The Value of Urinary NGAL, KIM-1, and IL-18 Measurements in the Early Detection of Kidney Injury in Oncologic Patients Treated with Cisplatin-Based Chemotherapy.

Cisplatin is still a widely used anticancer drug characterized by significant nephrotoxicity. Acute kidney injury (AKI), diagnosed based on the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, has limitations, including a delayed increase in creatinine. We determined the usefulness of neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and interleukin-18 (IL-18) in diagnosing AKI according to the KDIGO criteria in patients treated with cisplatin. We recruited 21 subjects starting cisplatin-based chemotherapy (Cisplatin-based group) and 11 treated with carboplatin-based chemotherapy or 5-fluorouracil regimens (non-cisplatin-based group). Blood and urine samples were collected during four subsequent cycles of chemotherapy (68 and 38 cycles, respectively). AKI occurred in four patients in the cisplatin-based group (5.9% of 68 cisplatin-based chemotherapy cycles). Among them, three urinary markers were increased by over 100% in two cases, two in one case and one in another. A doubling of at least one investigated parameter was observed more frequently during cisplatin-based chemotherapy (80.3% vs. 52.8%; OR = 3.65, 95% CI: 1.49-8.90; p < 0.01). The doubling of at least one new urinary AKI marker was more common in patients receiving cisplatin and frequently was not associated with overt AKI. Thus, a subclinical kidney injury detected by these markers occurs more frequently than deterioration in kidney function stated with creatinine changes.

Copeptin Concentrations in Plasma of Healthy Neonates in Relation to Water-Electrolyte Homeostasis in the Early Adaptation Period.

Copeptin (CTproAVP) is a stable by-product of arginine-vasopressin synthesis and reflects its secretion by the pituitary gland, considered as a potential new marker of dehydration. The objective of the study was to investigate CTproAVP measured after the first 48 h of postnatal life in relation to serum effective osmolality, urine osmolality, and vessels filling according to the following variables: delivery mode, postnatal weight loss, fluids administered intravenously to the mother, and fluids given orally to the neonate. A prospective observational study was conducted with 200 healthy term infants (53% male) enrolled. Serum CTproAVP concentrations were measured using the ELISA kit; haematocrit, urine osmolality, serum effective osmolality were assessed after 48 h of life. Sonographic measurements of inferior vena cava (IVC) and aorta (Ao) were performed and IVC/Ao ratios were calculated. No correlations were found between CTproAVP concentrations and both serum effective osmolality and urine osmolality. There was also no association between CTproAVP concentrations and vessel filling represented by IVC/Ao index at 48 h of life.

Severity of Vitamin D Deficiency Predicts Mortality in Ischemic Stroke Patients.

BACKGROUND: Vitamin D (VD) deficiency is considered an independent risk factor for death due to cardiovascular events including ischemic stroke (IS). We assessed the hypothesis that decreased levels of 25-hydroxyvitamin D (25-OH-D) are associated with increased risk of mortality in patients with IS. METHODS: Serum 25-OH-D, intact parathyroid hormone (iPTH), and intact fibroblast growth factor 23 (iFGF23) levels were assessed in serum of 240 consecutive patients admitted within the 24 hours after the onset of IS. Mortality data was obtained from the local registry office. RESULTS: Only three subjects (1.3%) had an optimal 25-OH-D level (30-80 ng/mL), 25 (10.4%) had a mildly reduced (insufficient) level, 61 (25.4%) had moderate deficiency, and 151 (62.9%) had a severe VD deficiency. 20% subjects had secondary hyperparathyroidism. The serum 25-OH-D level was significantly lower than that in 480 matched subjects (9.9 ± 7.1 vs. 21.0 ± 8.7 ng/mL). Of all the patients, 79 (32.9%) died during follow-up observation (44.9 months). The mortality rates (per year) were 4.81 and 1.89 in a group with and without severe VD deficiency, respectively (incidence rate ratio: 2.52; 95% CI: 1.44-4.68). There was no effect of secondary hyperparathyroidism and iFGF23 levels on mortality rates. Age, 25 - OH - D < 10 ng/mL, and functional status (modified Rankin scale) were significant factors increasing the risk of death in multivariable Cox proportional hazard regression test. CONCLUSIONS: Severe VD deficiency is an emerging, strong negative predictor for survival after IS, independent of age and functional status. VD supplementation in IS survivals may be considered due to high prevalence of its deficiency. However, it is uncertain whether it will improve their survival.

