Nitric Oxide Synthesis Metabolites-As Potential Markers in Chronic Kidney Disease in Children.

Nitric oxide (NO) is an important signaling molecule for many physiological and pathological processes. Diseases associated with abnormal NO synthesis include cardiovascular diseases, insulin-dependent diabetes, or chronic kidney disease (CKD). The aim of the paper was to evaluate NO synthesis metabolites, i.e., asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), dimethylamine (DMA), arginine, citrulline in plasma of patients with different severity of CKD and to seek possible links between these parameters and the development of this disease. Forty-eight CKD children and thirty-three age-matched controls were examined. Patients were divided into groups depending on the CKD stages (Group II-stage II, Group III-stage III, Group IV-stage IV, and Group RRT children on dialysis). To determine the concentrations of the above-mentioned metabolites in plasma liquid chromatography-mass spectrometry was used. There were significant differences observed in levels of ADMA, SDMA, DMA, and citrulline between control vis CKD groups (p values ranging from <0.001 to 0.029). Plasma arginine concentration was also higher in CKD patients compared to the control group but statistically insignificant. ADMA levels in CKD children were statistically significantly higher in relation to particular stages of CKD (RRT vis II stage of CKD: p = 0.01; RRT vis III-IV stages of CKD: p < 0.046). Citrulline levels in CKD children were statistically significantly higher in RRT group vis control (p < 0.001). Children with CKD develop disturbances in most metabolites of NO synthesis. Dialysis children treated show the greatest disturbances of plasma ADMA and citrulline levels. ADMA seems to be a good indicator of the gradual progression of the CKD, which is proved by the negative correlation with eGFR.

The Use of Artificial Intelligence Algorithms in the Diagnosis of Urinary Tract Infections-A Literature Review.

Urinary tract infections (UTIs) are among the most common infections occurring across all age groups. UTIs are a well-known cause of acute morbidity and chronic medical conditions. The current diagnostic methods of UTIs remain sub-optimal. The development of better diagnostic tools for UTIs is essential for improving treatment and reducing morbidity. Artificial intelligence (AI) is defined as the science of computers where they have the ability to perform tasks commonly associated with intelligent beings. The objective of this study was to analyze current views regarding attempts to apply artificial intelligence techniques in everyday practice, as well as find promising methods to diagnose urinary tract infections in the most efficient ways. We included six research works comparing various AI models to predict UTI. The literature examined here confirms the relevance of AI models in UTI diagnosis, while it has not yet been established which model is preferable for infection prediction in adult patients. AI models achieve a high performance in retrospective studies, but further studies are required.

Evaluation of Vascular Endothelial Function in Children with Type 1 Diabetes Mellitus.

Diabetic kidney disease belongs to the major complications of diabetes mellitus. Here, hyperglycaemia is a key metabolic factor that causes endothelial dysfunction and vascular changes within the renal glomerulus. The aim of the present study was to assess the function of the vascular endothelium in children with type 1 diabetes mellitus (type 1 diabetes) by measuring selected endothelial lesion markers in blood serum. The selected markers of endothelial lesions (sVCAM-1, sICAM-1, sE-SELECTIN, PAI-1, ADMA and RAGE) were assayed by the immunoenzymatic ELISA method. The study involved 66 patients (age: 5-18 years) with type 1 diabetes and 21 healthy controls (age: 5-16 years). In the type 1 diabetes patients, significantly higher concentrations of all of the assayed markers were observed compared to the healthy controls (p < 0.001). All of the evaluated markers positively correlated with the disease duration, the age, and BMI of the patients, while only PAI-1 and sE-SELECTIN were characteristic of linear correlations with the estimated glomerular filtration rate (eGFR). It can be concluded that endothelial inflammatory disease occurs in the early stages of type 1 diabetes mellitus in children. The correlations between PAI-1, sE-SELECTIN, and eGFR suggest an advantage of these markers over other markers of endothelial dysfunction as prognostic factors for kidney dysfunction in children with type 1 diabetes.

Adenine Nucleotide Metabolites in Uremic Erythrocytes as Metabolic Markers of Chronic Kidney Disease in Children.

