Measurement of Urea in the Saliva of Healthy Mice - a Pilot Study.

Salivary urea is studied as a non-invasive alternative for screening and monitoring of renal diseases. Its high variability prevents a wider clinical use. Animal experiments are needed to identify factors affecting this marker. The aim of this study was to describe the inter-individual variability of salivary urea in healthy mice, establish reference intervals, and analyse the effects of sex, age and body weight. Plasma and saliva samples were obtained from 37 male and 41 female healthy adult CD1 mice aged 13-69 weeks (body weight 22-51 g). The reference interval for salivary urea in heathy mice based on our results is 2.7-8.4 mmol/l (CV = 23 %). Multivariate analysis did not show any significant effect of age, sex, or body weight. In addition, salivary urea did not correlate with its plasma concentrations. The high variability of the promising salivary marker of kidney function in healthy mice requires further research before its use to diagnose or monitor renal failure in animal models of kidney diseases. Other potential confounders should be analysed, including intra-individual and pre-analytical variability. In addition, a normalization factor such as total salivary proteins or salivation rate is likely needed.

Increasing incidence of type 1 diabetes mellitus in young children in Slovakia.

OBJECTIVES: We aimed to study the prevalence of the early onset Type 1 diabetes in Slovakia during the years 1996-2017. BACKGROUND: Prevalence of Type 1 diabetes in young children is increasing worldwide. However, recent data from Slovakia are missing. METHODS: All children with newly diagnosed Type 1 diabetes included in the study were diagnosed in the Children Diabetes Centre in Bratislava during the years 1996-2017. The incidence of T1D in children aged below 3 and below 5 years was calculated and compared to the T1D incidence in older children. Incidence trends were calculated with the Poissed regression. RESULTS: Gender-adjusted incidence of T1D annually increased by 5.4 % (CI: 3.9-6.8; p < 0.001) in children <3 years, and by 3.4 % (95 % CI 2.2-4.6; p<0.001) in children <5 years during the last two decades. Moreover, the proportion of young children <3 years of age among all newly diagnosed children and adolescents increased over time (4.2±2.8 % in years 1996-1998; 12.2±5.8 % in years 2004-2008, and 13.7±7.4 % during the years 2013-2017). CONCLUSION: We found a significant increase in the incidence and proportion of T1D in young children during the last two decades. Similar data were also found in other European countries. This could be explained by changing environmental conditions (Fig. 1, Ref. 32).

Vitamin D status in apparently healthy medication-free Slovaks: Association to blood pressure, body mass index, self-reported smoking status and physical activity.

BACKGROUND: Vitamin D plays a role in protecting against chronic degenerative diseases. Slovak adults present one of the highest cardiovascular mortality rates among 27 EU countries. OBJECTIVES: We asked whether the 25(OH)D3 status in apparently healthy medication-free Slovaks deteriorates upon ageing, and in the presence of cardiometabolic risk factors. METHODS: We studied the impact of blood pressure, overweight/obesity, smoking, and physical activity on 25(OH)D3 levels determined using RIA method in 578 (5-81 years old) subjects. RESULTS: The average level of 25(OH)D3 was 36±17 ng/ml. A proportion of 15 % of participants were 25(OH)D3­deficient (≤20 ng/ml), 26 % presented insufficient (20-to-30 ng/ml), and 59 % satisfactory (> 30 ng/ml) levels. Neither mean 25(OH)D3 levels, nor the prevalence of hypovitaminosis D showed age dependence. Physically active normotensive non-smokers presented the highest (41±19 ng/ml), and their smoking counterparts with elevated BP the lowest 25(OH)D3 levels (30±12 ng/ml). CONCLUSION: In apparently healthy medication-free Slovaks the prevalence of hypovitaminosis D is high. Vitamin D status does not deteriorate in course of healthy ageing. Physical activity, normotension, and non-smoking status are associated with favorable vitamin D status while low 25(OH)D3 levels are associated with multiple cardiometabolic risk factors. Further studies in subjects at high cardiovascular risk are needed to elucidate the potential association of hypovitaminosis D with high cardiovascular mortality in Slovak adults (Tab. 1, Fig. 4, Ref. 42).

