Malignant Nephrosclerosis Research Articles

IS VASOPRESSIN INVOLVED IN THE PATHOGENESIS OF MALIGNANT DESOXYCORTICOSTERONE HYPERTENSION IN RATS?

Rats with unilateral nephrectomy were offered 1% sodium chloride as drinking fluid and were injected with desoxycorticosterone trimethylacetate (D.O.C.-T.M.A.) at weekly intervals. During the fourth to seventh week after the start of the experiment, malignant hypertension developed in most of the animals: body-weight fell, reflecting volume depletion; serum osmolality and serum sodium and urea concentrations increased; in the kidneys malignant nephrosclerosis occurred. In such animals, plasma concentrations of arginine-vasopressin were increased ten-fold in comparison with control animals; intravenous injection of a specific vasopressin antibody resulted in a transient fall of blood-pressure (B.P.) to normal or subnormal levels, while the injection of an angiotensin-I or angiotensin-n antibody did not affect B.P. In control animals none of the antibodies had an effect on B.P. It is concluded that in the pathogenesis of malignant D.O.C. hypertension vasopressin plays a role similar to that of renin-angiotensin in malignant renal hypertension.

Immunofluorescence studies on renal tissue, tonsils, adenoids, nasal polyps, and skin of atopic and nonatopic patients, with special reference to IgE

Immunofluorescence studies were performed on tissues from atopic and nonatopic patients. When these tissues were tested with a fluorescein-labeled sheep anti-human-IgE serum the cytoplasm of plasma cells and the outer zone of mast cells showed fluorescence. In a series of 196 patients a correlation was found between the clinical diagnosis and atopic disease and bright mast cell membrane IgE fluorescence. The intensity of the mast cell IgE fluorescence did not appear to correlate with the IgE level in the serum. Intraepithelial mast cells were incidentally observed in tonsils, adenoids, and nasal polyps. IgE was not found in glomeruli or vessels in renal tissue from 192 patients, among whom were patients with malignant nephrosclerosis and the nephrotic syndrome with minimal lesions.

Salt and water balance and renin activity in renal hypertension of rats.

In male Sprague-Dawley rats, renal artery constriction in the presence of an inact contralateral kidney induced sodium retention (for 2-3 wk), moderate potassium loss,elevation of blood volume (BV), and an increase in water turnover. It is suggestedthat renal artery constriction activates the renin-angiotensin-aldosterone system, resulting in disordered regulation of salt and water balance and in blood pressure (BP) elevation. Subsequently, sodium balance was reestablished in one group of hypertensive rats. The previously retained sodium was kept in the body, and BV and reninactivity remained elevated. In a second group of animals, a malignant course of hypertension developed: BP surpassed a critical level of about 180 mmHg; sodium, potassium, and water were lost; BV declined; renin activity was further stimulated; and in the contralateral kidney malignant nephrosclerosis occurred. It is assumed that pressure diuresis and natriuresis induce a vicious circle: the increasing renin activity may maintain or further increase BP level, therby inducing further salt and water loss, etc.; high BP levels and high renin activities induce vascular damage and deterioration of renal function.

Primary malignant nephrosclerosis (author's transl)

Primary malignant nephrosclerosis shows a haemolytic-uraemic symptomatology and can be differentiated from secondary malignant nephrosclerosis on clinical and histological grounds. The disease was observed in 4 patients: a 25-year-old man and 3 women aged 19, 28 and 49 years. The disease is characterized by a fulminating course, malignant hypertension with progressive retinopathy, and development of progressive renal failure with subsequent irreversible anuria. In addition haemolytic anaemia or posthaemolytic states as well as consumption coagulopathy occur. In 2 cases schizozytes and in particular helmet-shaped forms could be demonstrated. On histology an obliterating necrotizing vascular change is seen which is limited to the kidneys as was demonstrated in one case by angiography. Therapeutic attempts included antibiotics, steroids, heparin, streptokinase, antihypertensive drugs, and haemodialysis. The 3 female patients died, the man survived after bilateral nephrectomy.

Diazoxide in the Management of Severe Hypertension

Fourteen patients with severe hypertension have been given i.v. diazoxide in a dosage of 5 mg/kg b.wt. The material comprised 2 patients with malignant nephrosclerosis, 4 with chronic nephropathy and severe reduction of renal function, 1 patient with chronic pyelonephritis, 1 with renovascular hypertension and 6 patients with essential hypertension and in malignant phase. All patients attained a controllable blood pressure. Eight patients remaining needed only one injection, while the remaining patients required 2-5 injections, and concomitant furosemide therapy. The retinopathy improved in most patients and renal function was unchanged in the azotemic patients. No serious adverse effects were seen, except one hypotensive episode. Diazoxide is easy to handle, dosage can be predetermined, monitoring is simple and we find diazoxide to be a valuable drug in severe hypertension.

