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Glomerular Density in Renal Biopsy Specimens Predicts the Long-Term Prognosis of IgA Nephropathy

Nobuo Tsuboi^*, Tetsuya Kawamura^*, Kentaro Koike^*, Hideo Okonogi^*, Keita Hirano^*, Akihiko Hamaguchi^*, Yoichi Miyazaki^*, Makoto Ogura^*, Kensuke Joh, Yasunori Utsunomiya^*, and Tatsuo Hosoya^*

^* Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan; and Division of Renal Pathology, Clinical Research Center, Chiba-East National Hospital, Chiba, Japan

Correspondence: Dr. Nobuo Tsuboi,Division of Kidney and Hypertension, Department of Internal Medicine, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-Ku, Tokyo, Japan. Phone: 81-3-3433-1111; Fax: 81-3-3433-4297; E-mail: nobuotsuboi{at}aol.com

Background and objectives: An early histopathologic predictor of the renal prognosis, before the occurrence of advanced glomerular sclerosis/interstitial fibrosis and/or apparent renal dysfunction, remains to be established in IgA nephropathy (IgAN). This study aimed to determine whether the glomerular density (GD; nonsclerotic glomerular number per renal cortical area) of biopsy specimens obtained at an early stage of IgAN could predict the long-term renal outcome.

Design, setting, participants, & measurements: The predictive value of the factors at biopsy, including the GD, on the renal outcome was retrospectively analyzed for 98 patients who had IgAN with an estimated GFR of 60 ml/min per 1.73 m² at biopsy (87 ml/min per 1.73 m² on average).

Results: The individual value of GD in biopsy ranged from 1.2 to 8.1/mm² (i.e., approximately a seven-fold variation), and the GD showed a close inverse correlation with mean glomerular volume. Among the various clinicopathologic factors involved, both a cellular/fibrocellular crescent and the GD were found to be significant predictors of progression in multivariate analyses. A low GD in the biopsy specimens was frequently associated with a steeper slope of the renal function and a synergistically enhanced risk for progression with the presence of cellular/fibrocellular crescent. The renal function, proteinuria, degrees of glomerulosclerosis, and interstitial fibrosis at biopsy were not independent predictors of the prognosis in these patients.

Conclusions: A strong predictive relationship of low GD with progression observed in this study suggests that GD may serve as an early histopathologic marker of long-term renal prognosis in IgAN.