Chronic kidney disease (CKD) is associated with multifaceted pathophysiological lesions including metabolic pathways in red blood cells (RBC). The aim of the study was to determine the concentration of adenine nucleotide metabolites, i.e., nicotinamide adenine dinucleotide (NAD)-oxidized form, nicotinamide adenine dinucleotide hydrate (NADH)-reduced form, nicotinic acid mononucleotide (NAMN), ß-nicotinamide mononucleotide (NMN), nicotinic acid adenine dinucleotide (NAAD), nicotinic acid (NA) and nicotinamide (NAM) in RBC and to determine a relationship between NAD metabolites and CKD progression. Forty-eight CKD children and 33 age-matched controls were examined. Patients were divided into groups depending on the CKD stages (Group II-stage II, Group III- stage III, Group IV- stage IV and Group RRT children on dialysis). To determine the above-mentioned metabolites concentrations in RBC liquid chromatography-mass spectrometry was used. Results: the only difference between the groups was shown concerning NAD in RBC, although the values did not differ significantly from controls. The lowest NAD values were found in Group II (188.6 ± 124.49 nmol/mL, the highest in group IV (324.94 ± 63.06 nmol/mL. Between Groups II and IV, as well as III and IV, the differences were statistically significant (p < 0.032, p < 0.046 respectively). Conclusions. CKD children do not have evident abnormalities of RBC metabolism with respect to adenine nucleotide metabolites. The significant differences in erythrocyte NAD concentrations between CKD stages may suggest the activation of adaptive defense mechanisms aimed at erythrocyte metabolic stabilization. It seems that the implementation of RRT has a positive impact on RBC NAD metabolism, but further research performed on a larger population is needed to confirm it.

The importance of fetuin-A in vascular calcification in children with chronic kidney disease.

BACKGROUND: The status of the cardiovascular (CV) system in children with chronic kidney disease (CKD) is significantly influenced by increasing stiffness of the arterial wall. This largely depends on the shortage of local and systemic inhibitors of soft tissue calcification. OBJECTIVES: The aim of the study was to evaluate the role of fetuin-A in conjunction with other factors in the progressive hardening of the vascular wall in these children. We examined serum fetuin-A concentrations in relation to renal function, dialysis modality, and other clinical and biochemical markers promoting vascular calcification. MATERIAL AND METHODS: Twenty children on peritoneal dialysis (PD), 20 on hemodialysis (HD), 36 treated conservatively, and 26 healthy subjects were enrolled into a cross-sectional study. In all children, fetuin-A and numerous clinical and biochemical parameters were measured. RESULTS: The fetuin-A concentration was significantly lower in children on hemodialysis (HD) vs children on peritoneal dialysis (PD), conservatively treated subjects, and the control group. In sick children, fetuinA concentration negatively correlated with dialysis vintage, PWV/ht, phosphate concentration, calcium phosphate product (CaxP), cumulative doses of calcium, and vitamin D3. In the whole study population, fetuin-A negatively correlated with blood pressure (BP), pulse wave velocity indexed to height (PWV/ht), intact parathyroid hormone (iPTH), high sensitivity C-reactive protein (hsCRP), and cholesterol concentrations. CONCLUSIONS: In children with CKD, the decreased concentration of fetuin-A is related to other vascular calcification risk factors. Serum fetuin-A concentration may play a role in the identification of vascular disease risk factors in this population.

Disturbances in intraventricular conduction in children with end-stage renal disease on peritoneal dialysis: A pilot study.

BACKGROUND: The progression of chronic kidney disease is accompanied by multi-organ disorders, among which cardiovascular diseases have the status of a serious clinical problem. The body surface potential mapping (BSPM) technique is a non-invasive method which enables the detection of pathological changes in the bioelectrical activity of the heart. OBJECTIVES: The aim of this study was to identify possible disturbances in the intraventricular conduction system in peritoneally dialyzed children. MATERIAL AND METHODS: Cardiac examination consisted of 12-lead electrocardiography, echocardiography and BSPM. The evaluation of disturbances in the cardio-electrical field was performed by comparing the qualitative and quantitative features of the heart potentials on the isopotential map. RESULTS: Data was collected from 10 children treated with automatic peritoneal dialysis (APD) (mean age: 13.6 ±2.3 years) and 26 healthy children. The maps of dialyzed children showed a shift in positive isopotentials toward the left lower part of the thorax, while negative values were observed in its left upper part. A distribution of lines on the isopotential maps revealed disturbances in the stimulation spread within the heart ventricles, especially within the anterior fascicle of the left bundle branch of His. CONCLUSIONS: Intraventricular conduction disturbances were observed in the left bundle branch of His in the peritoneally dialyzed children. The body surface potential mapping was a more sensitive method in identifying the early stage of conduction disturbances within the heart ventricles than 12-lead electrocardiography. Further research involving a larger population of dialyzed children is planned.

