Membranous glomerulonephritis in renal allografts.
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Biomedical subjects
Publications and source records attributed to C Swartz.
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1. Haemodynamics, blood volume, plasma renin concentration and creatinine clearance were evaluated in 24 stable renal transplant recipients. 2. The mean cardiac index of the transplant recipients was not different from that of the normal subjects. 3. The transplant recipients comprised eight hypertensive and 16 normotensive patients. The mean cardiac index was the same in eight hypertensive and 16 normotensive patients. Thus the hypertension of stable renal transplant recipients is sustained by a high total peripheral resistance. 4. The mean blood volume, plasma renin concentration and creatinine clearance were similar in eight hypertensive and 16 normotensive patients. Therefore the hypertension of stable renal transplant recipients is not related to blood volume expansion, elevated peripheral renin or low creatinine clearance. The cause of the elevated total peripheral resistance in hypertension in stable renal transplant recipients remains to be elucidated.
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Evidence is presented implicating the renin-angiotensin system in the regulation of plasma erythropoietin concentration. Male and female rats were exposed to hypoxia at 0.43 atm for 8 hr. In male rats, individual erythropoietin values showed a positive correlation with renin, renin substrate, and angiotensin I after 8 hr of hypoxia. In female rats, renin was not elevated during hypoxia. However, after renin was injected subcutaneously, plasma renin values became similar to those in male rats and erythropoietin doubled. Individual erythropoietin values of the combined groups showed a positive correlation with plasma renin. A single oral dose of SQ 14225, an angiotensin I-converting enzyme inhibitor, reduced erythropoietin to undetectable levels in renin-injected female rats. Angiotensin II, in subpressor amounts, prevented the suppression of erythropoietin by SQ 14225. SQ 14225 also reduced renin substrate concentration at ambient pressure and during hypoxic exposure. The correlation coefficient between renin substrate and erythropoietin in rats given SQ 14225 to lower substrate or angiotensin II to increase substrate was 0.85; p < 0.0005. The increase in renin substrate that occurred during hypoxia in female rats given angiotensin II correlated positively with erythropoietin, r = 0.86; p < 0.0005.
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1. Pentolinium tartrate (a ganglionic blocker) was injected in conscious rats during the early and late phases of two-kidney renal hypertension produced by aortic ligation. 2. In the early phase ( 5 days after aortic ligation), ganglionic blockade resulted in a decrease in blood pressure equal to that obtained in normotensive rats. Later, at days 12 and 40, for equally severe hypertension, ganglion blockade resulted in a greater decrease in blood pressure. 3. A 30 min infusion of [Sar1, Ala8]angiotensin II during the pentolinium-induced nadir in blood pressure resulted in a further decrease in blood pressure at day 5. Later, at days 12 and 40, this effect was smaller. 4. A 300 min infusion of [Sar1, Ala8]angiotensin II normalized the blood pressure in hypertensive rats at day 40. This delay response may be secondary to a central effect of the antagonist, reducing neurogenic tone or peripheral antagonism of locally generated angiotensin II in the blood vessel walls. 5. At day 40, removal of the small left kidney resulted in a greater decrease in blood pressure. This suggests the presence of a renal factor other than renin in the chronic phase of this hypertension.
Thirteen patients with systemic lupus erythematosus (SLE) who had normal results of urinalysis, absence of proteinuria, and normal serum creatinine values underwent renal biopsy. Three of 13 patients had diffuse proliferative glomerulonephritis (group 1). Biopsy specimens showed segmental fibrinoid necrosis, diffuse mesangial hypercellularity, and substantial immunoglobulin deposition. Group 2 comprised those patients whose histologic findings did not portend a poor prognosis. Four had mesangial proliferative glomerulonephritis, three had focal proliferative glomerulonephritis, and three had minimal mesangial widening. The values of inulin clearance in group 1 did not differ significantly from those in group 2. Patients in group 1 had a mean age of 19 years, a value significantly lower than in group 2 (41.8 years). Review of previous reports also supports the thesis that this phenomenon is age related. Our study underscores the importance of renal biopsy in patients with SLE despite the absence of clinical evidence of renal involvement, particularly in patients under 30 years of age.
We performed renal biopsies on eight patients who had benign essential hypertension but laboratory abnormalities suggestive of glomerulonephritis. Persistent microscopic hematuria was detected in four patients, proteinuria in five, RBC casts in two, and decreased glomerular filtration in seven. In all eight biopsy specimens, we detected hyaline arterionephrosclerosis, focal glomerular obsolescence, and segmental, afibrillar thickening of glomerular basement membranes. Direct immunofluorescence studies performed on all eight samples were negative for immunoglobulins, complement, and fibrinogen. Although the patients in our study had laboratory findings suggestive of glomerulonephritis, the morphologic changes were indicative of benign essential hypertension.
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Minoxidil was used to treat 26 patients (17 to 67 years old) with severe hypertension and varying degrees of renal function. Our object was to assess long-term clinical efficacy, kinetics (acute and chronic), and bioavailability of minoxidil in chronic renal insufficiency. Minoxidil, 27 to 30 mg per day, decreased systolic and diastolic blood pressure during the first three months of therapy. Between the third and 24th months (30 months in one patient) there was no further change. Propranolol or clonidine was needed to control heart rate, and furosemide or dialysis was needed to control edema induced by minoxidil. Renal function improved in some of the mildy azotemic patients. Minoxidil kinetics after the customary dose did not differ whether the drug was taken as tablet or solution. Kinetic parameters during chronic administration of minoxidil did not differ from those after acute administration. The kinetics in chronic renal insufficiency do not differ from these in subjects with normal renal function.
1. Sar1-Ala8-Angiotensin II (an angiotensin antagonist) was infused in rats during the development and maintenance of renal hypertension produced by aortic ligation between renal arteries. 2. In the early phase (5 and 12 days after ligation), infusion of the antagonist markedly decreased blood pressure although it did not reach normal pressures. Later (day 40) only a modest decrease in blood pressure was noted. 3. Removal of the small left kidney always decreased the blood pressure to normal pressures. 4. It is concluded that the renin-angiotensin system is the major pressor component in the initiation of this hypertension. Later, other factors of renal origin assume a pressor function.
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1. Propranolol was administered to groups of mature rats before and during the development of renal hypertension induced by ligation of the aorta between the renal arteries. 2. At a dose 10 mumol (3 mg) of propranolol/kg, administered by intraperitoneal injection, the onset and severity of hypertension were not affected, although plasma renin concentration was significantly lower than in the untreated hypertensive rats in the first 5 days after the operation. 3. With 200 mumol (60 mg) of propranolol/kg, administered in the drinking water, peak blood pressure 5 days after aortic ligation was lower than in the untreated control rats, but plasma renin concentration was no lower than with the smaller dose. 4. The development of severe hypertension despite reduction in plasma renin concentration on the low dose of propranolol suggests the participation of renal vasopressor factors other than renin in this model. 5. A higher dose of propranolol reduced the rise in plasma concentration to an equal extent but the rise of blood pressure at 5 days was also reduced, which supports this concept.
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