Case-inspired exploration of renin mutations in autosomal dominant tubulointerstitial kidney disease: not all paths lead to the endoplasmic reticulum.

BACKGROUND: Autosomal dominant tubulointerstitial kidney disease (ADTKD) results from mutations in various genes, including REN, UMOD, MUC1, and HNF1B. ADTKD due to REN mutations (ADTKD-REN) is often characterized as a proteinopathy that triggers the endoplasmic reticulum stress (ERS) cascade, potentially sharing similarities with ADTKD-UMOD and ADTKD-MUC1 at the cellular level. This study, inspired by a patient harboring a W17R mutation, investigates ERS activation by this mutation alongside two other renin variants, W10R and L381P. METHODS: We established stable cell lines expressing both wild-type and mutated renin forms (W17R, W10R, and L381P). Using luciferase reporter assays, RT-qPCR, and confocal microscopy, we evaluated ERS activation, determined the cellular localization of the renin variants, and characterized the mitochondrial network in the W17R line. RESULTS: The L381P line exhibited ERS activation, including transcriptional upregulation of MANF and CRELD2. No ERS activation was observed in the W17R line, while the W10R line exhibited intermediate characteristics. Notably, the W17R variant was misrouted to the mitochondria resulting in changes of the mitochondrial network organisation. CONCLUSIONS: ERS activation is not a universal response to different renin mutations in ADTKD-REN. The pathogenesis of the W17R mutation may involve mitochondrial dysfunction rather than the ER pathway, albeit further research is needed to substantiate this hypothesis fully. Testing CRELD2 and MANF as targeted therapy markers for a specific subgroup of ADTKD-REN patients is recommended. Additionally, fludrocortisone treatment has shown efficacy in stabilizing the renal function of our patient over a four-year period without significant side effects.

Outcomes of steroid-resistant nephrotic syndrome in children not treated with intensified immunosuppression.

BACKGROUND: The aim of the current PodoNet registry analysis was to evaluate the outcome of steroid-resistant nephrotic syndrome (SRNS) in children who were not treated with intensified immunosuppression (IIS), focusing on the potential for spontaneous remission and the role of angiotensin blockade on proteinuria reduction. METHODS: Ninety-five pediatric patients who did not receive any IIS were identified in the PodoNet Registry. Competing risk analyses were performed on 67 patients with nephrotic-range proteinuria at disease onset to explore the cumulative rates of complete or partial remission or progression to kidney failure, stratified by underlying etiology (genetic vs. non-genetic SRNS). In addition, Cox proportional hazard analysis was performed to identify factors predicting proteinuria remission. RESULTS: Eighteen of 31 (58.1%) patients with non-genetic SRNS achieved complete remission without IIS, with a cumulative likelihood of 46.2% at 1 year and 57.7% at 2 years. Remission was sustained in 11 children, and only two progressed to kidney failure. In the genetic subgroup (n = 27), complete resolution of proteinuria occurred very rarely and was never sustained; 6 (21.7%) children progressed to kidney failure at 3 years. Almost all children (96.8%) received proteinuria-lowering renin-angiotensin-aldosterone system (RAAS) antagonist treatment. On antiproteinuric treatment, partial remission was achieved in 7 of 31 (22.6%) children with non-genetic SRNS and 9 of 27 children (33.3%) with genetic SRNS. CONCLUSION: Our results demonstrate that spontaneous complete remission can occur in a substantial fraction of children with non-genetic SRNS and milder clinical phenotype. RAAS blockade increases the likelihood of partial remission of proteinuria in all forms of SRNS. A higher resolution version of the Graphical abstract is available as Supplementary information.

Multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab in children with steroid-resistant nephrotic syndrome.