[Practice guideline and trends for immunosuppressive treatment of glomerulonephritides according to KDIGO (Clinical Practice Guideline for Glomerulonephritis)]. / Doporucené postupy a trendy v imunosupresivní lécbe glomerulonefritid podle KDIGO (Clinical Practice Guideline for Glomerulonephritis).

We summarize recommendations for glomerulonephritis treatment, established by internationally recognized experts in the field and sponsored by KDIGO (Kidney Disease Improving Global Outcomes). Up till now, the KDIGO review has been the most prestigious analysis of therapeutic trials on immunosuppressive treatment of glomerulonephritides. The 167 recommendations addresses the following forms of glomerulopathies: steroid-sensitive nephrotic syndrome and steroid resistant nephrotic syndrome in children; minimal change disease and idiopathic focal segmental glomerulosclerosis in children and adults; idiopathic membranous nephropathy; idiopathic membranoproliferative glomerulonephritis; glomerulonephritis associated with infection; immunoglobulin A nephropathy and Henoch-Schönlein purpura nephritis; lupus nephritis; pauci-immune focal and segmental necrotizing glomerulonephritis; and anti--glomerular basement membrane antibody glomerulonephritis. We focused our attention on progress in this topic in the last decade.

[To salt or not to salt in kidney diseases? Not more than quantum satis!]. / Solit nebo nesolit pri ledvinových chorobách? Ne více nez quantum satis!

The salt intake in former Czechoslovakia is twice as high as recommended 5 g/24 hours, which corresponds to 85 mmol//24 hours of sodium in the urine. In the population, the systemic blood pressure level correlates with a urinary excretion of sodium/24 hours. On the other hand, limited salt intake decreases blood pressure in salt-sensitive hypertensive patients. Albuminuria also positively correlates with a salt intake in the population. In patients with renal disease, a diet with low salt content suppresses proteinuria, and, in contrast, proteinuria is elevated with increased salt intake. The positive influence of the decreased salt intake on the progression of renal insufficiency was confirmed in many experimental studies. However, in humans, this finding was not unequivocally established in control randomized studies. The high salt intake worsens metabolic acidosis in patients with renal insufficiency. Salt is detrimental to the kidneys either by increased systemic and intraglomerular blood pressures or by pressure independent mechanisms of the tissue injury, which are mediated by a higher sodium concentration. The present knowledge concerning the relationship between sodium intake and extracellular fluid volume probably will be modified in light of new discoveries about the osmotically inactive sodium. The public enlightenment and medical application of these new findings related to harmful effects on an inappropriate salt intake in treatment of the kidney disease and in other fields of medicine is strongly desirable.

[Recurrent prosthetic endocarditis in a 21-year old patient with renal transplantation treated with allogeneic homograft]. / Recidivujúca protetická endokarditída u 21-rocného pacienta s transplantovanou oblickou riesená alogénnym homograftom.

Prosthetic infective endocarditis is a possible complication of implantation of a prosthetic cardiac valve. Without early and effective treatment, it can have fatal consequences. One treatment option is use of an allogeneic cryopreserved homograft. This case report presents a 21-year old patient after kidney transplantation due to hereditary nephrotic syndrome and aortic valve replacement with aortic conduits. After fever was noted in the patient, prosthetic infective endocarditis was diagnosed by echocardiography and also confirmed by CT-3D examination. The cryopreserved aortic homograft was implanted at the Department of Cardiac Surgery. This along with additional conservative management effectively treated the infection. Based on literature data and our own experience, we believe that the treatment of prosthetic endocarditis after aortic valve replacement with cryopreserved homograft can be a method of choice.

Advanced oxidation protein products and advanced glycation end products in children and adolescents with chronic renal insufficiency.

