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In a prospective study of 100 consecutive patients discharged after a Q-wave myocardial infarction, the value of reversible ischemia on thallium-201 scintigraphy to assess the risk of cardiac events (death or reinfarction) during 4 years was compared with variables from exercise testing and cardiac catheterization. Patients with markedly impaired left ventricular function [ejection fraction (EF) < or = 0.30] were excluded. During follow-up there were 20 cardiac events (10 cardiac deaths and 10 reinfarctions). Thallium-201 scintigraphy was significantly better than all exercise test variables and better than an EF < 0.40, with good sensitivity and specificity (75 and 51%, respectively). Exercise-induced reversible ischemia on scintigraphy yielded the same information as the presence of multivessel disease. Exercise test variables were of limited value to assess prognosis. Thus, thallium-201 scintigraphy can be used as the only tool to predict future cardiac events in low-risk patients after a Q-wave myocardial infarction.

Intrarenal sodium handling was studied in 8 patients with essential hypertension before spironolactone treatment (200 mg/day), on the 4th day of treatment, and after 3 months of treatment. The results were compared with similar studies with chlorthalidone (50 mg/day). Renal sodium handling was assessed by simultaneous determination of the glomerular filtration rate, sodium, and potassium excretion, and maximal free-water clearance (CH2O). We took CH2O as an index of 'distal' sodium chloride reabsorption from which the proximal sodium reabsorption was calculated. During the first days of spironolactone treatment a natriuresis and increase in urinary flow rate was found. It resulted in a decrease of the extracellular fluid volume amounting to 0.9 liters and a 2.5-fold increase in the plasma renin activity. Potassium excretion showed a small but significant rise. After 3 months, virtually the same degree of volume depletion was found, which was comparable to that obtained after 3 months of chlorthalidone treatment. CH2O, as a fraction of glomerular filtration rate, decreased by 24% both after 3 days and 3 months, whereas proximal sodium reabsorption increased from 87.8 to 90.4% of the filtered load. CH2O, corrected for the 'distal' delivery of sodium, decreased from 85.3 to 80.7%. These changes were nearly the same as those found after 3 months of chlorthalidone treatment. It is concluded from these calculated values that spironolactone inhibits sodium chloride reabsorption in the diluting segment of the nephron and that the resulting increase in sodium delivery or urinary flow to the potassium excretory site partly counteracts the blocking effect of spironolactone on this part of the nephron, thus increasing potassium excretion during the acute administration of this drug.

In 7 patients with moderate degrees of renal insufficiency the effect of high and low salt intake on renal NaCl handling was investigated by means of clearance techniques. After a steady state had been reached at low (1 g NaCl daily) and high (10 mmol NaCl daily for every ml X min-1 glomerular filtration rate) salt intake, proximal and distal fractional salt reabsorption (FSRprox and FSRdist) were estimated, maximal free water clearance being taken as an index of distal NaCl reabsorption. Mean FSRprox during low salt intake was 86.7% (range 80-90%) of the filtered load, and decreased to 77.9% (range 70.1-80.5%) during high salt intake. The water-loading procedure in these patients resulted in enhanced NaCl and nonelectrolyte solute excretion, especially during salt restriction. This made certain corrections obligatory for the proper calculation of FSRdist. Mean FSRdist during low salt intake was 96.5% (range 93.1-99.8%) of distal delivery, and decreased to 76.0% (range 68.0-82.1%) during high salt intake. This decrease of FSRdist also existed at comparable levels of distal delivery. It is concluded that renal response to chronic sodium loading in patients with chronic renal insufficiency is similar to that as in normal men, and consists of reduction of both proximal and distal fractional NaCl reabsorption.