Osteoprotegerin Assessment Improves Prediction of Mortality in Stroke Patients.

BACKGROUND: Elevated circulating osteoprotegerin (OPG) level is associated with an increased risk of hospitalization for ischemic stroke and coronary artery disease. The aim of the present study was to analyze whether OPG assessment may improve the prediction of mortality in patients with stroke. PATIENTS AND METHODS: Serum OPG, fetuin A, 25-OH-D3, intact parathyroid hormone levels were assessed in serum samples which were left over after routine tests in a hospital laboratory. This assessment was conducted in 240 consecutive patients with acute ischemic stroke, admitted within 24hours after the onset of symptoms to the Stroke Unit. Mortality data were obtained from the local registry office. RESULTS: The mean OPG serum level was 14.6 ± 6.0pmol/L (range: 3.7-43.4). There were no significant differences in the OPG values between men and women (13.9 ± 5.0 versus 15.1 ± 6.7 pmol/L; P = .12). Therefore, tertiles were calculated for the whole group. During the follow-up, 85 (35.4%) patients died and 92 (38.3%) died or had recurrent stroke. OPG level appeared a significant predictors of death and composite end-point (death/recurrent stroke), in addition to the well-established once (age, atrial fibrillation, diabetes RANKIN at admission and discharge, severity of stroke). In multivariable stepwise backward analyses, the OPG level persisted as a significant and independent predictor of death (hazard ratio [HR] = 1.084 (95% confidence intervals: 1.036-1.134)] and composite and point (HR = 1.082 [1.037-1.129]). CONCLUSIONS: OPG level may be considered as a predictor of mortality in stroke patients.

Plasma concentration of Retinol Binding Protein 4 (RBP4) in relation to nutritional status and kidney function in older population of PolSenior Study.

PURPOSE: The aim of the study was to assess plasma RBP4 concentration in elderly subjects in relation to nutritional status and kidney function in the population of the PolSenior Study. MATERIAL AND METHODS: We assessed RBP4, glucose, insulin, albumin, lipid profile, C-reactive protein, (hsCRP) and creatinine concentrations in 2614 PolSenior Study participants (1235 women and 1379 men). The study group was divided based on BMI and HOMA-IR values, and the occurrence of diabetes. RESULTS: Plasma RBP4 concentration was similar in normal weight, overweight, and obese subgroups, both in women (40.4 vs 40.8 vs 41.8 ng/ml, respectively), and men (41.2 vs 40.3 vs 42.9 ng/ml, respectively). Similar values were found in subjects with HOMA-IR <2.5; ≥2.5 and diabetes, while those with decreased eGFR (<60 ml/min/1.73 m2) were characterized by increased RBP4 levels [46.0 (32.0-64.8) vs 39.4 (28.2-54.9) ng/ml; p < 0.001]. Plasma RBP4 level variability was explained by: age, waist circumference or BMI, and eGFR, but not HOMA-IR and/or hsCRP. The standardized coefficients ß (slopes) for BMI and waist circumference were similar. CONCLUSIONS: The results revealed that in older subjects, circulating RBP4 levels are mostly affected by kidney function and modestly by age, gender, and nutritional status, but not insulin resistance.

Plasma Level of Retinol-Binding Protein 4, N-Terminal proBNP and Renal Function in Older Patients Hospitalized for Heart Failure.

