Renography with captopril. Changes in a patient with hypertension and unilateral renal artery stenosis.

In a 56-year-old man with severe familial hypertension and unilateral renal artery stenosis, captopril induced striking changes in the renograms of the affected kidney. After injection of orthoiodohippurate sodium I 131, the uptake phase was unchanged but the later curve showed continuous accumulation. In contrast, the uptake of technetium Tc 99m diethylenetriamine pentracetic acid was abolished. These changes are compatible with a cessation of filtration and maintenance of renal blood flow. After balloon dilatation of the stenosis, the blood pressure became lower, and these changes could no longer be demonstrated. The captopril renogram may provide useful information on the dependency of hypertension on unilateral renal artery stenosis.

The relevance of IgA deposits in vessel walls of clinically normal skin. A prospective study.

Granular deposits of IgA are known to occur in the walls of superficial vessels in apparently healthy skin of patients with primary IgA nephropathy, Henoch-Schönlein purpura, or alcoholic liver disease, but the specificity of the finding is still a matter of debate. We investigated the disease specificity of these deposits in the skin of patients with kidney and liver diseases. The sensitivity of the finding for the diagnosis of primary IgA was 75%, the specificity was 88%. The sensitivity for the diagnosis of alcoholic liver disease was 71%, but the specificity was only 60%. The specificity for the diagnosis of Henoch-Schönlein purpura, primary IgA nephropathy, or alcoholic disease (in a group of 1,030 patients with various diseases) was 94%. Immunoelectron-microscopic investigation showed the IgA deposits localized within the endothelial cell and in the subendothelial rim.

Blood and extracellular fluid volume in patients with Bartter's syndrome.

Blood and extracellular fluid volumes were measured in four adult patients with Bartter's syndrome and compared with those of 21 healthy control subjects. Extracellular fluid volumes were significantly lower than in the control group (-7%), whereas blood volumes were within the normal range. Consequently, the ratio of blood volume to interstitial fluid volume was significantly elevated (0.42 v normal 0.35). The results are consistent with the concept that a tubular reabsorption defect is present in Bartter's syndrome.

[Haemodialysis in Turkey]. / Hemodialyse in Turkije.

In Izmir, Turkey's third largest town, remarkably good treatment results have been achieved in haemodialysis patients. This success has been achieved by the formation of a close-knit and durable team of physicians and nurses at Ege University. This has enabled patients to be treated using a strict volume-control method and to be given individual attention and psychosocial support. This has been made possible by close collaboration with a producer of dialysis machines. Possible conflicts of interest were avoided as there were no personal connections between physicians and the production sector.

Enalapril attenuates natriuresis of atrial natriuretic factor in humans.

We studied the effect of converting enzyme inhibition with enalapril on the natriuresis observed after administration of atrial natriuretic factor (human ANF-[99-126], given as a 100-micrograms bolus i.v. injection) in eight healthy humans consuming a 100 mmol sodium diet. Without enalapril, sodium excretion rose from 127 +/- 19 (mean +/- SE) to 437 +/- 103 mumol/min in the first 20 minutes after ANF was administered. Clearance studies performed during maximal water diuresis indicated a rise in glomerular filtration rate (inulin clearance), free water clearance, phosphate, lithium, uric acid, and magnesium excretion. Four days of enalapril (20 mg b.i.d.) increased effective renal plasma flow (p-aminohippurate clearance) and reduced blood pressure (from 114/71 +/- 2/2 to 105/60 +/- 2/1 mm Hg). Under these conditions baseline sodium excretion was not different from the control study, but it rose less after ANF (from 117 +/- 22 to 242 +/- 63 mumol/min), and the increments in glomerular filtration rate, free water clearance, phosphate, lithium, uric acid, and magnesium were all blunted and nonsignificant. In addition, effective renal plasma flow tended to fall; this effect was not observed when ANF was given without enalapril. These results support the notion that the effects of ANF on renal hemodynamics and on tubular sodium handling depend on renal angiotensin II and that blood pressure reduction may interfere with the ANF-induced natriuresis.

Opposite effects of enalapril and nitrendipine on natriuretic response to atrial natriuretic factor. Renal function evaluated with clearance studies in humans.

