Clinicopathologic Changes in Children with Immunoglobulin A Nephritis and Henoch-Schonlein Purpura Nephritis after Cyclosporine A and Angiotensin-converting Enzyme Inhibitor Treatment

PURPOSE: To investigate the clinicopathologic effects of cyclosporine A (CsA) in children with diseases characterized by mesangial immunoglobulin A deposits such as immunoglobulin A nephropathy (IgAN) and Henoch-Schonlein purpura nephritis (HSPN). METHODS: We retrospectively reviewed the clinicopathologic outcomes of 54 children (IgAN, 36; HSPN, 18) treated with CsA. The starting dose of CsA was 5 mg/kg per day, and it was administered in 2 divided doses. The degree of proteinuria and pathologic changes in renal biopsies were evaluated before and after CsA treatment. RESULTS: The mean protein to creatinine ratio decreased from 3.7+/-1.5 to 0.6+/-0.4 (P<0.001), and 32 (59.2%) children achieved complete remission of proteinuria after 1-year CsA treatment. Among the 54 children, 24 maintained normal renal function and 25 exhibited microscopic hematuria or proteinuria at the end of CsA treatment. In the HSPN group, 3 children whose initial biopsies indicated class IIIb disease showed class II disease on follow-up, and the follow-up biopsies of 2 children who had class II disease indicated the same class II disease. In the IgAN group, cortical tubular atrophy occurred in 1 child, and no child with IgAN had cortical interstitial fibrosis or tubular atrophy after 1-year CsA treatment. No significant complications were found in the children treated with CsA. CONCLUSION: Our findings indicate that CsA treatment is effective and beneficial in reducing massive proteinuria and preventing progression to end-stage renal failure in children with glomerular diseases characterized by IgA deposits, such as IgAN and HSPN, within 1 year of treatment.

Diffuse Glomerular Basement Membrane Lamellation in Post-Transplant IgA Nephropathy

Diffuse glomerular basement membrane (GBM) lamellation, reminiscent of Alport's syndrome, has rarely, and exclusively, been reported in renal allografts from pediatric donors to adult recipients. We report on a similar lesion, identified in a 42-year-old male, who received a kidney from an unrelated 21-year-old living male donor. The disease of the recipient was unknown. Renal allograft biopsies were performed 3.5 and 4.8 years after the renal transplantation, due to massive proteinuria and serum creatinine elevation. The histological features of both biopsies were similar, but more advanced in the second biopsy. Glomerular mesangium was widened and had an IgA deposit in the first biopsy. In addition to the presence of mesangial electron dense deposits, the GBM showed diffuse lamellation and splintering on the subepithelial side, but no definite deposits. In the second biopsy, IgA deposits were extended to the peripheral capillary walls, but electron microscopic examination was not available. Two months after the second biopsy, the patient returned for hemodialysis.

Diffuse Glomerular Basement Membrane Lamellation in Post-Transplant IgA Nephropathy

Diffuse glomerular basement membrane (GBM) lamellation, reminiscent of Alport's syndrome, has rarely, and exclusively, been reported in renal allografts from pediatric donors to adult recipients. We report on a similar lesion, identified in a 42-year-old male, who received a kidney from an unrelated 21-year-old living male donor. The disease of the recipient was unknown. Renal allograft biopsies were performed 3.5 and 4.8 years after the renal transplantation, due to massive proteinuria and serum creatinine elevation. The histological features of both biopsies were similar, but more advanced in the second biopsy. Glomerular mesangium was widened and had an IgA deposit in the first biopsy. In addition to the presence of mesangial electron dense deposits, the GBM showed diffuse lamellation and splintering on the subepithelial side, but no definite deposits. In the second biopsy, IgA deposits were extended to the peripheral capillary walls, but electron microscopic examination was not available. Two months after the second biopsy, the patient returned for hemodialysis.

Electron microscopic study of the cases of minimal change nephrotic syndrome with mesangial IgA deposition

Twenty-five cases of minimal change nephrotic syndrome(minimal change disease, MCD) with mesangial IgA deposition were evaluated electron microscopically. The thickness of the glomerular basement membrane(GBM) was 3875 +/- 1271 A and 3056 +/- 1201 A in adults and children, respectively. Alteration of the GBM was noted in 3 adults and eight children: splitting in 4, focal thinning in one, widening of the lamina rara interna in 10, and widening of the lamina rara externa in 4 cases. Minimal mesangial electron dense deposits were found in all but one adult, and an increase of the mesangial matrix and minimal mesangial proliferation were observed in 8 and 6 cases, respectively. Electron microscopic findings show representative findings of MCD in our cases. A relationship between the GBM alterations in these cases and frequent association of hematuria is suggested and discussed.

Significance of mesangial IgA deposition in minimal change nephrotic syndrome: a study of 60 cases

We studied 60 cases of minimal change nephrotic syndrome (MCNS) with mesangial IgA deposits occurring over a 6 year period. There were 43 adults and 17 children. Hematuria occurred in 69.0% of the adults and 88.2% of the children. Two adults and six children had gross hematuria during the course of the disease. Mesangial IgA deposits were noted in 100% of the cases, and concomitant IgG or IgM deposits were found in 78.6% of adults and 73.7% of children. The fluorescent intensity of mesangial IgA deposits was trace (+/-) to 1+ in 86.1% and 70.6% of the adults and children respectively. Most of the patients showed electron microscopic findings consistent with minimal change nephrotic syndrome. We speculate that most of our cases are variants of minimal change nephrotic syndrome but are neither IgA nephropathy nor an overlapping syndrome, and that environmental or genetic factors may be related to the deposition of IgA in these MCNS patients.