herein the morphometric and biochemical variables) so that one score vector corresponds to one subject, having its own score vector. Observations situated far outside Hotelling’s T2 tolerance ellipse are outliers. Model reveals partial overlapping of NA and MA subjects (separation in direction of x-axis). Separation in direction of y-axis represents within group variability.</p

Characteristics of girls presenting normo- and microalbuminuria, and albumin-to-creatinine ratio (ACR) in the upper and lower quartiles of normoalbuminuric range.

<p>cf.: circumference; BMI: body mass index; ABSI: a new body shape index; SBP: systolic blood pressure; DBP: diastolic blood pressure; PP: pulse pressure; MAP: mean arterial pressure; FPG: fasting serum glucose; FPI: fasting serum insulin; IU: international units; QUICKI: quantitative insulin sensitivity check index; HDL: high density lipoprotein; C: cholesterol; LDL: low density lipoprotein; TAG: triacylglycerols; AIP: atherogenic index of plasma; hsCRP: high sensitive C-reactive protein; eGFR: estimated glomerular filtration rate; WBC: white blood cells count; PBC: red blood cells count; NS: not significant; <i>italics</i>: <i>not normally distributed data evaluated statistically after logarithmic transformation</i>; data presented as mean ± SD;</p><p>* p<0.05,</p><p>** p<0.01,</p><p>***p<0.001 vs. normoalbumiuria;</p><p>^† p<0.05,</p><p>^†† p<0.01,</p><p>^†††p<0.001 vs. lower quartile</p><p>Characteristics of girls presenting normo- and microalbuminuria, and albumin-to-creatinine ratio (ACR) in the upper and lower quartiles of normoalbuminuric range.</p

Albumin-to-creatinine ratio in lean and centrally obese girls.

<p>a/ whole cohort; b/ normoalbuminuric girls; c/ microalbuminuric girls. ACR: urinary albumin-to-creatinine ratio; CO: centrally obese subjects; box plot indicates quartiles and whiskers the 5^th and the 95^th percentiles.</p

Albumin-to-creatinine ratio in lean and centrally obese boys.

<p>a/ whole cohort; b/ normoalbuminuric boys; c/ microalbuminuric boys. ACR: urinary albumin-to-creatinine ratio; CO: centrally obese subjects; box plot indicates quartiles and whiskers the 5^th and the 95^th percentiles.</p

Plot of variables of importance contributing to between group separation among normoalbuminuric and microalbuminuric boys.

<p>Plot of variables importance for the projection (VIP) summarizes the importance of the variables both to explain X and to correlate to dummy variables (Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129311#pone.0129311.g001" target="_blank">1</a> and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129311#pone.0129311.g002" target="_blank">2</a>). VIP values >1 indicate „important”X variables, <0.5 “unimportant” X variables, in the “grey interval” (0.5-to-1) the importance depends on the sample size. This plot confirms the OPLS-DA loadings scatter plot (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129311#pone.0129311.g002" target="_blank">Fig 2</a>), showing that the variables adjacent to the origin in the former plot do not contribute to between group separation significantly. Abbreviations used in Figs <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0129311#pone.0129311.g002" target="_blank">2</a> and 3: ACR: urinary albumin-to-creatinine ratio; WHR: waist-to-height ratio; waist: waist circumference; BMI: body mass index; uRo: urine density; weight: body weight; PP: pulse pressure; eGFR: estimated glomerular filtration rate; QUICKI: quantitative insulin check index; SBP: systolic blood pressure; Hcy: homocysteine; Crea: serum creatinine; Ins: fasting serum insulin; HDL: high density lipoprotein cholesterol; ABSI: a new body shape index; hsCRP: high sensitivity C-reactive protein; Glu: fasting serum glucose; DBP: diastolic blood pressure; Alb: serum albumin; Chol: cholesterol; UA: serum uric acid; WBC: white blood cells count; LDL: low density lipoprotein cholesterol; AIP: atherogenic index of plasma; RBC: red blood cells count; Plt: platelet count; MAP: mean arterial pressure; TAG: triacylglycerols.</p