Steen Olsen

Cortical interstitial tissue and sclerosed glomeruli in the normal human kidney, related to age and sex

The relative amount of interstitial cortical tissue was measured by the point count method in kidney tissue from human individuals without renal disease. One series (54 kidneys) consisted of kidneys intended for transplantation and removed immediately after death from persons who died suddenly. The other series (69 kidneys) was obtained by autopsy. In both groups, the percentage of interstitial tissue was dependent on age and followed the equations of regression (1) y=12.45+0.11 x (donor series) and (2) y=23.8+0,10 x (autopsy series). The autopsy values were significantly greater than the donor-kidney-values. There was no difference due to sex. The relative number of sclerotic, obsolescent glomeruli was very small (0–1%) until the age of 40. Thereafter it increased, most markedly in the autopsy series, until it reached values of about 30% in persons more than 80 years old.

Endocapillary glomerulitis in the renal allograft

Endocapillary glomerulitis is characterized by an increase in number of mononuclear cells in the glomerular capillary lumina. This lesion has been described in the early posttransplant period, but its pathogenesis, relation to conventional rejection, and prognostic impact is not well known. Using the definitions, scorings, and gradings of the Banff system for classification and grading of histopathologic changes in the renal allograft, we have analyzed 444 consecutive renal allograft biopsies from the first 90 days posttransplant. Moderate or severe glomerulitis occurred in 13.5% of the biopsies. There was a strong tendency toward clustering of glomerulitis: if one biopsy from a patient had glomerulitis, there was a high probability that it occurred in other biopsies from the same patient. There was some correlation with conventional acute rejection, but 40% of all biopsies with glomerulitis had no rejection and 53% of all biopsies with rejection had no glomerulitis. Graft function at biopsy was nil or decreased in many patients, but this could largely be explained by the independent presence of primary graft dysfunction or conventional rejection, these conditions being a frequent indication for performing a graft biopsy. Moderate or even severe glomerulitis was, however, compatible with a functioning graft. No correlation between glomerulitis and active CMV infection was found. The one-year graft survival of grafts with early posttransplant glomerulitis was 66%. If early conventional acute rejection is taken into consideration, graft survival does not seem to be influenced by the presence of glomerulitis. Early posttransplant endocapillary glomerulitis may be a peculiar pattern of rejection with a pathogenesis different from that of conventional rejection, but the present investigation does not demonstrate any adverse effects on graft function or graft prognosis.

Morphologic renal changes during cyclosporine treatment of psoriasis: Studies on pretreatment and posttreatment kidney biopsy specimens

BACKGROUND Because of concern about long-term renal toxicity from low-dose cyclosporine therapy, we studied kidney biopsy specimens in psoriasis patients treated with this drug. OBJECTIVE The purpose of the study was to investigate whether any morphologic changes appear after approximately 1 year of treatment. METHODS Pretreatment and posttreatment renal biopsy specimens were performed in 12 psoriasis patients treated with cyclosporine in dosages from 1.8 to 6 mg/kg/day for 6 to 18 months. RESULTS The study disclosed a slight but significant increase in interstitial fibrous tissue, which negatively correlated with creatinine clearance. The findings were similar to those described in patients receiving higher dosages of cyclosporine. CONCLUSION The clinical relevance of these so-far minor changes is unknown and does not exclude the use of cyclosporine in severe psoriasis; however, they should be taken into consideration in so-called low-dose therapy.

Ultrastructural analysis of human proximal tubules and cortical interstitium in chronic renal disease (Hydronephrosis)

A systematic ultrastructural analysis of proximal tubule atrophy and cortical interstitial changes was carried out in human chronic nephropathy. The investigation was based on human hydronephrotic kidneys, which had been surgically removed and subsequently perfusion-fixed for light and electron microscopy. Normal kidney tissue, which was derived from nephrectomy specimens with pathological changes confined to part of the kidney or to the renal pelvis, was used for control material. A slight degree of proximal tubule atrophy was characterized by reduction of mitochondria and basolateral membranes, enlargement of large endocytic vacuoles and increased numbers of lysosomes containing lamellar material. In moderate atrophy these changes were further accentuated, and in addition there was an increasing loss of microvilli and a reduction of endocytic invaginations and small endocytic vacuoles. In severe atrophy all types of organelles were sparse and the architecture of the tubule cells greatly simplified. A distinctive feature of atrophic tubules was the presence in the tubule cells of large bundles of actin-like filaments, which were often associated with outpouchings of basal cell parts and basement membrane. The reduction of mitochondria and basolateral cell membranes and the changes of endocytic vacuoles and lysosomes indicate that proximal tubule atrophy also in early stages may be associated with impairment of tubular transport processes. Comparisons with previous observations in various types of experimentally induced tubule cell degeneration and with the ultrastructure of regenerating proximal tubule cells provide some evidence that degenerative changes as well as imperfect regeneration of tubule cells may contribute to the alterations of ultrastructure in tubular atrophy. It is suggested that changes of the cortical interstitium may be of pathogenic importance for the progression of tubular atrophy by altering the spatial relationships between tubules and capillaries.

