Regression of IgA nephropathy: a repeat biopsy study

Abstract

Histological cure of immunoglobulin A (IgA) nephropathy has been reported only rarely in adults. To elucidate the reversibility of established IgA nephropathy, we performed a repeat biopsy study. A second biopsy was performed in 35 patients with IgA nephropathy in whom hematuria, an essential finding of IgA nephropathy, had disappeared (proteinuria also had disappeared in 23 patients) after a treatment protocol involving high doses of methylprednisolone and tonsillectomy. The interval between the first and second biopsy was 18 to 138 months (mean, 77.1 months). Mean serum creatinine level was 1.11 +/- 0.35 (SD) mg/dL (range, 0.6 to 1.9 mg/dL) at the time of the first biopsy and 0.96 +/- 0.24 mg/dL at the time of the second biopsy. Mesangial proliferation was significantly reduced in second-biopsy specimens (mesangial proliferation score: first-biopsy specimens, 2.49 +/- 0.74; second-biopsy specimens, 0.91 +/- 0.89; P < 0.001). Acute inflammatory glomerular lesions, such as endocapillary proliferations, glomerular tuft necrosis, and cellular crescents, were present in 32 patients in first-biopsy specimens, whereas these were no longer present in any of the second-biopsy specimens. Although no significant difference in percentage of globally sclerotic glomeruli was observed between the first and second biopsy specimens, the percentage of segmentally sclerotic glomeruli was significantly lower in second-biopsy specimens (P < 0.001). Interstitial mononuclear cell infiltration was markedly reduced in second-biopsy specimens (P < 0.001). The area of renal cortex affected by interstitial fibrosis and/or edema was significantly reduced in second-biopsy specimens (first-biopsy specimens, 21.4% +/- 20.3%; second-biopsy specimens, 9.6% +/- 11.7%; P < 0.01). The distribution of IgA mesangial deposits had diminished in most patients, and no IgA deposits were seen in second-biopsy specimens from 8 patients. These findings indicate that mesangial proliferation and interstitial changes in IgA nephropathy are reversible to a considerable extent. A histological cure may be obtainable in a considerable proportion of patients, especially if treatment is initiated at a relatively early stage.