Dusan Paripovic

Underweight, overweight and obesity in paediatric dialysis and renal transplant patients

BACKGROUND The prevalence of childhood overweight is rising worldwide, but in children on renal replacement therapy (RRT) a poor nutritional status is still the primary concern. We aimed to study the prevalence of, and factors associated with, underweight and overweight/obesity in the European paediatric RRT population. Moreover, we assessed the evolution of body mass index (BMI) after the start of RRT. METHODS We included 4474 patients younger than 16 years from 25 countries of whom BMI data, obtained between 1995 and 2010, were available within the European Society for Paediatric Nephrology/European Renal Association-European Dialysis and Transplant Association Registry. Prevalence estimates for under- and overweight/obesity were calculated using age and sex-specific criteria of the World Health Organization (WHO, 0-1 year olds) and the International Obesity Task Force cut-offs (2-15 year olds). RESULTS The prevalence of underweight was 3.5%, whereas 20.8% of the patients were overweight and 12.5% obese. Factors associated with being underweight were receiving dialysis treatment and infant age. Among transplanted recipients, a very short stature (OR: 1.64, 95% CI: 1.40-1.92) and glucocorticoid treatment (OR: 1.23, 95% CI: 1.03-1.47) were associated with a higher risk of being overweight/obese. BMI increased post-transplant, and a lower BMI and a higher age at the start of RRT were associated with greater BMI changes during RRT treatment. CONCLUSIONS Overweight and obesity, rather than underweight, are highly prevalent in European children on RRT. Short stature among graft recipients had a strong association with overweight, while underweight appears to be only a problem in infants. Our findings suggest that nutritional management in children receiving RRT should focus as much on the prevention and treatment of overweight as on preventing malnutrition.

Hyperlipidemia, oxidative stress, and intima media thickness in children with chronic kidney disease.

BackgroundThe roles of dyslipidemia and oxidative stress in the early phases of atherosclerosis were tested in children with chronic kidney disease (CKD). Intima media thickness of common carotid arteries (cIMT) is used as a measure of early atherosclerosis.MethodsFifty-two pediatric CKD patients were enrolled in the study (10 with chronic renal failure [CRF], 22 with a renal transplant [RT], 20 with chronic hemodialysis (cHD) patients, and 36 healthy children (control group, CG). Lipid status, oxidative stress, and paraoxonase 1 (PON1) status were assessed. cIMT was measured by ultrasound, adjusted for age and sex, and presented as standard deviation scores (SDS).ResultsChildren with CKD had disturbed lipid content, which was most pronounced in cHD children, with higher free cholesterol and triglycerides compared with healthy children. Oxidative stress was markedly increased (malodialdehyde [MDA, μmol/L]: CRF 1.50 ± 0.26, RT 1.55 ± 0.40, cHD 1.77 ± 0.34, CG 0.97 ± 0.33, p < 0.001) and antioxidative defense was compromised (superoxide dismutase [SOD, U/L]: CG 120 ± 21, CRF 84 ± 25, RT 93 ± 12, cHD 119 ± 37, p < 0.001). Multiple linear regression analysis showed that a model that included disease duration, blood pressure, urea, lipid, and oxidative status parameters accounted for more than 90% of the variability of cIMT-SDS.ConclusionsEarly atherosclerosis in CKD children is caused, at least in part, by dyslipidemia and oxidative stress. Monitoring of vessel wall changes, along with assessment of oxidative stress status and high density lipoprotein (HDL) functionality is necessary to ensure better therapeutic strategies for delaying atherosclerotic changes in their asymptomatic phase.

