Showing papers by "Tilman B. Drüeke published in 1992"

Short- and long-term efficacy of total parathyroidectomy with immediate autografting compared with subtotal parathyroidectomy in hemodialysis patients

Abstract: A retrospective study was performed in chronic hemodialysis patients comparing total parathyroidectomy (PTX) followed by immediate autografting (IA) (total PTX+IA) with subtotal parathyroidectomy (subtotal PTX). One hundred six patients with severe, uncontrolled hyperparathyroidism were referred to this center and underwent surgery during the period from 1980 to 1990. Long-term follow-up after PTX was available in 49 of them: 28 patients had total PTX+IA and 21 had subtotal PTX. The two surgical methods were evaluated with respect to preoperative severity of hyperparathyroidism, immediate postoperative results, and long-term parathyroid status, as evaluated by an RIA measuring intact immunoreactive parathyroid hormone (intact iPTH; normal values, 15 to 65 pg/mL). The initial degree of hyperparathyroidism was comparable in the two groups. An excellent short-term control of hyperparathyroidism was achieved in the great majority (95%) of patients with either surgical procedure. However, long-term normalization of parathyroid gland activity was achieved in only one third of patients whereas 33% had elevated intact iPTH levels (> 130 pg/mL; i.e., higher than twice the upper range of normal) and 32% had low intact iPTH levels (< 15 pg/mL), consistent with permanent hypoparathyroidism. No difference was found in the immediate failure rates: 0 of 28 cases after total PTX+IA compared with 2 of 21 cases after subtotal PTX. Similarly, long-term intact iPTH levels were comparable: 400 +/- 105 versus 212 +/- 82 pg/mL (mean +/- SE; P = not significant). Interestingly, long-term serum intact iPTH levels were higher in patients with nodular (N = 18) than with diffusely (N = 26) hyperplastic glands: 556 +/- 146 versus 126 +/- 52 pg/mL (P < 0.001) and recurrence of hyperparathyroidism was more frequent with nodular hyperplasia (11 of 18) than with diffuse hyperplasia (4 of 26) (P < 0.02). In conclusion, although excellent short-term results were obtained with both procedures, satisfactory long-term control of parathyroid gland function was achieved in only one third of the patients, the other two third remaining either hypoparathyroid or developing recurrent hyperparathyroidism. Last, the histological subtype of parathyroid glands was partially predictive of the recurrence of hyperparathyroidism.

Permeability of Cellulosic and Non-Cellulosic Membranes to Endotoxin Subunits and Cytokine Production During In-Vitro Haemodialysis

Abstract: The possibility of endotoxin transfer across haemodialysis membranes remains a controversial issue. Additional concern has arisen because of the recent introduction in clinical practice of highly permeable, synthetic dialysis membranes and of bacteria-contaminated bicarbonate concentrate with potential short-term and long-term hazards for haemodialysis (HD) patients. Therefore, we performed experiments in an in-vitro dialysis recirculation system using three different types of HD membranes, namely standard regenerated cellulose (Cuprophan, CU), polyacrylonitrile AN-69 (PAN), and polysulphone F-60 (PS). When radiolabelled lipopolysaccharide (125I M-LPS) from E. coli, together with 10 micrograms/ml unlabelled LPS, was added to the recirculating solution in the dialysis compartment, radioactivity could be detected in the blood compartment after 15 min and increased progressively with time up to respectively 6.7% (CU), 10.3% (PAN), and 10.3% (PS) of initial activity on the dialysate side. The addition of albumin to the solution on the blood side led to a decreased permeability of radioactivity (7.3% vs 10.3%), compared to the absence of albumin (tested only for PS membrane). Furthermore, 73% of 125I M-LPS transferred across the PS membrane in the presence of albumin was TCA-precipitable. In contrast, free iodine (Na 125I) incubated in an albumin-containing solution did not precipitate with albumin after the addition of TCA (precipitation of only 0.6%). Moreover, kinetics of transmembranous transfer of Na-125I were strikingly different from that of 125I M-LPS. Analysis by the method of sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) of the blood side solution, after LPS addition in the dialysis solution and 30 min of back-filtration, revealed the presence of several silver-stainable and autoradiographic bands of low-molecular-weight range, probably LPS fragments. Finally, the presence of LPS in the dialysate compartment led to a moderate increase in interleukin 1 (IL-1) and tumour necrosis factor alpha (TNF) concentrations in plasma as well as in monocyte culture supernatants after isolation from recirculating normal human whole blood exposed to CU, PAN, or PS membrane. In conclusion, our study provides evidence for the permeation of low-molecular-weight LPS subunits across cellulosic and non-cellulosic HD membranes. The clinical significance, if any, of such a transfer has, however, still to be demonstrated.

Tumoral calcifications in hemodialysis patients: possible role of aluminum intoxication.

Abstract: Uremic patients may develop extraskeletal calcifications. Among the latter, periarticular tumoral calcifications (TC) represent massive, multiloculated calcium-phosphate deposits. The aim of this report was to analyze a series of 10 cases of TC in hemodialysis patients who were admitted at the Necker Hospital between 1974 and 1988. They were all male. An increased plasma calcium × phosphorus product was observed in 8 of the 10 patients. Plasma calcium level was increased in only 2 patients. In contrast, hyperphosphatemia was a constant feature in all the patients, as was the absence of an increase in plasma alkaline phosphatase activity. Using the bone histomorphometry technique, osteitis fibrosa of mild degree was observed in 2 patients, of moderate degree in 2 and of severe degree in 2 others. Evidence of aluminum (AT) overload was found in the 8 patients in whom it was searched based on bone histomorphometry, bone histochemistry, bone Al content and increased serum Al levels either in the basal state or after a deferoxamine test. In addition, Al overload was strongly suspected in the 2 remaining patients because of prolonged exposure to Al-contaminated dialysate. Various treatment strategies, including parathyroidectomy (PTx), were undertaken that remained unsuccessful in modifying the course of TC to a significant extent. Remarkably, TC occurred for the first time after PTx in 1 patient and worsened after PTx in 2 others. In conclusion, overt secondary hyperparathyroidism appears not to be an essential prerequisite for TC development in hemodialysis patients, and PTx must not be performed in such patients on the sole basis of the presence of TC. A preexisting Al intoxication and the attendant disturbances of bone mineralization could be directly or indirecty involved in the occurrence of TC. In addition, other factors must also play a role, the nature of which has still to be defined.