The aim of the study was a multicenter analysis of the efficacy and safety of a non-standard immunosuppressive therapy with rituximab (Rtx) in children with steroid-resistant nephrotic syndrome (SRNS) with particular emphasis on the possibility of permanent discontinuation or dose reduction of other immunosuppressive drugs such as glucocorticoids and cyclosporine A after 6 months of observation. The study group consisted of 30 children with idiopathic nephrotic syndrome, who were unresponsive to standard immunosuppressive treatment, and hospitalized in the years 2010-2017 in eight paediatric nephrology centres in Poland. The children were administered a single initial infusion of rituximab at the dose of 375 mg/m2 of the body surface area. Proteinuria, the daily supply of glucocorticoids, and cyclosporine were assessed at the moment of the start of the treatment and after 6 months since its commencement. Before Rtx therapy, complete remission was found in 13 patients (43%) and partial remission was found in 8 patients (26%). These numbers increased to 16 (53%) and 12 (40%), respectively. At the start of the treatment 23 patients (76.6%) were treated with cyclosporine A. After 6 months, this number decreased to 15 patients (35%). At the start of the treatment, 18 patients (60%) were treated with prednisone. After 6 months, this number decreased to 8 patients (44%). Children with SRNS may potentially benefit from Rtx treatment despite relative risk of side effects. The benefits may include reduction of proteinuria or reduction of other immunosuppressants.

What has changed in the prevalence of hypertension in dialyzed children during the last decade?

BACKGROUND: Hypertension very often accompanies progression of chronic kidney disease (CKD) in children. A cross-sectional analysis of hypertension prevalence in dialyzed children in Poland was designed with a comparison with the data previously recorded 10 years earlier. METHODS: Two cohorts of children were analyzed: 59 subjects dialyzed in 2013, and 134 children from the previous study performed in 2003 that were reevaluated according to the current methodology. The incidence of hypertension (defined by SDS of sBP or dBP >1.64), clinical data, medical history, dialysis modalities and selected biochemical parameters of dialysis adequacy were analyzed. RESULTS: The prevalence of hypertension increased from 64% in 2003 to 78% in 2013. The efficacy of antihypertensive treatment remained unsatisfactory (61% proper BP control). Preservation of residual urine output and strict fluid balance may prevent development of hypertension in children on dialysis. CONCLUSIONS: Despite the higher awareness of hypertension and its complications in dialyzed children, the incidence of this entity has increased during the last decade, with the percentage of undertreated patients comparable to that observed 10 years ago. Thus, more attention should be paid to therapy efficacy in this population to prevent further damage to the cardiovascular system and to decrease morbidity.

Depressive disorders in children with chronic kidney disease treated conservatively.

BACKGROUND: Children with chronic kidney disease (CKD) experience a lot of mental and emotional stress, which can lead to the development of depressive disorders. The prevalence of depressive disorders in CKD children is estimated to be between 7% and 35%. OBJECTIVES: The aim of our study was to analyze the prevalence and characteristics of depression and depressive symptoms in children and adolescents with CKD treated conservatively. MATERIAL AND METHODS: The cross-sectional, multicenter study was conducted in 73 CKD children aged 8-18 and in 92 of their parents. To assess the mental wellbeing of CKD children, Kovacs's Children's Depression Inventory 2 (CDI2) was used as CDI2: Self-Report and CDI2: Parent Form. RESULTS: The majority of CKD children acquired medium scores in CDI2, 11% of participants reported symptoms suggesting depressive disorder, and among them 8.2% met the criteria for depression. A significant relationship was found between age and interpersonal problems, age at CKD diagnosis, and total score and ineffectiveness, CKD duration and total score/emotional problems. Depressive symptoms were associated with the stage of CKD, and they differed significantly between stages III and IV. We noticed the child-parent disagreement on reported depressive symptoms. Parents perceive their children's mental state as worse than the children themselves. CONCLUSIONS: There is a problem of depression in children with CKD treated conservatively. Variables associated with depressive symptoms in CKD children treated conservatively require further study. Key factors predisposing to the development of depression seem to be age at the time of diagnosis, disease duration, and progression of CKD from stage III to IV. Disparities between depressive symptoms self-reported by CKD children and their parents' assessment require further analysis. However, these disparaties indicate that the final diagnosis of the occurrence of depressive disorders should be based on a multidimensional assessment of the patient's situation.