Clinical Application Neutrophil Gelatinase-Associated Lipocalin and Kidney Injury Molecule-1 as Indicators of Inflammation Persistence and Acute Kidney Injury in Children with Urinary Tract Infection

Background. The aim of this study was to examine the novel renal biomarkers neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) to assist pediatricians in the assessment of longer duration of inflammation and acute kidney injury (AKI) development during urinary tract infection (UTI). Methods. The patients enrolled in the study comprised 50 children (mean age was 6 months) with UTI. NGAL in serum and urine (sNGAL and uNGAL, resp.) and KIM-1 in urine were measured by enzyme-linked immunosorbent assays. Results. uNGAL levels in subjects with longer duration of inflammation were higher (115.37 ng/mL) than uNGAL levels in subjects with shorter duration of inflammation (67.87 ng/mL, P = 0.022). Difference in sNGAL and KIM-1 levels was not significant (P = 0.155 and P = 0.198, resp.). Significant difference was seen in KIM-1 excretion among groups with and without AKI (P = 0.038). KIM-1 was not able to discriminate between subjects with and without AKI (area under the curves (AUC) = 0.620, P = 0.175). Conclusions. uNGAL cannot be used for screening of the duration of inflammation during UTI. Accuracy of KIM-1 in screening of AKI development in children with UTI is low. We suggest larger studies to check the negative predictive value of KIM-1 for the development of AKI.

Epidemiology of chronic kidney disease in children in Serbia

BACKGROUND The epidemiological information from well-defined populations regarding childhood chronic kidney disease (CKD), particularly those concerning non-terminal stages, are scanty. The epidemiology of CKD in children is often based on renal replacement therapy (RRT) data, which means that a considerable number of children in earlier stages of CKD are missed as they will reach end-stage renal disease (ESRD) in adulthood. Here, we report the basic epidemiological data on childhood CKD in Serbia, gathered over the 10-year period of activity of the Serbian Pediatric Registry of Chronic Kidney Disease. METHODS Since 2000-09, data on incidence, prevalence, aetiology, treatment modalities and outcome of children aged 0-18 years, with CKD Stages 2-4 and CKD Stage 5, were collected by reporting index cases from paediatric centres. RESULTS Three hundred and thirty-six children were registered (211 boys, 125 girls, male/female ratio 1.7). The median age at registration was 9.0 years [interquartile range (IQR) 3-13]. Median follow-up was 4.0 years (IQR, 1-9). The median glomerular filtration rate (GFR) at the time of the registration was 39.6 mL/min/1.73m(2) (IQR, 13.8-65.4). Median annual incidence of CKD 2-5 stages was 14.3 per million age-related population (p.m.a.r.p.), while those of CKD 2-4 or CKD 5 were 9.1 and 5.7 p.m.a.r.p., respectively. The median prevalence of CKD 2-5 was 96.1 p.m.a.r.p., 52.8 p.m.a.r.p. in CKD 2-4 and 62.2 p.m.a.r.p. in CKD 5. The main causes of CKD were congenital anomalies of kidney and urinary tract and hereditary nephropathies. Kidney survival was the worst in children with glomerular diseases and in those with advanced CKD. Haemodialysis was the most common first modality of RRT. Mortality rate was 4.5%, mainly due to cardiovascular and infectious complications. CONCLUSIONS Epidemiology of paediatric CKD in Serbia is similar to that reported from developed European countries. The knowledge of the epidemiology of earlier stages of CKD is essential for both institution of renoprotective therapy and planning of RRT, a fact of paramount importance in countries with limited resources.

Renal functional reserve in children with apparently normal congenital solitary functioning kidney

OBJECTIVE The aim of the study was to investigate renal functional reserve (RFR) and to assess its relationship with serum cystatin C and blood pressure in children with apparently normal congenital solitary functioning kidney (SFK). MATERIAL AND METHODS RFR was obtained from the difference of endogenous creatinine clearance (CrCs) before and after a meat-free oral protein load (OPL) in the patients who were pre-treated with cimetidine. Serum cystatin C and urinary protein excretion were determined before and after OPL. RESULTS Among 22 patients (13 boys), aged 9.5 ± 4.3 years, 72.7% had increased serum cystatin C, and 54.5% had decreased RFR. Following OPL, CrCs and urine creatinine increased, while serum creatinine and cystatin C remained unchanged. The multiple regression analysis demonstrated that cystatin C could predict more than 90% of RFR variability. CONCLUSION Half of the patients with apparently normal SFK had decreased RFR. Serum cystatin C is one of the best predictors of RFR.