In clearance studies, we analyzed the effect of Ca2+ entry blockade with nitrendipine treatment (20 mg b.i.d. for 4 days) and of converting enzyme inhibition with enalapril treatment (20 mg b.i.d. for 4 days) on renal response to atrial natriuretic factor (ANF) (25 micrograms bolus followed by an infusion of 0.03 microgram/kg/min for 90 minutes) in six healthy volunteers who were taking 300 mmol sodium daily. In a control study ANF was administered without Ca2+ entry blockade or converting enzyme inhibition. Natriuresis rose from 239 +/- 38 to 605 +/- 137 mumol/min in the control study (p less than 0.05), from 330 +/- 53 to 943 +/- 152 mumol/min with Ca2+ entry blockade (p less than 0.05), and from 236 +/- 22 to 344 +/- 39 mumol/min with converting enzyme inhibition (NS). ANF induced a rise in maximal free water clearance, inulin clearance, and in the excretion of multiple electrolytes except potassium. Fractional lithium reabsorption fell. In general, these effects were stronger during Ca2+ entry blockade and blunted during converting enzyme inhibition. p-Aminohippurate clearance tended to decrease during the control study (NS), remained constant during Ca2+ entry blockade, and decreased significantly when ANF was infused during converting enzyme inhibition (p less than 0.05 vs. control and vs. Ca2+ entry blockade study). Blood pressure was lowered by Ca2+ entry blockade and, to a somewhat greater extent, by converting enzyme inhibition, but ANF administration induced no additional fall except for a short-term drop during Ca2+ entry blockade.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium balance in renal failure. A comparison of patients with normal subjects under extremes of sodium intake.

To gain insight into the factors involved in the maintenance of sodium balance in patients with chronic renal failure, we studied 10 patients with a creatinine clearance of 11.5 +/- 4.0 ml/min after equilibrium on 20 and 120 mEq of sodium per day. The measurements included blood pressure, plasma volume, blood volume, extracellular fluid volume, plasma renin activity, plasma aldosterone, and plasma norepinephrine. For comparison, eight normal volunteers were studied after equilibration on 20, 200, and 1128 mEq of sodium per day. The latter intake was chosen to match the high sodium intake per residual renal function in the patients. In the patients, equilibrium after raised sodium intake was accompanied by a marked increase in blood pressure and blood volume, a moderate fall in plasma renin activity and levels of aldosterone and norepinephrine, and only little expansion of the interstitial space. The 24-hour creatinine clearance rose by 21.2 +/- 7.2%. Fractional sodium excretion (X 100%) was 5.3 +/- 0.8% during the 120 mEq sodium diet. In the normal volunteers, increasing the sodium intake from 20 to 1128 mEq/day evoked no consistent change in blood pressure but caused a comparable rise in blood volume, considerable suppression of plasma renin activity, aldosterone, and norepinephrine, and a much larger increase in interstitial volume. Their creatinine clearance had risen by 22.4 +/- 6.5%, and their fractional sodium excretion during the 1128 mEq sodium intake was 3.9 +/- 0.2%.(ABSTRACT TRUNCATED AT 250 WORDS)

Renovascular hypertension identified by captopril-induced changes in the renogram.

Radioisotope renography was performed in 21 patients with hypertension and unilateral renal artery stenosis with and without premedication with 25 mg of captopril, and the results were compared with the effect of percutaneous transluminal angioplasty on the blood pressure, assessed 6 weeks after angioplasty. Angioplasty caused a considerable decrease in blood pressure in 15 of the 21 patients. In 12 of these 15 patients, captopril induced changes in the time-activity curves of the affected kidney only, suggesting deterioration of the excretory function of that kidney, while the function of the contralateral kidney remained normal. After angioplasty the asymmetry in the time-activity curves diminished despite identical pretreatment with captopril. Such captopril-induced unilateral impairment of the renal function was not seen in the six patients with unilateral renal artery stenosis whose blood pressure did not change after percutaneous transluminal angioplasty or in 13 patients with hypertension and normal renal arteries. The functional impairment of the affected kidneys was characterized by a decrease of 99mTc-diethylenetriamine pentaacetic acid uptake and a delay of 131I-hippurate excretion, while the 131I-hippurate uptake remained unaffected. These data are in agreement with a reduced glomerular filtration rate and diuresis during preservation of the renal blood flow, changes that can be expected after converting enzyme inhibition in a kidney with low perfusion and an active, renin-mediated autoregulation of the glomerular filtration rate. These data suggest that functional captopril-induced unilateral changes, shown by split renal function studies with noninvasive gamma camera scintigraphy, can be used as a diagnostic test for renovascular hypertension caused by unilateral renal artery stenosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Enhanced natriuretic effect of atrial natriuretic factor during mineralocorticoid escape in humans.