Valve bladder syndrome in children: On the trail of the best strategies to prevent chronic kidney disease.

Pediatric patients suffering from valve bladder syndrome (VBS) are at risk of developing chronic kidney disease (CKD) and renal failure in later life. Therefore, it is of vital importance to determine the risk factors and the best possible strategies for diagnosis and treatment in patients with VBS that would minimize the risk of developing CKD. In this review we have presented the current knowledge of CKD risk factors in patients with posterior urethal value (PUV). We have also discussed possible recommendations for prenatal diagnostics procedures to be undertaken in patients with PUV, postnatal monitoring and therapeutic strategies that could reduce the risk of developing CKD in this population. Although in most cases there are no clear guidelines for appropriate clinical actions that can be undertaken in patients with PUV to minimize the risk of kidney failure, we have tried to present concise and accurate advice for physicians taking care of patients with PUV.

Skin autofluorescence as a novel marker of vascular damage in children and adolescents with chronic kidney disease.

BACKGROUND: Skin autofluorescence (sAF) was examined as a marker of the accumulation of advanced glycation end products (AGEs) in tissues of children with chronic kidney disease (CKD) in relation to renal function, dialysis modality and markers of endothelial inflammation and dysfunction. METHODS: A total of 76 children with CKD were enrolled in the study, of whom 20 children were on hemodialysis (HD), 20 were on peritoneal dialysis (PD) and 36 were treated conservatively. A control group of 26 healthy subjects was also included in the study. In all children, sAF intensity, carotid intima-media (cIMT) thickness and plasma concentrations of sE-selectin, matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase 1 (TIMP-1), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and plasminogen activator inhibitor type 1 (PAI-1) were measured. RESULTS: Compared to the controls, children with CKD had significantly elevated sAF levels. sAF in the children with CKD was positively correlated with sE-selectin, MMP-9, TIMP-1, ADMA, SDMA and PAI-1 levels. In the predialysis group (conservative treatment) sAF levels were positively correlated with sE-selectin and ADMA levels and negatively correlated with glomerular filtration rate. Multiple regression analysis showed a significant association of sAF with sE-selectin and MMP-9 in CKD children. CONCLUSIONS: The results reveal that AGEs were accumulated in the children with CKD. This accumulation was related to early vascular changes and a number of biochemical vascular risk markers. sAF measurement, as a noninvasive method, may be useful for identification of clinical risk factors of vascular disease in CKD children.

Maps of Ventricular Activation Time (VAT) Differences in Children on Peritoneal Dialysis - a Pilot Study.

BACKGROUND: Decrement of glomerular filtration rate leads to many serious complications that cause both functional and structural impairments of the other organs. Long-term clinical observations of children and teenagers with end-stage renal disease (ESRD) showed that more than one third of those patients manifested various cardio-vascular conditions. The aim of the study was to analyze possible disturbances in the heart ventricular conduction system by using a technique of ventricular activation time (VAT) differences in ESRF children on peritoneal dialysis (PD) with normal electrocardiogram (ECG) examinations. MATERIAL AND METHODS: The study group comprised 10 ESRD children (mean age: 13.6 ± 2.31 years) on peritoneal dialysis - group I. The control group (group II) consisted of 26 age-matched healthy children with no clinical evidence of renal or cardiac disease and with normal 12-lead ECG recordings. Each of the ESRD patients was also subjected to the standard ECG examination. In order to capture possible heart conduction abnormalities, body surface potential mapping (BSPM) recordings were performed in PD patients between the successive dwells ('on empty abdomen') with a HPM-7100 Fukuda Denshi system. Based on the source ECG data, the original technique of a VAT difference map was then applied. RESULTS: Differences between VAT values for the two examined groups of children, controls and ESRD patients on PD, were significantly pronounced in the region of the right upper anterior thorax, the entire left thorax and nearly in the total back. Such a pattern of VAT delays indicates a pathological electric transmission in the intraventricular conduction system of the left anterior fascicle of His bundle. CONCLUSION: 1. VAT maps (isochrone maps) can be useful to detect abnormal spreading and depolarization through the heart ventricles. 2. Map of VAT value differences makes it possible to identify early disturbances in the left His bundle branch in ESRD children treated with peritoneal dialysis regardless of normal 12-lead ECG. 3. Further studies on a larger group of children with ESRD on PD are required to verify the preliminary observations presented herein.

