Treatment of renovascular hypertension: one year results of renal angioplasty.

During the ten year period from 1981 to 1991, percutaneous transluminal renal angioplasty (PTRA) was performed in 180 renal arteries in 137 patients, where the underlying renovascular disease was fibromuscular dysplasia (FMD) in 30 patients (22%) and arteriosclerotic vascular disease (AVD) in 107 (78%). A preinterventional work-up and a re-evaluation of the patients after one year was designed for the assessment of the clinical, functional and technical outcome. Successful technical dilatation was achieved in 97% of procedures with FMD patients and in 82% of procedures with AVD patients. A beneficial effect on the blood pressure and the renal function was registered in both groups. The overall cure and improvement rate for hypertension was 86% in the FMD group and 64% in the AVD group after one year's follow-up. A significant gain in the total renal function was registered in both groups, the average increase in glomerular filtration rate being 13% (P < 0.001) for the FMD group and 11% (P < 0.001) for the AVD group one year after PTRA. Renal function was improved or unchanged in 89% of FMD patients and 74% of AVD patients. The improvement in renal function was made by the revascularized kidney. Renal vein renin investigation predicted the clinical outcome with an excellent diagnostic accuracy as no renin negative patient became normotensive, and renin positive patients, who did not turn normotensive, were in almost 90% of the cases affected by technical failure or restenosis/contralateral stenosis. Thus, the sensitivity of renal vein renin investigation was 95% and the specificity 75%. The outcome for patients with hypertension and renal insufficiency was considerably poorer than for the whole group of patients, with only a 20% success rate for hypertension, but 50% in this group had increased or unchanged GFR after intervention. The angiographic one-year follow-up revealed a recurrence rate of 6.7% for FMD and 15.1% for AVD. For the entire series of patients, the incidence of major complications was 5.4%, including one indirect fatality, while the incidence of minor complications was 5%. In conclusion, PTRA will cure or improve blood pressure in most patients with renovascular hypertension, and it preserves and even improves renal function in these patients. Complications and recurrence are in fact not very common and PTRA appears be the best first approach in all but ostial lesions for treatment of renovascular hypertension.

Serum concentrations of calcitriol and PTH in hemo-dialysis patients on treatment with calcium carbonate.

The effects of calcium carbonate and aluminium hydroxide as phosphate binders were investigated in nine patients on chronic hemodialysis. Aluminium hydroxide, 1 g X 3, was given during four weeks followed by a period of four weeks without any phosphate binders and after this calcium carbonate, 2.5 g X 3, was introduced for four weeks. Calcium carbonate resulted in lowering of bioactive PTH in serum from 22.4 to 16.4 pM and a rise of serum calcitriol from 8.0 to 11.5 pg/ml with maintained control of phosphate and without significant difference in the calcium-phosphate product. Calcium in serum rose from 2.27 to 2.57 mM and mild hypercalcemia (less than 3.0 mM) in five of the patients could be controlled by dose reduction of calcium carbonate without losing control of serum phosphate levels. We conclude that calcium carbonate offers advantages as a phosphate binder compared to aluminium hydroxide in that it offers equal control of serum phosphate and elevates serum calcium which helps to control the hyperparathyroidism secondary to uremia.

Plasma noradrenaline and dopamine in renin-mediated hypertension.

