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Notes: 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 〈link href="#t1"〉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 (〈link href="#t1"〉Table 1).〈tabular xml:id="t1"〉1〈title type="main"〉 Histological scoring 〈table frame="topbot"〉〈tgroup cols="5" align="left"〉〈colspec colnum="1" colname="col1" align="left"/〉〈colspec colnum="2" colname="col2" align="center"/〉〈colspec colnum="3" colname="col3" align="center"/〉〈colspec colnum="4" colname="col4" align="center"/〉〈colspec colnum="5" colname="col5" align="center"/〉〈thead valign="bottom"〉〈row rowsep="1"〉Score0123〈tbody valign="top"〉〈entry namest="col1" nameend="col5" align="left"〉AI: Activity Index〈entry namest="col1" nameend="col5" align="left"〉G: glomerularm: mesangial hypercellularity−〈 40%〈 80%≥ 80%i: intracapillary macrophage infiltration−+++e: cellular crescent0〈 30%≥ 30%〈entry namest="col1" nameend="col5" align="left"〉I: tubulointerstitiali: interstitial inflammation−+++t: tubulitis−+++〈entry namest="col1" nameend="col5" align="left"〉CI: Chronicity Index〈entry namest="col1" nameend="col5" align="left"〉G: glomerulars: 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%〈note xml:id="t1_note5" numbered="no"〉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 (〈link href="#t2"〉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) (〈link href="#t3"〉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 (〈link href="#t4"〉Table 4).〈tabular xml:id="t2"〉2〈title type="main"〉 Application criteria of steroid therapy 〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP15:NEP_15_t2"/〉〈tabular xml:id="t3"〉3〈title type="main"〉 Comparison of steroid (−) with steroid (+) in the group of ‘necessary’ 〈table frame="topbot"〉〈tgroup cols="4" align="left"〉〈colspec colnum="1" colname="col1" align="left"/〉〈colspec colnum="2" colname="col2" align="center"/〉〈colspec colnum="3" colname="col3" align="center"/〉〈colspec colnum="4" colname="col4" align="center"/〉〈thead valign="bottom"〉〈row rowsep="1"〉steroid therapy+− P 〈row rowsep="1"〉no.1320〈tbody valign="top"〉〈entry namest="col1" nameend="col4" align="left"〉At Renal Biopsyage (years)〈entry align="char" char="[plusmn]"〉31.5 ± 12.936.3 ± 13.0nsUP (g/day)〈entry align="char" char="[plusmn]"〉2.3 ± 1.91.3 ± 0.5〈 0.05Cr (mg/dL)〈entry align="char" char="[plusmn]"〉0.8 ± 0.30.9 ± 0.1nsCCr (mL/min)〈entry align="char" char="[plusmn]"〉111 ± 4392 ± 34nsHypertension (n)19ns+ ACEI (n)410nsFollow-up years from
 renal biopsy〈entry align="char" char="[plusmn]"〉6.8 ± 2.39.2 ± 4.0ns〈entry namest="col1" nameend="col4" align="left"〉End of follow-upCr (mg/dL)〈entry align="char" char="[plusmn]"〉0.8 ± 0.35.5 ± 6.6〈 0.01 Normal renal function
 (n)127 Renal insufficiency (n)16〈 0.01 Dialysis (n)07〈tabular xml:id="t4"〉4〈title type="main"〉 Change of urine protein in the 13 cases with steroid treatment in the group of 'necessary' 〈mediaResource alt="image" href="urn:x-wiley:13205358:NEP15:NEP_15_t4"/〉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.

Notes: Abstract Background. Tissue amyloid P component is a normal constituent of the human glomerular basement membrane (GBM) and is immunologically identical to the serum amyloid P component, a major DNA binding protein in serum. We postulate that DNA or nucleosome core particles could bind to human GBM via the amyloid P component. Methods. An immunofluorescence study was used to detect the amyloid P component of the GBM. An enzyme-linked immunosorbent assay system was used to test the binding capacity of calf thymus DNA and chicken erythrocyte nucleosome core particles to a preparation of human GBM. Results. Amyloid P component was detected along the capillary wall of the human glomerulus by immunofluorescence. DNA and nucleosome core particles bound to human GBM in a dose-dependent manner in the presence of Ca2+. Digestion of GBM with trypsin resulted in the reduction of binding of anti-serum amyloid P antibody, DNA, and nucleosome core particles to the GBM. Anti-serum amyloid P component (SAP) IgG blocked the binding of DNA and nucleosome core particles to the GBM. Conclusion. DNA and nucleosome core particles bind to the GBM through amyloid P components.

Notes: Abstract  A case of diffuse mesangial sclerosis (DMS) associated with Kawasaki disease is reported. A previously healthy Japanese girl, aged 4 months, presented with clinical features of Kawasaki disease. At week 10 of the illness, she developed the nephrotic syndrome, which was refractory to steroid therapy. Renal biopsy demonstrated a diffuse mesangial proliferative glomerulonephritis with microcystic tubular dilatation and, ultrastructurally, marked thinning of the lamina densa in the glomerular basement membrane (GBM) and the tubular basement membrane (TBM) of the proximal tubule. She went into chronic renal failure and died at the age of 11 months. At autopsy, the kidney revealed DMS. Histologically, we found Finnish microcystic disease in its early stages in the biopsy. Using a newly developed monoclonal antibody, we analysed the alpha chains (α1–α6) of type IV collagen in the GBM and TBM. There was no defective constitution of alpha chains on the thin GBM, but the thin TBM of the microcystic proximal tubule showed a weak or discontinuous reactivity for α1 and α2 chains, suggesting faulty formation of the basement membrane. The sclerosing glomeruli of the DMS did not depend on collapse of the GBM, which was positive for α3–α5 chains, but mainly on the proliferation of mesangial matrix, which was positive for α1 and α2 chains.

Notes: Abstract  Renal involvement is rare in chronic active Epstein-Barr (EB) virus infection. We report a case of a 7-year-old girl with recurrent EB virus infection. She had fever, lymphadenopathy, hepatosplenomegaly, and persistently high titres of IgG to EB virus capsid antigen (VCA) and IgG to EB early antigen with low titres of IgM to VCA. She showed mild haematuria and proteinuria, but had no symptoms of renal failure. Renal biopsy revealed immune complex-mediated glomerulonephritis, which may have been due to a persistently high titre of antibody against EB virus. In addition, a peculiar form of tubulointerstitial nephritis was found. The morphology was characterized by a papillary infolding of the tubular epithelial cell layer into the tubular lumen. The interstitium was surrounded by the infolded epithelium and contained a large number of B-cell dominant lymphocytes. EBV-encoded RNA 1 (EBER-1) gene was detected in the nuclei of some tubuloepithelial cells by in situ hybridization and may have been associated with the pathogenesis of tubulointerstitial nephritis.