OBJECTIVE: Advanced oxidation protein products (AOPPs) represent dityrosine-containing cross-linked protein modifications formed mainly via myeloperoxidase reaction, supposed to accelerate the uremia-associated atherogenesis and renal fibrosis. DESIGN, SUBJECTS, AND MAIN OUTCOME MEASURES: In a cross-sectional study, we investigated the accumulation of AOPPs and advanced glycation end product (AGE)-specific fluorescence corrected for albumin in children and adolescents with chronic renal failure (CRF, n = 42), end-stage renal disease (ESRD, n = 12), kidney transplanted patients (Tx, n = 16), and age-matched healthy controls (n = 38). RESULTS: AOPP levels were 2.4-fold higher in the CRF and ESRD patients, and 1.6-fold higher in the transplanted subjects when compared with the controls (P < .001). In comparison with healthy controls, AGE levels rose 2-fold in the CRF, 7-fold in the ESRD, and 5-fold in the kidney transplanted children and adolescents, (P < .001). Patients with cardiovascular affliction presented with higher AGE levels than those without diagnosed cardiovascular disease (P < .02). In patients with stabilized renal function, AOPP and AGE levels did not change significantly during 12 months. CONCLUSION: Pattern of accumulation of AOPP and AGE in children and adolescents with chronic renal disease differs. Accelerated rise in AOPP levels in some children and adolescents in predialysis stage of chronic renal insufficiency, inadequate to deterioration of renal function, might require further attention.

Heat shock protein polymorphism predisposes to urinary tract malformations and renal transplantation in children.

BACKGROUND: Anatomical malformations of the kidney and urinary tract account for 17% of pediatric renal transplantation procedures. Heat shock proteins (HSPs) are molecular chaperones with a protective function that promotes cell survival. HSP72 is an endogenous ligand for toll-like receptor TLR4, thereby stimulating innate immunity. Both in adults and children, decreased expression of HSP70s is associated with a number of kidney diseases. OBJECTIVE: To assess the prevalence of HSPA1A G(190)C, HSPA1B A(1267)G, and TLR4 A(896)G polymorphisms in children who had undergone kidney transplantation. PATIENTS AND METHODS: Genotypes were analyzed using allele-specific polymerase chain reaction in 41 pediatric recipients. Allelic prevalence was related to reference values in 65 age- and sex-matched healthy children. RESULTS: Clinical data did not reveal a difference between any of the groups. HSPA1B (1267)GG genotype and HSPA1B (1267)G allele were observed more frequently in the transplant recipients compared with the control group: AA vs AG: odds ratio [OR], 12.6; 95% confidence interval [CI], 1.58-100.0; P = .004; AA vs GG: OR, 20.80; 95% CI, 2.32-187.00; P = .01; and A vs G: OR, 2.10; 95% CI, 1.19-3.07; P = .01. Furthermore, the prevalence of the HSPA1B (1267)GG genotype was greater in transplant recipients with vs without urinary tract malformations: AG vs GG: OR, 0.10; 95% CI, 0.09-0.48; P = .007. No differences were observed in the other studied polymorphisms. CONCLUSION: Our findings suggest an association between the carrier status of HSPA1B (1267)G with urinary tract malformations, leading to end-stage renal disease requiring kidney transplantation. This observation raises further questions about the clinical and therapeutic relevance of this polymorphism to pediatric nephrology.

Elevated brain natriuretic peptide is associated with abnormal heart geometry in children with chronic kidney disease.