We examined the question of whether escape from the sodium-retaining effect of mineralocorticoid involves an increased natriuretic effect of atrial natriuretic factor (ANF). Seven healthy volunteers taking a 170 mmol Na/100 mmol K diet received an intravenous bolus (25 micrograms) followed by a 1-hour infusion (0.02 micrograms/kg/min) of ANF (human ANF-[99-126]) before and after 10 days of 9-fludrocortisone acetate, 0.5 mg b.i.d. Escape was accompanied by an increase in body weight (from 72.2 +/- 12.9 to 74.0 +/- 12.6 kg; p less than 0.05), mean arterial pressure (from 95 +/- 4 to 109 +/- 3 mm Hg; p less than 0.01), plasma ANF (from 9 +/- 2 to 24 +/- 4 pmol/L; p less than 0.01), and inulin clearance (from 124 +/- 9 to 137 +/- 7 ml/min; p less than 0.05). Indexes for renal sodium handling (lithium and free water clearance) were compatible with a decreased "proximal" and an increased "distal" tubular reabsorption fraction. ANF infusion raised inulin clearance comparably before and after escape to 138 +/- 10 and 152 +/- 7 ml/min, respectively, but the natriuretic effect was much larger (p less than 0.05) after escape (from 366 +/- 34 to 1294 +/- 278 mumol/min) than before (from 248 +/- 48 to 630 +/- 124 mumol/min). Indexes for tubular reabsorption were consistent with greater suppression of both "proximal" and "distal" tubular sodium reabsorption by ANF after versus before mineralocorticoid expansion. These results indicate that escape is accompanied not only by a rise in plasma ANF but also by potentiation of the natriuretic effect of ANF.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of atenolol and propranolol when added to long-term antihypertensive diuretic therapy.

The antihypertensive effects of atenolol and propranolol were compared in a double-blind crossover study of 19 patients with essential hypertension (World Health Organization, I and II) who were receiving long-term diuretic treatment (chlorthalidone, 50 mg daily) during the study. After a 3-wk placebo period, a beta-adrenergic antagonist was administered once daily (atenolol, 50 mg daily, or propranolol, 80 mg daily) for a week. If the MAP was more than 108 mm Hg at the end of the week, dosage of the beta-blocker was doubled the following week; when necessary, doubling was repeated to a maximum dose of 640 mg propranolol and 400 mg atenolol daily. Fifty milligrams atenolol had a greater effect than 80 mg propranolol and was as effective as 160 mg propranolol. The dose-response curve flattened off after 160 mg propranolol and 50 mg atenolol daily. The two highest doses of atenolol lowered MAP more than the highest doses of propranolo. Heart rate slowing was the same for both drugs and did not correlate with the fall in blood pressure. PRA was suppressed by all doses of propranolol, whereas atenolol suppressed PRA only at the 2 highest doses, (200 and 400 mg daily). With the lower propranolol doses, the percent MAP change correlated weakly with the percent PRA change (80 mg--r = 0.41, p less than 0.1; 160 mg--r = 0.64, p less than 0.05). Side effects were minimal, and were noted only with 640 mg propranolol; with this exception, the percentage of patients with no complaints rose when placebo was replaced by beta-blockers.

One and three doses of propranolol a day in hypertension.

In 26 patients with essential hypertension who were on continuous chlorthalidone therapy, 1 and 3 daily doses of propranolol were compared in a crossover study. Plasma propranolol levels and heart rates had larger daily fluctuations on single-dose therapy than on 3 times daily; plasma renin activity was more constant. There was no significant difference in blood pressures. Once-daily propranolol dosage was well tolerated and possibly gave less rise to the troublesome side effect of vivid dreaming.

Changes in blood pressure and body fluid volumes during diuretic therapy in patients with essential hypertension who receive enalapril.

