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K Olgaard

Publications and source records attributed to K Olgaard.

At least 19 recordsLinked to original sources
PubMed1992

Effects of methylprednisolone and uremia on renal and intestinal calbindin-D in the rat.

The effects of glucocorticoids on renal and intestinal calcium binding protein (calbindin-D28K and calbindin-D9K) were examined in normal and uremic rats. Chronic uremic rats and normal controls were treated with either methylprednisolone (MP) 1.3 mg/kg/d or isotonic saline given as a continuous intraperitoneal infusion for 1 week before sacrifice. Renal calbindin-D28K was measured by rocket immunoelectrophoresis and intestinal calbindin-D9K was measured by an enzyme-linked immunoadsorbent assay. Methylprednisolone treatment of chronic uremic rats increased plasma phosphate levels (P < 0.05), but plasma calcium and 1,25-dihydroxyvitamin D3 were unchanged in all groups. MP treatment did not affect the renal calbindin-D28K in either normal or uremic rats. In normal rats, MP treatment reduced intestinal calbindin-D9K by 28% when compared to placebo (P < 0.05). In contrast, chronic uremia increased renal calbindin-D28K by 51% and 38% (P < 0.001) in placebo and MP treated uremic rats, respectively, while intestinal calbindin-D9K was unchanged. Thus, MP treatment and chronic uremia induced different changes in renal and intestinal calbindin-D of the rat suggesting that different mechanisms are involved in the regulation of these vitamin D dependent proteins.

Animals↗
PubMed1992

[Cyclosporin A treatment of adult patients with severe nephrotic syndrome].

This investigation is an assessment of the cyclosporin A-prednisone treatment which has been employed in all cases of therapy-resistant nephrotic syndrome in adults (n = 18) since January 1985 at the Department of Nephrology at the State University Hospital. Following an average duration of treatment of 20.7 months, five patients were in complete and eight in partial remission. All of the patients with minimal change disease (three patients) achieved complete remission. Recurrence after withdrawal of cyclosporin A occurred in three out of five patients. Cyclosporin A was withdrawn in five patients on account of suspected cyclosporin A nephrotoxicity. Hypertension, which was slight to moderate in the majority of cases, occurred frequently during treatment. Compared with the prognosis and frequency of complications in the untreated nephrotic syndrome and the frequency of side effects with the previously administered immunosuppressive treatment, the frequency of side effects with cyclosporin A treatment was acceptable. Until the indications are elucidated, adult patients with otherwise intractable nephrotic syndrome should be referred to special nephrological departments for possible cyclosporin A treatment.

Adult↗
PubMed1992

Glucocorticoid-induced osteoporosis in the lumbar spine, forearm, and mandible of nephrotic patients: a double-blind study on the high-dose, long-term effects of prednisone versus deflazacort.

The long-term effects of high dose steroid treatment with either prednisone (PDN) or deflazacort (DFZ) were examined on various parts of the skeleton in 29 patients with nephrotic syndrome. All had normal skeleton at the start of the steroid treatment. At the beginning, PDN was given as 80 mg/day and tapered down to 20 mg/day for 1 year and DFZ was given in an equipotent dosage. Twenty-three patients completed 6 months of treatment, and 18 patients completed 12 months of treatment. Beside laboratory parameters to ensure the effect of treatment on the nephrotic syndrome, all had measurements of the bone mineral content (BMC) at 0, 6, and 12 months of treatment. BMC was measured by single photon absorptiometry of both forearms and by dual photon absorptiometry of the mandible, forearms, and lumbar spine. The effect of DFZ was compared to that of PDN due to a potential "calcium sparing" effect of DFZ. The therapeutical effects on the nephrotic syndrome were not different between the two drugs. Urinary 24-hour protein decreased from 9.9 to 1.1 g in the DFZ-treated patients and from 8.0 to 1.4 g in the PDN-treated patients. Plasma albumin concentration normalized in both groups. Both groups of steroid-treated patients had a significant reduction of the BMC levels in all parts of the skeleton. However, the bone decay rates per month were significantly different between different bone regions and between different drug regimes. In the forearm, the bone decay rate was 5.3%/year in the PDN group and 2.0%/year in the DFZ group (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon↗
PubMed1992

Influence of glucocorticoid on the metabolism of aldosterone in the isolated perfused rat liver and kidney.