Genetic screening in adolescents with steroid-resistant nephrotic syndrome.

Genetic screening paradigms for congenital and infantile nephrotic syndrome are well established; however, screening in adolescents has received only minor attention. To help rectify this, we analyzed an unselected adolescent cohort of the international PodoNet registry to develop a rational screening approach based on 227 patients with nonsyndromic steroid-resistant nephrotic syndrome aged 10-20 years. Of these, 21% had a positive family history. Autosomal dominant cases were screened for WT1, TRPC6, ACTN4, and INF2 mutations. All other patients had the NPHS2 gene screened, and WT1 was tested in sporadic cases. In addition, 40 sporadic cases had the entire coding region of INF2 tested. Of the autosomal recessive and the sporadic cases, 13 and 6%, respectively, were found to have podocin-associated nephrotic syndrome, and 56% of them were compound heterozygous for the nonneutral p.R229Q polymorphism. Four percent of the sporadic and 10% of the autosomal dominant cases had a mutation in WT1. Pathogenic INF2 mutations were found in 20% of the dominant but none of the sporadic cases. In a large cohort of adolescents including both familial and sporadic disease, NPHS2 mutations explained about 7% and WT1 4% of cases, whereas INF2 proved relevant only in autosomal dominant familial disease. Thus, screening of the entire coding sequence of NPHS2 and exons 8-9 of WT1 appears to be the most rational and cost-effective screening approach in sporadic juvenile steroid-resistant nephrotic syndrome.

Anxiety in children and adolescents with chronic kidney disease--multicenter national study results.

BACKGROUND/AIMS: Chronic medical illness is a significant risk factor for the development of psychiatric disorders. The aims of the study were: to investigate the level of anxiety in children with chronic kidney disease (CKD) and to identify factors associated with the presence of that emotional problem. METHODS: CKD children on hemodialysis (HD, n=22), peritoneal dialysis (PD, n=20,) and on conservative treatment (CT, n=95) were enrolled in the study. We used State-Trait Anxiety Inventory (STAI) for adolescents and STAI-C for children. Socio-demographic and physical factors were assessed. RESULTS: There was a significantly higher level of anxiety-state among HD children (8-12 years) compared with other groups of participants of the same age and Polish population norms. The level of anxiety among adolescents (13-18 years), both anxiety-state and anxiety-trait, was significantly higher in the HD group compared with other groups, which did not differ among themselves. In the HD adolescents, there was a correlation between the anxiety-state and the duration of the disease as well as with the number of hospitalizations. PD adolescents in the mainstream education had higher levels of anxiety-state and anxiety-trait compared with home schooled patients. CONCLUSIONS: Even though children and adolescents with CKD are at risk of developing a variety of emotional disorders, the level of anxiety among the researched group, with the exception of HD patients, was not significantly different than the level of anxiety among healthy subjects. Adolescents on HD who present a high level of anxiety should undergo long-term psychological treatment.

Psychosocial aspects of children and families of children treated with automated peritoneal dialysis.

