Ajm Donker

The effect of indomethacin on kidney function and plasma renin activity in man.

125Iothalamate and 131I-hippuran clearances, sodium excretion and plasma renin activity (PRA) before and during indomethacin administration in an oral dose of 3 x 50 mg/day were studied in volunteers with a normal or reduced kidney function, as well on non-sodium-restricted as on sodium-restricted diet. Indomethacin induced a temporary sodium and water retention and a decrease in glomerular filtration rate. It also lowered PRA. The latter phenomenon did not depend on sodium retention and was present within 2 h after an oral dose of 50 mg. The results may be explained by indomethacin-induced inhibition of prostaglandin synthesis.

NEPHROPTOSIS AND HYPERTENSION

The degree of renal mobility was measured in patients with and without hypertension to evaluate a suggested causal relation between nephroptosis and hypertension. In contrast to men, women often showed pronounced renal mobility and the degree of renal mobility correlated positively with the blood-pressure. Fibromuscular dysplasia of the renal artery was always accompanied by a considerable degree of renal mobility on the side involved. The results of this study indicate that in women there may be an association between abnormal renal mobility and the development of high blood-pressure.

Acute effects of cis-diamminedichloroplatinum (CDDP) on renal function

SummaryTen previously untreated patients with metastatic non-seminomatous testicular carcinoma received cis-diamminechloroplatinum (CDDP). Renal function studies were performed before and following the first CDDP infusion. A decrease in effective renal plasma flow (ERPF) and an increase in filtration fraction (FF) was found in all patients. These findings suggest primary changes in renal hemodynamics during CDDP infusion.

Treatment of the Nephrotic Syndrome with Indomethacin

In 25 patients with nephrotic syndromes of different origin, indomethacin caused an immediate decrease in glomerular filtration rate (GFR) and urinary protein excretion. This effect of indomethacin on GFR and proteinuria was more pronounced when the renin-angiotensin system was stimulated by a low-sodium diet and 50 mg hydrochlorothiazide daily, and resulted in a significant rise in serum albumin. Withdrawal of indomethacin after 1--3 years of administration was followed by an increase in proteinuria to pretreatment levels in 9 out of 15 patients. A harmful renal effect of long-term indomethacin administration was found to be unlikely. The results suggest that the steroid-resistant nephrotic syndrome can be treated symptomatically by indomethacin.

THE EFFECTS OF DIETARY SUPPLEMENTATION WITH FISH OIL ON RENAL-FUNCTION IN CYCLOSPORINE-TREATED RENAL-TRANSPLANT RECIPIENTS

The effect of a daily supplementation of 6 g fish oil (30% C20:5 omega-3 (EPA) and 20% C22:6 omega-3 for three months on renal function variables was investigated in a placebo-controlled (6 g corn oil, 50% C18:2 omega-6) prospective, randomized, double-blind study in stable cyclosporine-treated renal transplant recipients, at least nine months after grafting. Ten patients ingested placebo capsules and eleven patients fish oil. When measuring glomerular filtration rate and effective renal plasma flow (ERPF) before (baseline [BL]) and after 3 months of oil ingestion nothing changed in the placebo-treated group: GFR-BL = 64.5 GFR-3 months = 60 ml/min/1.73m2 (NS; median, Wilcoxon test) ERPF BL = 229.5 and ERPF-3 months = 242.5 ml/min/1.73m2 (NS). In the fish oil-treated group GFR rose by 20.3% from GFR-BL = 56 to GFR-3 months = 68 ml/min/1.73m2 and ERPF by 16.4% from ERPF-BL 218 to ERPF-3 months = 245 ml/min/1.73m2, (P less than 0.01). In the placebo-treated group mean arterial pressure and calculated total renal vascular resistance (TRVR) did not change: MAP-BL = 106 mmHg and MAP-3 months = 109 mmHg, TRVR being 20856 dyne.sec/cm5 and 19862 dyne/sec/cm5, respectively (NS). In the fish oil-treated group MAP and TRVR fell by 8.6% and 21.1%, respectively: MAP-BL = 106 mmHg and MAP-3 months = 98 mmHg (P less than 0.01), TRVR-BL = 21952 dyne/sec/cm5 and TRVR-3 months = 17087 dyne/sec/cm5 (P less than 0.01). According to these results fish oil supplementation has considerable effects on renal function and blood pressure in stable CsA-treated renal transplant recipients.

Diuretic effects of angiotensin-converting enzyme inhibition: comparison of low and liberal sodium diet in hypertensive patients.