The effect of glucocorticoid deficiency and excess on the extraadrenal metabolism of D-[4-14C]aldosterone (at 4 nM) was studied by radioimmunoassay and by high-performance liquid chromatography in the isolated perfused liver and kidney of adult Wistar rats. Bilateral adrenalectomy was performed 3 weeks before experiments. In nonadrenalectomized rats, 0.3 mg/kg/day dexamethasone was continuously infused subcutaneously for 1 week before experiments. Adrenalectomy did not affect hepatic or renal metabolism of aldosterone. Dexamethasone treatment did not change the renal handling of aldosterone. However, the hepatic clearance of aldosterone was 19% lower (P less than 0.05) in livers of dexamethasone treated rats than in livers of normal rats. After 5 minutes, perfusate [4-14C]aldosterone metabolites were lower in livers of dexamethasone-treated than in livers of normal rats (P less than 0.05). Similar perfusate levels were then obtained. Radiometabolite peaks with similar relative retention times were found in the hepatic perfusate of all groups. However, the ratio between circulating polar metabolites of aldosterone and the metabolites less polar than tetrahydroaldosterone, after 5 and 15 minutes, was highest in livers of dexamethasone-treated rats. Biliary elimination of 14C was similar in all groups. Significant amounts of conjugated tetrahydroaldosterone were only excreted in the bile of dexamethasone-treated rats. In conclusion, glucocorticoid excess reduced the hepatic clearance of aldosterone and changed the pattern of the hepatic metabolites of aldosterone both in circulation and in bile.

Adrenalectomy↗
PubMed1992

Steroid-induced mandibular bone loss in relation to marginal periodontal changes.

Long-term high-dose glucocorticosteroid treatment may be suspected as causing profound marginal periodontal bone loss due to the immunosuppressive/antiinflammatory effects and due to the osteoporotic side-effects. This study comprised an analysis of the loss of the mandibular and forearm bone mineral content (BMC), measured in vivo by dual-photon scanner, in relation to the concomitant changes of the periodontal indices (visible plaque, gingival bleeding, loss of attachment) in 17 acute nephrotic dentate patients undergoing intensive steroid treatment for 12 months. The measurements were performed at start of treatment, when all patients were considered healthy as regards the skeleton, and at the 6-month and 12-month follow-up. The mean BMC loss at the standard sites of the mandible and the forearm bones was 5.6%/year at both sites. No significant changes could be demonstrated in the periodontal indices (P greater than 0.10), and no relation was found between the mandibular BMC loss and the periodontal condition (R = 0.06, P greater than 0.10). In conclusion, profound marginal periodontal bone loss does not seem to be a prominent side-effect of long-term glucocorticosteroid treatment, although the degree of induced osteopenia in the mandible corresponds to that in other cortical bones of the skeleton.

Adult↗
PubMed1992

Aldosterone metabolism in the isolated perfused liver of R and S hypertension-prone Dahl rats.

