Henrik Daugaard

Five to 10 years follow-up after total parathyroidectomy and autotransplantation of parathyroid tissue : evaluation of parathyroid function by use of ischaemic blockade manoeuvre

The aim of the present study was to assess the long-term function of autotransplanted parathyroid tissue in patients with chronic renal disease. We examined the medical records of a consecutive series of 21 patients with chronic renal failure, who had undergone total parathyroidectomy with autotransplantation. During the time of follow-up, on average 79 months, one patient developed graft-dependent recurrent hyperparathyroidism and one patient suffered from persistent hypoparathyroidism. Nine of the patients were available for a clinical study. In these patients we measured the plasma concentration of intact PTH in blood from the arm contralateral to the graft-bearing arm at rest and during a short-lasting ischaemic blockade of the graft site from the circulating blood. At rest all nine patients had parathyroid hormone (PTH) values within the normal range. The ischaemic blockade produced a marked reduction in the plasma concentration of intact PTH in eight of the patients indicating well functioning autografts. Prior to the examination the patient with recurrent hyperparathyroidism had undergone resection of the autograft. In this patient, ischaemia of the former graft site did not cause any change in the concentration of PTH indicating normally functioning residual parathyroid tissue in the neck. Thus, the ischaemic blockade manoeuvre seems suitable for the assessment of autografted parathyroid tissue. Our results indicate that total parathyroidectomy with autotransplantation provides a rational alternative to the surgical treatment of secondary hyperparathyroidism.

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.

Effect of uremia on aldosterone metabolism in the isolated perfused rat liver

The effect of uremia on hepatic metabolism of aldosterone was studied in the isolated perfused liver of female Wistar rats. Uremia was induced by five-sixths partial nephrectomy 4 weeks before experiments. Isolated livers of normal and uremic rats were perfused at a constant flow rate with a hemoglobin-free medium, to which 4-14C-D-aldosterone was added at 3 nmol/L. Aldosterone was analyzed by radioimmunoassay (RIA) and 4-14C-D-aldosterone radiometabolites in perfusate and bile were assayed by high-performance liquid chromatography (HPLC). Uremic rats had a 10% lower body weight (P < .01) and increased plasma urea, creatinine, and parathyroid hormone (PTH) levels (258%, 200%, and 208%, respectively; P < .01-.001). Blood pressure and plasma K+, Na+, and aldosterone levels were similar. Plasma renin activity was suppressed by 68% in uremic rats (P < .001). Liver wet weight and hepatic function were similar in livers of both groups of rats. Hepatic elimination of aldosterone was compatible with a first-order kinetics. Hepatic clearance of aldosterone per liver and per gram liver was similar; however, when expressed per 100 g rat body weight, a 21% higher value was observed in uremic rats (11.6 +/- 1.8 mL/min) compared with normal rats (9.6 +/- 1.5 mL/min, P < .01). Polar aldosterone radiometabolites accumulated in the perfusate to approximately 40% of the initial 14C added at 15 minutes, and were eliminated in bile at a similar rate in both groups. No qualitative difference was found in the pattern of radiometabolites of aldosterone in perfusate and bile.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Enhancement of the Stimulatory Effect of Ca++ on Aldosterone Secretion by PTH

In previous clinical investigations we found a stimulatory effect of the presence of hyperparathyroidism on the Ca++ induced secretion of aldosterone and vasopressin. The present investigation, therefore, examined the possible effect of PTH on the Ca++ mediated aldosterone secretion from purified rat zona glomerulosa cells.