BACKGROUND/AIM: Elevated plasma concentration of retinol-binding protein 4 (RBP4) has recently emerged as a potential new risk factor for cardiovascular diseases, including hypertension (HT) and coronary artery disease (CAD). Limited data suggest that RBP4 promotes inflammatory damage to cardiomyocytes and participates in the development of heart failure (HF). This study aimed to analyze the relationship between concentrations of plasma RBP4 and serum N-terminal proBNP (NT-proBNP), a powerful biomarker of left ventricle dysfunction, in the older Polish population. METHODS: The study sample consisted of 2,826 (1,487 men) participants of the PolSenior study, aged 65 years and older, including a subgroup hospitalized for HF (n = 282). In all subjects, plasma concentrations of RBP4, interleukin-6 (IL-6), serum level of NT-proBNP, and hs-CRP were measured. Additionally, BMI, estimated glomerular filtration rate (eGFR), and HOMA-IR were calculated. The prevalence of HT, CAD, atrial fibrillation (AF), and medication were considered as potential confounders. RESULTS: Similar RBP4 levels were found in subjects with NT-proBNP < 125 and ≥125 ng/mL, with and without AF, and in the subgroups hospitalized for HF with and without AF. Regression analysis revealed no association between log10(NT-proBNP) and log10(RBP4). Plasma levels of RBP4 were increased by HT occurrence and diuretic therapy, while diminished with regard to female gender, age, eGFR values, AF, and IL-6 levels. CONCLUSION: Our results show that RBP4 is affected by GFR but cannot be considered as an independent biomarker of heart muscle dysfunction.

Socio-economic determinants of vitamin D deficiency in the older Polish population: results from the PolSenior study.

OBJECTIVE: Numerous studies have reported an association between vitamin D (25-hydroxyvitamin D; 25(OH)D) deficiency and low economic status, lower educational level, drugs exposure, smoking and reduced physical activity. Our study analysed the association between sociodemographic factors and 25(OH)D status in Polish (Caucasian) seniors. DESIGN: Cross-sectional study (part of the PolSenior study). Serum 25(OH)D concentration was measured by a solid-phase ELISA method; a standardized questionnaire evaluated educational level, economic status, alcohol consumption, current or past cigarette smoking, physical activity, activities of daily living (ADL) and instrumental activities of daily living. SETTING: Community-dwelling randomly selected individuals aged 65 years or older, selected using three-stage stratified, proportional draw. SUBJECTS: Seniors (n 3472; 1658 women and 1814 men). RESULTS: Mean serum 25(OH)D concentration was 20·5 (sd 9·6) ng/ml. Values below the recommended level (30 ng/ml) were detected in 82·8 % of men and 90·4 % of women. Regression analysis revealed that the difference between sexes was associated with decreased walking activity in women, probably resulting in less sunlight exposure. There was a positive association between any disability in ADL and the presence of vitamin D deficiency/insufficiency. In the sex-adjusted analysis, older age, alcohol abstinence and lack of cycling and long-distance walking were explanatory variables for vitamin D deficiency. CONCLUSIONS: Vitamin D deficiency/insufficiency is frequent in the older Polish population and associated with functional disability and impaired mobility of seniors.

Zonulin: A Potential Marker of Intestine Injury in Newborns.

INTRODUCTION: Zonulin (ZO), a new diagnostic biomarker of intestinal permeability, was tested in newborns presenting symptoms of infection and/or inflammation of the gut or being at risk of intestinal pathology. MATERIAL AND METHODS: Serum ZO was assessed in 81 newborns diagnosed with sepsis, necrotizing enterocolitis (NEC), rotavirus infection, and gastroschisis, also in extremely low gestational age babies, and in controls (healthy newborns). ZO concentration was compared to C-reactive protein (CRP) and procalcitonin (PCT) values, leucocyte and platelet count, basic demographic data, and the value of the Neonatal Therapeutic Intervention Scoring System (NTISS). RESULTS: Median values of ZO were markedly higher in groups with rotavirus infection and gastroschisis (36.0 (1-3Q: 26.0-43.2) and 20.3 (1-3Q: 17.7-28.2) ng/ml, resp.) versus controls (3.5 (1-3Q: 2.7-4.8) ng/ml). Its concentration in the NEC group was twice as high as in controls but did not reach statistical significance. ZO levels were not related to NTISS, CRP, and PCT. CONCLUSIONS: Zonulin is a promising biomarker of intestinal condition, markedly elevated in rotavirus infections. Its role in defining the severity of necrotizing enterocolitis and the risk for perforation is not well described and needs further evaluation. An increase in zonulin may not be parallel to the release of inflammatory markers, and low CRP should not exclude an injury to neonatal intestine.

Increased plasma RBP4 concentration in older hypertensives is related to the decreased kidney function and the number of antihypertensive drugs-results from the PolSenior substudy.