Inhibitors of the angiotensin-converting enzyme (ACE) acutely increase sodium excretion. Whether or not continued treatment induces net negative sodium balance is not clear, and may depend on initial sodium balance. We therefore investigated the effects of 8 days of treatment with enalapril, 10 mg b.i.d., on sodium balance in 10 subjects with uncomplicated essential hypertension, in balance on a low (50 mmol sodium/24 h) and a liberal (200 mmol sodium/24 h) sodium intake. Sodium excretion exceeded intake during the first days of treatment, amounting to sodium losses of 101 ± 24 and 112 ± 15 mmol in the low and the liberal sodium diets, respectively. The sodium loss was accompanied by a fall in body weight with both regimens. The blood pressure response to enalapril was potentiated by the sodium-restricted diet. The net increase in sodium excretion after enalapril administration, however, was similar for both diets. This was particularly true for individual patients, suggesting an individual response pattern to ACE inhibition.

Effects of Chronic and acute protein administration on renal function in patients with chronic renal insufficiency

In 6 volunteers with normal renal function, we investigated the effects of various kinds of protein (soy, lactoprotein and beef) and various amounts of an intravenously administered amino acid solution on glomerular filtration (GFR) and effective renal plasma flow (ERPF). As for the protein-induced changes in renal function, rises in GFR and ERPF were lowest with soy protein, and highest with beef (baseline GFR, 110 +/- 5; soy, 122 +/- 5; beef, 131 +/- 5 ml/min/1.73 m2; mean +/- SEM). High doses of intravenous amino acids induced a rise in GFR comparable to that after beef (132 +/- 5 ml/min/1.73 m2). In a combined test a liquid mixed meal together with intravenously administered amino acids induced a comparable increase of the GFR (baseline 114 +/- 5 versus 129 +/- 5 ml/min/1.73 m2). When investigating 9 patients with chronic renal insufficiency after 4 weeks of low protein intake (LP) and after 4 weeks of high protein intake (HP), GFR and ERPF rose significantly under baseline conditions (GFR-LP41 +/- 9 versus GFR-HP 45 +/- 9 ml/min/1.73 m2, p less than 0.02; ERPF-LP 169 +/- 39 versus ERPF-HP 180 +/- 40 ml/min/1.73 m2, p less than 0.02; paired Wilcoxon). At the end of both dietary periods a comparable rise in renal function could be induced through acute stimulation (GFR-LP 20 +/- 5, GFR-HP 16 +/- 4; ERPF-LP 23 +/- 7, ERPF-HP 22 +/- 3%).(ABSTRACT TRUNCATED AT 250 WORDS)

PNEUMATOSIS INTESTINALIS IN PATIENTS AFTER CADAVERIC KIDNEY-TRANSPLANTATION - POSSIBLE RELATIONSHIP WITH AN ACTIVE CYTOMEGALOVIRUS-INFECTION

Four patients are described with pneumatosis intestinalis following cadaveric kidney transplantation, all with severe cytomegalovirus (CMV) infection. Two patients had a primary infection and 2 patients had a reactivation of CMV. One patient died because of disseminated CMV infection. Multiple inclusion bodies were found at postmortem examination in lungs and liver, and at the site of the ulcers in the gastrointestinal tract. Two patients had, concomitantly, an active, nonobstructive duodenal ulcer. In a control population of 17 patients who suffered from a duodenal ulcer post-transplant without any evidence of CMV-infection, we could not demonstrate pneumatosis intestinalis. We suggest a possible causal relationship between pneumatosis intestinalis and active CMV infection. The mechanisms that could be responsible for this relationship are discussed.

Restenosis Prevalence and Long-Term Effects on Renal Function after Percutaneous Transluminal Renal Angioplasty

We studied the frequency of restenosis and the effects of percutaneous transluminal renal angioplasty (PTRA) on blood pressure (BP) and particularly on renal function in all patients in whom successful dilatation was performed. Restenosis was found in 42% of the patients with an atherosclerotic renal artery stenosis and in 22% of the patients with fibromuscular dysplasia. BP improvement was seen in 70-80% of the patients with unilateral stenosis or with successful bilateral dilatation (group I) whereas only seldom was an effect on BP observed in patients with more complicated disease, such as those with an occlusion of the contralateral artery (group II). Remarkably, however, both in group I and in group II, in about half of the patients an improvement in renal function was found, even 2-3 years after the procedure. Our results thus indicate that PTRA can be useful in preservation or even improvement of renal function, even if no effect on blood pressure can be expected.

INFLUENCE OF PLATINUM-INDUCED RENAL TOXICITY ON BLEOMYCIN-INDUCED PULMONARY TOXICITY IN PATIENTS WITH DISSEMINATED TESTICULAR-CARCINOMA

Pulmonary function tests, including T1CO, and renal function tests were performed and GFR and ERPF measured in 18 patients with disseminated testicular non-seminoma before and after remission induction according to the Einhorn regimen. We found a significant positive correlation between delta GFR and delta T1CO (p less than 0.05). No significance could be demonstrated between delta ERPF and delta T1CO. It is concluded that caution should be exercised in administrating bleomycin to patients with severely impaired renal function.