Search

This case report describes a patient with malignant hypertension and phaeochromocytoma in whom blockade of angiotensin II receptors by the competitive antagonist 1-sar-8-ala-angio-tensin II (Saralasin®) resulted in a partial correction of the elevated BP. Plasma renin activity was high and rose further during the blockade. Competitive inhibition of angiotensin II by Saralasin does not abolish the pressor effect of catecholamines. It was therefore interesting to observe that in this patient with phaeochromocytoma, independently, both α-adrenergic receptor blockade and angiotensin II receptor blockade were effective in lowering BP.

In order to study why the diagnostic sensitivity of I-123-hippurate renography for a renal artery stenosis is improved by angiotensin converting enzyme (ACE-) inhibition we used the model of the conscious chronically instrumented two-kidney, one-clip Goldblatt hypertensive dog. Urine flow (UV), renal blood flow (RBF), glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured (with constant infusion of I-125-iothalamate and I-131-hippurate, respectively) for both kidneys separately before and after a bolus injection of a mild unilateral renal artery stenosis (approximately 30% reduction of RBF). During ACE-inhibition, there were remarkable falls in poststenotic GFR (from 37 +/- 5 to 4 +/- 2 ml/min, p

Objective: To study the tubular site or sites of the natriuretic action of atrial natriuretic factor and the possible differences between healthy subjects and patients with essential hypertension. Design: Nine healthy volunteers and six patients with essential hypertension were studied on four test days under standard conditions, water loading and hydropenia with mannitol or saline loading. On each test day baseline, atrial natriuretic factor infusion (1 mu g/min) and recovery measurements were performed after equilibrium had been reached. The measurements included the atrial natriuretic factor (ANF) plasma levels, blood pressure, glomerular filtration rate (GFR), effective renal plasma flow, urinary osmolality and the (fractional) excretions of (free) water, sodium and potassium. Methods: Fractional free-water excretion and free-water reabsorption (as a function of osmolar clearance) were calculated during water loading and hydropenia with mannitol or saline loading, respectively, using standard formulae. [I-125]-iothalamate and [I-131]-hippuran were infused continuously for the measurement of GFR and effective renal plasma flow respectively. Results: The plasma ANF concentration rose five- to eightfold during the infusion of ANF, which induced an increase in urinary sodium excretion, a small increase in GFR and a decrease in the effective renal plasma flow. Moreover, ANF induced an increase in fractional free-water excretion and a decrease in fractional free-water reabsorption. These changes did not correlate with changes in GFR. The blood pressure and potassium excretion were not affected. The effects of ANF on the plasma ANF levels, natriuresis and renal haemodynamics did not differ between the normotensives and the essential hypertensives. However, the increase in fractional free-water excretion was significantly greater in the patients with essential hypertension and correlated significantly with blood pressure (r=0.56, P Conclusions: These results indicate that the infusion of ANF at a low dose induces a similar natriuretic response in normotensive subjects and in patients with essential hypertension, This natriuresis is probably the result of both a glomerular and a tubular effect of ANF. Proximal as well as distal tubular sites seem to be involved. In essential hypertension an enhanced proximal as well as an impaired distal tubular action of ANF can be hypothesized.

Peripheral mononuclear blood cells isolated from nephrotic subjects with minimal-change nephrotic syndrome (selective proteinuria greater than 3.5 g/24 h) or various other forms of glomerulonephritis (non-selective proteinuria greater than 3.5 g/24 h) were stimulated with concanavalin A and cultured for 20 h in the presence of kidney tissue under standard conditions. Identical cultures were developed with phosphate-buffered saline from normal control donors. Triplicate cultures of each subject (3 X 10(6) cells/ml) were incubated with or without 5, 10, or 20 micrograms/ml concanavalin A per milliliter serum-free tissue culture medium upon cryostat sections from normal rat kidney. The cells were subsequently removed, and the tissue sections were washed and stained for sialoprotein using the colloidal iron method and evaluated for stainability of glomerular polyanion using light microscopy. The results show that peripheral mononuclear blood cells from subjects with minimal-change nephrotic syndrome had affected glomerular polyanion in vitro during incubation with kidney tissue in a significantly (p less than or equal to 0.005) higher number of cases (15/17) as compared with the number of glomerulonephritis patients who scored positive in 4 out of 14 cases, whereas this was the case in 3 out of 18 cases of the normal donors. It is concluded that stimulated cellular immune reactivity of peripheral mononuclear blood cells from subjects with minimal-change nephrotic syndrome in vitro is associated with the potential impairment in vitro of an important part of the glomerular filtration barrier. Since this cellular activity occurred to a significant lesser extent in other nephrotic subjects, this response is not related to the nephrotic state per se.

We studied renal function in nine patients with disseminated testicular carcinoma before and after remission-induction and maintenance therapy with a drug combination containing cis-platinum. The median glomerular filtration rate (GFR) decreased during remission-induction therapy from 146 to 118 ml/min. No effect of cumulative toxicity on the median GFR was found during maintenance therapy, nor did the median GFR improve. The median effective renal plasma flow (ERPF) decreased during the total period from 705 to 514 ml/min. No significant changes in median filtration fraction (FF) and serum creatinine were observed. It is suggested that intrarenal hemodynamic effects are important in the nephrotoxicity of cis-diamminedichloride platinum (CDDP).

