Measurement of proliferation in renal biopsy specimens: Evidence of subclinical tubular damage in the nephrotic syndrome

Background. Proliferating cells can be detected in histological material in various ways, This investigation was to study the feasibility and usefulness of application of proliferation markers to routine renal biopsy specimens. Methods. One hundred and thirteen renal biopsies fixed in formalin and embedded in paraffin were studied immunohistologically using antibody MIB 1, which recognises the Ki-67 antigen. Twenty-two biopsies were also immunostained with antibody PC10 against proliferating cell nuclear antigen. Results. PC10 stained nuclei in all biopsies, including those that were negative with MIB 1. MIB 1 stained nuclei in endocapillary sites to various extents, and there was an average of less than one stained endocapillary nucleus per glomerulus in biopsies with IgA nephropathy and IgM nephropathy, conventionally regarded as types of proliferative glomerulonephritis. Glomerular extracapillary nuclei were stained by MIB 1 in vasculitic disorders and at the site of tip changes. MIB 1 also stained nuclei in the arterial intima, especially in vascular rejection, and in interstitial tissues, correlating with renal excretory function. Tubular nuclei stained by MIB 1 were common in biopsies from patients with renal impairment and in a group with the nephrotic syndrome, in many of whom renal function was normal. Conclusions. The main conclusions are that (1) immunohistological markers of proliferation can be applied to routine renal biopsy material; (2) PC10 appears to overestimate proliferation compared with MIB 1; and (3) there is evidence of subclinical tubular damage in the nephrotic syndrome, shown by increased tubular proliferation without clinical renal impairment. This observation seems not to have been made previously.