Association of Serum Soluble Urokinase Receptor Levels With Progression of Kidney Disease in Children

Importance Conventional methods to diagnose and monitor chronic kidney disease (CKD) in children, such as creatinine level and cystatin C–derived estimated glomerular filtration rate (eGFR) and assessment of proteinuria in spot or timed urine samples, are of limited value in identifying patients at risk of progressive kidney function loss. Serum soluble urokinase receptor (suPAR) levels strongly predict incident CKD stage 3 in adults. Objective To determine whether elevated suPAR levels are associated with renal disease progression in children with CKD. Design, Setting, and Participants Post hoc analysis of 2 prospectively followed up pediatric CKD cohorts, ie, the ESCAPE Trial (1999-2007) and the 4C Study (2010-2016), with serum suPAR level measured at enrollment and longitudinal eGFR measured prospectively. In the 2 trials, a total of 898 children were observed at 30 (ESCAPE Trial; n = 256) and 55 (4C Study; n = 642) tertiary care hospitals in 13 European countries. Renal diagnoses included congenital anomalies of the kidneys and urinary tract (n = 637 [70.9%]), tubulointerstitial nephropathies (n = 92 [10.2%]), glomerulopathies (n = 69 [7.7%]), postischemic CKD (n = 42 [4.7%]), and other CKD (n = 58 [6.5%]). Total follow-up duration was up to 7.9 years, and median follow-up was 3.1 years. Analyses were conducted from October 2016 to December 2016. Exposures Serum suPAR level was measured at enrollment, and eGFR was measured every 2 months in the ESCAPE Trial and every 6 months in the 4C Study. The primary end point of CKD progression was a composite of 50% eGFR loss, eGFR less than 10 mL/min/1.73 m2, or initiation of renal replacement therapy. Main Outcomes and Measures The primary end point in this study was renal survival, defined as a composite of 50% loss of GFR that persisted for at least 1 month, the start of renal replacement therapy, or an eGFR less than 10 mL/min/1.73 m2. Results Of the 898 included children, 560 (62.4%) were male, and the mean (SD) patient age at enrollment was 11.9 (3.5) years. The mean (SD) eGFR was 34 (16) mL/min/1.73 m2. The 5-year end point–free renal survival was 64.5% (95% CI, 57.4-71.7) in children with suPAR levels in the lowest quartile compared with 35.9% (95% CI, 28.7-43.0) in those in the highest quartile (P < .001). By multivariable analysis, the risk of attaining the end point was higher in children with glomerulopathies and increased with age, blood pressure, proteinuria, and lower eGFR at baseline. In patients with baseline eGFR greater than 40 mL/min/1.73 m2, higher log-transformed suPAR levels were associated with a higher risk of CKD progression after adjustment for traditional risk factors (hazard ratio, 5.12; 95% CI, 1.56-16.7; P = .007). Conclusions and Relevance Patients with high suPAR levels were more likely to have progression of their kidney disease. Further studies should determine whether suPAR levels can identify children at risk for future CKD.

Long-term renal outcome in children with OCRL mutations: retrospective analysis of a large international cohort

Background Lowe syndrome (LS) and Dent-2 disease (DD2) are disorders associated with mutations in the OCRL gene and characterized by progressive chronic kidney disease (CKD). Here, we aimed to investigate the long-term renal outcome and identify potential determinants of CKD and its progression in children with these tubulopathies. Methods Retrospective analyses were conducted of clinical and genetic data in a cohort of 106 boys (LS: 88 and DD2: 18). For genotype-phenotype analysis, we grouped mutations according to their type and localization. To investigate progression of CKD we used survival analysis by Kaplan-Meier method using stage 3 CKD as the end-point. Results Median estimated glomerular filtration rate (eGFR) was lower in the LS group compared with DD2 (58.8 versus 87.4 mL/min/1.73 m2, P < 0.01). CKD stage II-V was found in 82% of patients, of these 58% and 28% had moderate-to-severe CKD in LS and DD2, respectively. Three patients (3%), all with LS, developed stage 5 of CKD. Survival analysis showed that LS was also associated with a faster CKD progression than DD2 (P < 0.01). On multivariate analysis, eGFR was dependent only on age (b = -0.46, P < 0.001). Localization, but not type of mutations, tended to correlate with eGFR. There was also no significant association between presence of nephrocalcinosis, hypercalciuria, proteinuria and number of adverse clinical events and CKD. Conclusions CKD is commonly found in children with OCRL mutations. CKD progression was strongly related to the underlying diagnosis but did not associate with clinical parameters, such as nephrocalcinosis or proteinuria.