Two siblings are described with hypertension, hyperreninism, hyperaldosteronism and hypokalemia. Propranolol therapy lowered blood pressure markedly, but failed to normalize serum potassium. Indomethacin orally decreased blood pressure and normalized all biochemical abnormalities. We suggest that in these patients there exists a renin-dependent hypertension in combination with a state of hyperprostaglandinism. It is likely from our studies in these 2 patients, that the state of hyperprostaglandinism is secondary to a hypertension with increased sympathetic tone.

125Iothalamate and 131I-hippuran clearances, sodium excretion and plasma renin activity (PRA) before and during indomethacin administration in an oral dose of 3 x 50 mg/day were studied in volunteers with a normal or reduced kidney function, as well on non-sodium-restricted as on sodium-restricted diet. Indomethacin induced a temporary sodium and water retention and a decrease in glomerular filtration rate. It also lowered PRA. The latter phenomenon did not depend on sodium retention and was present within 2 h after an oral dose of 50 mg. The results may be explained by indomethacin-induced inhibition of prostaglandin synthesis.

Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined in 8 patients with disseminated testicular carcinoma before, during and 1 year after termination of a combination chemotherapy with cis-diamminedichloroplatinum (CDDP). The decrease in median GFR in comparison with the pretreatment value was 15.5% at the start of the maintenance therapy, 23% at the end of the maintenance therapy and 15.5% 1 year after termination of therapy. The comparable reduction in ERPF at those instants was 15.5, 19 and 23.5%, respectively. At all intervals the changes in GFR were significantly reduced in comparison with pretreatment values. No significant change in both GFR and ERPF was found either during or after discontinuation of maintenance treatment. The fall in ERPF was significant during the total period of treatment as well as during the total time of observation. Thus, no cumulative nephrotoxicity during therapy, nor improvement in renal function thereafter was found. Serum levels of creatinine and beta-2-microglobulin did not express the changes in renal function.

Three patients with rapidly progressive glomerulonephritis due to Wegener’s granulomatosis are described. In one patient, acute renal failure was initially the sole manifestation of the disease. Treat

We studied the frequency of restenosis and the effects of percutaneous transluminal renal angioplasty (PTRA) on blood pressure (BP) and particularly on renal function in all patients in whom successful dilatation was performed. Restenosis was found in 42% of the patients with an atherosclerotic renal artery stenosis and in 22% of the patients with fibromuscular dysplasia. BP improvement was seen in 70-80% of the patients with unilateral stenosis or with successful bilateral dilatation (group I) whereas only seldom was an effect on BP observed in patients with more complicated disease, such as those with an occlusion of the contralateral artery (group II). Remarkably, however, both in group I and in group II, in about half of the patients an improvement in renal function was found, even 2-3 years after the procedure. Our results thus indicate that PTRA can be useful in preservation or even improvement of renal function, even if no effect on blood pressure can be expected.

In 19 nephrotic patients on a dietary intake of 20 mEq sodium/24 hours, indomethacin caused an immediate decrease in glomerular filtration rate (GFR) and urinary protein excretion, an effect completely reversible upon withdrawal of the drug. As a consequence of lower protein excretion, there was eventually a rise in GFR. It is proposed that the therapeutic effect of indomethacin in nephrotic syndrome is caused by its inhibiting action on renal prostaglandin synthesis, thereby potentiating the effect of the renin-angiotensin system on the kidney. The difference between the decrease in GFR (mean 35%) and proteinuria (mean 55%) and the more selective proteinuria during indomethacin administration may be explained by quantitative and qualitative differences in protein leakage between outer cortical and inner cortical nephron populations.

A new externally adjustable constrictor device for renal artery stenosis in the dog is described. The constrictor combines hydraulic and mechanical characteristics, and is connected to the exterior of the animal by a thin catheter. Applying hydraulic pressure via the catheter causes the plunger in the device to compress the renal artery to any desired degree of stenosis. A mechanical catch prevents backward movement of the plunger, thus ensuring a stable, irreversible renal artery constriction. This constrictor was implanted in 13 dogs, together with an electromagnetic blood flow sensor around a renal artery. In twelve dogs the constriction procedure was performed 3–12 weeks after implantation, and in all 12 cases the intended degree of stenosis [defined as percentage renal blood flow reduction (RBF)] was achieved within a range of 10%. In 5 dogs the long-term stability of the stenosis was studied and the RBF reduction appeared to be stable up to at least 6 weeks after constriction. In conclusion, the presented constrictor device is easily externally adjustable, and allows induction of a stable renal artery stenosis of various degrees in the conscious dog.

Ten previously untreated patients with metastatic non-seminomatous testicular carcinoma received cis-diamminedichloroplatinum (CDDP). Renal function studies were performed before and following the first CDDP infusion. A decrease in effective renal plasma flow (ERPF) and an increase in filtration fraction (FF) was found in all patients. These findings suggest primary changes in renal hemodynamics during CDDP infusion.

Renal function studies were performed in 18 patients with nonseminomatous testicular cancer during four platinum-containing chemotherapy courses. The first 9 patients received chemotherapy alone, the second 9 also captopril, an angiotensin I converting enzyme inhibitor, in order to prevent cis-diamminedichloroplatinum-induced nephrotoxicity. In the first group a decrease in glomerular filtration rate, that was preceded by a fall in effective renal plasma flow, was observed. In the second group, captopril was able to prevent the initial decrease in effective renal plasma flow, but failed to prevent the ultimate decrease in glomerular filtration rate.