Renal microvasculature in chronic renal failure.

The renal microvasculature was examined stereoscopically after intraarterial injection of silicone rubber. Specimens studied were: 29 cases of normal kidney, 4 cases of sclerotic kidney, 10 cases of acute renal failure, and 10 cases of chronic renal failure from the final stage of chronic glomerulonephritis, malignant nephrosclerosis, diabetic nephropathy, and cortical necrosis. The following were common evidences for chronic renal failure: much reduction and wide deficiencies of filling in the cortex, increased filling of vasa recta, narrowing and spiralling of interlobular arteries and cortical afferent arterioles, appearance of giant glomeruli, rarefaction of the peritubular capillary plexus, and relative preservation of glomeruli in the juxtamedullary zone and vasa recta in the medulla may be the major pathway, after the interlobular arteries and afferent arterioles in the subcapsular cortex are destroyed, and these vascular architectural changes may be intimately related to the pathophysiology of chronic renal failure.

Mast cells in the cortical tubular epithelium and interstitium in human renal disease

Review of 1 μ Epon embedded sections from 42 renal biopsy specimens revealed a striking and consistent increase in the number of interstitial mast cells in several types of kidney disease. Interstitial mast cells were increased more than 25-fold in case of chronic glomerulonephritis (6), chronic pyelonephritis (5), chronic renal allograft rejection (5), analgesic nephropathy (1), and malignant nephrosclerosis (1). In addition, accumulation of a heretofore unrecognized type of renal cell with a hypervacuolated cytoplasm and varying numbers of metachromatic cytoplasmic granules was observed within tubular epithelium, particularly in chronic glomerulonephritis and chronic pyelonephritis. Similar appearing cells have been observed in exceptional circumstances in other epithelia where they have been termed “schollenleukocyten” or “globule leukocytes.” The frequency of occurrence of these cells in several forms of renal disease is documented, and light and electron microscopic evidence indicating that they are degranulated mast cells is presented. These tubular mast cells are poorly visualized in routine histologic sections, even with toluidine blue, staining. The mechanism by which they appear in renal tubular epithelium and their function in renal disease are not known.

The vicious circle in acute malignant hypertension of rats.

1. In renal hypertensive rats, increase in blood pressure above 180 mmHg may induce sodium and water loss, reduced growth rate, elevated haematocrit, a marked rise in plasma renin concentration, an increase in renin extractable from the clamped and the contralateral kidney and malignant nephrosclerosis of the contralateral kidney. These symptoms characterize the malignant phase of renal hypertension in rats. 2. When water was given as drinking fluid, ten of eighteen rats developed signs of malignant hypertension and malignant nephrosclerosis within 3–4 weeks. Administration of 0.9% saline instead of water induced higher blood-pressure levels, but only five of eighteen rats showed malignant nephrosclerosis. When drinking fluid was changed from water to saline shortly before or shortly after the onset of malignant hypertension, the condition improved, and in only one of twelve rats was malignant nephrosclerosis observed. 3. It is concluded that in renal hypertensive rats sodium supplements may improve or prevent signs of malignant hypertension and the development of malignant nephrosclerosis.

Bilateral nephrectomy and renal homotransplantation for malignant nephrosclerosis.

The effects of hemodialysis, bilateral nephrectomy, and renal homotransplantation were evaluated in 12 patients with renal failure due to primary malignant hypertension. The blood pressure was difficult to control with hemodialysis, moderately high doses of antihypertensives, and dietary restriction. Bilateral nephrectomy resulted in significant reduction of diastolic blood pressure and reduction in the number and quantities of antihypertensive medication. Fourteen renal homografts were performed. Patient survival and transplant function compare favorably with other patients transplanted by us and those reported to the Human Transplant Registry. In the posttransplant period, hypertension was a problem in only two patients. The mean diastolic blood pressure was similar to that achieved by bilateral nephrectomy. Renal transplantation is an acceptable therapy for patients who have been treated by bilateral nephrectomy for malignant nephrosclerosis.

Peracute primary malignant nephrosclerosis with irreversible kidney failure and malignant hypertension following ovulation inhibitors

After brief treatment with 2 different estrogen-progestagen combinations, a previously normotensive 21-year-old woman developed malignant hypertension and progressive and irreversible renal failure. After 4 months of conservative treatment, bilateral nephrectomy was performed, normalizing the blood pressure. Nephrosclerosis was found in both kidneys. It was concluded that 1) oral contraceptives initiated a renal vascular process which was initially blood pressure independent and histologically described as malignant nephrosclerosis with secondary malignant hypertension and renal failure; 2) "primary" malignant nephrosclerosis should be differentiated from the "secondary" form, which results from accelerated hypertension; 3) the blood pressure should be checked regularly during the 1st months of oral contraceptive treatment.

