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Biomedical subjects

M Aurell

Publications and source records attributed to M Aurell.

At least 145 records · Page 8Linked to original sources

Kidney function in an unselected lithium population. A cross-sectional study.

We studied kidney function in 124 short-term and long-term lithium outpatients from a population of 127 patients. Glomerular and distal tubular function were measured and correlated with a number of demographic and treatment variables. There was a significant negative correlation between age and glomerular filtration rate. There were no other significant correlations. Tubular function was below normal in 51% of the patients. Glomerular function was below normal in 3% of the patients. We conclude that lithium treatment in non-toxic dose affects kidney function and that tubular function is more affected than glomerular function. Tubular function probably is better than our figures indicate, glomerular function not as good. Types of lithium preparation do not affect kidney function differently nor does combined treatment with neuroleptics.

Adult↗

Renal denervation and sodium balance in young spontaneously hypertensive rats.

In 7-week-old male, spontaneously hypertensive rats (SHR) and matched normotensive control rats, Wistar Kyoto Rats (WKY), a bilateral renal denervation was performed. In two additional groups of rats a sham denervation was done (SHRS, WKYS). The animals were then kept in metabolic cages during a 10-day period during which sodium intake, urine volume, urinary sodium excretion, fecal sodium excretion, urinary aldosterone excretion and plasma renin activity were determined. Fractional urinary excretion of sodium was higher in the denervated SHR (p less than 0.1) and WKY (p less than 0.05) during the first 3 days after denervation, but during the following 3-day periods no difference between denervated and sham-operated groups was noted. The difference in fractional urinary excretion of sodium initially was due to a diminished urinary sodium excretion in the sham-operated groups since both SHRS and WKYS exhibited a significant increase between the first and the last 3-day period. Urine volume increased significantly in both SHR and WKY after denervation. Urinary aldosterone excretion on the 7th day after denervation was significantly lower in SHR compared to WKY, but there was no significant difference between the denervated and sham-operated groups. PRA was also significantly lower in SHR but no significant decrease was seen after denervation.

Aldosterone↗

Effect of captopril on blood pressure, renal function, the electrolyte balance and the renin-angiotensin system in Bartter's syndrome.

3 patients with Bartter's syndrome were studied under metabolic ward conditions before and during administration of captopril 25 mg t.i.d. The drug induced an immediate and sustained reduction of blood pressure (by 14 and 18% after 1 h and 3 days, respectively) with no change in heart rate. During treatment renal plasma flow increased by 29%, but the glomerular filtration rate was unchanged. Renal vascular resistance decreased by 41%. There was an increase in urinary sodium excretion with a corresponding reduction of body weight. The potassium balance was not affected. The concentration of angiotensin II became normal but the plasma renin concentration rose tenfold. Plasma renin substrate, initially rather low, was further reduced. The blood pressure responsiveness to angiotensin II increased without being completely normalized. An abnormal production of vasodilating prostaglandins is thought to be an important feature of Bartter's syndrome. Our findings, notably the marked renal vasodilatation, may reflect the effect of these prostaglandins when unopposed by an increased angiotensin II production.

Adult↗

Renal degradation of insulin in patients with renal hypertension.

Renal processing of insulin was studied over plasma insulin levels of 5-80 mU/l by renal vein catheterization in 14 patients. Kidneys of patients with a normal GFR removed around 30% of the insulin from arterial plasma. In 6 patients having unilateral renal artery stenosis but only moderately impaired renal blood flow and unchanged PAH-extraction, a higher or unchanged fractional insulin extraction was seen in all but one, compared with the contralateral kidney. Due to the high fractional extraction of insulin by the kidneys with renal artery stenosis, a preserved total insulin uptake by these kidneys was seen. In 4 patients with renal hypoplasia (2 of them had renal artery stenosis) low values for insulin extraction and insulin uptake were seen on the affected side. One patient with chronic pyelonephritis and uremia had an extremely low renal insulin extraction and uptake. The results suggest that estimation of renal insulin extraction may be an important renal functional test in renovascular patients.

Adult↗

Late results of pyeloplasty for idiopathic hydronephrosis in adults.

