The Outcome of Childhood Immunoglobulin A Nephropathy with Acute Kidney Injury at the Onset of the Disease-National Study.

Introduction: IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide. Decreased glomerular filtration rate is a known risk factor for disease progression. Aim: We aimed to examine factors that may contribute to disease progression in children that present with impaired eGFR at the onset of IgAN. Materials and methods: Of the 175 patients with IgAN from the Polish Registry of Children with IgAN and IgAVN, 54 (31%) patients with IgAN who had an onset of renal function impairment (GFR < 90 mL/min) were eligible for the study. All of them were analyzed for initial symptoms (GFR according to Schwartz formula, creatinine, proteinuria, IgA, C3), renal biopsy result with assessment by Oxford classification, treatment used (R-renoprotection, P-prednisone+R, Aza-azathioprine+P+R, Cyc-cyclophosphamide+P+R, CsA-cyclosporine+P+R, MMF-mycophenolate mofetil+P+R), and distant follow-up. Based on the GFR score obtained at the end, patients were divided into two groups: A-GFR > 90 mL/min and B-GFR < 90 mL/min. Results: In the study group, the mean age of onset was 12.87 ± 3.57 years, GFR was 66.1 ± 17.3 mL/min, and proteinuria was 18.1 (0-967) mg/kg/d. Renal biopsy was performed 0.2 (0-7) years after the onset of the disease, and MESTC score averaged 2.57 ± 1.6. Treatment was R only in 39% of children, P+R in 20%, Aza+P+R in 28%, Cyc+P+R in 9%, CsA+P+R in 7%, and MMF+P+R in 3%. The length of the observation period was 2.16 (0.05-11) years. At the follow-up, Group A had 30 patients (56%) and Group B had 24 patients (44%). There were no significant differences in any of the other biochemical parameters (except creatinine) or proteinuria values between the groups and the frequency of the MESTC score ≥ 2 and <2 was not significantly different between Groups A and B. Patients with normal GFR at the follow-up (Group A) were significantly more likely to have received prednisone and/or immunosuppressive treatment than those in Group B (p < 0.05) Conclusions: In a population of Polish children with IgAN and decreased renal function at the onset of the disease, 56% had normal GFR in remote observation. The use of immunosuppressive/corticosteroids treatment in children with IgAN and impaired glomerular filtration rate at the beginning of the disease may contribute to the normalization of GFR in the outcome, although this requires confirmation in a larger group of pediatric patients.

Predictors of Progression in IgA Nephropathy in Childhood.

The aim of this retrospective study was to assess the usefulness of potential predictors of poor prognosis in IgA nephropathy in children. The study population consisted of 55 children aged 11 ± 4 years, diagnosed on the basis of the Oxford classification and MEST score of kidney biopsy findings. Proteinuria, glomerular filtration rate (GFR), and the IgA/C3 serum ratio were assessed in all patients twice: at onset and at follow-up. The patients were treated with steroids, immunosuppressive drugs, and/or angiotensin-converting enzyme inhibitors. Follow-up was at 3.9 ± 2.9 (median 2.7) years. The patients were subdivided into two groups: with GFR <90 and ≥90 mL/min at follow-up. ROC AUC curves and logistic regression were used to evaluate the power of prognostic factors. The two groups did not differ regarding the level of proteinuria, MEST score, and the IgA/C3 ratio at onset of disease. There was a significant association between GFR reductions at onset and follow-up (AUC = 0.660; p < 0.05). In patients with nephrotic range proteinuria at onset, proteinuria at follow-up was more frequent compared with other patients (AUC = 0.760; p < 0.05), MEST score ≥3 tended to be associated with reduced GFR (AUC = 0.650; p = 0.07) but not with proteinuria (AUC = 0.608; p = 0.47), and the IgA/C3 ratio was higher (p < 0.05) at follow-up. No significant associations were found between the IgA/C3 ratio at onset and reduced GFR (AUC = 0.565; p = 0.46) or proteinuria at follow-up (AUC = 0.263; p = 0.20). We conclude that predictors of poor outcome in childhood IgAN include the following: GFR reduction, nephrotic range proteinuria at onset of disease, and high MEST score in Oxford classification of kidney biopsy. Despite a higher serum IgA/C3 ratio in children with impaired renal function in long-term follow-up, we failed to demonstrate a significant association between this ratio at onset of disease and reduced GFR or persistent proteinuria at follow-up. Thus, IgA/C3 ratio is not a good foreteller of progression of IgA nephropathy in childhood.

IgA Nephropathy in Children: A Multicenter Study in Poland.

IgA nephropathy (IgAN) is the most common form of glomerulonephritis in pediatric population. The clinical presentation of the disease in children ranges from microscopic hematuria to end-stage kidney disease. The aim of the study was to retrospectively assess clinical and kidney biopsy features in children with IgAN. We assessed a cohort of 140 children, 88 boys, 52 girls with the diagnosis of IgAN in the period of 2000-2015, entered into the national Polish pediatric IgAN registry. The assessment included the following: proteinuria, hematuria, glomerular filtration rate (GFR), arterial blood pressure, and the renal pathological changes according to the Oxford classification and crescents formation, as modifiable and unmodifiable risk factors. The incidence of IgAN in Poland was set at 9.3 new cases per year. The mean age at onset of IgAN was 11.9 ± 4.3 years, and the most common presentation of the disease was the nephritic syndrome, recognized in 52 % of patients. Kidney biopsy was performed, on average, 1.3 ± 2.0 years after onset of disease. Based on the ROC analysis, a cut-off age at onset of disease for GFR <90 mL/min/1.73 m2 (risk factor of progression) was calculated as 13.9 years. Unmodifiable lesions: segmental sclerosis, tubular atrophy/interstitial fibrosis (S1, T1-2) in the Oxford classification and crescents in kidney biopsy were significantly more common in Gr 1 (>13.9 years) compared with Gr 2 (<13.9 years), despite a significantly shorter time to kidney biopsy in the former. We conclude that IgAN in children may be an insidious disease. A regular urine analysis, especially after respiratory tract infections, seems the best way for an early detection of the disease.