AIM: It was to establish whether brain natriuretic peptide (BNP) might predict cardiac dysfunction in children with chronic kidney disease (CKD). METHODS: The relation between BNP, echocardiography and risk factors (hypertension, anemia, lipids, CRP, hyperparathyroidism) was investigated in 46 children (10 pre-dialysis patients, 14 on dialysis, 11 children with kidney transplants, and 11 healthy controls). Data on BNP were transformed into common logarithms (log(10) BNP, log BNP). RESULTS: log BNP was significantly higher in dialysis patients when compared to controls (2.09 +/- 0.78 vs. 1.43 +/- 0.34 pg/ml, p = 0.012) and patients in the pre-dialysis stage (2.09 +/- 0.78 vs. 1.52 +/- 0.42 pg/ml, p = 0.039). log BNP in transplanted children was not significantly different from healthy children (2.09 +/- 0.78 vs. 1.71 +/- 0.46 pg/ml, p = 0.19). Abnormal heart geometry (concentric and eccentric hypertrophy, concentric remodeling) was found in 19 patients (54.28%). A significant correlation was observed between log BNP and ventricular hypertrophy (r = 0.515, p = 0.001). Compared to controls higher log BNP was seen in children with eccentric hypertrophy than in children with concentric hypertrophy (2.178 +/- 0.956 vs. 1.496 +/- 0.395 pg/ml, p = 0.05, or 1.982 +/- 0.618 vs. 1.496 +/- 0.395, p = 0.04). CONCLUSIONS: BNP might predict an abnormal geometry in children with CKD.

[Brain natriuretic peptide might predict the abnormal geometry of heart in children with chronic kidney disease]. / Mozgový natriuretický peptid môze predikovat' zmenu geometrie srdca u detí s chronickou oblickovou chorobou.

BACKGROUND: Cardiovascular diseases are the leading course of morbidity/mortality in children with chronic kidney disease. Recently it has been shown that a brain natriuretic peptide is a sensitive cardiac marker for classification of the cardiovascular risk in adults. Whether it has the same diagnostic value in children with chronic kidney diseases has to be established. The purpose of the study was to evaluate whether the brain natriuretic peptide can predict cardiac dysfunction in children with chronic kidney disease. METHODS AND RESULTS: Relation between serum level of the brain natriuretic peptide, echocardiography and cardiovascular risk factors (hypertension, anaemia, lipids, C-reactive protein, secondary hyperparathyreoidism) has been studied in 46 children (10 patients at predialysis, 14 patients on dialysis, 11 children with kidney transplant and 11 healthy controls). Brain natriuretic peptide was significantly higher in dialysed patients (2.09 +/- 0.78) in comparison with healthy children (1.43 +/- 0.34, p = 0.012) and with both groups of patients at pre-dialysis stage (1.52 +/- 0.42, p = 0.039) and after kidney transplant (1.71 +/- 0.46, p = 0.19). Abnormal heart geometry was found in 19 patients (54.28%). Compared to controls, brain natriuretic peptide was higher in children with eccentric but not in those with concentric hypertrophy (2.178 +/- 0.956 vs. 1.496 +/- 0.395, p = 0.05, resp. 1.982 +/- 0.618 vs. 1.496 +/- 0.395, p = 0.04). Significant correlation was found between levels of brain natriuretic peptide and ventricular hypertrophy (p = 0.001), with the level of parathyroid hormone (p = 0.03) and with the degree of anaemia (p = 0.027). CONCLUSIONS: Brain natriuretic protein can predict an abnormal geometry of heart in children with chronic kidney disease. Our preliminary results suggest that it is a suitable marker of cardiovascular classification in paediatrics.

[Cyclosporin A versus cyclophosphamide in the treatment of nephrotic syndrome in children]. / Cyklosporín A verzus cyklofosfamid v liecbe detí s nefrotickým syndrómom.

BACKGROUND: The majority of cases of nephrotic syndrome in children is corticosensitive, however in some individuals aggressive cytotoxic therapy is necessary. Cyclosporin A and cyclophosphamide are widely used; however their relative effectiveness in maintaining remission of childhood nephrotic syndrome remains controversial. METHODS AND RESULTS: Effectiveness of long-term cytotoxic therapy (mean follow-up 7.4 years) in 63 children (mean age 6.19 +/- 4.30 years) with nephrotic syndrome was retrospectively analyzed; 14 patients suffered from corticosensitive, 33 from corticodependent and 16 from corticoresistant nephrotic syndrome. Corticotherapy alone was used in 15 patients (23.8%), cyclophosphamide was added in 27 (42.9%) and cyclosporin A in 38 cases (60.3%), while 17 patients (27%) were on both immunosuppressive agents. 84% children relapsed within 24 months after cessation of cyclosporin A. In 8 corticoresistant nephrotic syndrome patients (61.5%) from 13 children treated with cyclosporin A no remission occurred, in 5 children (38.5%) was remission obtained within 10 weeks, however in 4 of them relapsed disease during cyclosporin A therapy. 19 (70.4%) of 27 patients on cyclophosphamide therapy were in remission, in 8 of them (42.1%) even 2 years after cyclophosphamide therapy. CONCLUSIONS: Cyclophosphamide therapy of childhood nephrotic syndrome is more effective in maintaining long-term remission than cyclosporin A treatment.