The effect of a chronic oral salt load on hepatic metabolism of aldosterone was examined in isolated livers of salt-resistant (R) and salt-sensitive (S) hypertension-prone male Dahl rats perfused with d-[4-14C]aldosterone (10(-9) M). Aldosterone was analyzed by radioimmunoassay and [4-14C]aldosterone radiometabolites by high-performance liquid chromatography. In salt-loaded S rats, systolic blood pressure was 30 mmHg higher than in the other three groups (P less than 0.01). In S rats, on standard and high-salt diets, plasma renin activity was 64% (P less than 0.001) and 50% (P less than 0.01) lower, and, on the standard diet, plasma aldosterone was 50% (P less than 0.01) lower than in R rats. Salt loading suppressed plasma renin activity by 42% (P less than 0.05) in R rats and plasma aldosterone by 66 and 33% (P less than 0.01) in R and S rats, respectively. In isolated perfused liver, hepatic function did not differ between various groups. Hepatic clearance of aldosterone in R rats given water and saline and in S rats given water did not differ, whereas hepatic clearance of aldosterone was 28 and 35% higher in salt-loaded S rats when compared with S rats on water (P less than 0.01) and with salt-loaded R rats (P less than 0.001), respectively. Polar and reduced metabolites of [4-14C]aldosterone were released into the circulation in livers of R and S rats on both diets, but highest relative levels of polar metabolites of aldosterone were found in salt-loaded S rats. In all groups, only polar metabolites of aldosterone were excreted in bile.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Long-term suppression of secondary hyperparathyroidism by intravenous 1 alpha-hydroxyvitamin D3 in patients on chronic hemodialysis.

The effect of intravenous 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] on circulating levels of intact parathyroid hormone (PTH 1-84) and COOH-terminal immunoreactive PTH(PTH 53-84) was examined in 13 patients on chronic hemodialysis. Thirteen patients were treated for 300 days (10 months), 9 patients for 520 days (14 months) and 6 patients for 720 days (2 years) with increasing doses of 1 alpha(OH)D3 intravenously under careful control of plasma Ca2+. Blood samples were obtained 1 week before start of treatment and then at every 2nd week. None of the patients had previously been treated with oral vitamin D metabolites. Intact PTH levels were maximally suppressed after 27-33 weeks of treatment by approximately 73%. At the end of the study periods, PTH 1-84 was still suppressed by 78 +/- 4.3% after 300 days, 78 +/- 8.8% after 520 days and 85 +/- 6.5% after 720 days. Plasma Ca2+ was kept within normal levels, but showed an initial increase from 1.14 +/- 0.03 to 1.27 +/- 0.15 mmol/l, and an adjustment of the doses of 1 alpha(OH)D3 was necessary. The present investigation demonstrated (1) that intravenous administration of the 1-hydroxylated vitamin D metabolite 1 alpha(OH)D3 induced a significant decrease in circulating levels of biologically active intact PTH, and (2) that it was possible to maintain the marked suppression of PTH secretion by intravenous treatment of 1 alpha (OH)D3 for up to 2 years. Hypercalcemia could be avoided by careful monitoring of plasma Ca2+ and adjustment of the doses of 1 alpha(OH)D3.

Adult↗
PubMed1991

[The significance of brain death as a criterion for renal transplantation. Status after 9 months].

The effect of introduction of the brain-death criterion in Denmark on the course of cadaver kidney transplantation was evaluated by comparing the course of 31 consecutive patients transplanted after introduction of brain-death criterion with the course of a similar consecutive group of patients transplanted just before the new death criterion. The consequences of the new death criterion were significantly earlier onset of graft function, diminished need for posttransplant dialyses, reduced need for immunosuppressive treatment with Minnesota-antilymphocytglobulin and briefer hospital stays. The easier postoperative course had great psychological effects for the patients and the staff, and the cost of each transplantation was estimated to be reduced by at least 50,000 DKr per patient (approximately 5,000 pounds).

Brain Death↗
PubMed1991

Aldosterone metabolism in combined isolated perfused rat liver and kidney.