Oxidative status parameters in children with urinary tract infection

Introduction: Urinary tract infection (UTI) is one of the most common bacterial infectious diseases in children. The aim of this study was to determine the total prooxidant and antioxidant capacity of children with UTI, as well as changes of oxidative status parameters according to acute inflammation persistence and acute kidney injury (AKI) development. Materials and methods: The patients enrolled in the study comprised 50 Caucasian children (median age was 6 months) with UTI. Total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), inflammation marker C-reactive protein (CRP) and renal function parameters urea and creatinine were analyzed in patient’s serums. Results: According to duration of inflammation during UTI, TAS values were significantly higher (0.99 vs. 0.58 mmol/L, P = 0.017) and OSI values were significantly lower (0.032 vs. 0.041 AU, P = 0.037) in the subjects with longer duration of inflammation than in the subjects with shorter duration of inflammation. We did not find significant difference in basal values of oxidative status parameters according to AKI development. Conclusions: OSI values could detect the simultaneous change of TAS and TOS due to change in the oxidative-antioxidant balance during the recovery of children with UTI. TAS and OSI as markers of oxidative stress during UTI are sensitive to accompanying inflammatory condition. Further investigations are needed to evaluate whether TAS, TOS and OSI could be used to monitor disease severity in children with UTI.

Association of Myeloperoxidase and the Atherogenic Index of Plasma in Children with End-Stage Renal Disease

Summary Background: The aim of this study was to explore oxidative stress status, especially the enzyme myeloperoxidase in children with end-stage renal disease. Also, we investigated possible associations between the atherogenic index of plasma and these parameters. Methods: Lipid status parameters, oxidative stress status parameters, and myeloperoxidase concentration were measured in the sera of 20 children in the last stage of chronic renal disease (ESRD) and 35 healthy children of matching age and sex. The Atherogenic Index of Plasma (AIP) was calculated according to the appropriate equation. Results: We did not find any significant differences in myeloperoxidase concentrations between the investigated groups (p=0.394). Oxidative stress parameters were, however, significantly higher in the patient group (p<0.001), as well as the atherogenic index of plasma (p<0.001). Myeloperoxidase concentration and advanced oxidation protein product (AOPP) concentration were independently associated with increased AIP in the patient group (p<0.05). Conclusions: Changes in AIP in children with ERSD are associated with the oxidative stress status and myeloperoxidase concentration.

Henoch-Schönlein purpura outcome in children: A ten-year clinical study

INTRODUCTION Henoch-Schönlein purpura (HSP) is the most common vasculitis of childhood. It is characterized by symptoms including nonthrombocytopenic purpura, abdominal pain, haematuria/proteinuria, and arthralgia/arthritis. The pleiomorphism of clinical signs in HSP could be confused with other conditions or other vasculitis forms. OBJECTIVE Evaluation of HSP clinical presentation, the onset and severity of renal manifestation in affected children and their outcome. METHODS A retrospective study of 49 patients diagnosed with HSP was conducted from September 1999 to September 2009. Children with severe renal manifestations (nephrotic range proteinuria, with or without nephrotic or nephritic syndrome) have undergone kidney biopsy. RESULTS Twenty-five patients developed renal manifestations after onset of the disease. In our study childs older age was a risk factor for association with HSP nephritis. Six of the patients required kidney biopsy. They were successfully treated with various immunosuppressive protocols, as well as three of nine patients with nephrotic range proteinuria. Two patients developed most severe form of HSP nephritis, nephrotic-nephritic syndrome with histology grade IIIb/IVb. During the study period (average followup 6 years), all patients had a normal global renal function with mild proteinuria in only two cases. The prognosis of renal involvement was better than reports from other patient series. CONCLUSION Long-term morbidity of HSP is predominantly attributed to renal involvement. During the study period, no patient had renal insufficiency or end stage renal disease after various combinations of immunosuppressive treatment. It is recommended that patients with HSP nephritis are followed for longer periods of time with a regular measurement of renal function and proteinuria.