[Urinary tract infections in children caused by uropathogenic strains of Escherichia coli and the role of the innate immune response mediated by the toll-like receptor 4 and antimicrobial peptide cathelicidin in their clinical course]. / Infekcie mocových ciest u detí spôsobené uropatogénnymi kmenimi Escherichia coli a vplyv vrodených imunitných mechanizmov toll-like receptora 4 a antimikróbneho peptidu katelicidínu, na ich klinický priebeh.

Uropathogenic Escherichia coli (UPEC) are the causative organisms in more than 80% of urinary tract infections. The bacteria are introduced to the urinary tract that, except for the external part of the urethra, is free from microbial colonization, and thus can cause acute, potentially life-threatening infections with possible progression to chronic disease. The course of such infection depends not only on the agent involved but also on the activation of protective mechanisms. The recently described Toll-like receptor family and antimicrobial peptide cathelicidin appear to play an important role in the recognition and activation functions.

The antimicrobial peptide cathelicidin protects the urinary tract against invasive bacterial infection.

The urinary tract functions in close proximity to the outside environment, yet must remain free of microbial colonization to avoid disease. The mechanisms for establishing an antimicrobial barrier in this area are not completely understood. Here, we describe the production and function of the cathelicidin antimicrobial peptides LL-37, its precursor hCAP-18 and its ortholog CRAMP in epithelial cells of human and mouse urinary tract, respectively. Bacterial contact with epithelial cells resulted in rapid production and secretion of the respective peptides, and in humans LL-37/hCAP-18 was released into urine. Epithelium-derived cathelicidin substantially contributed to the protection of the urinary tract against infection, as shown using CRAMP-deficient and neutrophil-depleted mice. In addition, clinical E. coli strains that were more resistant to LL-37 caused more severe urinary tract infections than did susceptible strains. Thus, cathelicidin seems to be a key factor in mucosal immunity of the urinary tract.

A family outbreak of haemolytic uraemic syndrome and haemorrhagic colitis caused by verocytotoxigenic Escherichia coli O157 from unpasteurised cow's milk in Slovakia.

This report describes a family outbreak of verocytotoxigenic Escherichia coli O157 (VTEC) infection, involving nine persons from one extended family, which occurred in eastern Slovakia. Three children suffered from haemolytic uraemic syndrome, two children had bloody diarrhoea, and four adults were asymptomatic carriers. Fourteen sorbitol-non-fermenting E. coli O157 isolates harbouring the vtx2, eae and ehxA genes were obtained. Verocytotoxin 2 activity was demonstrated in all 14 isolates. After epidemiological surveillance, the source of infection was identified as unpasteurised cow's milk.

Diagnostic monitoring of urine by means of synchronous fluorescence spectrum.

A novel approach to clinical-biochemical analysis of urine is presented in this work. Urine composition is defined graphically as a record of synchronous fluorescence spectra (SFS). The graphical standard has been made from SFS of urine samples from healthy children. Simple comparison of a standard record with that of an analyzed urine sample will immediately reveal changes in its composition. Reproducibility of the graphical definition is very high and it maintains its characteristic shape during repeated measurements over a span of 2 years. It is possible to elaborate patients' own standard for those with chronic illness. It differs from a normal course but it is characteristic for a given patient and it enables the clinician to monitor changes or the outcome of therapy at regular medical examinations. Application of this method for monitoring of urine composition for selected cases is a new alternative with several advantages. Analysis without any added reagents very quickly detects some illnesses near onset when they may be clinically asymptomatic and classical screening methods show negative results. Computerization of spectral measuring and filing the results enables to give a likely diagnosis or a deviation from standard. This method can also serve a doctor-clinician either to confirm or to exclude a concrete diagnosis.