The metabolism of aldosterone (Aldo) at 4 nM was studied by radioimmunoassay and by high-performance liquid chromatography in isolated perfused liver (IPL), isolated perfused kidney (IPK), and combined isolated perfused liver and kidney (CIPLK) of male Wistar rats. Effect of D[4-(14)C]aldosterone (D [4-(14)C]Aldo) on the function of IPK of intact and adrenalectomized (ADX) rats was also studied. Aldo clearance in the liver was most important, 16.3 +/- 1.7 ml/min. In IPK, the total clearance of Aldo was 0.27 +/- 0.36 ml/min (39% of the glomerular filtration rate) (GFR). Fractional excretion (FE) of Aldo was 16 +/- 8%. Metabolic clearance of Aldo was (0.21 +/- 0.23 ml/min), 78% of total renal clearance. In CIPLK, the kidney inhibited hepatic clearance of Aldo by 23% when compared with IPL (P less than 0.05). Hepatic Aldo metabolites were predominantly eliminated by biliary excretion of polar metabolites. Several hepatic polar metabolites and tetrahydroaldosterone (THA) accumulated in perfusate and were excreted in the urine in a similar pattern. After hydrolysis of the polar metabolites, some coeluated with THA and dihydroaldosterone (DHA), whereas other metabolites remained more polar than Aldo. Without addition of Aldo, in IPK of ADX rats FENa was higher (P less than 0.01), and FEK was lower (P less than 0.01), resulting in three- to fourfold higher urinary Na-K ratio (P less than 0.01) when compared with IPK and CIPLK of intact rats. In IPK of ADX rats with Aldo in perfusate, only FEK was restored. Addition of Aldo to IPK of intact rats had no effect. However, only in CIPLK, addition of Aldo resulted in an increasing kaliuresis in three subsequent periods of 30 min (0.56-0.95, P less than 0.01). Thus the hepatic metabolites of Aldo could in part mediate the kaliuretic effect of Aldo.

Adrenalectomy↗
PubMed1991

Renal and intestinal calcium-binding proteins in normal and uraemic rats.

The effect of chronic uraemia on the concentrations of the 28 kDa renal and 9 kDa intestinal calcium-binding proteins (calbindin-D28K and calbindin-D9K) was investigated in rats. Calbindin-D9K was measured by a competitive enzyme-linked immunoadsorbent assay and calbindin-D28K by rocket immunoelectrophoresis. Chronic uraemia was induced by 5/6 nephrectomy and the results were compared to sham-operated animals. Rats were fed on a diet containing 0.9% calcium and 1.2% phosphorous. Plasma creatinine and plasma urea were elevated in the nephrectomized rats (p less than 0.001), while plasma-1,25-dihydroxycalciferol vitamin D and fractional calcium absorption were unchanged. Plasma parathyroid hormone was significantly elevated in the uraemic rats. The concentration of calbindin-D28K in renal tissue was increased (p less than 0.001) in rats with chronic uraemia and a direct correlation was found between renal calbindin-D28K and plasma urea (p less than 0.05). Intestinal calbindin-D9K correlated inversely with plasma creatinine (p less than 0.05), but the mean level of calbindin-D9K was unchanged in this model of moderate chronic uraemia. Thus, different regulatory mechanisms control levels of calbindin-D9K and calbindin-D28K.

Animals↗
PubMed1990

Metabolism of parathyroid hormone in isolated perfused rat kidney and liver combined.

Metabolism of synthetic, intact, human parathyroid hormone (PTH) 10(-9) M was studied in a new experimental model using the isolated perfused rat kidney and liver combined. The combined organs cleared intact PTH significantly faster than the single kidneys (P less than 0.02) or livers (P less than 0.02), but not faster than the sum of the clearances in the single organs. The kidneys cleared intact PTH without accumulation of NH2-terminal, mid-molecule or COOH-terminal iPTH, and high-performance liquid chromatography (HPLC) studies did not reveal any PTH fragments. The livers cleared mid-molecule and COOH-terminal iPTH significantly slower (P less than 0.002) than intact PTH, and HPLC demonstrated generation of mid-molecule and COOH-terminal PTH fragments. The combined organs accumulated significantly less mid-molecule (P less than 0.001) and COOH-terminal (P less than 0.03) iPTH than the single livers, and HPLC demonstrated mid-molecule peaks that were smaller but not qualitatively different. In conclusion, the predominance of COOH-terminal PTH fragments in plasma may be maintained by differential clearance mainly in the liver, excessive accumulation being prevented by filtration in the kidneys.

Animals↗
PubMed1990

Cyclosporin A treatment of severe steroid resistant nephrotic syndrome in adults.