BACKGROUND: The aim of this study was to analyze psychosocial aspects of chronic kidney disease (CKD) in children treated with automated peritoneal dialysis (APD). METHODS: The study assessed 41 children > 2 (range 2.1-18) years of age and their parents. Data concerning the illness and sociodemographic parameters were collected. Patients completed the Paediatric Quality of Life Inventory (PedsQL) and their parents the PedsQL-proxy version, General Health Questionnaire (GHQ-12), Berlin Social Support Scales (BSSS), and Caregiver's Burden Scale (CBS). RESULTS: Parents rated their children's overall health-related quality of life (QoL) as well as their physical and emotional functioning lower than the patients themselves. The majority of primary caregivers had a medium level of the total burden index in the CBS and higher values in the scales need for support and perceived available support than in the received support (BSSS). In the GHQ-12, 51.2% of primary caregivers had scores >2 points, which indicated the possible occurrence of abnormal mental functioning. CONCLUSIONS: Financial support for patients' families is necessary. Parents who provide primary care to children on PD require, above all, emotional support and assistance in self-fulfilment. More than half of them may have impaired mental function. There is the strong need to provide continuous psychological care for caregivers. Differences in perception of the children's activity in varied areas by the patients themselves and their caregivers may contribute to further problems within families.

Perception of health-related quality of life in children with chronic kidney disease by the patients and their caregivers: multicentre national study results.

OBJECTIVE: The aim of the study was to analyse the health-related quality of life (HRQoL) in Polish children with chronic kidney disease (CKD) dependant on the CKD stage, treatment modality and selected social life elements in families of the patients. Furthermore, potential differences between self-report and parent/proxy reports and the factors influencing them were assessed. METHODS: A total of 203 CKD children (on haemodialysis (HD), peritoneal dialysis (PD) and conservative treatment (CT)) and their 388 parent/proxies were enrolled into a cross-sectional national study. The demographic and social data were evaluated. We used the Paediatric Quality of Life Inventory 4.0 Generic Core Scales to assess the HRQoL in children. RESULTS: Health-related quality of life scores for all CKD groups were significantly lower in all domains compared with population norms, the lowest one being in the HD group. In CT children, HRQoL did not depend on the CKD stage. Both parents assessed the HRQoL of their children differently depending on their involvement in the care. There are differences between the HRQoL scores of the children and their parents. CONCLUSION: The HRQoL in children with CKD is lower than in healthy children. This is already observed in the early stages of the disease. The disease itself influences the child's mental state. Children on HD require special support on account of the lowest demonstrated overall HRQoL. Children's lower rating of the quality of life observed by their parents may render the patients unmotivated and adversely affect their adjustment to life in later years. It may also create conflicts between the parents and the children.

Alpha-1 Acid Glycoprotein and Podocin mRNA as Novel Biomarkers for Early Glomerular Injury in Obese Children.

INTRODUCTION: Obesity, which is a serious problem in children, has a negative impact on many organs, including kidneys, and obesity-related glomerulopathy (ORG) is an increasingly common cause of ESKD (end-stage kidney disease) in adults. Early-detected and -treated glomerular lesions are reversible, so it is important to find a useful marker of early damage. The study aimed to evaluate the albumin-to-creatinine ratio (ACR), urinary alpha-1-acid glycoprotein (α1-AGP), and mRNA of podocyte-specific proteins as indicators of glomerular injury and their relationship with the degree of obesity and metabolic disorders. MATERIALS AND METHODS: A total of 125 obese children and 33 healthy peers were enrolled. Patients were divided into two groups, depending on SDS BMI values. ACR, α1-AGP, mRNA expression of nephrin, synaptopodin, podocin, and C2AP protein in urine sediment were measured. RESULTS: ACR values did not differ between groups and were within the normal range. α1-AGP and mRNA expression were significantly higher in obese children compared with controls. mRNA expression of the remaining podocyte proteins was similar in both groups. No significant differences concerning all examined parameters were found depending on the degree of obesity. There was a positive significant correlation between α1-AGP and ACR. CONCLUSIONS: Increased α1-AGP before the onset of albuminuria suggests its usefulness as a biomarker of early glomerular damage in obese children. An increased podocin mRNA expression also indicates podocyte damage and may be linked to ORG development. The lack of increase in expression of other podocyte proteins suggests that podocin mRNA may be a more specific and sensitive biomarker. The degree of obesity has no impact on the tested parameters, but further studies are needed to confirm it.