[Characteristics of the cytokine response in patients with various forms of juvenile idiopathic arthritis]. / Charakteristika cytokínovej odpovede u pacientov s rôznymi formami juvenilnej idiopatickej artritídy.

BACKGROUND: Impairment of the dynamic balance between the first and second type of cytokine response with the prevalence of cytokines of the first type plays and important role in the pathogenesis of several autoimmune diseases, including the juvenile idiopathic arthritis (JIA). The aim of our work was to analyse cytokine profile in lymphocytes in the peripheral blood of patients with JIA, and to evaluate the mutual ration between T lymphocytes producing cytokines of the first and second type in different forms of the disease. METHODS AND RESULTS: We studied a group of 42 children aged 6 to 16 years, 32 of them were patients with JIA, 10 children with non-autoimmune diseases represented the control group. Expression of intracellular cytokines INF-gamma and IL-4 were assayed in activated T lymphocytes using recommended protocol (FastImmune Cytokine system, BD). For the sample analysis, flow cytometer FACScan (BD) was used. No differences in incidence of CD3+INF-gamma + Ly was found between patients with oligoarticular and polyarticular form of JIA (19.3 +/- 8.65 vs. 19.2 +/- 9.7%), and values were equal to that of the control group (19.5 +/- 5.85%). Similarly, no difference was found in incidence of CD3+INF4+ Ly between the JIA patients and controls (2.4 +/- 0.9 vs. 2.8 +/- 0.45%). Patients with polyarticular form of disease had statistically lower incidence of CD3+INF4+ Ly than it was among the control group (1.8 +/- 0.9 vs. 2.8 +/- 0.45%, p < 0.05). CONCLUSIONS: In the studied group of 32 patients with different forms of JIA, lower activity of cytokine response of the type 2 was found in children with polyarticular form of the disease.

Detection of Shiga toxins, intimin and enterohemolysin in Escherichia coli strains isolated from children in eastern Slovakia.

Fifty Escherichia coli strains isolated from stool samples of 51 healthy children, 143 strains isolated from stool samples of 327 children with diarrhea and 24 strains isolated from stool samples of 21 children with suspected hemolytic uremic syndrome were examined for the presence of Shiga toxin-producing E. coli virulence factors (shiga toxin 1 and 2, intimin and enterohemolysin) and their genes. Vero-cell assay and latex agglutination were used for detection of Shiga toxin 1 and 2, TSB agar with washed erythrocytes was used for detection of enterohemolysin; genes encoding shiga toxin 1 and 2, intimin and enterohemolysin were detected using multiplex PCR. The presence of E. coli strains harboring genes encoding shiga toxin 1 and 2 (12 strains), intimin (34 strains) and enterohemolysin (12 strains) was demonstrated.

Plasma levels of advanced glycation end products in children with renal disease.

