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.

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.

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.

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.

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.

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.

Effect of kidney transplantation on heart conduction disturbances in children treated with chronic hemodialysis--a pilot study.

Aim of the study was to assess the effect of KT on heart conduction in HD children. Non-invasive electrocardiographic method of BSPM was used. Isochrone maps, presenting a VAT distribution, were taken from eight HD patients and 26 normal subjects. Patients were divided into two groups: I--three children were HD <12 months prior to KT; II--five children were HD >12 months prior to KT. After KT, the groups were marked as IP and IIP. Serum iPTH and phosphate levels were significantly higher in both HD groups than in controls, with a considerable normalization after transplantation. HD patients demonstrated neither conduction abnormalities on ECG nor left ventricular hypertrophy. Group-mean VAT maps revealed: I and II--similar patterns of complete LBBB; IP--partial normalization to a pattern of anterior fascicle block; IIP--preserved pattern of LBBB. Intraventricular conduction disturbances found in HD children using BSPM were alleviated by KT. Short HD therapy increases a chance of conduction disturbances regression after KT, contrary to the longer HD treatment. BSPM is more sensitive than standard ECG in detecting heart conduction impairments in the HD patients.

[Genetics of congenital anomalies of the kidney and urinary tract]. / Podloze genetyczne wrodzonych wad nerek i ukladu moczowego.

Congenital anomalies of the kidney and urinary tract (CAKUT) occur at a frequency of 1 in 500 live births and are a common cause of renal insufficiency in childhood. CAKUT encompass a wide spectrum of malformations including anomalies of the kidney, collecting system, bladder and urethra. Most cases of CAKUT are sporadic and limited to the urinary tract, but some of them are syndromic or associated with positive family history. To understand the basis of human renal anomalies, knowledge of kidney and urinary tract development is necessary. This process is very complicated, requires precise integration of a variety of progenitor cell populations of diverse embryonic origins and is controlled by many factors at every stage of development. This review focuses on the genetic factors leading to developmental errors of important morphogenetic processes, particularly in metanephric kidney induction and ureteric bud branching. The essential results of genetic studies in regard to CAKUT, performed on experimental models and in humans, are presented. However, further investigations are required to complete understanding of the complex molecular network, which will help us to determine novel preventive and therapeutic strategies for CAKUT.

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 endogenous modulators of Ca2+-Mg2+-dependent ATPase in children with chronic kidney disease (CKD).

BACKGROUND: Calcium homeostasis is disturbed in many ways in the course of chronic kidney disease (CKD). The concentration of free cytoplasmic calcium in erythrocytes is increased. Maintenance of a high concentration gradient (between the cystoplasmic and extracellular space) is possible only due to a finely tuned cooperation between many regulating systems in the cytoplasmic membranes and cell organelles. The aim of our study was to evaluate the activity of Ca(2+)-Mg(2+)-dependent ATPase (PMCA), calmodulin and calpain-calpastatin (CANP-CAST) system in erythrocytes of CKD children treated conservatively in the stages II-IV. METHODS: A total of 36 patients with CKD were enrolled in the study. Group A contained patients with CKD stage II; group B with CKD stage III; and group C with CKD stage IV. The control group D consisted of 30 healthy subjects. In the serum, we determined the following: intact parathormon, total calcium, creatinine; in the red blood cells: free cytosolic calcium concentration (Ca(i)(2+)), activity of Ca(2+)-Mg(2+)-transporting ATPase (PMCA), basal PMCA (bPMCA), calmodulin (CALM), CANP, CAST. RESULTS: In all groups, Ca(i)(2+) concentrations were significantly higher, whereas PMCA and bPMCA activity were lower than in the controls. CANP concentrations in group A were elevated compared to the controls, whereas in groups B and C they were significantly lower. In group C, the mean CAST activity reached the highest values. CALM concentrations were decreased versus controls in all groups of patients. CONCLUSIONS: The intracellular Ca(i)(2+) homeostasis is disturbed in children with CKD and aggravates the deterioration of renal function as well. The reasons for the progressing increase of erythrocyte calcium concentration are multifactorial. Undoubtedly, the decreased PMCA activity, the calmodulin deficiency and the dysregulated CANP-CAST system are responsible for that phenomenon. The impact of many other biological modulators, creating a network defending the cell against the calcium accumulation, cannot be excluded.

Ca(2+)-Mg (2+)-dependent ATP-ase activity in hemodialyzed children. Effect of a hemodialysis session.