Noradrenaline (NA) and dopamine (DA) have opposite effects on the kidney; NA causes vasoconstriction and increased sodium reabsorption while DA promotes vasodilation and natriuresis. In 15 patients investigated for renin-mediated hypertension measurements of plasma renin activity (PRA), NA and DA concentrations were made in arterial and renal venous blood from both kidneys before and after acute stimulation of renin release by i.v. dihydralazine. Nine patients had unilateral renin secretion and were classified as renin-positive, while the remaining six patients were renin-negative. Renin-positive patients had higher arterial and renal venous PRA, NA and DA levels than the negative ones. In the renin-positive group V-A differences for NA and DA were present on both sides despite unilateral secretion of renin. NA but not DA levels were higher in the renin-secreting kidney, which can partly be explained by the reduced plasma flow to the involved kidney. After dihydralazine the arterial NA and DA rose similarly in renin-positive and renin-negative patients, while PRA rose only in the renin-positive cases. In the renin-positive patients where stimulation of renin secretion caused a marked increase of the PRA gradient on the affected side only, renal gradients for NA and DA increased bilaterally. The increase in DA was more pronounced than that of NA yielding a rise in DA/NA ratio on the affected side. Arterial PRA was positively correlated to the plasma concentrations of NA and DA. V-A differences for PRA and NA or DA were positively correlated on the involved renin-secreting side. In summary, patients with renin-dependent hypertension have elevated plasma NA and DA concentrations. Stimulation of renin release by dihydralazine increases the DA/NA ratio in arterial and renal venous blood indicating release of 'precursor dopamine' from noradrenergic fibres and/or activation of dopaminergic nerves. There seems to be a relationship between renal nerve activity and renin release in renin-dependent hypertension.

Renal function and upper urinary tract configuration following urinary diversion to a continent ileal reservoir (Kock pouch): a prospective 5 to 11-year followup after reservoir construction.

We followed 17 patients who underwent urinary diversion via a continent ileal reservoir (Kock pouch) with yearly examinations for 5 to 11 years postoperatively. The examinations involved control of renal function and configuration of the upper urinary tract. In 5 patients the upper urinary tract had become dilated during followup and in 2 of these renal scarring also had developed. All 5 patients had endured temporary outflow obstruction or reflux (stricture, overdistension of the reservoir or a defective antireflux valve). Of the patients 1 had a marked decrease in renal function before the outflow obstruction was corrected by an operation. Routine blood chemistry study was normal and hyperchloremic acidosis was not noted in any patient. After peroral loading of 6 patients with ammonium chloride significant excretion of titratable acid was found in the urine. Substitution with vitamin B12 was given to 6 patients due to subnormal values in 2 and borderline values in 4.

Longitudinal study of specific IgE and IgG antibodies in a patient sensitized to ethylene oxide through dialysis.

IgE and IgG antibodies to ethylene oxide (EO) were monitored by RAST and by ELISA in serum from a patient with hypersensitivity reactions during hemodialysis. Serum samples from the patient covering a 7-year period were analyzed. The changes in titers of IgE and IgG antibodies correlated to the time of EO exposure as well as to clinical symptoms. EO-specific IgG antibodies were, however, also found in sera from hemodialysis patients without any hypersensitivity symptoms. Assay of specific IgG antibodies will only indicate whether a patient has been exposed to, and immunostimulated by, EO, whereas specific IgE antibodies appear to be clearly related to hypersensitivity symptoms. The hapten and carrier specificity of EO-induced IgE antibodies was studied. The antibodies were found to be solely hapten specific because carriers of different types could be used in RAST without changing the outcome of the test. The existence of new antigenic determinants related to the carrier could not be demonstrated.

Pharmacokinetics and pharmacodynamics of ramipril in renal failure.

The pharmacokinetics and pharmacodynamics of the novel angiotensin converting enzyme (ACE) inhibitor ramipril were studied in 6 patients with a glomerular filtration rate of less than 20 ml/min/1.73 m2 of body surface area. A single oral dose of 5 mg was given and serum concentrations of the compound and its diacid, the active metabolite (ramiprilat), as well as ACE activity, blood pressure and pulse rate were monitored for 28 days. The original compound reached peak serum concentrations of 42.8 +/- 26.5 ng/ml about 1 hour after dosing and was completely eliminated from the serum after 24 hours. Ramiprilat reached peak values of 14.4 +/- 11.6 ng/ml after about 6 hours. In contrast with the parent compound, low concentrations of ramiprilat were still detected in the serum after 28 days. ACE activity decreased to approximately 5% of baseline values, remained low for the next 48 hours, then increased slowly thereafter but reached only 84.5% of initial values after 28 days. Blood pressure decreased significantly and remained low for 24 hours after dosing. The drug was well tolerated in all patients. It is concluded that a single 5 mg dose of ramipril was effective in inhibiting plasma ACE activity and lowering blood pressure in patients with renal failure. There was a slower decline in ramiprilat concentrations compared with subjects with normal renal function.

