Renal acid-base excretion in normotensive salt-sensitive humans.

Reduced extracellular pH and bicarbonate levels recently have been reported in normotensive salt-sensitive subjects. To assess the possible role of altered renal acid-base handling in the perturbation of acid-base status in these individuals, we measured the renal acid-base excretion after an acute oral administration of either an alkali or acid load in normotensive salt-sensitive and salt-resistant men. Twenty-four young (22 to 29 years old), healthy male volunteers were placed on a low-salt diet (20 mmol NaCl per day) for 2 weeks with either 220 mmol NaCl or placebo added to the low-salt diet for 1 week each in a randomized single-blind crossover order. Salt sensitivity was defined as a significant drop in mean arterial pressure (> 3 mm Hg, mean of 60 readings taken on the seventh day of each diet, P < .05) during the low-salt diet. On the fifth and seventh days of each week, subjects were given an oral load of either sodium citrate (0.7 mmol/kg) or ammonium chloride (2.2 mmol/kg), respectively, in a randomized order, and arterial and urinary acid-base status was assessed at baseline and followed for 8 hours thereafter. According to the above definition, 13 subjects were considered salt sensitive. During the high-salt diet, mean arterial pressure was higher in the salt-sensitive than in the salt-resistant group (P < .01). Cumulative urinary bicarbonate excretion after the administration of sodium citrate was lower in the salt-sensitive than in the salt-resistant subjects during both the low-salt (46%, P < .001) and high-salt (32%, P < .01) diets.(ABSTRACT TRUNCATED AT 250 WORDS)

Salt sensitivity in young normotensive subjects is associated with a hyperinsulinemic response to oral glucose.

Insulin resistance associated with a hyperinsulinemic response to oral glucose intake has been found in patients with essential hypertension and is believed to play a role in inducing hypertension by causing renal sodium and water retention. We therefore examined whether salt-sensitive, young normotensives, assumed to be predisposed to essential hypertension, exhibit impaired glucose tolerance in a similar way. The plasma insulin and glucose response to oral glucose intake (75 g) was assessed in 23 healthy, lean, male volunteers ingesting either 20 mmol or 260 mmol NaCl/day for 6 days each in a single-blind randomized crossover study. Salt sensitivity was defined as a significant drop in mean arterial blood pressure greater than 3 mmHg (means of 30 readings in the supine subject; P less than 0.05) under the low-salt diet. Following the glucose load, plasma levels of both glucose and insulin were significantly higher (P less than 0.01) in the salt-sensitive (n = 10) compared with the salt-resistant subjects (n = 13) during the high-salt diet but not during the low-salt diet. Whereas in the salt-sensitive group glucose tolerance improved with dietary salt restriction (P less than 0.01), it deteriorated in the salt-resistant group (P less than 0.05). Following the glucose load under the high-salt diet, there was a significant drop in blood pressure in the salt-sensitive (P less than 0.005) but not the salt-resistant subjects. The hyperglycemic and hyperinsulinemic response in salt-sensitive subjects suggests that insulin resistance is present in these subjects prior to the development of hypertension and that it can be ameliorated by salt restriction.(ABSTRACT TRUNCATED AT 250 WORDS)

Color-coded duplex sonography for noninvasive diagnosis and grading of renal artery stenosis.

The accuracy of color-coded duplex sonography (CCDS) in screening hypertensive patients for renal artery stenosis (RAS) was assessed using a semi-quantitative waveform analysis. Our special aims were to separate between moderate and high grade stenoses and to evaluate the accuracy of the method in imaging both the whole course of the renal arteries and accessory renal arteries. Included in the prospective, angiographically controlled study were 135 consecutive patients with 268 renal arteries, of which 195 arteries (73%) could be visualized both proximally and distally by CCDS. Only three of 15 accessory renal arteries could be identified by CCDS. In 42 RAS > or = 50% sensitivity of CCDS was 93%, specificity 92%, and overall accuracy 92%. The sensitivity in identifying RAS > or = 75% was 92%, and none of the high grade stenoses were missed. Because of difficulties in visualizing the middle portion of the renal artery, we carefully examined this part of the artery in 116 additional patients. Whereas the proximal and the distal parts could be visualized in 77% of the renal arteries, signals from the middle third could be derived only in 60% on the right, and in 39% on the left side. Provided that the renal arteries were visualized both proximally and distally, a hemodynamically effective RAS could be excluded with high probability. Moreover, exact grading of high-grade stenoses was possible in all cases but one. An advantage of CCDS over conventional duplex sonography appears to be the time-saving examination. Since a low prevalence of RAS impairs the positive predictive value of CCDS, the examination should be reserved for patients with a strong clinical suspicion of renovascular hypertension.

Diagnostic procedure in renovascular hypertension.

Detection of a renal artery stenosis (RAS) as a cause of arterial hypertension is of great practical importance because dilatation of the stenosis frequently results in an improvement or cure of the hypertension. In recent years, a number of screening procedures aimed at diagnosing renovascular hypertension have been developed, e.g., duplex sonography of the renal arteries, determination of plasma renin activity, or renal scintigraphy following administration of captopril. The possibilities and limitations of these screening procedures are described here. The best method for detecting renal artery stenosis is angiography, which can now be performed on an outpatient basis, using thin catheters.