Kidney transplantation and other methods of renal replacement therapy in children: 30 years of observations in one center.

BACKGROUND: Kidney transplantation (Tx) is regarded as the optimal treatment method for renal replacement therapy (RRT) for end-stage renal disease (ESRD) patients. Children qualified for Tx should receive the organ as soon as possible in order to improve their chances for healthy development. In our center, RRT for children with ESRD has been conducted for 36 years: hemodialysis (HD) since 1982, peritoneal dialysis (PD) since 1992 and the first transplant in 1987. OBJECTIVES: To analyze the rates of different RRT methods in children with ESRD. Special attention was paid to Tx. MATERIAL AND METHODS: We compared the rates of RRT methods over 3 subsequent decades (1987-1996, 1997-2006 and 2007-2017). RESULTS: In the period analyzed, 153 children aged from 2 weeks to 18 years were dialyzed. The mean age of the start of RRT was 9.4 years. In 80 children (52.2%), first method was HD, while in 73 patients (47.7%) it was PD. In 25 children, the type of dialysis was changed. Kidney transplantation was performed in 40%, 60.34% and 73% of patients dialyzed in the periods 1987-1996, 1997-2006 and 2007-2017, respectively. The average waiting time for a transplant in the abovementioned decades was 2.25 years, 2.65 years and 1.97 years, respectively. Three children underwent transplantation with a family donor; 1 boy received a transplanted kidney and liver. Two children underwent a preemptive transplant from a deceased donor. CONCLUSIONS: The percentage of children with ESRD treated with Tx continues to increase, but in our assessment, it still remains too low. Among the types of dialysis, PD was much more frequently used, which is consistent with pediatric recommendations. Small number of transplants from a living donor and preemptive transplants indicates the need to promote organ donation in Polish society.

[Serum adiponectin and resistin level in children with idiopathic nephrotic syndrome]. / Stezenie adiponektyny i rezystyny we krwi u dzieci ze steroidowrazliwym idiopatycznym zespolem nerczycowym.

UNLABELLED: The adipose tissue was recognized as an active endocrine organ. The adipopkines seem to play an important role in the modulation of inflammatory response and have a pleiotropic function. The aim of this study was to evaluate serum resistin and adiponectin level in children with idiopathic nephrotic syndrome (INS). MATERIALS AND METHODS: 39 children with INS aged 2.5-17 year (mean 9.35 +/- 5.6), 15 children in relapse, 24 in remission and 8 healthy were included into the study. Serum total protein, albumin, cholesterol, daily proteinuria and BMI were measured in children with INS. Serum resistin and adiponectin levels were determined by ELISA. RESULTS: Increased resistin and adiponectin levels were observed during relapse and remission of INS, compared to controls. No significant difference between adipocytokines in relapse and remission INS was found. Serum resistin level decreased in remission of INS, compared to relapse, but the value did not reach statistical significance. Between resistin and cholesterol, resistin and proteinuria positive correlation was found. Negative correlation between resistin and serum albumin was observed. CONCLUSION: Increased serum level of resistin and adiponectin was observed in children with relapse of INS or in early phase of remission. These finding suggests that they may play a role in the pathogenesis of INS in children. It requires further investigation based on a broad study.

Interleukin-18 in urine and serum of children with idiopathic nephrotic syndrome.