Dissociation of renin and noradrenaline release in the renal circulation. Studies on patients with renal hypertension.

Plasma renin activity (PRA) and noradrenaline concentration (NA) were measured in the renal veins (V) and arterial blood (A) in 30 patients investigated for renin-mediated hypertension. Both PRA and NA concentrations in arterial blood were above our reference limits and they were positively correlated. In 18 of the patients renin secretion was unilateral from the diseased side. Their renal vein NA concentration was always higher on that side, compared to the contralateral one, but there were V-A gradients for NA on both sides in all but two cases. In 15 of the patients with such lateralisation of renin secretion the changes of PRA and NA V-A gradients were determined 30-60 min after an i.v. injection of dihydralazine. Both PRA and NA increased more markedly in the renal vein on the affected side where the estimated renal plasma flow was lower than on the contralateral side. The NA gradients increased less than the PRA gradients when changes on the renin secreting side were compared in patients with proven increase of renin secretion. We conclude that patients with renal hypertension have a high sympathetic nervous activity as evidenced by increased plasma NA concentrations and (V-A) gradients for NA on both sides. The release of NA into the renal circulation in renin mediated hypertension is thus not invariably accompanied by renin release. The higher renal vein NA concentration on the involved renin secreting side is explained by reduced RPF on this side.

Hydration affects the result of a desmopressin test in adults.

Desmopressin tests to measure renal concentrating capacity, preceded by two different fluid regimens, have been compared in 19 adult subjects. The results show that peak osmolality in urine after 40 micrograms desmopressin intranasally is higher after fluid restriction. This observation confirms the need of a standardised fluid restriction before the desmopressin test.

Effects of cardiopulmonary bypass and prostacyclin on plasma catecholamines, angiotensin II and arginine-vasopressin.

Infusion of prostacyclin during cardiopulmonary bypass (CPB) reduces platelet activation, diminishes postoperative blood loss and decreases arterial blood pressure. In spite of continuous prostacyclin infusion, there is a delayed gradual rise in arterial pressure and resistance from low initial levels. We measured epinephrine (E), norepinephrine (NE), serotonin (5-HT), angiotensin II (ATII) and arginine-vasopressin (AVP) in plasma and carried out hemodynamic studies in 19 patients operated for coronary vascular disease. Eight patients served as a control group and were subjected to routine CPB. Eleven patients received prostacyclin 50 ng/kg/min during CPB. E and NE increased four- to sixfold during CPB from about 0.5 ng/ml (P less than 0.001). There was no difference between the groups. During CPB AVP increased sixfold from about 20 pg/ml in both groups (P less than 0.001), decreased early after CPB and increased again to high levels 3 h after CPB. The combined action of E, NE and AVP is of likely importance for the rise in systemic vascular resistance and/or need of vasodilation during CPB in the control group. ATII did not increase in the control group, but increased fourfold to about 20 pg/ml (P less than 0.01) during CPB in the prostacyclin group. The addition of AT II to E, NE and AVP seems responsible for the gradual return of arterial pressure and resistance during prostacyclin infusion. Postoperative hypertension and/or need of vasodilation 3 h after CPB was associated with high AVP levels in both groups. Hypotension caused by prostacyclin infusion did not increase E, NE or AVP above levels produced by CPB and moderate hypotension alone.

Captopril in Hpertension After Renal Transplantation.