A series of 91 cases of unilateral obstruction of the pelviureteric junction is reviewed. Primary nephrectomy was performed in 13 cases (14%) because of severe hydronephrosis and renal function less than 10% that of the normal kidney. Pyeloplasty was performed according to Anderson-Hynes in 74 cases and with a Culp-De Weerd flap in four cases. Nephrostomy was performed concomitantly with the pyeloplasty in 14 cases. The parenchymal function was normal before pyeloplasty in 78% of the 78 kidneys, though the drainage function was severely impaired in 76 of the kidneys and moderately impaired in two. Urine cultures were positive before pyeloplasty in two patients, and 13 of the treated kidneys contained calculi. Follow-up examination was performed 5 to 12 years (mean 8.5 years) after pyeloplasty in all 78 patients. Of the 17 kidneys with preoperatively impaired parenchymal function, 12 (71%) showed improvement. The drainage function was improved in 68 (91%) of the 75 studied kidneys. Persistently impaired drainage function after pyeloplasty was found only in kidneys with infection secondary to retrograde passage of a ureteral catheter for treatment of postoperative urinary leakage. Urinary infection occurred in 11 of the 33 cases with such leakage. Retrograde ureteral catheterization thus favoured the occurrence of urinary infection. Its importance as a risk factor for severe infection was shown by the necessity for secondary nephrectomy in three cases. Since nephrostomy tended to reduce the incidence of urinary leakage, and thereby the need for indwelling ureteral catheter, and since nephrostomy as such was not associated with urinary infection, we recommend its use in the management of idiopathic hydronephrosis.

Adult↗

Response to slow, graded bleeding in salt-depleted rats.

The response to slow bleeding was studied in rats on low sodium intake (0.04%) versus 'ordinary' (0.4%) intake. After 12 days on the diets acute experiments were performed on paired, conscious rats. Initially the salt-depleted rats had slightly lower mean arterial pressure (121 +/- 2 versus 129 +/- 3 mmHg, n = 30 pairs, P less than 0.02). Heart rate (HR), cardiac output, plasma volume, extracellular volume and plasma renin activity (PRA) did not differ significantly, while haematocrit was slightly higher in the salt-depleted rats (46.5 +/- 0.3 versus 45.1 +/- 0.5%, P less than 0.05). The animals were then slowly bled 1 ml every 5 min until mean arterial pressure (MAP) fell and remained below 50 mmHg. The controls tolerated up to a 55 +/- 1% loss of initial blood volume, while the salt-depleted rats turned into irreversible shock already after losing 38 +/- 2% (P less than 0.001). At this stage compensatory haemodilution, HR and PRA increases were less pronounced than in the controls, suggesting that chronic sodium restriction had somehow interfered with the neurohormonal defences against accidental salt fluid losses.

Animals↗

Renal extraction ratios for 51Cr-EDTA, PAH, and glucose in early insulin-dependent diabetic patients.

Renal clearances and extraction ratios for 51Cr-EDTA and PAH were studied in six young patients with insulin-dependent diabetes. The duration of the disease was 1 to 4 years, and no patient had signs of diabetic complications. Catheterization of the right renal vein and the left brachial artery was performed. The extraction ratios for 51Cr-EDTA, PAH, and glucose were determined at two different levels of blood glucose. Clearance for 51Cr-EDTA was increased by 9.7% and for PAH by 8.5% compared to normal control subjects while the extraction ratios for 51Cr-EDTA and PAH were normal. Extraction ratio for glucose was very low. There was no correlation between the individual HbA1 values and the clearances for 51Cr-EDTA and PAH. Extraction ratios for these substances were not influenced by acute changes in blood glucose level. The normal PAH extraction ratio indicates that PAH clearance is a reliable estimate of RPF in early insulin-dependent diabetes.

Adult↗

Blood pressure in relation to the renin-angiotensin-aldosterone system.

The relationship between blood pressure (BP) and the renin-angiotensin-aldosterone system was studied in a stratified random sample (n=120) of 49-year-old men selected from a BP screening and covering a wide range of BPs. Only subjects not on antihypertensive treatment were included. None had malignant or secondary hypertension. Plasma renin activity, plasma concentrations of angiotensin II, aldosterone, sodium, potassium and noradrenaline and the 24-hour urinary excretions of sodium, cortisol and noradrenaline were determined. Of these variables, only p-aldosterone was significantly correlated wtih BP, both in the whole study group (R=0.22, p less than 0.02, n=119) and in the subjects with the highest BP range (R=0.36, p less than 0.02, n=30). Of the clinical groups compared, the hypertensive subjects had significantly higher mean p-aldosterone than the borderline and normotensive subjects. Multiple regression analysis showed that the 24-hour urinary excretion of noradrenaline was the factor most strongly correlated to p-aldosterone, suggesting that the sympathetic nervous system might stimulate aldosterone secretion. Our findings indicate that aldosterone may be of importance for the development and maintenance of essential hypertension.

Aldosterone↗

Biochemical and immunological characterization of ectopic tumoral renin.