BACKGROUND/AIMS: Interleukin (IL)-18, a member of the IL-1 cytokine superfamily, is recognized as an important regulator of immune responses. The aim of our study was to investigate the IL-18 levels in serum and urine from children with idiopathic nephrotic syndrome (INS) during relapse and remission, and to evaluate the role of IL-18 in this disease. METHODS: 67 children with INS, aged 3-16 years, and 15 normal controls were included in the study. The patients were divided into two groups according to activity of the disease: I (n = 37) - INS in relapse, II (n = 30) - INS in remission. Serum and urinary IL-18 were determined by ELISA and in urine related to the urinary creatinine (Cr) concentration. Serum creatinine, protein, albumin and 24-hour proteinuria were measured in children with INS. RESULTS: Urinary IL-18 concentration was significantly higher in group I (213.51 +/- 162.15 pg/mg Cr) compared to group II (64.74 +/- 10.95 pg/mg Cr) and to normal controls (37.03 +/- 4.1 pg/mg Cr, p < 0.001). Serum IL-18 concentration was significantly higher in group I than in the controls (146.4 +/- 30.2 and 113 +/- 10 pg/ml, respectively; p < 0.05); the differences between either groups I and II or group II and controls were not significant. Urinary IL-18 correlated positively with serum IL-18 and with urinary protein excretion, but no correlations were found with other laboratory data. CONCLUSION: Increased serum and urine IL-18 levels were observed during relapse of INS. These findings indicate the association between the active phase of INS and the levels of IL-18 and can suggest the role of this cytokine in the INS development. The changes in urinary IL-18 excretion in the course of INS are connected with the disease activity.

[Carriage of Streptococcus pneumoniae in nasopharynx in children with nephrotic syndrome aged 2-5 years in Poland]. / Nosicielstwo nosogardiowe Streptococcus pneumoniae u dzieci w wieku 2-5 lat z zespolem nerczycowym w Polsce.

Children with nephrotic syndrome (NS) are at increased risk of Streptococcus pneumoniae infections. Streptococcus pneumoniae carrier state in the nasopharynx is an early stage of this infections. The aim of the study was to assess carriage rate and characterise bacterial isolates of Streptococcus pneumoniae among children with NS in a prospective multicentre study involving 10 nephrologic centres in Poland. We studied 95 children including 56 boys (59%) i 39 girls (41%) with NS in mean age 3 i 7/12 +/- 11 miesiecy. All children had throat and nasopharynx swabs taken in two epidemiological seasons (Oct-Dec 2006 and Feb-Apr 2007). Streptococcus pneumoniae isolates were serotyped with PCR. Carriage of Streptococcus pneumoniae was diagnosed in 13 children (13.7%) including 13 boys (100%). Following serotypes were found: 6B (38.5%), 9V (15.3%), 23F (15.3%), 19F (7.6%). There were 23.3% isolates without identifiable serotype. Carriage of Streptococcus pneumoniae was diagnosed mostly in boys with NS. Serotype 6B was dominant in this age group.

[Hearing organ function in children with nephrotic syndrome in the course of primary glomerulopathy]. / Stan czynnosciowy narzadu sluchu w zespole nerczycowym w przebiegu pierwotnej glomerulopatii u dzieci.

UNLABELLED: Nephrotic syndrome (NS) is connected with an increase of glomeral permeability. It generates numerous, reversible electrolic and biochemical disturbances. THE AIM of the work was complex evaluation of hearing organ in children in the course of NS. MATERIAL: 28 children aged from 7 to 17 years suffering from primary glomerulopathy, without renal failure and 28 healthy children in the relative age (control group). METHOD: In children with NS hearing tests (pure tone audiometry, impedance audiometry, BAEP, DPOAE) have been performed twice: in acute phase and in non-symptomic phase. Such parameters as total protein, albumines, globulins, cholesterol, sodium, potassium, calcium, magnesium were evaluated. RESULTS: In oedematous stage the concentration of total protein, albumines and calcium were significantly decreased and the concentration of cholesterol was increased. Children with NS presented much worse hearing than healthy subjects, even after the symptoms dissapeared in acute phase such parameters of BAEP as peak III latency and interpeak I-III interlatency were elongated and DPOAE values were decreased. In normal phase BAEP parameters were similar to those in normal group but DPOAE parameters were still much worse than in healthy children. Some of the biochemical parameters correlated with hearing results in children with NS. CONCLUSIONS: Hearing organ in children with NS in the course of chronic glomerulopathy is significantly worse than in healthy children. It is probably connected with repeated biochemical and electrolytic disturbances that cause partly reversible alterations in the cochlea, acoustic nerve and brain stem. It may be also caused by ototoxic drugs.