In the course of chronic kidney disease (CKD) the intracellular erythrocyte calcium (Ca (i) (2+) ) level increases along with the progression of the disease. The decreased activity of Ca(2+)-Mg(2+)-dependent ATP-ase (PMCA) and its endogenous modulators calmodulin (CALM), calpain (CANP), and calpastatin (CAST) are all responsible for disturbed calcium metabolism. The aim of the study was to analyze the activity of PMCA, CALM, and the CANP-CAST system in the red blood cells (RBCs) of hemodialyzed (HD) children and to estimate the impact of a single HD session on the aforementioned disturbances. Eighteen patients on maintenance HD and 30 healthy subjects were included in the study. CALM, Ca (i) (2+) levels and basal PMCA (bPMCA), PMCA, CANP, and CAST activities were determined in RBCs before HD, after HD, and before the next HD session. Prior to the HD session, the level of Ca (i) (2+) and the CAST activity were significantly higher, whereas bPMCA, PMCA, and CANP activities and the CALM level were significantly lower than in controls. After the HD session, the Ca (i) (2+) concentration and the CAST activity significantly decreased compared with the basal values, whereas the other parameters significantly increased, although they did not reach the levels of healthy children. The values observed prior to both HD sessions were similar. Ca (i) (2+) homeostasis is severely disturbed in HD children, which may be caused by the reduction in the PMCA activity, CALM deficiency, and CANP-CAST system disturbances. A single HD session improved these disturbances but the effect is transient.

Usefulness of body surface potential mapping for early identification of the intraventricular conduction disorders in young patients with chronic kidney disease.

BACKGROUND: Cardiovascular complications are considered a significant problem in patients with chronic kidney disease (CKD). Body surface potential mapping (BSPM) is a noninvasive method that is useful in detecting early changes involving the heart. The aim of the study was to evaluate possible abnormalities within the cardiac intraventricular conduction system in young patients with CKD using the BSPM method. METHODS: Based on the BSPM registrations, the QRS-T isointegral maps were created in 42 young patients with CKD (on hemodialysis, subgroup Ia; on peritoneal dialysis, subgroup Ib; on conservative treatment, group II) and in 26 healthy subjects. Serum levels of electrolytes, urea, and creatinine were also assessed in the entire study population. RESULTS: In the healthy subjects, the maximums of the group mean QRS-T isointegral map were located in the left lower anterior part of the thorax, whereas in the Ia patients, the maximums were focused at the medial sternum line. The QRS-T maps, both for Ib and II groups, showed the positive integrals covering the left part of the anterior thorax. In all the patients with CKD, standard 12-lead electrocardiogram (ECG) and echocardiography findings were within the reference range. CONCLUSIONS: In the hemodialyzed patients with CKD, the group-mean QRS-T isointegral map distribution suggested a significant delay of excitation propagation in the left bundle branch, although no abnormalities were found with standard ECG. In the patients with CKD treated with peritoneal dialysis or conservatively, the group-mean QRS-T isointegral maps were characteristic for the early phase of conduction disturbances within the left bundle branch, which again was not observed on the standard ECG recordings.

[The influence of hemodialysis on heart's intraventricular conduction system--pilot study]. / Wplyw zabiegu hemodializy na uklad bodzco-przewodzacy serca u dzieci i mlodziezy--badanie pilotazowe.

UNLABELLED: The highest percent of cardiac muscle damages is written down in children which are exposed to hemodialysis. In this group the heart examinations using body surface heart potential mapping (BSPM) method have been carried out. The aim of the study was to assess the influence of hemodialysis on heart's electrodynamics in children and adolescent during replacement therapy. MATERIAL AND METHODS: Multielectrode recording have been done in every kid before and after hemodialysis. For every record it was created isopotential map. By the comparing our maps with model maps for healthy children it was affirmed that in greater part of studied examples of hemodialysed children there are present early changes indicating conducting disturbances in left bundle of fasciculus atrioventricularis (His) and initial stage of left ventricular hypertrophy (LVH). That changes haven't been confirmed in classic ECG, which suggests that the disturbances in excitation conductance observed on isointegral maps are far beyond the area detected by 12-electrode classic ECG recording. RESULTS: The maps made before dialysis are characterised by large, unsymmetrical isopotential lines changes over the left and right ventricle. After carried out of hemodialysis the image of ECG records was improving. In all of cases the isoline distribution in sternal and anterior lower left part of chest comes back to norm. Changes are visible merely over the left ventricle and in anterior upper right part of chest what is connected with just stabilised conducting disturbances in the left branch of His bundle, left bundle of fasciculus atrioventricularis (His bundle). CONCLUSIONS: 1. In children who are treated by repeated hemodialysis approach to disturbances in the cardiac intraventricular conduction system. 2. Those disturbances are improved by a singular hemodialysis. 3. BSPM method detects earlier changes in the cardiac intraventricular conduction system than the classical ECG.

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.