Ultrastructural lesions in lightmicroscopically defined types of glomerulonephritis. A blind and semiquantitative study.

Current classification of glomerulonephritis (GN) is based primarily on light microscopical (LM) histopathological criteria. The aim of the present study was to investigate the occurrence and severity of a number of electron microscopical (EM) lesions in different LM defined classes of GN in order to determine the degree of homogeneity of these classes and the degree of specificity of various EM lesions seen in GN. The analysis was performed using a blind, systematic and semiquantitative method and applied on 91 consecutive biopsies from patients with GN as well as on 11 reference biopsies. Most of the EM lesions were not restricted to a single or a few light microscopically defined classes of GN. EM lesions having direct LM counterparts used as classification criteria were generally present with high scores in the corresponding LM classes but were also present in other types of GN. When the EM-findings were compared with our original classification of the 91 biopsies it was found that about 13% of all biopsies were classified erroneously using only LM. Thus, the groups obtained with the presently used LM classification system are quite heterogenous with respect to ultrastructure and probably with respect to pathogenesis. On the other hand, it appears that many ultrastructural lesions display a more or less continuous spectrum of changes which therefore are difficult to use for classification purposes.

Chronic interstitial nephropathy in patients on long-term lithium treatment.

One-hundred and ten patients treated with lithium for more than six months were studied in order to determine the prevalence of lithium induced nephropathy. Eighteen of 69 patients (26 per cent) who had been treated for more than two years presented a chronic interstitial nephropathy characterized by a marked decrease in renal concentrating ability with a disproportionate preservation of glomerular filtration rate. Histologically, increased amounts of fibrotic tissue in the medulla and the cortex were found together with tubular atrophy. In 40 per cent of the patients who underwent renal biopsy, cystic formations in the cortex were found. The impairment of renal concentrating ability could be related to the duration of lithium treatment and the degree of tubular damage correlated with the degree of impairment of renal concentrating ability. Lithium induced, chronic nephropathy is a rather common complication of long-term lithium treatment and reduces the patients capacity to regulate water and electrolyte metabolism. As water and electrolyte loss appears to precede the slowly progressing lithium intoxication, the main hazard of lithium induced nephropathy is lithium intoxication.

Evaluation of a procedure for systematic semiquantitative analysis of glomerular ultrastructure in human renal biopsies.

A method is described for systematic semiquantitative investigation of glomerular ultrastructure in renal biopsies from patients with glomerulonephritis. Three glomeruli per biopsy were studied by electron microscopy. Ten systematically recorded micrographs at x12,000 and a montage covering the whole glomerular cross-section at x3,000 were analyzed from each glomerulus. The severity of each of 34 different ultrastructural lesions was semiquantitatively evaluated on a 4-degree scale, 0 to +++. The usefulness of the method was evaluated by calculating different parameters for the reproducibility of semiquantitative scoring, representativeness of micrographs, and representativeness of glomeruli. The reliability of the method was considered good or acceptable with respect to 17 of the lesions. Ten lesions obtained a high reproducibility of scoring but the usefulness of the scores was limited due to a segmental and/or focal distribution of these lesions. The evaluation of these lesions can be improved by analyzing a larger number of micrographs, or glomeruli, or both. Seven lesions were so rare in the present biopsies that no statistical evaluation was possible. When applied to a large number of biopsies, this practical and useful method allows a reproducible comparison of the patterns of ultrastructural lesions in various types of glomerulonephritis.

Lithium-induced focal interstitial fibrosis in the rat kidney.

An early stage of focal cortical interstitial fibrosis and nephronic atrophy was found by light microscopy in the kidneys of nine out of twelve rats which had received lithium for 9 weeks. The animals had excessive polyuria and increased requirement for sodium. The histological changes were in their distribution and the morphological structure similar to the lesions recently found in renal biopsy specimens from patients on long-term lithium treatment.

Renal function and renal pathology in patients with lithium-induced impairment of renal concentrating ability.

Lithium-induced impairment of renal concentrating ability is regarded as a harmless side effect of lithium treatment. This report presents investigations of renal function and renal pathology in 13 patients with reduced renal concentrating ability arising during lithium treatment. The reduced concentrating ability parallels histological damage and is a sign of lithium-induced chronic nephropathy.