Increased Serum IgA in Children with IgA Nephropathy, Severity of Kidney Biopsy Findings and Long-Term Outcomes.

The aim of the study was to determine whether an elevated IgA level at the time of the diagnosis of IgA nephropathy has an effect on the severity of kidney biopsy findings and long-term outcomes in children. We retrospectively studied 89 children with IgA nephropathy who were stratified into Group 1- elevated serum IgA and Group 2 - normal serum IgA at baseline. The level of IgA, proteinuria, hematuria, glomerular filtration rate (GFR) and hypertension (HTN) were compared at baseline and after the end of the follow-up period of 4.0 ± 3.1 years. Kidney biopsy findings were evaluated using the Oxford classification. The evaluation of treatment included immunosuppressive therapy and renoprotection with angiotensin converting-enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB), or no treatment. The elevated serum IgA was found in 46 (52 %) patients and normal serum IgA level was found in 43 (48 %) patients. No differences were found between the two groups regarding the mean age of patients, proteinuria, and the number of patients with reduced GFR or HTN at baseline. In kidney biopsy, mesangial proliferation and segmental sclerosis were significantly more common in Group 1 compared with Group 2 (p < 0.05). Immunosuppressive therapy was used in 67 % children in Group 1 and 75 % children in Group 2. The Kaplan-Meier survival curves for renal function (with normal GFR) and persistent proteinuria did not differ significantly depending on the serum IgA level at baseline. We conclude that in IgA nephropathy the elevated serum IgA at baseline may be associated with mesangial proliferation and segmental sclerosis contribute to glomerulosclerosis, but has no effect on the presence of proteinuria or on the worsening of kidney function during several years of disease course.

Are oxidized low-density lipoprotein and C-reactive protein markers of atherosclerosis in nephrotic children?

BACKGROUND: Lipid disorders are known to be linked to disturbance in oxidative reactions and play an important role in the progression and complications of idiopathic nephrotic syndrome (INS). AIMS: The aim of this study was to assess oxidized low-density lipoprotein (oxLDL), high-sensitive C-reactive protein (hs-CRP) serum concentrations and other parameters of lipid metabolism in children with INS during relapse and remission of proteinuria. METHODS: The examination was performed on 23 children and adolescents diagnosed with INS. Reference group consisted of 22 participants. The study was carried out twice: in the relapse of INS (A) and in remission of proteinuria during glucocorticoid treatment (B). RESULTS: OxLDL was higher in INS patients, in both examinations when compared with reference participants. hs-CRP showed no differences between nephrotic and healthy children. We found higher concentration of oxLDL in children, who where frequent relapsers. Cholesterol, triglycerides/high density lipoprotein cholesterol and platelets were higher in INS patients (both A and B) in comparison with healthy children. CONCLUSIONS: We observed presence of pro-atherogenic lipid profile in INS. Elevation of oxLDL may reflect increased oxidative stress and higher risk of atherosclerosis in INS, therefore it seems to be relevant to find patients of risk of atherosclerosis to consider lipid lowering treatment with antioxidants.

Serum osteoprotegrin (OPG) and receptor activator of nuclear factor kappaB (RANKL) in healthy children and adolescents.

UNLABELLED: Most metabolic bone diseases are characterized by a disturbance in bone resorption, therefore biochemical markers concerning this process are of special interest. Recent investigations in bone biology identified the RANKL/ RANK/OPG system, the set of cytokines or cytokine receptors belonging to the tumor necrosis factor (TNF) family that are required for control of bone modeling and remodeling. The imbalance between OPG and RANKL was found not only in pathology of bone, but also in the control of the immune and vascular systems. However, clinical application of new bone markers in children may be difficult due to lack of reference data in relation to age, sex and physiological development. AIM: To investigate the relationship of serum concentrations of OPG, RANKL and OPG/RANKL ratio in relation to age, sex and parameters of physical development in healthy children and adolescents. CHILDREN AND METHODS: The study was performed on a group of 70 healthy children and adolescents, divided into subgroups according to sex and age. OPG and sRANKL serum concentrations were determined using ELISA. RESULTS: Serum OPG did not differ between boys and girls or younger and older children. There was no correlation between OPG level and height, weight and BMI percentiles. The level of sRANKL was 3 times higher in males than in females (p < 0.01) and almost 3 times higher in older than younger children (p < 0.01). There was a positive correlation between sRANKL concentration and body weight percentile (r = 0.268, p < 0.05). There was no correlation between serum OPG and sRANKL levels. CONCLUSION: In healthy children and adolescents the serum level of OPG is not influenced by age, sex or parameters of physical development, in contrast to sRANKL and sRANKL/OPG ratio, which are dependent on these factors. Age and sex reference data should be established.