We evaluated the effect of additional chlorthalidone therapy on blood pressure and body fluid volumes in 10 patients with essential hypertension who did not respond to chronic converting enzyme inhibition with enalapril. Values assessed after 3 days and 6 weeks of combined enalapril and chlorthalidone therapy were compared with initial values during enalapril monotherapy. After 3 days the mean arterial pressure (MAP), plasma volume (PV), blood volume (BV), and extracellular fluid volume (ECFV) decreased. There was a positive correlation between the percentage decreases in MAP and BV. After 6 weeks the MAP decreased further, but the decreases in PV, BV, and ECFV were less pronounced. At this time there was a positive correlation between the percentage decreases in MAP and ECFV. Our results support the hypothesis that contraction of the ECFV is an antihypertensive mechanism of diuretics. The antihypertensive effect of diuretics is enhanced during converting enzyme inhibition, while the body remains protected against volume deficits, possibly by the lower blood pressure itself.

Absorption kinetics of oxalate from oxalate-rich food in man.

The absorption of oxalate was investigated in a healthy subject after ingestion of oxalate-rich meals (spinach and rhubarb) with and without addition of 14C-labeled oxalic acid and calcium oxalate, and after oxalate-free meals with addition of nonlabeled sodium oxalate and calcium oxalate. Under these conditions, calcium oxalate was absorbed to the same extent as soluble oxalate; only a small percentage (2.4 +/- 0.7) of the total oxalate load was absorbed. Significant oxalate absorption occurred within 1 to 8 h after ingestion. The results suggest that under normal conditions the proximal part of the small bowel is a major absorption site.

No effect of APD (amino hydroxypropylidene bisphosphonate) on hypercalcemia in patients with renal osteodystrophy.

Hypercalcemia, due to autonomous functioning of the parathyroids following long standing secondary hyperparathyroidism, is a well known complication in patients with renal osteodystrophy, which can on most cases be treated by parathyroidectomy only. While patients with renal osteodystrophy react favorably to supplementation of active vitamin D metabolites to prevent or reverse renal osteodystrophy, the use of these drugs is bound to result in greater hypercalcemia in those patients who are already hypercalcemic. The question rose if the bisphosphonate amino hydroxypropylidene bisphosphonate (APD) would decrease plasma calcium concentration sufficiently in order to create room for the use of vitamin D to cure the osteomalacia component of the osteodystrophy and simultaneously block the excessive bone resorption. Therefore, five patients with renal osteodystrophy and hypercalcemia were treated for up to 9 months with APD. Three of them, who were on chronic hemodialysis, received 15 mg APD i.v. 3 times a week, the 2 other patients with severe renal failure received 200 mg APD orally. Ionized calcium in plasma did not decrease. Histological investigation of bone samples, obtained before and after therapy, showed an increase of fibrous tissue and a remarkable increase in the number of osteoclasts or osteoclast-like cells not only along the bone-margin, but mainly within the bone-marrow. We conclude that in patients with renal failure with hypercalcemia, APD in the doses used had no effect on plasma calcium level, but caused a striking change in bone histology. Although the consequences of these findings are not yet clear, they do not seem to indicate improvement of bone structure.

Comparison of the effects of enalapril and theophylline on polycythemia after renal transplantation.

Posttransplant erythrocytosis (PTE) is a potentially serious complication for which (apart from phlebotomy) two alternative treatments have been proposed: theophylline (Theo) and angiotensin-converting enzyme inhibitors. We investigated 28 patients with PTE, who were assigned to 3 matched groups. Group 1 (10 patients) received 10 mg of Enalapril (Ena)/day. After 2 months, mean hematocrit (Ht) had dropped from 0.57 (range 0.52-0.62) to 0.45 (0.34-0.49). Ena was stopped and, after a period of 3.8 +/- 0.3 months, Ht had risen again to baseline values (0.56, range 0.52-0.61) in 8 of them. These 8 patients were then given 5 mg/day Ena. Ht decreased more slowly, and after 3 months reached a mean of 0.49 (0.44-0.54). Group 2 (9 patients) received 600 mg/day Theo in 2 doses. After 2 months, Ht had decreased from 0.56 (0.52-0.61) to 0.52 (0.46-0.63), but in 5 patients, Ht remained above 0.51. After 1 month discontinuation of treatment, PTE persisted in 7 patients. These patients were given 10 mg/day Ena, whereupon Ht decreased from 0.55 (0.52-0.64) to 0.46 (0.40-0.53) after 2 months and to 0.41 (0.33-0.47) after 3 months. Group 3 did not receive medical treatment. After 3 months, PTE persisted in 8 out of the 9 patients and remained unchanged during the following 3 months. Mean values for Ht were: baseline, 0.55 (0.52-0.58); after 3 months, 0.56 (0.53-0.59); and after 6 months, 0.55 (0.52-0.60). We conclude that Ena is superior to Theo in the treatment of PTE. There were no resistant patients, but individual sensitivity differs. Its effect is dose dependent, reversible, and reproducible. Excessive Ht decrease may occur; thus, doses should be titrated individually.