Increased plasma retinol-binding protein 4 (RBP4), a novel adipokine, has been associated in previous studies with obesity, type 2 diabetes, dyslipidemia, hypertension (HT), atherosclerosis, and coronary artery disease. This study aimed to analyze the relationship between HT occurrence and its treatment, and plasma RBP4 concentrations in the older polish population. The study sample consisted of 1728 (890 men and 838 women) PolSenior study participants aged 65 years and older with available plasma samples and NT-proBNP values below 2000 pg/mL. The analysis included body mass index, waist circumference, blood pressure, antihypertensive medication, estimated glomerular filtration rate, serum glucose and insulin (and the homeostatic model assessment of insulin resistance), and plasma RBP4 levels. RBP4 plasma concentrations were higher in hypertensive (N = 645) than normotensive (N = 236) men (43.4 [30.4-64.8] vs. 38.1 [27.1-54.4] ng/mL, respectively; P < .01) but not in women (44.6 [29.6-63.5] vs. 40.7 [29.1-58.1] ng/mL, respectively; P = .21). In the subanalysis, higher plasma RBP4 levels were observed in women with treated than untreated HT and in subjects taking four of more antihypertensive drugs. The linear regression shown that estimated glomerular filtration rate (ß = -0.015), thiazide diuretics (ß = 0.041), and α-blockers (ß = 0.049) were explaining log10RBP4 plasma levels variability in the study group. Older male Caucasians with HT are characterized by elevated plasma RBP4 levels. This increase is proportional to the number of antihypertensive drugs and decreased glomerular filtration rate. Among the antihypertensive drugs, only thiazide diuretics and α-blockers had a significant influence on RBP4 levels.

The relationship between circulating visfatin/nicotinamide phosphoribosyltransferase, obesity, inflammation and lipids profile in elderly population, determined by structural equation modeling.

BACKGROUND: The available literature suggests that circulating visfatin/Nicotinamide Phosphoribosyltransferase (NAMPT) level variability in humans is related to obesity, insulin resistance, inflammation, and lipid profile. The aim of the study was to assess the relationship between circulating visfatin/NAMPT, obesity, insulin resistance, inflammation, and lipid profile in a large population-based, elderly cohort, applying structural equation modeling. MATERIALS AND METHODS: The analysis included 2983 elderly participants of the PolSenior study with assessed total blood count, fasting concentrations of lipids, glucose, insulin, hs-CRP, interleukin-6, and visfatin/NAMPT (by ELISA), and calculated HOMA-IR. RESULTS: The circulating visfatin/NAMPT levels were higher in obese compared to normal weight subjects, in those with hs-CRP above 3 mg/L, with low serum HDL cholesterol, and in insulin resistant subjects. Based on results of the exploratory factor analysis, a baseline model of mutual relationship between four latent and measured variables was created and a final model was developed by maintaining only two significant categories. The important variables for 'latent inflammation' proved to be hs-CRP and IL-6 serum levels. In the case of 'nutritional status', important variables were BMI, waist circumference, and to a lesser extent insulin resistance. Additionally, the residual correlation between those two constructs was also statistically significant. CONCLUSION: The structural equation modeling provided support for the existence of a link between nutritional status, inflammation and circulating visfatin/NAMPT level. This indicates that circulating visfatin/NAMPT can be considered as a novel surrogate marker of systemic inflammation associated with fat depot, especially visceral, in the elderly population.

Plasma visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) concentration in elderly subjects with metabolic syndrome.