Effects of hemodialysis on ventricular activation time in children with end-stage renal disease.

Patients with end-stage renal disease are affected by cardiovascular complications, including disturbances of the heart intraventricular conduction. Body surface potential mapping is a non-invasive electrocardiographic detection method of initial disturbances in heart activation propagation. A goal of the study was to analyze the effects of single hemodialysis (HD) session on ventricular activation time (VAT) maps obtained from hemodialyzed children. The study group consisted of 13 hemodialyzed children (age: 6-18 years). The control group is composed of 26 healthy subjects. In each HD patient, 12-lead electrocardiogram and echocardiography examinations were performed. Isochrone heart maps, reflecting body surface distribution of VAT isolines, were recorded from an 87-electrode HPM-7100 system for body surface potential mapping, before (group B) and after HD session (group A). The distribution of isochrones and VAT values, as recorded in the HD patients, differed significantly from the reference VAT map for controls. The highest VAT maximal value was noted in group B (Me: 110 vs. 62 ms in the control group; P < 0.001), becoming significantly lower after HD session (Me: 98 ms for group A vs. 110 ms for group B; P < 0.001). Ventricular activation time maps, recorded before HD session, showed significant VAT delays with isochrone arrangement specific for the left bundle branch block. After HD session, VAT maps presented significant changes, suggesting a normalization process. Ventricular activation time maps in children with end-stage renal disease exhibited disturbances of intraventricular conduction within the left bundle branch block, undetectable on standard electrocardiogram. A single HD session resulted in VAT map improvement related to overall HD treatment duration.

SIRT1 and NAD as regulators of ageing.

The recent research on ageing processes in mammals throws new light on the biochemistry of circadian clock. The already known regulatory pathways for biological rhythms and metabolism, combined with newly discovered functions of sirtuins, unveil a perspective for new hypotheses, regarding possible links between ageing and circadian rhythms. The NAD World hypothesis - postulated as a systemic regulatory network for the metabolism and ageing, linked with mammalian, NAD+ dependent Sirtuin 1 - conceptually involves two critical elements. One is the systemic, Nampt-controlled NAD+ (nicotinamide phosphoribosyltransferase) biosynthesis, where Nampt (nicotinamide phosphoribosyltransferase) acts as "propulsion" for metabolism and the other is NAD+ dependent deacetylase (SIRT1) - a regulator responsible for various biological effects, depending on its localisation in organism. In this approach, the role of sirtuins, which are evolutionary conservative, NAD+ dependent histone deacetylases, may be very important for the mammalian metabolic clock. This paper is a review of current research on possible links among SIRT1 (Sirtuin 1), metabolism and ageing with particular consideration of the NAD World hypothesis.

Nephroprotective action of sirtuin 1 (SIRT1)

Sirtuins, silent information regulator 2 (Sir 2) proteins, belong to the family of NAD+-dependent enzymes with deacetylase or mono-ADP-ribosyltransferase activity. These enzymes are responsible for processes of DNA repair or recombination, chromosomal stability and gene transcription. In mammals, sirtuins occur in seven varieties, from 1 to 7 (SIRT1–SIRT7), differing among themselves with location. SIRT1, the best known variety, exerts its effects on proteins via NAD+ coenzymes, being thus associated with cellular energetic metabolism and the ‘red–ox’ state. Its deficits are, among others, concomitant with stressful situations and associated with pathophysiologies of many medical conditions, including diabetes mellitus, cardiovascular diseases, neurodegenerative syndromes and kidney diseases. In kidney disorders, it promotes (stimulates) the survival of cells in an affected kidney by modulating their responses to various stress stimuli, takes part in arterial blood pressure control, protects against cellular apoptosis in renal tubules by catalase induction and triggers autophagy. More and more available in vitro and in vivo data indicate SIRT1 activity to be oriented, among others, towards nephroprotection. Thus, SIRT1 may become a novel element in the therapy of age-related renal diseases, including diabetic nephropathy (AU)

Nephroprotective action of sirtuin 1 (SIRT1).