Platelet embolic injury; the healing process

The impaction of emboli composed mainly of platelets at the bifurcation of arterioles in the renal cortex has been shown previously to produce severe endothelial injury and lipid accumulation in arteriolar smooth muscle, followed by a marked thickening of the intima. In this study magnesium aluminum wire was inserted into the rabbit aorta as a source of emboli composed of platelet aggregates. The healing of renal arteriolar lesions produced by the emboli was examined at intervals from 3 to 21 days. The distinctive electron microscopic features of the mononuclear cells, endothelial cells, and smooth muscle cells were described. The mononuclear cells were found to remove fibrin, red cell and platelet remnants, and to produce a mucopolysaccharide matrix. Endothelium then grew into the matrix displacing the monocytes. Lipid in smooth muscle was always associated with myofilament fragmentation and mitochondrial vacuolization suggesting that the lipid accumulation is a result of injury. Plaques of concentric intimal thickening were found to consist of condensed matrix and myointimal cells. At each stage the cell types remained distinctive and there was no suggestion that monocytes are transformed to endothelial cells. These lesions serve as a model for some of the features of the encrustation concept of atherosclerosis, in that intimal thickening follows on thrombosis, in this case thromboemoblism and is associated with lipid accumulation in smooth muscle cells. The injury begins with endothelial damage and disruption. The subsequent intimal thickening resembles the vascular lesion in chronic allograft rejection and malignant nephrosclerosis and also involves the intertubular arterioles and small arteries of the kidney.

Oliguric acute renal failure in malignant hypertension

Four cases of oliguric acute renal failure due to malignant nephrosclerosis are described. Four similar cases were found in a review of the English language literature. The main features in these patients were severe hypertension with diastolic pressures of 130 mm Hg or above, advanced hypertensive retinopathy and oliguria accompanied by rapidly progressive azotemia. Characteristically the patients demonstrated marked weight loss, left ventricular hypertrophy and microangiopathic hemolytic anemia. Kidney size was either normal or slightly reduced, and many had red blood cells and red cell casts in the urine sediment. The diagnosis of malignant nephrosclerosis was not suspected initially in any of the patients but was clearly established by renal biopsy. No restoration of renal function occurred despite vigorous antihypertensive therapy and maintenance dialysis. It is concluded that malignant nephrosclerosis should be a diagnostic consideration in patients with acute oliguric renal failure complicated by severe hypertension.

Morphological findings in microangiopathic hemolytic anemia.

The clinical diagnosis of microangiopathic hemolytic anemia (MHA) can be ascertained only by the prove of fragmentocytes (schistocytes) in the peripheral blood. Those fragmented red cells caused by different processes of microangiopathy are partly destroyed in the blood vessels, partly absorbed by the reticuloendothelial system and may produce typical histomorphological changes. Therefore, besides the histological classification of the microangiopathy in 15 autopsy cases (Moschcowitz’ syndrome 4, hemolytic uremic syndrome 2, glomerular microthrombosis 1, eclampsia 1, malignant nephrosclerosis 1, anaphylactoid purpura 1, and metastatic tumors 5) parameters of MHA are additionally studied, which are depending on the hemolysis in this disease. The earliest morphological findings in MHA are hemoglobin casts in distal convoluted tubules of the kidney and siderosis of the reticuloendothelial system (RES) in spleen and liver and siderosis of the proximal convoluted tubules of the kidney. Extramedullary hematopoiesis of spleen and sometimes of liver is seen in a later phase of MHA. These indicative signs of MHA, hitherto widely unrecognized, show a good correlation to the duration of the disease and the extent of microangiopathy.

A case of renovascular hypertension with the nephrotic syndrome.

A case of a 6 year old boy is presented in which unilateral renal artery stenosis assumed to be congenital based on histological findings and subsequent malignant nephrosclerosis of the contralateral kidney and nephrotic syndrome probably due to gross albuminuria were observed.

Evidence for the Renal Origin of the Malignant Phase of Essential Hypertension.