INTRODUCTION: Visceral adipose tissue is the main source of circulating proinflammatory adipokine, visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT), whose role in the pathogenesis of metabolic syndrome (MS) components such as hypertension and carbohydrate and lipid disturbances is still uncertain, due to commonly used low specific C-terminal immunoassays to determine visfatin/NAMPT levels. OBJECTIVES: The aim of the study was to assess the association between the occurrence of MS components and circulating visfatin/NAMPT levels in elderly popula tion. PATIENTS AND METHODS: The analysis included 2174 elderly participants of the PolSenior study without heart failure, severe chronic kidney disease, cancer, and malnutrition. MS was defined according to the modified International Diabetes Federation criteria. Plasma visfatin/NAMPT concentrations were measured by a highly specific enzyme-linked immunosorbent assay. Additionally, high-sensitivity C-reactive protein (hsCRP), interleukin 6 (IL-6), and insulin levels were assessed, and the homeostasis model assessment for insulin resistance was calculated. RESULTS: Women were diagnosed with MS more often than men (71.2% vs 56.8%; P <0.001) and had a greater prevalence of all MS components except for type 2 diabetes. Women with MS had higher concentrations of hsCRP and IL-6 than those without MS. Visfatin/NAMPT concentrations were higher in women with MS than in those without MS (1.06 ng/ml [0.65-1.87] vs 0.85 ng/ml [0.54-1.40]; P <0.001), but no differences were observed in men (0.97 ng/ml [0.59-1.61] vs 0.90 ng/ml [0.56-1.60], respectively; P = 0.5). In women, there was a stronger association between the number of components of MS and increased plasma visfatin/NAMPT levels than in men. CONCLUSIONS: Plasma visfatin/NAMPT levels are increased only in elderly women with MS. It is difficult to distinguish the components of MS specifically associated wit h increased visfatin/NAMPT levels.

Factors limiting usefulness of serum and urinary NGAL as a marker of acute kidney injury in preterm newborns.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a highly sensitive and specific marker of acute kidney injury (AKI). The aim of this study was to assess the factors affecting serum and urine total NGAL in preterm newborns, limiting the role of this new potential marker of AKI. METHODS: Serum and urinary total NGAL concentrations were determined in 57 preterm infants admitted to the Neonatal Intensive Care Unit in the following points of time: first week of life, between 8 and 14 days of life, and after the fourth week of life. Patients' clinical conditions were evaluated based on NTISS (Neonatal Therapeutic Intervention Scoring System). Two gestational age subgroups were distinguished: ≤29 and 30 to 35 weeks of gestation. We sought correlation between total NGAL values and gestational age, birth weight, Apgar score and severity of clinical condition, with particular interest in inflammatory status. RESULTS: Serum and urinary total NGAL concentration correlated with inflammatory markers, such as CRP and procalcitonin, as well as with NTISS values. Birth weight and gestational age influence urinary NGAL (uNGAL) values in the first two weeks of life. In AKI (N = 8) patients uNGAL values were significantly higher than in non-AKI newborns. CONCLUSIONS: We conclude that inflammatory status and prematurity limits the specificity of total NGAL measurement as a marker of AKI.

Plasma visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) concentration is not related to kidney function in elderly subjects.

BACKGROUND: Studies assessing plasma visfatin/nicotinamide phosphoribosyltransferase (NAMPT) concentrations in chronic kidney disease with the ELISA method are restricted mainly to subjects with end-stage kidney disease. Therefore, little is known about to what extent glomerular filtration rate (GFR) affects the plasma levels of visfatin/NAMPT. The aim of this study was to assess the relations between circulating visfatin/NAMPT levels and estimated GFR (eGFR), independently of potential confounders such as inflammation, nutritional status, and insulin resistance in the elderly population. METHODS: The analysis included 3023 elderly subjects (1076 with impaired kidney excretory function - eGFR <60 mL/min/1.73 m2) who were participants of the PolSenior study. Serum insulin, glucose, creatinine, C-reactive protein, interleukin-6, and plasma visfatin/NAMPT concentrations were measured by a highly specific ELISA method. Insulin resistance was assessed on the basis of homeostasis model assessment for insulin resistance, and kidney excretory function was assessed using the full MDRD formula. RESULTS: Similar plasma visfatin/NAMPT levels were found in subjects with eGFR ≥60 and <60 mL/min/1.73 m2 (0.96 ng/mL in both groups), and even in those subjects with eGFR 15-30 mL/min/1.73 m2 (0.83 ng/mL). Additionally, there was no association between plasma visfatin/NAMPT concentrations and eGFR values in models of regression analysis including confounding factors. CONCLUSIONS: The results of our study suggest that plasma visfatin/NAMPT levels are not affected by impaired kidney excretory function in elderly subjects.

Plasma visfatin/nicotinamide phosphoribosyltransferase levels in hypertensive elderly - results from the PolSenior substudy.