Segmental localization and quantitative characteristics of tubulitis in kidney biopsies from patients undergoing acute rejection

The term tubulitis denotes infiltration of the renal tubular epithelium by mononuclear cells. Tubulitis is one of the most reliable signs of acute renal allograft rejection. However, its segmental localization and quantitative characteristics are not precisely known. To investigate this question, formalin-fixed kidney biopsy specimens from 15 patients with transplanted allografts undergoing acute rejection were studied stereologically by identifying cortical tubules with segment-specific markers. The periodic acid-Schiff reaction, peanut lectin, and antibodies against Tamm-Horsfall protein and epidermal cytokeratins, all applied to the same section, were used to identify the profiles of proximal tubules (PTs), distal convoluted tubules (DCTs), distal straight tubules (DSTs), and the cortical collecting system (CCS, connecting tubules and cortical collecting ducts), respectively. Two parameters, the relative intrasegmental length and the average intensity of tubular damage, were determined to describe the degree of tubulitis quantitatively. Tubulitis was most prominent in the DCTs, followed by the CCS. The average intensity of tubulitis was lowest in the DSTs. The results indicate that the PTs are not the main site of tubulitis, despite the fact that they are regarded primary targets of the rejection response.

Acute tubulointerstitial nephritis: phenotype of infiltrating cells and prognostic impact of tubulitis

The prognostic impact of tubulitis and the phenotype of the infiltrating cells in the tubules were studied in ten percutaneous renal biopsies from six patients with acute tubulointerstitial nephritis (ATIN). The inflammatory cell subsets in the tubules and interstitium (CD3+, CD4+, CD8+, CD20+, CD45RO+, CD56+, CD57+, CD68+ and TIA-1+ cells), the expression of vimentin and the proliferation-associated antigen Ki-67 by cortical tubular cells, and the grade of tubulitis, interstitial infiltration and fibrosis were analysed. Cytotoxic injury to tubular cells in the vicinity of tubular-wall-localized lymphocytes was studied ultrastructurally. ATIN was drug-induced in three patients, related to Legionella infection in two and idiopathic in one patient. Four patients recovered, one with reduced renal function. Two patients developed end-stage renal disease. CD8+ and CD4+ lymphocytes, and a smaller number of macrophages, infiltrated the tubules. The predominant lymphocyte subset in the tubules was the same as in the interstitium. Cytotoxic injury to tubular cells was not seen electron microscopically. The tubular cells exhibited increased proliferative activity and expressed vimentin, indicating non-specific tubular damage. The cell subset, the severity of tubulitis, and the tubular expression of vimentin were not related to outcome. the main prognostic factor was the severity of the interstitial fibrosis. Tubulitis in ATIN may be a harmless non-immune reaction, mediated by tubular expression of cytokines, together with adhesion and other molecules.

Spontaneous dissecting aneurysm of the renal arteries

A case of dissecting aneurysm of the renal arteries is presented. The patient suffered from an intractable subarachnoid bleeding and the kidneys had been selected for transplantation. One kidney was never transplanted, the other was transplanted and rejected after few days. Dissecting aneurysms were present in the main artery and its major ramifications in both kidneys. Many investigators have claimed that dissecting aneurysm and fibromuscular dysplasia of the renal artery are different stages of but one disease. A review of the accumulated literature on dissecting aneurysm of the renal artery reveals, however, that this disorder shows a preponderance of middle-aged men, whereas fibromuscular dysplasia of the renal artery affects adolescent girls. It is concluded that the two disorders of the renal artery most likely represent different vascular diseases.

Hereditary progressive cerebral leucodystrophy.

Hereditary progressive cerebral leucodystrophy is the designation introduced by Bielschowsky & Henneberg (1928) for those disease groups which may be regarded as hereditary abiotrophies, the terminal stage of which is widespread and elective destruction of the white matter of the entire cerebrum. Even since Pelizaeus (1885) described five cases of hereditary disease of the CNS, quite a number of case reports and reviews have appeared in the literature. Classifications of the leucodystrophies have been proposed by several authors, for example Krabbe (1947), Einarson, Nee1 & Sfromgren (1944) , Poser & van Bogaert (1956) and Greenfield (1958) . These classifications are established on a clinical, genetic, pathological or histochemical basis. A s intensive histochemical, electron-microscopic and neurochemical studies have been made in recent years, and as other current studies will undoubtedly yield further results, the above classifications must be regarded as merely provisional. Poser (1961) proposed the theory in 1957 that the leucodystrophies should really be regarded as “dysmyelinating diseases”, in contrast to true demyelinating diseases such as multiple sclerosis, diffuse sclerosis of the Schilder (1912) type, Balo’s disease and Devic’s disease. The leucodystrophies appear to be characterized by a disturbance of myelin anabolism, which may be regarded as the end result of an “inborn error of metabolism”. On this view the leucodystrophies would be closely related to the lipidoses; such a relationship was suggested by Wicke (1939) , Norman (1947) and Einarson (1951) , and later developed by Poser (1961) , who quotes the recent neurochemical studies of Diezel (1955) and Edgar (1957), for example, as bearing out this relationship. On the basis of our present knowledge, therefore, it would appear that the leucodystrophies and the lipidoses should be classified together. It would be of value in clinical studies to classify this large collective