Evaluation on the effect of steroid therapy for the outcome of IgA nephropathy in adults on the basis of histological scoring: A clinicopathologic study of 104 cases

Application criteria of steroid therapy for the patients of IgA nephropathy (IgAN) have not yet been established. The purpose of the present study was to establish retrospectively the clinical and pathological criteria for the steroid therapy by using a histological scoring on 104 adult patients of IgAN. Steroid therapy was designated as an administration of prednisolone in the amount of more than 30 mg per day in the period of more than 4 weeks within 1 year of kidney biopsy. We developed our own scoring system for the following main glomerular and tubulointerstitial changes as shown in Table 1. The histological scoring was expressed by evaluating semiquantitatively the extent of glomerular and tubulointerstitial lesions in terms of activity index (AI) and chronicity index (CI). Activity index is the sum of graded score according to the extent of glomeruli with mesangial hypercellularity, intracapillary macrophagic infiltration and cellular crescent as well as to the extent of interstitial inflammation and tubulitis. Chronicity index is the sum of graded score according to the extent of glomeruli with global sclerosis, increase of extracellular matrices or periglomerular fibrosis, and tuft adhesion or fibrous (or fibrocellular) crescent as well as to the extent of interstitial fibrosis ( Table 1). 1 Histological scoringScore 0 1 2 3AI: Activity Index G: glomerular m: mesangial hypercellularity − < 40% < 80% ≥ 80% i: intracapillary macrophage infiltration − + ++ e: cellular crescent 0 < 30% ≥ 30% I: tubulointerstitial i: interstitial inflammation − + ++ t: tubulitis − + ++ CI: Chronicity Index G: glomerular s: global sclerosis < 10% < 30% < 50% ≥ 50% i: increase of extracellular matrix < 10% < 30% < 50% ≥ 50% e: fibrous (or fibrocellular) crescent, adhesion < 10% < 30% < 50% ≥ 50%I: tubulointerstitial
 interstitial fibrosis < 10% < 30% < 50% ≥ 50%AI: AGm + AGi + AGe*2 + AIi + Ait, CI: CGS + CGi + CGe + CIFor the applicability of steroid therapy, three groups were categorized by evaluating the statistical significance for the correlation of AI, CI and daily amount of urine protein to the outcome of the patients as follows ( Table 2). In group A (inappropriate indication of steroid therapy) which showed CI ≥ 5 alone, 10 out of 11 cases revealed decline of renal function (Cr ≥ 1.2 mg/dL and Ccr < 80 mL/min) within 2.2–19.3 years (mean 9.0 ± 6.4 years) without respect to steroid therapy. In group B (unnecessary indication of steroid therapy) which showed CI < 5, AI < 5, and UP < 1 g/day, 58 out of 60 cases showed normal renal function (Cr < 1.2 mg/dL and Ccr ≥ 80 mL/min) within 4.2–21.6 years (mean 10.1 ± 4.7 years). In group C (necessary indication of steroid therapy) which showed CI < 5 and AI ≥ 5 or UP ≥ 1 g/day, patients with steroid therapy revealed significantly higher incidence of outcome with normal renal function (12 out of 13 patients, final evaluation of renal function in 6.8 ± 2.3 years after renal biopsy) than that of the patient without steroid therapy (seven out of 20 cases, evaluation of renal function in 9.2 ± 4.0 years after renal biopsy) ( P < 0.01) ( Table 3). In the 13 patients with steroid therapy in group C (steroid pulse in four patients, prednisolone 40 mg/day internally in three patients, predonisolone 30 mg/day internally in six patients) showed a significant decrease of proteinuria and remained until final evaluation time ( Table 4). 2 Application criteria of steroid therapy3 Comparison of steroid (−) with steroid (+) in the group of ‘necessary’steroid therapy + − Pno. 13 20At Renal Biopsy age (years) 31.5 ± 12.9 36.3 ± 13.0 ns UP (g/day) 2.3 ± 1.9 1.3 ± 0.5 < 0.05 Cr (mg/dL) 0.8 ± 0.3 0.9 ± 0.1 ns CCr (mL/min) 111 ± 43 92 ± 34 ns Hypertension (n) 1 9 ns + ACEI (n) 4 10 ns Follow‐up years from
 renal biopsy 6.8 ± 2.3 9.2 ± 4.0 ns End of follow‐up Cr (mg/dL) 0.8 ± 0.3 5.5 ± 6.6 < 0.01Normal renal function
 ( n ) 12 7Renal insufficiency ( n ) 1 6 < 0.01Dialysis ( n ) 0 74 Change of urine protein in the 13 cases with steroid treatment in the group of 'necessary'From the results above, our evaluation system using histological scoring together with grading proteinuria was proven to be useful in estimating the applicability of steroid therapy for adult IgAN patients.