Visfatin/nicotinamide phosphoribosyltransferase (NAMPT), is a 52 kDa adipokine with proinflammatory properties produced mostly by macrophages and adipocytes from visceral adipose tissue. It seems that visfatin/NAMPT plays a role in the pathogenesis of arterial hypertension. As this condition is frequently present in the elderly, the aim of the study was to assess the plasma visfatin/NAMPT levels in normotensive and hypertensive subjects from the Polish elderly population. Visfatin/NAMPT levels were measured by specific enzyme-linked immunosorbent assay method in plasma samples from 2789 elderly subjects (1338 females, 1451 males) without heart failure, the PolSenior study participants, in addition to previously estimated serum concentrations of insulin, glucose, creatinine, C-reactive protein, and interleukin-6. Homeostasis model assessment for insulin resistance was calculated and used as a marker of insulin resistance. In the study group, 591 subjects were normotensive, 449 had untreated hypertension, and 1749 had treated hypertension. Plasma visfatin/NAMPT levels were not related to the presence of hypertension or the use of antihypertensive drugs, including angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists. The regression analysis revealed that plasma visfatin/NAMPT concentration variability is increased in subjects with high-sensitivity C-reactive protein concentration above 3 mg/L and with homeostasis model assessment for insulin resistance ≥2.5, and decreased in those aged over 80 years. Our study shows that the presence of hypertension is not associated with the plasma levels of visfatin/NAMPT in elderly subjects. Plasma visfatin/NAMPT concentrations positively correlate with inflammation and insulin resistance, and are decreased in the oldest.

Relationship between circulating visfatin/NAMPT, nutritional status and insulin resistance in an elderly population - results from the PolSenior substudy.

BACKGROUND: Circulating visfatin/nicotinamide phosphoribosyltransferase (visfatin/NAMPT) levels according to some studies are related to nutritional status and insulin resistance. These associations have not been studied in large elderly populations. Therefore, the aim of our study was to assess the relationships between circulating visfatin/NAMPT levels, nutritional status, and insulin resistance in a large population of the elderly. MATERIALS AND METHODS: Concentrations of glucose, albumin, creatinine, CRP, interleukin-6, insulin, and visfatin/NAMPT (by ELISA) were assessed, and HOMA-IR calculated in 3050 elderly participants of the PolSenior study. RESULTS: The highest plasma visfatin/NAMPT levels were observed in obese, as well as in non-diabetic insulin resistant subjects; however there were only significant differences found in women. The regression models showed that plasma visfatin/NAMPT levels decline with age and increased with waist circumference, BMI, and hs-CRP. Waist circumference was better correlated than BMI for visfatin/NAMPT levels in statistical models not adjusted by sex, and just the opposite in models which were. We demonstrated a 0.023ng/mL increase of Visfatin/NAMPT levels for 1mg/L increase of hs-CRP, and a 0.007ng/mL decline for each year of age. CONCLUSION: Our study revealed that in elderly subjects, circulating visfatin/NAMPT levels are related to age, nutritional status, especially visceral obesity, and inflammation.

Serum and urinary NGAL in septic newborns.

Neutrophil gelatinase-associated lipocalin (NGAL) is postulated to be a potentially new and highly specific/sensitive marker of acute kidney injury (AKI). The aim of this study was to assess the impact of inflammation on serum and urine NGAL in newborns that were treated due to infection. We determined serum and urine NGAL concentrations in 73 infants (51 with sepsis; 22 with severe sepsis) admitted to the Intensive Care Unit in the first month of life, for three consecutive days during the course of treatment for infection. 29 neonates without infection served as the control group. Septic patients, in particular, severe sepsis patients, had increased serum and urinary NGAL levels in the three subsequent days of observation. Five septic patients who developed AKI had elevated serum and urinary NGAL values to a similar extent as septic neonates without AKI. A strong correlation was found between the concentration of serum and urinary NGAL and inflammatory markers, such as CRP and procalcitonin. Serum and urinary NGAL levels were also significantly associated with NTISS (neonatal therapeutic intervention scoring system) values. We conclude that increased serum and urinary NGAL values are not solely a marker of AKI, and more accurately reflect the severity of inflammatory status.