In adults, advanced glycation end products (AGEs) rise slowly in tissues and circulation during aging, and accumulate at an accelerated rate both in diabetes and chronic renal insufficiency (CRI). We aimed to investigate the pattern of AGE accumulation in children/adolescents with CRI and on renal replacement therapy by dialysis and transplantation. Concentrations of fluorescent AGEs, carboxymethyllysine (CML) and lipofuscin-like substance (LFLS, a marker of lipid peroxidation) were followed. Data were obtained from 11 CRI patients on conservative treatment (age 12.6+/-1.7 years, serum creatinine: 205.7+/-17.5 micromol/l), ten patients on renal replacement therapy with dialysis (13.6+/-1.7 years, 698.2+/-48.9 micromol/l) and nine patients after kidney transplantation (15.9+/-1.1 years, 115.9+/-12.0 micromol/l) and comparison made with the data from 28 healthy controls (11.8+/-8.2 years, 44.1+/-8.2 micromol/l). In controls, an age-dependent rise of fluorescent AGE and CML levels was observed. In the CRI group, fluorescent AGEs [0.38+/-0.03x105 arbitrary units (AU)] and CML (369+/-26 ng/ml) concentrations were doubled compared with controls (0.16+/-0.03x105 AU and 189+/-42 ng/ml, respectively) and even higher levels were revealed in dialyzed patients (0.80+/-0.05x105 AU; 650+/-94 ng/ml). Successful kidney transplantation significantly reduced but did not normalize fluorescent AGE levels (0.39+/-0.03 x105 AU), while the decline in CML levels (550+/-47 ng/ml) was insignificant. Plasma LFLS was elevated in CRI (19.6+/- 1.7 AU) and was even higher in dialyzed children (32.0+/-5.3 AU) compared with healthy controls (7.1+/- 1.4 AU). Kidney transplantation did not normalize LFLS levels (20.3+/-5.3 AU), pointing to persistently enhanced lipid peroxidation. Our study provides the first data on enhanced fluorescent AGEs and CML levels in children/adolescents with CRI and on dialysis. Successful renal transplantation decreased but did not normalize AGE levels, probably because of still-impaired renal function with enhanced oxidative stress, as well as the influence of immunosuppressive therapy.

Enhanced plasma levels of advanced glycation end products (AGE) and pro-inflammatory cytokines in children/adolescents with chronic renal insufficiency and after renal replacement therapy by dialysis and transplantation--are they inter-related?

AIMS: Advanced glycation end products (AGEs) are formed by non-enzymatic glycation or glycoxidation. After their interaction with specific receptors, they may induce expression of various proinflammatory cytokines. AGEs were shown to accumulate with advanced age, in diabetes mellitus and, in particular, in patients with chronic renal failure. In contrast to numerous investigations in adults, there are no data on plasma levels of AGEs in children with chronic renal insufficiency (CRI) and after renal replacement therapy. To elucidate the specific role of renal impairment for the formation of AGEs, these data become especially interesting by exclusion of the age-dependent modulatory effects occurring in adults. Therefore, we investigated the concentrations of fluorescent (FL) AGEs, carboxymethyllysine (CML) and markers of inflammation (CRP, IL-6, TNF-alpha) in children/adolescents with chronic renal insufficiency (CRI) and on renal replacement therapy with maintenance dialysis (D) or renal transplantation (TX). PATIENTS: Eleven CRI patients on conservative treatment (CRI, age: mean 12.6, median 12.80, SD 5.8 +/- 1.7 years, serum creatinine: 205.7, 157.5, 58.0 micromol/l, respectively), 10 patients on D (13.6, 13.0, 5.4 years, and 698.2, 633.8, 296.1 micromol/l, respectively) and 9 patients after TX (15.9, 16.0, 3.4 years, and 115.9, 128.0, 35.1 micromol/l, respectively) were included. METHODS: Plasma levels of CML, TNF-alpha, and IL-6 were determined by ELISA, FL-AGEs spectrofluorimetrically (lambda(ex)/lambda(em): 370/440 nm). RESULTS: FL-AGEs and CML levels were increased in all 3 groups with the highest levels in the D patients, a successful renal transplantation did not lead to normalization of plasma AGEs. The mean CRP and IL-6 concentrations were marginally elevated, and no significance among groups was revealed. TNF-alpha was noticeably elevated in all groups, with the highest values in CRI and TX patients, while in the dialysis patients the rise was less pronounced. Stepwise multiple regression did not reveal any correlation between AGEs and proinflammatory parameters, even after exclusion of the TX group from analysis. CONCLUSIONS: In children with CRI and on maintenance dialysis therapy, plasma AGE levels are markedly increased. After renal transplantation, AGE levels decrease without normalization. Proinflammatory parameters (except for TNF-alpha) are only mildly to moderately elevated. No association between AGE levels and data characterizing a proinflammatory state was revealed.