Dilated uremic cardiomyopathy in a dialysis patient cured by persistent ultrafiltration.

A patient is presented who after 2 years of hemodialysis showed all of the features of congestive cardiomyopathy to a very severe degree: dilation of all cardiac compartments, increased left ventricular mass, low ejection fraction, diastolic disturbances, third- to fourth-degree mitral and tricuspid regurgitation, ascites, and low blood pressure. All of these abnormalities gradually but completely disappeared during 5 months of persistent ultrafiltration during or between dialysis sessions. It was concluded that chronic fluid overload was a major factor in the cardiac disease of this patient. Unrecognized hidden fluid overload has long been known (but also neglected), and its prevention deserves top priority in chronic dialysis patients.

Treatment of hypertension in dialysis patients by ultrafiltration: role of cardiac dilatation and time factor.

We retrospectively analyzed the blood pressure (BP) and cardiothoracic index (CTi) of 67 hemodialysis patients with hypertension who could be followed up for at least 8 months. A new treatment policy was adopted, aimed at strict volume control. Dietary salt restriction was strongly emphasized. Ultrafiltration (UF) was applied during regular dialysis sessions and sometimes in additional sessions, as long as BP and CTi remained at greater than normal values. All antihypertensive drugs were discontinued at the beginning of treatment. Average BP decreased from 173 +/- 17/102 +/- 9 to 139 +/- 18/86 +/- 11 mm Hg after 6 months and to 118 +/- 12/73 +/- 6 mm Hg after 36 months. Corresponding values for CTi were 52% +/- 4%, 47% +/- 3%, and 42% +/- 4%, respectively. Conventional relatively short dialysis (three times weekly for at least 4 hours) can achieve normal BPs with prolonged effort in most patients, whereas improvement in heart condition facilitates this.

An unusual form of renal disease associated with gout and hypertension.

A family is described many of whose members suffered from renal insufficiency, hypertension, gout, and hyperuricaemia in conjunction. Adequate information was obtained on 72 subjects from five generations. In 17, one or more of the above mentioned abnormalities was or had been present. The hereditary distribution suggested an autosomal dominant disease entity. The renal disease was characterized by an early loss of urinary concentrating power, minimal proteinuria, and death at a relatively early age dominating the clinical picture. The histological picture in three biopsies and one necropsy showed predominant tubular atrophy and interstitial fibrosis, with striking tubular basement membrane thickening. It is suggested that these patients suffered from a hereditary degenerative renal disease. The question whether hyperuricaemia was primary or secondary in these cases is discussed.

Renovascular hypertension in three children from one family.

Hypertension as a result of stenosis of a renal artery was diagnosed in three patients, aged 20, 17, and 9 respectively, among 14 siblings from one family. The oldest patient was treated by vasoplasty; a hypoplastic kidney had previously been removed in an unsuccessful attempt to control hypertension. Nephrectomy was performed in the other two patients. The pathological picture of the main renal artery that could be examined differed from that usually seen in the fibromuscular dysplasia group. The absence of microscopic signs of atrophy in the small kidneys behind the stenosis argues for a developmental defect. More than three years after operation blood pressure and renal function in all three patients have remained normal.

Transthoracic electrical impedance as an index of extracellular fluid volume in man.

Findings in 76 subjects without cardiac failure were analyzed to detect relationships between observed changes in transthoracic electrical impedance (TEI) and total body extracellular fluid volume (ECFV) during various manoeuvres and between absolute TEI and ECFV values. TEI was normalized to electrode distance (Z0/delta el) and ECFV to lean body mass (ECFV/LBM). A distinct relation was found between percent changes of TEI and ECFV (r = -0.76, p less than 0.0001) and between absolute Z0/delta el and ECFV/LBM values (r = -0.66, p less than 0.0001 for men; r = -0.61, p less than 0.0001 for women). It is concluded that in the same subject a change in TEI is possibly a sensitive index for a change in ECFV and that a single measurement of TEI, normalized to electrode distance, gives information about the state of hydration (ECFV) of patients without cardiac failure.