NDT Advance Access originally published online on August 25, 2006
Nephrology Dialysis Transplantation 2006 21(12):3466-3474; doi:10.1093/ndt/gfl455
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Histological differences in new-onset IgA nephropathy between children and adults
1Department of Pediatrics, Niigata University Medical and Dental Hospital, 2Division of Clinical Nephrology and Rheumatology and 3Department of Cell Biology, Institute of Nephrology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan, 4Department of Nephrology and 5Monash University Department of Medicine, Monash Medical Centre, Clayton, Victoria, Australia
Correspondence and offprint requests to: Yohei Ikezumi, MD, PhD, Department of Pediatrics, Niigata University Medical and Dental Hospital, Asahimachi-dori, Niigata 951-8510, Japan. Email: ikezumi{at}med.niigata-u.ac.jp
Background. It is suggested that IgA nephropathy (IgAN) manifests differently in children vs adults on the basis of biopsy findings. However, this has been difficult to establish owing to the uncertainty of the timing of disease onset in adult IgAN. We addressed this question by comparing both histology and leucocyte accumulation in biopsies of recently diagnosed childhood and adult IgAN.
Methods. Biopsies taken within 2 years from the onset of renal abnormalities in 33 childhood (10 ± 3 years of age) and 38 adult (35 ± 6 years) cases of IgAN were examined for histological changes (cellularity in mesangial, endocapillary and extracapillary areas, matrix expansion, adhesions/crescents and interstitial damage), glomerular deposition of immunoglobulin and complement, and the presence of macrophages, activated macrophages and T cells by immunohistochemistry.
Results. Glomerular hypercellularity owing to increased cells in mesangial area was prominent in paediatric IgAN and significantly greater than in adult IgAN. In contrast, glomerular matrix expansion, crescent formation and interstitial damage were more severe in adults compared to paediatric IgAN. Indeed, glomerular hypercellularity correlated with proteinuria in paediatric but not in adult IgAN, whereas glomerular matrix correlated with proteinuria and renal function in adult but not in paediatric IgAN. The degree of C3c deposition was significantly greater in paediatric IgAN, while deposition of fibrinogen was greater in adult IgAN. Glomerular and interstitial CD68+ macrophages and a subset of sialoadhesin (Sn)+ activated macrophages were identified in both paediatric and adult IgAN, being significantly greater in number in adult IgAN. Glomerular leucocyte infiltration correlated with proteinuria while interstitial leucocyte infiltration correlated with interstitial damage in both groups. However, only the subset of Sn+ macrophages gave a significant correlation with renal function, glomerular hypercellularity and glomerular matrix.
Conclusions. This study has demonstrated significant differences in the early glomerular lesions of IgAN in children vs adults. Furthermore, Sn+ activated macrophages are implicated in the pathogenesis of IgAN in both patient groups. The prognostic significance of these findings warrants further study.
Keywords: activated macrophage; childhood; glomerular hypercellularity; glomerular matrix; IgA nephropathy
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