Meeting Abstracts1 May 1970Evidence for the Renal Origin of the Malignant Phase of Essential Hypertension.Gaddo Onesti, M.D., Kwan Eun Kim, M.D., (Associate), Albert N. Brest, M.D., F.A.C.P., Charles Swartz, M.D., F.A.C.P.Gaddo Onesti, M.D.Search for more papers by this author, Kwan Eun Kim, M.D., (Associate)Search for more papers by this author, Albert N. Brest, M.D., F.A.C.P.Search for more papers by this author, Charles Swartz, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-72-5-802_4 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptSix uremic patients with malignant phase of essential hypertension were studied before and after bilateral nephrectomy. All patients had documented essential hypertension for 2 to 10 years. Histologic examination of all kidneys demonstrated malignant nephrosclerosis but no primary renal parenchymal disease or renal artery stenosis. The following values were measured twice a week before and after nephrectomy for 6 to 16 months: intra-arterial pressure, cardiac output, total peripheral resistance, blood volume, total exchangeable sodium, peripheral plasma renin. Diastolic blood pressure averaged 158 mm Hg before nephrectomy and 93 mm Hg after nephrectomy. The decrease in blood pressure after nephrectomy was... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Philadelphia, Pa. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 May 1970Volume 72, Issue 5Page: 802-802KeywordsBlood pressureBlood volumeCardiac outputHypertensionKidneysNephrectomyRenal arteriesRenal diseasesSodiumStenosis Issue Published: 1 May 1970 PDF DownloadLoading ...

Marfan's syndrome accompanied by renovascular hypertension.

A 26-year-old male with Marfan's syndrome complicated by renovascular hypertension was reported. Stenosis of the main renal artery among the left multiple renal arteries was proved. In the present case, a high incidence in cerebrovascular disturbance was found on the paternal side. The patient expired on account of malignant nephrosclerosis following an attack of cerebral apoplexy. The causative relationship between Marfan's syndrome and reno-vascular hypertension was discussed.

Study on the histogenesis of arteriosclerosis of organ arteries, with special emphasis on renal arteriosclerosis.

Renal arteriosclerosis was studied with a concept based on a sudden elevation of the hemodynamic pressure due to a pressure imbalance occurring between the glomerular and pre‐glomerular circulation.Congenital pre‐sclerosis of the renal arteries and ‘physiological arteriosclerosis’ in various age groups were described. Pathological arteriosclerotic forms seen in arteriosclerotic diseases of the brain and the heart and hypertension were compared with those in the controls.‘Dysorie’ changes observed in the malignant phase of chronic glomerulo‐nephritis and malignant nephrosclerosis were presented and discussed.In order to clarify the most characteristic feature of renal circulatory disiurbance, some other renal diseases were demonstrated, and the relation between renal circulatory disorder and arteriolar damages was discussed. ACTA PATH. JAP. 18: 107–121, 1968.

A case of renovascular hypertension caused by aortitis of Takayasu's type.

A case of aortitis of Takayasu's type was reported. The distribution of the lesions was not confined to the thoracic, but extended to the abdominal aorta and their major branches. Most severely affected arteries were the left subclavian and the left renal arteries, and the abdominal aorta was remarkably narrowed. The patient's clinical course was exclusively that of a renovascular hypertension and the patient died of its malignant phase. There were necrotizing angitis distributed in several organs and unilateral malignant nephrosclerosis of the right kidney. The juxtaglomerular granular indices were O for the right and 186 for the left.The association of renovascular involvement and difference in weight of two kidneys were discussed. Renovascular hypertension appeared to be not infrequently associated with this disease, although little attention has hitherto been paid to the condition. ACTA PATH. JAP.

Malignant Nephrosclerosis in Women Post Partum

A case of malignant nephrosclerosis with microangiopathic hemolytic anemia developed in a young woman post partum. Diastolic hypertension first appeared two weeks after admission but papilledema never developed. An explanation for this phenomenon may be that the partially occluded renal arterioles caused activation of the renin-angiotensin system. Similar cases in other institutions suggest that such a syndrome occurs occasionally in women in the postpartum period. Microangiopathic hemolytic anemia, as well as malignant hypertension and nephrosclerosis, has been produced by treating rats with salt and desoxycorticosterone. Red blood cell fragmentation may occur by the shearing action of blood flow on erythrocytes observed to be adherent to arteriolar and glomerular capillary walls.

Lupus erythematosus with fatal hemorrhage into the liver and lesions resembling those of periarteritis nodosa and malignant hypertension: Immunocytochemical observations

Immunocytochemical studies were made in a patient with lupus erythematosus also exhibiting lesions resembling those seen in periarteritis nodosa and malignant nephrosclerosis, including healed and healing vascular lesions in medium-sized arteries in various abdominal organs, rupture of an aneurysm of a branch of the hepatic artery, and necrotizing lesions in the renal arterioles. Gamma globulin, complement, albumin and fibrinogen were found in the vascular lesions; in the renal glomeruli, gamma globulin was associated only with complement. It is suggested that these lesions have a common pathogenesis: harmful antigenantibody complexes and complement are localized in glomeruli and vessels, the latter injured by hypertension, producing increased permeability and secondary imbibition with plasma proteins.