Intrarenal handling of uric acid was studied in 12 patients with essential hypertension under spironolactone treatment (200 mg/day). The degree of volume depletion during treatment was assessed from the changes in body weight and plasma renin activity (PRA). The results are compared with those in patients treated with chlorthalidone (50 mg/day). During spironolactone treatment, the serum uric acid level remained constant despite a progressive volume depletion which after 3 months reached levels identical to those achieved in the chlorthalidone-treated patients, whose serum uric acid level showed the expected rise (21%). The uric acid excretion during spironolactone treatment was markedly diminished (-28%), and thus the 24-hour clearance of uric acid was correspondingly decreased (-22%). It is concluded that spironolactone affects uric acid metabolism in two ways: it causes a decrease in uric acid renal clearance (probably mediated by the induced volume depletion and PRA elevation, as with other saluretics) and, probably, inhibits endogenous uric acid production to approximately the same degree as the clearance is decreased, so that no change in the serum uric acid level occurs. The purpose of the study was to investigate the effect of spironolactone on uric acid handling by the kidney. We found a decrease in uric acid clearance and uric acid excretion. Serum uric acid concentration did not change.

Literature data on renin in the nephrotic syndrome are conflicting: renin values are reported to be elevated as the rule, but sometimes normal or low; data on renin substrate are scanty and pointing to low values. In the present study, plasma renin activity (PRA) and plasma renin substrates (PRS) were measured in 27 episodes of the nephrotic phase in 24 patients with nephrotic syndrome with various lesions. 10 patients were reinvestigated after remission; 1 patient could be followed during development of the edema phase as well as during prednisone-induced remission. During the nephrotic phase, PRS was suppressed in 8%, normal in 44 and elevated in 48%, while PRA was suppressed in 41%, normal in 48 and elevated in 11% of the patients. After remission, PRA increased in 70% and PRS decreased in 20 and increased in 50% of the cases. The purpose of this study was to investigate PRA and PRS in nephrotic patients; it is concluded that low PRS and high PRA are not as characteristic for the nephrotic syndrome as they are generally thought to be.

In 10 patients with the nephrotic syndrome (NS) and edema persisting despite a NaCl-poor diet, the effect of a single infusion of hyperoncotic albumin (75 g) on NaCl excretion was studied. 6 patients had minimal lesions, and 2 patients were studied twice. On half of the occasions the glomerular filtration rate was reduced. Blood volume (BV), calculated from plasma volume and hematocrit, was slightly elevated before infusion, and increased to 136 and 120% of normal at 4 and 20 h after it, respectively. Plasma renin activity (PRA) and plasma aldosterone (PA) both decreased to suppressed levels at 20 h after infusion. Sodium excretion increased from 9.2 +/- 7.6 muEq/min before, to 3.10 +/- 22.4 (0-4 h) and 43.1 +/- 36.3 muEq/min (4-20 h) after infusion. In 6 of these patients clearance studies were done before and after the infusion, maximal free water clearance being used as marker for distal NaCl reabsorption. Proximal fractional NaCl reabsorption was elevated before (94.9 +/- 1.4%) and decreased after the infusion (92.8 +/- 1.7%). Distal fractional NaCl reabsorption was also elevated before (93.0 +/- 6.4%), but unaltered after infusion (93.0 +/- 5.6%). Thus, after marked expansion of BV and suppression of PRA and PA, sodium excretion remained low despite the present edema. The results indicate that in many patients with the NS, including minimal lesion NS, intravascular hypovolemia is not the sole cause of sodium retention.

In normal subjects a relation was found between the log plasma aldosterone concentration (PAC) and the ratio of renal potassium excretion (UK) and sodium delivery to the sodium-potassium exchange site (UNa + K). This relationship was independent of plasma renin activity (PRA). On these grounds, the UK/UNa + K ratio disturbance was considered to be a function of the PAC, and this relation was considered to reflect an altered sensitivity of the distal tubule to aldosterone. In several pathological conditions involving the kidney, the relation between the PAC and UK/UNa + K remained normal while the glomerular filtration rate was within normal limits. Under these conditions, however, the serum potassium concentration had some influence on this relation, in that a low potassium concentration was accompanied by an elevated (though still normal) PAC relative to the UK/UNa + K ratio. The relation was completely abolished when the effect of endogenous aldosterone was impaired by chronic renal disease made it possible to classify them according to the pathophysiological disturbance in question. We conclude that determination of the UK/UNa + K ratio and its relation to the PAC, PRA, and serum potassium level is very useful for the analysis of disorders of potassium metabolism.