John A. Nordquist

An analysis of the relationship of malignant lesions of the kidney to hypertension.

Abstract This study, designed in a “blind” fashion, presents, for the first time, a relationship of the histopathology of the kidneys with mean arterial blood pressure (MAP) and age in hypertensive species. Kidneys from 46 spontaneously hypertensive rats (SHR) aged 8–104 weeks were studied using light and electron microscopy (LM and EM, respectively), and their findings were compared with those in age-matched 35 normotensive Wistar rats (NR) and 28 Wistar-Kyoto rats (WKY). A scoring system for the severity of the renal changes (index scores) was developed, and the grading of the renal changes was made without any knowledge of age, MAP, or strain of rat from which kidneys were obtained. The severe (or malignant) renal lesions were found only in old SHR (av: 91 weeks), in contrast to mild or moderate renal lesions (benign) in young SHR (52 weeks or less). The findings of highly significant ( P P

Glomerular thrombosis in spontaneously hypertensive rat. II. Immunofluorescence microscopy. III. Effect of heparin

Abstract This study describes immunofluorescence microscopy (IFM) of kidneys of untreated (or saline-treated) spontaneously hypertensive rats (SHR) and compares the findings with those in age-matched, untreated normotensive Wistar Kyoto rats (WKY), and heparin treated (150 units aqueous heparin subcutaneously twice daily for 30 days) SHR. The rats varied in age from 30 to 112 weeks (before treatment) and were divided into young ( 3 ), and albumin. The kidneys were evaluated also by light microscopy (LM) in all of the rats and by electron microscopy (EM) in half of the rats. A semiquantitative assessment of IFM findings on a 0 to 4+ scale and scoring of LM findings on a 0 to 39 scale were made. The glomerular lesions were more striking and uniform than the arterial vascular lesions in old SHR. The glomeruli of old SHR (av: 93 weeks) were positive for all the fluorescence materials except albumin. Fib was most marked (3+ to 4+) involving 50 to 75% of the glomeruli in 75% untreated (or saline treated) old SHR. Thrombi were found in the glomeruli also by LM and EM (large amounts of fibrin and platelet aggregates). The arterial vessels were unimpressive by IFM with the exception of those with arteritis in which 3+ to 4+ Fib was found. These findings in untreated (or saline treated) old SHR contrast with the inconspicuous LM, EM, and IFM findings in young SHR and WKY of all ages. Heparin-treated old SHR had significant ( P P

An etiology of nephrotic syndrome in chronic interstitial nephritis (pyelonephritis); an electron microscopic study.

Renal tissues were studied using electron microscopy (EM) and immunofluorescence microscopy (IFM) from three patients who were found to have chronic interstitial nephritis (pyelonephritis) by light microscopy (LM). By LM, 90% of the glomeruli in two patients and all glomeruli in one patient were normal. By EM, glomerular capillaries in all patients revealed generalized fusion of epithelial foot processes. In two patients, IFM for immunoglobulins, third component of complement and fibrinogen were negative. These two patients received corticosteroids for 6 to 12 weeks. In one, proteinuria markedly decreased (from 17.9 to 1.1 gm) in four weeks and in the other follow-up studies of renal histology revealed normal glomeruli and partial restoration of foot processes by LM and EM respectively. Thus, this study offers evidence for lipoid nephrosis (or minimal lesion disease) as an etiology of nephrotic syndrome in chronic interstitial nephritis (pyelonephritis). The impaired renal function in these patients is attributed to tubulo-interstitial disease rather than glomerular pathology. It remains to be determined whether the two disparate pathological conditions have coexisted or chronic interstitial nephritis had led to the appearance of lipoid nephrosis through an unidentified mechanism.

Membranous Glomerulonephritis: Virus-Like Inclusions in Glomerular Basement Membrane

Excerpt To the editor: Although numerous reports have been published on viral-like particles inside glomerular endothelial cells in collagen diseases (1-3), only rarely have such particles been fou...

Diabetic nephropathy associated with fibrin formation

This communication describes the electron microscopic study of a renal biopsy specimen from a patients with diabetic nephropathy, the nephrotic syndrome, and renal insufficiency. There were large amounts of electron dense materials within glomerular basement membranes and masses of fibrin within glomerular capillaries and Bowmans spaces. The presence of glomerular fibrin suggests that thrombosis may be pathogenetically related to diabetic nephropathy.

Glomerulopathy and arteriolopathy in congenital nephrotic syndrome: Light, electron, and fluorescence microscopy studies

This report describes the light, electron, and fluorescence microscopy studies of the kidney from a one month old, prematurely born infant with the nephrotic syndrome. Light microscopy revealed enlargement of Bowmans space, an excessive number of glomerular epithelial cell nuclei, and cystic dilatation of cortical tubules. By electron microscopy two disparate types of glomerular lesions were found: a thin basement membrane with fusion of foot processes suggestive of lipoid nephrosis and linear electron-density in the basement membrane with excessive mesangial matrix and capillary collapse suggesting an antibasement membrane type of glomerulonephritis or mesangial sclerosis. Conspicuous cystic spaces were found in the proximal tubules only. In the arterioles there were cystic spaces in the endothelial cells and smooth muscle cells, thickening of the basement membranes of endothelial cells and smooth muscle cells, and excessive amounts of nonstriated fibrils in the subendothelial basement membrane. Masses of fibrin were noted in the lumina of veins, peritubular capillaries, and interstitium between veins and peritubular capillaries. Such multiple glomerular and arteriolar lesions have not been reported previously in congenital nephrotic syndrome. These lesions suggest an antigen-antibody reaction in the mother that might have been directed toward the glomerular basement membrane in the fetus, producing these lesions.

Alterations in the Renal Medullary and Papillary Interstitial Cells in Experimental and Spontaneous (Essential) Hypertension

It is reasonably well established that renal medulla and papilla of animals (rat, dog, rabbit) contain vasodepressor or antihypertensive substances that consistently reduce blood pressure in hypertensive animals (Muirhead, 1976). Much indirect evidence points toward the presence of similar vasodepressor substance(s) in human kidneys (Muehrcke et al., 1970; Prezyna et al., 1973; Mandal et al., 1979). This hypothesis is further supported by the finding of large amounts of prostaglandins in human renal papilla (Vance et al., 1973). However, the question of where in the papilla the vasodepressor substances are synthesized and/or stored has yet to be completely resolved. Within the papilla exist many interstitial cells that appear to be secretory, since they contain dilated endoplasmic reticulum, ribosomes, and conspicuous granules. These renal papillary interstitial cells (RIC) are considered by many to be the most probable site for the formation of vasodepressor substance(s). Furthermore, the location of the RIC, juxtaposed as they are between the tubules and the peritubular capillaries, strongly supports this proposed function.