Krister Delin

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.

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.

Renin Secretion in Advanced Diabetic Nephropathy.

Low basal and stimulated plasma renin activity (PRA) levels have been reported in patients with diabetic nephropathy (DN). We have measured PRA before and after stimulation with captopril in 28 patients with DN and in 25 control patients. Renal function impairment was similar in both groups. Most patients were treated with furosemide. In 19 patients with DN the PRA-response to dihydralazine was also studied. PRA before and after captopril were higher in the DN than in the control group (p less than 0.001). PRA increased from 4.6 +/- 3.6 to 6.3 +/- 5.3 in the DN, and from 1.8 +/- 2.7 to 2.7 +/- 3.4 in the control patients. The increases in PRA, caused by decreased angiotensin II feed-back inhibition, were comparable. PRA did not increase after dihydralazine despite a pronounced blood-pressure reduction. The difference in response to these stimuli indicate selective lesions involving both the sympathetic innervation and the renal baroreceptor function in DN. Overhydration is a plausible explanation to the low PRA earlier reported in DN. The results thus indicate that a preserved renin secretion capacity is present in DN. Differences in PRA between the both groups can only partly be explained by other factors than DN. Our findings indicate a role for the reninangiotensin-system in hypertension in DN.

Captopril Treatment in Hypertensive Dialysis Patients

Captopril was used for treatment resistant arterial hypertension in 17 dialysis patients. Excellent blood-pressure control with diastolic blood-pressure less than 95 mmHg was obtained in 10 out of 17 patients (59%), with captopril as only drug in 8 patients. Six patients have been treated more than 6 months and 4 patients have been on the treatment for 1 year. The dosage of captopril could be kept low with maintained antihypertensive and angiotensin converting enzyme blocking effects. The acute blood-pressure lowering effect of captopril in dialysis patients was correlated to the initial plasma renin activity (p less than 0.001) but not long-term treatment, which was successful also in several low-renin patients. A few adverse reactions were encountered, e.g. urticaria and bullous exanthema, but all resolved when captopril treatment was stopped. Plasma potassium increased only from 4.8 +/- 0.1 to 5.0 +/- 0.1 mmol/l at the end of 1 months treatment. Captopril appears to be a valuable drug for treatment of arterial hypertension in dialysis patients and offers an alternative to bilateral nephrectomy for the management of treatment resistant hypertension in these patients.

CAPTOPRIL IN HYPERTENSION 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 treatment the mean s-creatinine concentration was 225 +/- 143 mumol/l. Fifty-four patients were treated for more than four weeks and 28 of them for six months or more. The mean daily dose of 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 less than 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 low and white cell counts and s-creatinine levels are closely monitored.

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.

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.