Sirtuins, silent information regulator 2 (Sir 2) proteins, belong to the family of NAD(+)-dependent enzymes with deacetylase or mono-ADP-ribosyltransferase activity. These enzymes are responsible for processes of DNA repair or recombination, chromosomal stability and gene transcription. In mammals, sirtuins occur in seven varieties, from 1 to 7 (SIRT1-SIRT7), differing among themselves with location. SIRT1, the best known variety, exerts its effects on proteins via NAD(+) coenzymes, being thus associated with cellular energetic metabolism and the 'red-ox' state. Its deficits are, among others, concomitant with stressful situations and associated with pathophysiologies of many medical conditions, including diabetes mellitus, cardiovascular diseases, neurodegenerative syndromes and kidney diseases. In kidney disorders, it promotes (stimulates) the survival of cells in an affected kidney by modulating their responses to various stress stimuli, takes part in arterial blood pressure control, protects against cellular apoptosis in renal tubules by catalase induction and triggers autophagy. More and more available in vitro and in vivo data indicate SIRT1 activity to be oriented, among others, towards nephroprotection. Thus, SIRT1 may become a novel element in the therapy of age-related renal diseases, including diabetic nephropathy.

Skin autofluorescence as a marker of cardiovascular risk in children with chronic kidney disease.

BACKGROUND: We examined skin autofluorescence (sAF) in chronic kidney disease children (CKD) in relation to renal function and dialysis modality. METHODS: Twenty children on hemodialysis (HD), 20 on peritoneal dialysis (PD), 36 treated conservatively, and 26 healthy subjects were enrolled into the study. In all children sAF, pulse-wave velocity indexed to height (PWV/ht), left ventricular mass index (LVMI), blood pressure (BP), serum lipid profile, phosphate (P), calcium (Ca), and homocysteine were measured. RESULTS: sAF was significantly elevated in CKD groups vs. controls and was significantly associated with PWV/ht, LVMI, BP, P, Ca × P product and homocysteine. sAF in HD and PD groups was positively correlated with dialysis vintage, and in the predialysis group negatively correlated with glomerular filtration rate (eGFR). Multiple regression analysis showed significant association of sAF with LVMI and P in the CKD patient group, and with dialysis treatment duration and BP in dialyzed children. CONCLUSIONS: In CKD children, tissue accumulation of advanced glycation end-products (AGEs) was observed. This was aggravated as eGFR declined and was related to early cardiovascular changes and some biochemical cardiovascular disease (CVD) risk markers. sAF as a non-invasive method may be a useful tool for identification of a clinical risk factors of cardiovascular disease in CKD children.

Crossed renal ectopia: can it be a diagnostic problem?

Crossed renal ectopia (C-RE) is a rare congenital anomaly in which both kidneys are located unilaterally. The crossed kidney is situated on the side opposite to its ureteral orifice and usually lies below the normal kidney. The frequency of this malformation is estimated at 0.05% to 0.1%. Most of the patients remain asymptomatic. In other cases C-RE is diagnosed incidentally on routine ultrasonography, due to the presence of unspecific symptoms. The diagnosis of C-RE is possible due to a wide range of imaging techniques: US, IVU, CT, MRI, and TcDMSA scan. Among them IVU, CT, and MRI have the highest degree of confidence. The aim of this retrospective study was to present our own experience with 5 children affected with C-RE, emphasizing the differences in clinical picture and low sensitivity of ultrasound images. In all of them the final diagnosis was established by IVU or MRI.

Heart ventricular activation in VAT difference maps from children with chronic kidney disease.

Children with chronic kidney disease (CKD) are affected by cardiovascular complications, including disturbances in the intraventricular conduction system. Body surface potential mapping (BSPM) is a non-invasive method of assessing the cardioelectrical field. Our aim was to investigate conduction disturbances in young CKD patients using ventricular activation time (VAT) maps. Our study comprised 22 CKD children (mean age: 13.1 ± 2.5 years) treated conservatively and 29 control patients. For each child 12-lead electrocardiogram (ECG) readings were taken, and blood pressure and serum concentrations of iPTH, Pi, t-Ca, creatinine, Fe(+3), ferritin, and Hb, as well as eGFR were measured. All children underwent registration in the 87-lead BSPM system, and group-mean VAT maps and a difference map, which presents statistically significant differences between the groups, were created. The VAT map distribution in CKD patients revealed abnormalities specific to left anterior fascicle block. The difference map displays the areas of intergroup VAT changes, which are of discriminative value in detecting intraventricular conduction disturbances. Intraventricular conduction impairments in the left bundle branch may occur in children with CKD. BSPM enables conduction disturbances in CKD children to be detected earlier than using 12-lead ECG. The difference map derived from the group-mean isochrone maps precisely localizes the sites of disturbed conduction in the heart intraventricular conduction system.