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.

[Urinary fibronectin excretion as a marker of disease activity in children with IgA nephropathy and Henoch-Schönlein nephropathy]. / Ocena wydalania fibronektyny w moczu jako wskaznika aktywnosci choroby u dzieci z nefropatia IgA i Schönleina-Henocha.

UNLABELLED: The increase of extracellular matrix proteins synthesis including fibronectin (FN) is associated with development of renal sclerosis. The aim of the study was to examine urinary FN excretion as a marker of renal changes in patients (pts) with IgAN and HSN. The study group consisted of 34 children: IgAN n=11 and HSN n=23, mean age 12.44 +/- 3.83 years. At the onset of illness we observed erytrocyturia in all children, proteinuria in 28: nephrotic sydrome in 14 pts (IgAN--4, HSN--10) and proteinuria in 14 children (IgAN--6, HSN--8). In mean time 0.6 years from the onset of illness renal biopsies were performed. Changes in light microscopy were graded I-V degrees according to the classification of WHO. FN was measured in 24-h urine collections (ng/mg of creatinine), using specific antibody (DAKO) and proteinuria (mg/24h). Mean time from the biopsies to examine FN was 0.76 +/- 1.16 years. FN excretion was analysed in 2 group pts: group A--with proteinuria (n=28); group B--with erytrocyturia (n=6). The control group (K) consisted of 14 healthy children. Renal function was normal in all. RESULTS: The FN concentration higher than normal we observed in 22 pts (78.6%) in group A and 3 (50%) in group B. Mean FN value A was higher (NS) 274 +/- 213.0 than in B 132.0 +/- 68.8 and significant (p<0.01) than in group K (59.9 +/- 31.3). We found a positive correlation between FN and proteinuria in the moment of measurement the FN concentration (p=0.01, r=0.51). The higher values of FN (NS) we observed in pts with higher proteinuria at the onset of illness. FN excretion was significantly eleveted in younger children (p<0.001, r=-0,58). We not found a correlation between mean FN value and the grade of changes in renal biopsies (WHO). CONCLUSION: Urinary FN excretion may be a marker of disease activity in children with IgAN and HSN.

[Evaluation of prednisone treatment in children with IgA nephropathy and Schönlein-Henoch nephropathy according to the Waldo protocol with regard to pathomorphologic changes in renal biopsy]. / Ocena leczenia prednisonem dzieci z nefropatia IgA i nefropatia Schönleina-Henocha wg protokolu Waldo z uwzglednieniem zmian patomorfologicznych w biopsji nerki.

UNLABELLED: The aim of the study was to analyse effectiveness of long term alternate-day prednisone treatment according the protocol of Waldo (Pediatr. Nephrol. 1993, 7, 529) in children with IgA nephropathy (IgAN) and Schönlein-Henoch nephritis (HSN). Eight pts: 6 with IgAN, mean age 10.1 yrs and 2 with HSN aged 10.3 and 14.3 yrs were treated with use of alternate-day prednisone for 2.3 to 3.92 (mean 2.90 yrs). Renal biopsies were performed in all patients 2 to 72 (mean 16 mths) after onset and were graded according the classification of WHO. All pts had normal serum creatinine concentrations at presentation. 3 pts had proteinuria > 1 g/1.73 m2 per day at onset and 5 pts had macroscopic or microscopic haematuria and/or increased proteinuria and/or III grade WHO in renal biopsy. After treatment haematuria and proteinuria disappeared in 2 pts and decreased in 6 pts. Hypertension (2/8), hypercalciuria (2/8), mild weight gain (6/8) and low bone density in lumbar region (5/8) were observed during the treatment. CONCLUSIONS: 1. Long term alternate-day prednisone treatment according the protocol of Waldo allows to decrease haematuria and proteinuria in children with IgAN and HSN 2. Side effects of therapy were observed in 62.5% pts.

[Generalized tuberculosis as a cause of renal amyloidosis in a 9-year- old girl]. / Uogólniona gruzlica jako przyczyna wtórnej amyloidozy nerek u 9-letniej dziewczynki.

We present a case of a 9 years old girl with generalized tuberculosis diagnosed at the age of 5. Renal amyloidosis was diagnosed 21 months later. Clinically amyloidosis has been presented with steroid-resistant nephrotic syndrome, which within 15 months led to end stage renal failure. The girl is on automatic peritoneal dialysis with no signs of active tuberculosis up to now.

[Index of histopathological changes in rapidly progressive glomerulonephritis: a preliminary report]. / Indeks zmian histopatologicznych w gwaltownie postepujacym klebuszkowym zapaleniu nerek--doniesienie wstepne.

We present the case of an 8-year-old girl with rapidly progressive glomerulonephritis. The activity and chronicity index of histopathological changes in this patient was determined in 2 renal biopsies performed in a 25-month interval. The determination of this index in renal biopsies may be useful in the choice of glomerulonephritis with bad prognosis therapy.