Pediatric IgA Nephropathy in Europe

Abstract

Background: In Europe IgA nephropathy (IgAN) is detected in 20% of children with glomerular diseases diagnosed by renal biopsy. The outcome during childhood is generally good, but progression in the long-term follow-up may occur in about 20% of children after 20 years. Summary: In Europe, urine screening programs are not active, and there is variability in the policy to perform renal biopsies in oligo-symptomatic children. Hence, a suitable observational approach to pediatric IgAN is offered by the VALIGA study which included 174 children aged < 18 years from 13 European countries followed over a median of 4.4 (2.5–7.5) years. Renal pathology lesions were centrally scored according to the Oxford Classification of IgAN (mesangial hypercellularity, M; endocapillary hypercellularity, E; segmental glomerulosclerosis, S; tubular atrophy/interstitial fibrosis, T; crescents, C [MEST-C]). Children had renal biopsy mostly with normal estimated glomerular filtration rate (eGFR) and moderate proteinuria of a median of 0.84 g/day/1.73 m² (< 0.30 g/day/1.73 m² in 30% of the cases). Children showed M1 in 21.8%, E1 in 13.8%, S1 in 42.5%, T1–2 in 6.3%, and C1 in 14.9%. The survival at the combined endpoint of 50% eGFR decrease or end-stage renal disease at 15 years was 94%. The slow progression rate and the limited number of cases progressing to the combined endpoint (6.4%) did not allow the detection of a predictive value of the MEST-C score. Moreover, the predictive value of clinical and pathological features was likely blunted by the use of corticosteroid/immunosuppressive treatment (CS/IS) in 50% of the cases. The survival tree analysis also proved that children < 16 years old with IgAN without mesangial hypercellularity (M0) and well preserved eGFR (> 90 mL/min/1.73 m²) had a high probability of proteinuria remission during follow-up. Moreover, in this subgroup of children, the benefits of CS/IS therapy reached statistical significance. In Europe, the use of CS/IS treatment in IgAN is still a debated issue, but most children tend to be treated more commonly than adults with CS/IS. A recent uncontrolled study reports a favorable outcome in European children with IgAN and very active acute forms of IgAN with improvement in eGFR and reduction in proteinuria. Key Messages: In Europe, children with IgAN have a favorable prognosis in the short term, and this may be due also to the frequently adopted CS/IS therapy, particularly with acute and active pathological features. The risk of progression over decades of follow-up remains an unsolved problem which needs to be addressed by controlling subtle chronic pathogenetic factors which work in children as well as in adult cases of IgAN.

Updating the International IgA Nephropathy Prediction Tool for use in children

“…The median eGFR at biopsy was 98 ml/min/1.73m 2 (interquartile range (IQR) 79, 118) with proteinuria 1.2g/day/1.73m 2 (IQR 0.5,3.0). Over a median follow-up of 3.9 years (IQR 2.1, 6.4), 63.4% of patients were treated with medications that block the renin-angiotensin system (RASB), 58.1% were treated with immunosuppression, and 48.0% were followed into adulthood.…”

“…Therefore, the analysis was repeated using the secondary outcome with selective re-estimation allowed in up to 7 predictor variables. At each step of the updating process, model fit was assessed using R 2 D and the Akaike Information Criterion (AIC) 39 , with an increase in R 2 D and a reduction in the AIC indicating better model J o u r n a l P r e -p r o o f fit. Discrimination is the ability of a model to differentiate those who did versus did not experience an outcome event, and was assessed using the C-statistic adapted for censoring 40 .…”

“…Using the adult Prediction Tool models directly to predict the secondary outcome had poor R 2 D (3.3% 5.0%), AIC values of 1324 and 1307, on average overestimated risk given by the calibration slopes, but had good C-statistics (0.78 and 0.76) ( Table 2). After partial updating using an overall recalibration and new baseline survival, there was no improvement in R 2 D and the C-statistics decreased to 0.58 and 0.59. Using forward selection, up to 7 predictor variables were identified for re-estimation of their beta-coefficients.…”

“…IgA nephropathy (IgAN) is detected in 20-40% of kidney biopsies and is the most common type of pathologyproven glomerular disease in children and adults worldwide [1][2][3][4][5][6] . Substantial kidney function decline during the pediatric age range is uncommon 2,6 .…”

“…IgA nephropathy (IgAN) is detected in 20-40% of kidney biopsies and is the most common type of pathologyproven glomerular disease in children and adults worldwide [1][2][3][4][5][6] . Substantial kidney function decline during the pediatric age range is uncommon 2,6 . In contrast, adults with IgAN have a significant risk of kidney failure with progression to a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD) occurring in 30% of patients over 10 years 7 .…”