Biochemical and immunological characteristics of renin secreted by two malignant renin-secreting tumors [pulmonary (PT) and paraovarian (POT)] were studied. They both contain inactive renin (IR), as renin activity of tumoral extracts was able to be increased after acid activation or trypsin treatment (10.1 to 20.8 Goldblatt units/g tissue for PT and 1.4 to 3.71 for POT). Renin activity after activation reached the value obtained by direct RIA of human renin (23 and 3.4, respectively), as both forms are recognized by renin antiserum. Both enzymatic activities could be completely inhibited by renin antiserum. Displacement curves for the two tumoral renins paralleled the MRC renin in the direct RIA. After chromatography on affigel blue, active renin was not bound to the gel, and inactive renin eluted only with 1 M NaCl. On pepstatin A Sepharose and CBL-pepstatin Sepharose (an N-modified-pepstatin), a separation of the two forms of pulmonary renin was obtained; inactive renin eluted with breakthrough proteins, whereas active renin was strongly bound to the gel. After this affinity chromatography, the molecular weights of inactive and active renin, determined on Ultrogel, were very close (46,000 and 42,500). We conclude that 1) ectopic renin in these cases in similar to the renal enzyme; 2) renin can be secreted in an inactive form, supporting the hypothesis of an inactive initial state of renin; and 3) molecular weight differences between the two forms are very slight.

Adenocarcinoma↗

Captopril in treatment-resistant essential and renal hypertension.

Captopril, an angiotensin converting enzyme inhibitor, was used to treat 25 patients with treatment-resistant hypertension of long duration. Seven patients had essential hypertension, 10 renovascular hypertension and 8 renoparenchymatous hypertension. All patients had GFR greater than 25 ml/min/1.73 m3 BSA. The acute blood-pressure-lowering response to the drug was shown to be dependent on the prevailing activity in the renin-angiotensin system. Its long-term effect was not correlated to the activation of the renin-angiotensin system as the mean blood-pressure decrease was not significantly different for high renin and normal renin patients (21 +/- 3% vs. 19 +/- 2%). All patients needed addition of diuretics and betablockers for optimum control. Nine patients have been well controlled for one year and several of them are now approaching two years' treatment. A few adverse effects were observed, including taste disturbances and increased proteinuria. The latter side effect occurred in two patients with decreased renal function and pre-existing proteinuria. Upon reduction of the dose the proteinuria returned to pre-treatment levels within a few months. We conclude that altogether 78% of these patients with treatment-resistant hypertension obtained greatly improved long-term blood-pressure control on treatment including captopril.

Blood Pressure↗

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 month's 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.

Blood Pressure↗

Hormonal pattern during development of hypertension in spontaneously hypertensive rats (SHR).

Urinary excretion of sodium, noradrenaline, dopamine, aldosterone, prostaglandin E2 and plasma renin activity were determined in 7 and 16 weeks old spontaneously hypertensive rats (SHR) and in two normotensive control strains, ordinary Wistar control rats (NCR) and Wistar-Kyoto normotensive rats (WKR). Each group consisted of 10-11 rats. The animals were kept in metabolic cages. Experiments were performed on standard diet (5-8 mmol Na+/100 g food) and with an increased (15.6 and 56.0 mmol Na+/100 g food) salt intake. At 7 weeks of age, when SHR are in a borderline phase of hypertension, they exhibited a decreased urinary sodium excretion, and an increased urinary noradrenaline excretion compared to controls. The latter might reflect an increased overall activity of the sympathetic nervous system. Urinary dopamine excretion was also increased probably mirroring a higher activity in a renal natriuretic dopamine system. Plasma renin activity and urinary aldosterone excretion were depressed. At 16 weeks of age, when SHR are in an early establishment phase of hypertension, urinary sodium excretion was still lower in SHR, while urinary noradrenaline and dopamine excretions had become normal compared to controls. Plasma renin activity and urinary aldosterone excretion remained depressed. Urinary PGE2 excretion, only determined in this age group, was significantly higher in SHR.

Aldosterone↗

Impairment of renal function in patients on long-term lithium treatment.

A survey of the renal function in 278 patients on long-term lithium treatment maintained on plasma lithium concentration of 0.7-1.2 mmoles/l was conducted. The extent of renal damage were studied with urinary concentration tests, beta-2-microglobulin excretion and measurement of glomerular filtration rate. The mean treatment time was 6.5 years and the longest treatment time was 15 years. Forty-nine per cent of the patients could not concentrate their urine to above 800 mOsm/kg of water, which did not correlate with the presence of polyuria. The urine concentration capacity decreased as a function of time in the lithium treated group, and it was also influenced by the type of tablet administration (readily soluble or sustained release), but not by combination with other drugs, such as neuroleptics. Beta-2-microglobulin excretion was not increased. A reduced glomerular filtration rate was found in 17% and the filtration rate in the whole group of patients was clustered around the lower limit of normal. The filtration rate decreased as a function of the duration of treatment. It was found that the concentrating capacity and the filtration rate decreased in parallel and that there was no selective impairment of the concentrating capacity. We conclude that severe impairment of renal function is uncommon in well controlled patients. Urinary concentration tests are shown to be the most suitable test for detection of kidney damage in long-term lithium treatment.

Adult↗