Psychosocial aspects of children and families treated with hemodialysis.

INTRODUCTION: The aim of this study was to analyze the selected psychosocial aspects of chronic kidney disease in children treated with hemodialysis (HD). METHODS: The study included 25 children treated with HD aged 2 to 18 years and their parents. Data concerning the illness and socio-demographic parameters was collected. We used the Paediatric Quality of Life Inventory (PedsQL) for patients and for their parents the PedsQL-proxy version, General Health Questionnaire (GHQ-12), Berlin Social Support Scales (BSSS), and the Caregivers Burden Scale (CBS) to evaluate health-related quality of life (QoL) of HD children and their primary caregivers. FINDINGS: In the PedsQL test, the QoL of HD children was lower than in healthy children. Children treated with HD assessed their QoL on the PedsQL questionnaire higher than the primary caregivers, on all subscales as well as an overall health-related QoL. Scoring below 2 on the GHQ-12 test was reported in 56% of mothers, which may indicate that psychological symptoms have intensified. There was no correlation between BSSS, CBS, and GHQ-12. DISCUSSION: The assessment of QoL in pediatric patients would allow for the earliest possible identification of their nonsomatic problems and irregularities. This could, consequently, contribute to improving QoL in both children with chronic kidney disease and their families.

Antihypertensive treatment prescription in pediatric dialysis patients in Poland: A comparison between two nationwide studies 2003/2004-2013.

BACKGROUND: Blood pressure in pediatric dialyzed patients is under poor control. OBJECTIVES: The aim of the study was to assess the strategy and efficacy of antihypertensive drugs used for the treatment of hypertension in pediatric dialyzed patients in 2013 in comparison with the data collected in 2003/2004. The results have been viewed against present strategies of antihypertensive treatment in children. There is still limited data concerning the treatment of hypertension in dialyzed pediatric patients. MATERIAL AND METHODS: The study embraced 10 of 12 pediatric dialysis units in Poland treating 59 pediatric patients (mean age - 132 months). Collected information included present antihypertensive treatment with regard to drug classes and the dose of antihypertensive agent. The treatment was regarded as effective if both systolic and diastolic values of blood pressure were below 1.64 SDS. The results from 2013 were juxtaposed with previously analyzed data from a similar study on hypertension in dialyzed children conducted in 2003/2004. RESULTS: Forty subjects have been provided with antihypertensive treatment. In monotherapy and polytherapy 50% of the subjects were treated with ACEI (enalapril and ramipril), 67.5% with amlodipine, 50% with beta-blockers. Only 10% of the subjects were treated with angiotensin II receptor blocker (losartan). Thirty percent of the subjects received furosemide, whereas 5% were given doxazosin. Antihypertensive drugs regarded as the 2nd and 3rd choice in treating high blood pressure (doxazosin, beta-blockers and furosemide) were applied as monotherapy in 46% of the patients. Satisfactory control of treated blood pressure was reached in 45% of them. CONCLUSIONS: Antihypertensive treatment in dialyzed children did not change significantly during the last decade with regard to the groups of drugs being used. Despite a wider feasibility of antihypertensive substances, the effectiveness of this therapy was still unsatisfactory.

[Blood and urine endothelin and nitric oxide levels in predialysis children with chronic renal failure]. / Stezenie endoteliny i tlenku azotu we krwi i w moczu u dzieci z przewlekla niewydolnoscia nerek leczonych zachowawczo.