Ten adult patients with a severe nephrotic syndrome resistant to conventional immunosuppression were treated with cyclosporin A (CyA) for a mean period of 11 months. CyA was effective in all but two patients, as evaluated by 24-h urine protein excretion and clinical appearance. In general the best effect of CyA was seen in patients with minimal change disease and in those who had normal kidney function before CyA was initiated. CyA-induced nephrotoxicity was observed in four patients. There was no correlation with the duration of CyA therapy. Hypertension was accentuated and required multidrug treatment in five patients. This side-effect tended to be most pronounced among patients with reduced kidney function at onset of CyA therapy. In conclusion, CyA is effective in the treatment of severe steroid resistant adult nephrotic syndrome. For most patients in the present study, CyA reduced proteinuria by at least 70% to less than 3.5 g of protein per day in 8 of 10 patients; only two patients were unresponsive to CyA treatment.

Adult↗
PubMed1990

Influence of calcium on the metabolism of intact parathyroid hormone by isolated perfused rat kidney and liver.

The metabolism of synthetic human PTH [PTH-(1-84)] 10(-9) M was studied in isolated rat kidneys and livers, perfused at a calcium concentration of 1 mM or 4 mM. Clearances were measured by an assay specific for intact PTH, and by assays specific for NH2-terminal, mid-molecule, and COOH-terminal immunoreactive PTH (iPTH). Production of PTH fragments was analyzed by HPLC. The kidneys cleared PTH mainly by filtration. The glomerular filtration rate was not lower at 4 mM calcium than at 1 mM calcium, and no significant differences were found between the clearance of PTH at 4 mM and at 1 mM calcium. At 1 mM calcium the kidneys cleared intact PTH without release of detectable fragments. At 4 mM calcium there was significant (P less than 0.05) accumulation of mid-molecule and COOH-terminal iPTH in the perfusate. Both at low and at high calcium the livers cleared NH2-terminal iPTH at the same rate as intact PTH, whereas mid-molecule and COOH-terminal iPTH was cleared significantly (P less than 0.005) slower. In the livers, metabolic clearance of PTH was 60% faster at 4 mM calcium than at 1 mM calcium (P less than 0.001). Assuming that the hepatic metabolism of PTH represents degradation of the biologically active hormone and hormone fragments, rather than activation of the hormone, the present results suggest a homeostatic control of PTH degradation in the liver to enhance inactivation of the hormone at high serum levels of calcium.

Animals↗
PubMed1989

[Simultaneous transplantation of the pancreas and kidney in terminal diabetic nephropathies].

Transplantation of the pancreas in late stages of type I diabetes has been performed increasingly frequently during recent years. By improved surgical techniques and immunsuppressive therapy including cyclosporin A, the 1-year graft function has increased to 60-70% and the patient survival to 85-95% in the institutions with greatest experience. These results are so good, that they nearly reach those from kidney transplantation. Most of the pancreas transplantations have been performed simultaneously with kidney transplantation in patients with end stage diabetic uremia. The results should therefore be evaluated according to these circumstances. In a few institutions transplantation of the pancreas is now performed in patients with persistent proteinuria and proliferative retinopathy in an attempt to avoid development of severe diabetic complications. The first pancreas transplantation in Denmark was performed Januar 31 st 1987, and since then, 17 further transplantations have been performed. All patients had severe diabetic nephropathy and received simultaneous kidney transplantation. According to the Danish heart death criteria the organs were perfused and cooled during the donor operation to keep the warm ischemia as brief as possible. The pancreatic vessels are anastomosed to the iliac vessels. In one group of patients the exocrine pancreatic function was preserved by anastomosis to the jejunum, and in another group of patients the exocrine function was abolished by injection of latex into the pancreatic duct system. The patients receive immunosuppression therapy with methylprednisolone, azatioprine and ciclosporin A and anti-coagulation therapy.

Denmark↗
PubMed1989

Effect of intravenous 1-alpha-hydroxyvitamin D3 on secondary hyperparathyroidism in chronic uremic patients on maintenance hemodialysis.