Effect of water and bicarbonate loading in patients with chronic renal failure.

Animal studies suggest that alkalinization and increased intake of free water both serve to decrease the rate of progression in chronic renal failure. However, clinicians have been reluctant to apply either strategy because of concerns regarding volume overload and water intoxication. We tested the effects of 2 1 daily water supplementation, with either an electrolyte-poor or a HCO3-rich (47.5 mmol/1) water in 11 patients with chronic renal failure (creatinine clearance 10 +/- 5 ml/min). The patients were brought into balance on a diet containing 80 mmol/24 h Na+, 80 mmol/24 h Cl- and 70 mmol/24 h K+. After a 3-day equilibration period, the patients were randomized to one or the other regimen for 7 days. After a 3-day washout period, the alternate regimen was given for another 7 days. Neither regimen led to weight gain or hyponatremia. The supplemental 95 mmol/24 h HCO3- lowered the serum Cl- concentration and raised the serum HCO3- concentration, as well as the pH value, to normal. Creatinine clearance and protein excretion were not affected. Serum beta 2-microglobulin concentrations decreased with the NaHCO3-containing water. Na+/H(+)-antiporter activity was not consistently influenced since an order effect of the regimens was apparent. We conclude that 2 1/24 h water and NaHCO3 supplementation is well tolerated, causes no deleterious effects, and may evoke improvement in patients with chronic renal failure.

[Screening and diagnosis for eliminating renovascular hypertension. Value of 24-hour blood pressure monitoring and color-coded duplex ultrasound diagnosis]. / Screening and Diagnostik zum Ausschluss einer renovaskulären Hypertonie. Stellenwert der 24-Stunden-Blutdruckmessung und der farbkodierten Duplexsonographie.

BACKGROUND: Direct renal angiography is still the method of choice for identification of renal artery stenosis. Newer non-invasive diagnostic methods include color coded duplex sonography and also ambulatory 24-h blood pressure monitoring, since in a large proportion of patients with secondary forms of hypertension the usual blood pressure fall during nighttime disappears. PATIENTS AND METHODS: In a prospective in-hospital study we investigated 86 patients with suspected renovascular hypertension. Circadian blood pressure was measured oscillometrically and color coded duplex sonography was performed immediately before direct renal angiography. RESULTS: Angiography revealed renal artery stenosis (> or = 50%) in 42 patients. This compared to a sensitivity of 92.9% and specificity of 91.7% for the use of sonography in those patients (70.4%) who could be adequately examined. Mean 24-h pressure values as well as standard deviations of blood pressure means as an indicator for blood pressure variability were not different in the 2 groups of patients, when all the data were analysed together and also when the data for nighttime and daytime were examined separately. The percent of blood pressure fall during nighttime was also not different in the 2 groups. In both groups 4 hypertensive patients had a blood pressure increase during nighttime. In 11 patients without renal artery stenosis a blood pressure fall of < 10% was observed, compared to 12 patients with renal artery stenosis. The circadian pattern of pulse rate was similar in both groups. CONCLUSION: We conclude that ambulatory blood pressure monitoring has a considerably lower diagnostic value for renal artery stenosis compared to angiography and also to color duplex sonography. This method therefore does not appear to be an appropriate screening approach for this kind of secondary hypertension. The color coded duplex sonography, however, seems to be the best non-invasive diagnostic method in those patients, who can be adequately examined.

Alcoholism and carcinoma change the intracellular pH and activate platelet Na+/H+-exchange in men.

The occurrence of carcinoma in chronic alcoholics exceeds that of the general population. Cytoplasmic alkalinization, due to the influence of different factors on the transmembrane Na+/H+ exchange (NHE), has been put forward as a triggering event in cell growth and division. In accordance with these findings, the carcinogenic potential of NHE deficient cell types is reported to be diminished. The aim of this study was to investigate whether the intracellular pH and the NHE activity is altered in chronic alcoholics. Seventy-two Caucasian males were assigned to one of four groups: non-alcoholics without carcinoma, chronic alcoholics without carcinoma, non-alcoholics with carcinoma and chronic alcoholics with carcinoma. Alcoholism was diagnosed according to DSM-III-R. The groups did not differ in relation to basic patient characteristics, such as age and blood pressure. Intracellular calcium, pH and NHE in platelets were determined by spectrofluorometry before and after thrombin stimulation. In chronic alcoholics with carcinoma, the intracellular pH was significantly more alkaline and the NHE activity was elevated. In contrast, a decrease in intracellular pH associated with an increased activity of NHE and a more acidic set point was found in chronic alcoholics without carcinoma. Basal and thrombin stimulated intracellular Ca2+ did not differ between groups except in chronic alcoholics with carcinoma in whom a thrombin-induced increase of Ca2+ due to liberation of Ca2+ from intracellular stores was demonstrated. In chronic alcoholics with carcinoma, cytoplasmic alkalinization was observed and this may be an indication of an increase in cell proliferation. The possibility that the increased incidence of carcinomas in chronic alcoholics is related to the increased activity of NHE and whether this may be prevented by NHE inhibitors requires further investigation.