UNLABELLED: Endothelial dysfunction was observed in patients with chronic renal failure (CRF). Endothelial cells produce a lot of factors among them endothelin and nitric oxide. The aim of this study was to evaluate the plasma/serum and urine levels of edothelin 1 (ET 1) and nitric oxide (NO) in children with CRF treated conservatively. 52 children (23 girls and 29 boys) aged 2-20 years (mean 13.19 years) were enrolled into the study. Patients were divided into 2 groups according to the creatinine level: group I--children with CRF and creatinine level below 265.2 micromol/l, group II CRF children with creatinine level above 265.2 micromol/l. We evaluated serum and urine metabolites of NO (nitrates + nitrites). IN CONCLUSION: in children with chronic renal failure elevated level of ET1 and enhanced excretion of ET1 were observed. Decreased plasma and urine NOx levels were found in CRF children. The disorders are connected with progression of renal failure.

[Interleukin-17 concentration in serum and urine of children with idiopathic nephrotic syndrome]. / Stezenie interleukiny-17 w surowicy i w moczu dzieci z idiopatycznym zespolem nerczycowym.

UNLABELLED: T-cells and their cytokines play an important role in the pathogenesis of idiopathic nephrotic syndrome (INS) in children. IL-17 secreted by activated CD4+ Tcells induces production of proinflammatory mediators, enhances T-cell-mediated immune responses and Th1 type reactions. The aim of the study was to evaluate IL-17 concentrations in serum and urine of children with INS and determine the possible role of this cytokine in the course of disease. PATIENTS AND METHODS: 67 children with INS, aged 3 to 16 years (mean 9 +/- 4) and 15 normal controls were included in the study. The patients were divided into 2 groups according to activity of the disease: I (n=37)--INS in relapse, II (n=30)--INS in remission. Serum (s) and urinary (u) IL-17 were determined by immunoenzymatic method. In children with INS serum biochemical parameters, clearance of endogene creatinine and 24 hour proteinuria were measured. RESULTS: sIL-17 and uIL-17 concentrations (51.66 +/- 8.38 pg/mg and 56.29 +/-14.24 pg/mg creatinine (cr), respectively) were significantly higher (p<0.001) in group I compared with group II (35.7 +/- 10.18 pg/ml and 17.47 +/- 3.46 pg/mg cr) and normal controls (27.17 +/- 1.87 pg/ml and 13.91 +/- 1.22 pg/mg cr). UIL-17 correlated positively with sIL-17 (r=0.783, p<0.0001). A positive correlations between uIL-17 and sIL-17 and urinary protein excretion were found (r=0.58, r=0.42, respectively; p<0.05). IN CONCLUSION: elevated serum and urinary IL-17 levels in children with relapse of nephrotic syndrome suggest the role of IL-17 in the pathophysiology of INS. IL-17 concentrations in serum and urine may reflect the disease activity of INS.

Growth and nutritional status in children with chronic kidney disease on maintenance dialysis in Poland.

PURPOSE: Despite vast availability of modern methods of treatment of chronic kidney disease and its complications, the short stature still is a major point of concern in adolescents with chronic kidney disease. The aim of the study was to assess changes in growth and nutritional status of Polish children on renal replacement therapy in the decade, 2004-2013. MATERIAL AND METHODS: The study was designed as a cross-sectional analysis of anthropometric values and selected indices of growth status amongst children receiving dialysis in Poland between the years 2004 and 2013. Data were acquired during two different multicentre studies on hypertension in dialyzed children in Poland. Basic anthropometric parameters (body weight, body height/length, body mass index - BMI), dialysis adequacy and duration of RRT were assessed. RESULTS: The study showed that anthropometric parameters of children undergoing renal replacement therapy had not significantly changed in the last 10 years of observation. Children on RRT were still of short stature despite availability of modern methods of hormonal therapy and nutrition. Median of height z-score was -2.10 in 2004 and -2.19 in 2013. Expected clinical improvement in these measures was not proven. CONCLUSIONS: The cause of chronic kidney disease, method of dialysis, time on dialysis or dialysis adequacy did not influence the anthropometric parameters significantly in dialyzed children in Poland.