The effect of intravenous 1 alpha(OH)D3 on circulating intact parathyroid hormone (PTH) and COOH-terminal immunoreactive PTH was examined in 21 patients on chronic hemodialysis. The patients were treated for 3 months with increasing doses of 1 alpha(OH)D3 under careful control of serum Ca2+. 1 alpha(OH)D3 was given intravenously at doses of up to 4 micrograms three times a week, and blood samples were obtained every week, including 1 week before treatment (basal control). No patients were treated with oral vitamin D metabolites. At the end of the study intact PTH levels were reduced by an average of 67 +/- 6%, and COOH-terminal immunoreactive PTH levels were reduced by 35 +/- 6%. Serum Ca2+ was kept within normal levels, but showed a slight increase from 1.17 to 1.30 mmol/l. An effect of calcium on PTH secretion could not be excluded, but an effect of 1 alpha(OH)D3, independent of serum Ca2+ was also found. This effect may be mediated by 1,25(OH)2D3, assuming a large capacity of the 25-hydroxylase in the liver to convert 1 alpha(OH)D3 to 1,25(OH)2D3. Also, the parathyroid glands may possess receptors for 1 alpha(OH)D3 with an effect similar to that established for the 1,25(OH)2D3 receptors. Thus, although the exact mechanisms of the action of 1 alpha(OH)D3 have not yet been completely clarified, it is concluded that intravenous administration of 1 alpha(OH)D3 may be of benefit in the treatment of secondary hyperparathyroidism of uremia.

Adolescent↗
PubMed1989

Aldosterone metabolism in the isolated perfused liver of female and male rats.

A sex-dependent metabolism of aldosterone has been reported in intact rats. To further characterize the hepatic elimination of aldosterone and its sex dependence, the metabolism of d-[4-14C]aldosterone was studied in isolated perfused liver from male and female Wistar rats, from male rats castrated 3 weeks before experiments, and from younger male rats (same body weight as the female rats). The livers were perfused at a constant flow rate in a recirculating mode with a hemoglobin-free medium containing aldosterone at initially 1 nM. Perfusate aldosterone was measured by a specific RIA. Total 4-14C radio-activity in perfusate and bile was determined. The perfusate [4-14C]aldosterone radiometabolite concentration was calculated. The radiometabolite pattern in additional experiments was studied by HPLC. The male rats exhibited 10% higher systolic blood pressure (P less than 0.05) and 51% higher fasting values of plasma aldosterone (P less than 0.05) compared to those in the female rats. In female rats the hepatic clearance rate of aldosterone per 100 g BW was 72% higher than that in male rats (11.2 +/- 2.7 to 6.5 +/- 1.8 ml/min: P less than 0.01), and that expressed per g liver wet wt was 75% higher (3.5 +/- 1.0 to 2.0 +/- 0.7 ml/min; P less than 0.01). When female rats were compared to younger male rats with the same body weight, 33% higher hepatic aldosterone clearance rates were still found in female rats (21.0 +/- 5.4 to 15.8 +/- 3.2 ml/min; P less than 0.05), and 51% higher values when expressed per g liver wet wt (3.5 +/- 1.0 to 2.3 +/- 0.5 ml/min; P less than 0.01). No difference in the aldosterone clearance rate was observed in castrated male rats compared to that in noncastrated male rats. 4-14C-Labeled radiometabolite levels accumulated similarly in the perfusate of livers of both sexes. Perfusate 4-14C-labeled radiometabolites after 90 min of perfusion were lower in livers of castrated male rats than in noncastrated male rats (P less than 0.001). The final perfusate 14C-labeled radiometabolite concentration correlated inversely with the total 14C in bile (P less than 0.01). All 14C-labeled radiometabolites detected in perfusate and bile after 90 min were more polar than aldosterone. After enzymatic hydrolysis, some of the metabolites from the male livers cochromatographed with tetrahydro- and dihydroaldosterone, while other fractions remained more polar. Only more polar metabolites were detected in the perfusate and bile of female livers.(ABSTRACT TRUNCATED AT 400 WORDS)

Aldosterone↗