The experience with captopril is limited in patients who are hypertensive after renal transplantation. An increased risk of side effects has been expected because of immunosuppressive therapy and a reduced renal function. We have used captopril in 58 transplanted patients with hypertension. On previous antihypertensive treatment diastolic blood pressure could not be maintained below 100 mm Hg. All patients were on immunosuppressive therapy using prednisolone in combination with azathioprine or cyclosporin. Before captopril went mean s-creatinine concentration was 225 ± 143 µmol/l. Fifty-four patients were treated for more than four weeks and 28 of them for six months or more. The mean daily dose captopril was 90 mg. All patients also used furosemide and 2/3 were on a beta-blocker. Captopril was discontinued in nine cases within the first two months, in three because of an unsatisfactory effect on BP, in four because of side effects and in two after successful treatment of a renal artery stenosis of the transplant. The Patients who were treated with captopril within the first year after transplantation responded better than patients where treatment was started more than one year after transplantation (p < 0.05). Half of the patients given captopril early even showed a decrease of s-creatinine during treatment. Captopril in combination with a diuretic and a beta-blocker, reduces blood pressure in patients with treatment resistant hypertension following renal transplantation. The risk for serious side effects is small provided that the captopril dose is and white cell counts and s-creatinine levels are closely monitored.

Factors regulating sodium balance in proctocolectomized patients with various ileal resections.

Patients subjected to proctocolectomy together with an ileal resection will lose increased amounts of sodium with the ileostomy excreta and may develop sodium and water depletion. Studies of sodium balance and measurements of renin activity, aldosterone, and arginine vasopressin in plasma were made in 23 such patients, 8 of them under metabolic-ward conditions while receiving various salt loads. Salt loss never resulted in subnormal sodium levels in serum. The earliest sign of salt depletion was a nearly total inhibition of renal sodium excretion, which could precede activation of the renin-aldosterone axis in these patients. Secretion of vasopressin remained unaffected by sodium-water depletion and by activation of the renin system. The routine monitoring of these patients should include measurements of renal sodium excretion. Measurement of renin and aldosterone levels should be used for evaluation of the severity of a sodium deficiency.

Saluretics and converting-enzyme blockade in the treatment of resistant hypertension.

Blockade of the actions of the renin-angiotensin-aldosterone axis by inhibition of the angiotensin-converting enzyme with captopril is a new tool in the field of hypertension. As treatment with captopril makes pressure control volume-dependent, the addition of a saluretic is considered the best choice if an additional hypotensive agent is needed. The reason for and experience of the use of captopril in combination with saluretics for treatment of severe hypertension is reviewed. Published results indicate that captopril alone is insufficient, but as many as a third of the patients with previously uncontrollable hypertension manage well when a saluretic is added. Only one in six remains uncontrolled despite the addition of several other hypotensive agents. These observations apply to both essential and secondary forms of hypertension.

Preoperative diagnosis of renovascular hypertension. The use of acute stimulation of renin secretion.

The gain in the diagnostic power of the routine preoperative bilateral renal vein renin investigation by the inclusion of an acute stimulation of renin release was studied in 25 hypertensive patients with fibromuscular (FMD) and 44 with arteriosclerotic (AS) renovascular disease. Nine FMD and 17 AS patients had renal vein renin ratios greater than or equal to 1.50 under unstimulated conditions. Of these 26 patients, 8 in each group improved after surgical treatment. Among the 14 FMD and 24 AS patients with ratios less than 1.50, another 9 FMD and 7 AS patients improved after operation. After acute stimulation of renin release, no less than 18 FMD and 26 AS patients had a unilateral renin secretion from the diseased kidney and of these, 14 FMD and 14 AS patients were successfully treated with operation of the stenosis. Thus the stimulation was necessary for correct preoperative diagnosis in 38% of 32 successfully operated patients, and at the same time the predictive value of a negative test increased from 0.58 to 0.80. It is concluded that acute stimulation of renin release greatly improves the diagnostic power of the renal vein renin investigation in renovascular hypertension.