Insulin-like growth factor I: a modulator of erythropoiesis in uraemic patients?

Abstract: Anaemia is a feature almost invariably complicating chronic renal failure. Its pathophysiology is multifactorial but the most important cause is erythropoietin (Epo) deficiency. However, either no relation or even a weakly positive relation generally exists between serum immunoreactive (i) Epo and haematocrit values in uraemic anaemia, whereas in anaemias of non-renal origin the correlation is most often strongly negative. Recent evidence indicates that growth hormone also stimulates erythropoiesis. Moreover, late erythroid progenitor cells (CFU-E) require insulin and/or insulin-like growth factor I (IGF-I) for development in vitro. IGF-I has been shown to have a synergistic action with Epo. We have measured serum iEpo and IGF-I levels in 17 haemodialysis patients with severe hyperparathyroidism (mean +/- SEM serum iPTH, 988 +/- 88 pg/ml). Mean age and duration of dialysis treatment were 46.1 +/- 3.4 and 8.8 +/- 1.0 years respectively. Mean haematocrit and haemoglobin values wer 28.1 +/- 1.7% and 9.39 +/- 0.54 g/dl respectively. Mean serum iEpo and IGF-I levels were 20.3 +/- 4.7 mU/ml and 320 +/- 20 ng/ml respectively (normal values for serum iEpo and IGF-I, 17.9 +/- 6 mU/ml and 91 +/- 23 ng/ml respectively). We found that serum IGF-I concentrations were well correlated with haematocrit values (r = 0.68, n = 15, P less than 0.004) whereas serum iEpo values were not (r = 0.41, n = 12, P = 0.18). IGF-I could therefore be an important factor regulating erythropoiesis in uraemic patients, at least when associated with severe hyperparathyroidism.

Effect of erythropoietin on hematocrit and blood pressure in normotensive and hypertensive rats.

Abstract: Treatment with recombinant human erythropoietin (rHuEPO) successfully reverses anemia in uremic patients. Of major concern, however, are blood pressure (BP) increases during rHuEPO therapy, observed particularly in persons with a history of hypertension. To determine whether preexisting hypertension enhances BP increases to rHuEPO, BP responses to 2 wk of rHuEPO or placebo were observed in spontaneously hypertensive rats (SHR) and their normotensive genetic controls (Wistar-Kyoto [WKY] rats. In addition, the role of endothelial-released nitric oxide (NO) in BP alterations caused by rHuEPO through i.v. infusions of endothelium-dependent and independent vasoactive agents were indirectly examined. At trial completion, rHuEPO elevated hematocrit, hemoglobin, and mean cell volume more in SHR than in WKY rats (P less than 0.001). Despite the considerable increase in hematocrit, rHuEPO did not alter BP in either strain. An infusion of NG-monomethyl-L-arginine (L-NMMA), a specific inhibitor of NO formation, elevated BP more in rHuEPO-treated SHR than in identically treated WKY rats (P less than 0.05). Further, the administration of L-arginine caused a greater decrease in blood pressure in SHR than in WKY rats, independent of treatment condition (P less than 0.01). Because changes in BP with endothelium-independent agents were similar across groups, responses to L-NMMA and L-arginine were specific to the endothelium and probably independent of basal BP. Thus, rHuEPO provoked greater erythropoiesis in SHR than in WKY rats but did not elevate BP. L-NMMA stimulated higher BP in SHR treated with rHuEPO, suggesting a compensatory increase in vasodilatory NO synthesis to protect against a hypertensive effect of the drug in SHR.(ABSTRACT TRUNCATED AT 250 WORDS)

Long-term effects of a somatostatin analogue on renal haemodynamics and hypertrophy in diabetic rats.

Abstract: 1. To determine whether treatment with octreotide, a somatostatin analogue, may diminish or prevent long-term diabetic renal hypertrophy and nephropathy, uninephrectomized streptozotocin-diabetic rats maintained under moderate glycaemic control (approximately 300 mg/dl) were treated with either placebo (n = 10 rat/group) or octreotide for 14 weeks. Uninephrectomized non-diabetic rats given either placebo or octreotide served as controls. 2. Average body weight was diminished and kidney weight, daily urinary protein excretion, glomerular filtration rate and renal plasma flow were elevated in both diabetic groups relative to controls. 3. Administration of octreotide reduced average body weight and packed cell volume in non-diabetic and diabetic rats compared with their respective controls, but did not affect glomerular hyperfiltration or the increase in urinary protein excretion. 4. Histological examination at 14 weeks disclosed unequivocal glomerular hypertrophy and mild glomerular and tubulointerstitial lesions consistent with early diabetic renal alterations in all diabetic rats, but there was no independent effect of octreotide treatment. 5. Thus, long-term treatment with octreotide did not afford protection against the development of renal hypertrophy-hyperfiltration and the evolution of early diabetic nephropathy in rats.