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Fractional intestinal absorption of calcium (FACa) was measured using radioactive calcium and 200 mg of calcium carrier provided either by yogurt or by CaCl2 in 7 lactase-deficient (L(-] and 7 normal (L(+] subjects. During the control period prior to yogurt consumption, mean calcium intake was 819 mg per day in L(-) and 931 mg per day in L(+) subjects (NS). In both groups of subjects yogurt increased FACa from 20.8 +/- 3.9% to 26.9 +/- 7.2% (P = 0.065) in L(+) subjects and from 20.2 +/- 5.6% to 23.5 +/- 6.4% (P = 0.050) in L(-) subjects. The significant increase in FACa observed in L(-) subjects indicates that yogurt, which is an autodigesting source of lactose, does not impair calcium absorption. FACa increase could reflect the lower dietary calcium intake in L(-) subjects when compared with L(+) subjects, due to avoidance of milk and non-fermented dairy products which could cause intestinal discomfort. It is concluded that yogurt is a well-tolerated and efficient source of calcium in subjects with lactase deficiency.

Two hemodialysis patients, one male and one female, aged 46 and 54 years, were treated with preceed respectively for refractory ascites secondary to hepatic cirrhosis and for large polycystic liver. Preceed was decided because of the rapid reappearance of effusion following repeated puncture and albumin infusion, the poor tolerance to ultrafiltration (UF) and the poor nutritional status of the patients, with severe hypoalbuminemia. Abdominal paracentesis was performed on initiation of the dialysis session. Reinjection of the ascites fluid was made into the arterial line, allowing its UF and control of its flow. The procedure was performed whenever necessary, i.e., when inter-dialysis weight gain and ascites volume were high. In both cases, improvement was quickly obtained, with less rapid and less severe reappearance of the effusion and correction of albuminemia. Dialysis sessions with UF were better tolerated. No notable side effect was observed. The first patient was treated for 2 months, when he died of an unrelated cause. The other patient was treated for 6 months and then could be transferred to a dialysis center near her home. Twenty five months after start of dialysis treatment, kidney and liver transplantation were performed in this same patient. After transplantation, reappearance of moderate ascites and oedema is attributed to e degradation of renal function, without liver dysfunction. Five weeks after transplantation, improvement of renal function and ascites regression were noted. Preceed is an effective method of treating refractory ascites in the hemodialysis patient. Compared to classical paracentesis, it has the advantage of good tolerance, patient comfort and moderate cost.

Human apolipoprotein (apo) AIV might play a role in post-transplant reverse cholesterol transport, which appears to be comparable to that seen in healthy subjects. However, there may be subtle differences between healthy individuals and renal transplant recipients, given the other abnormalities of lipoprotein metabolism in the latter. Therefore, the aim of the present study was to investigate possible changes of serum apo AIV levels in renal transplant recipients, and to evaluate potential factors influencing these levels.Total and free serum apo AIV was determined in 36 clinically stable renal transplant recipients and in 20 sex- and age-matched healthy control subjects.Mean total serum apo IV concentrations (+/- SD) were significantly higher in renal transplant recipients than in control subjects (202 +/- 102 vs 79 +/- 45 mg/l, p0.01). The percentage of lipoprotein-free fractions of apo AIV was comparable in both groups. The elevated total serum concentrations of apo AIV were mainly related to creatinine clearance and partially to serum triglyceride levels in renal transplant recipients.Our data suggest that the observed elevation of serum apo AIV concentrations in renal transplant recipients is essentially related to the presence of impaired renal function.

Recently, it has been hypothesized that salt intake may be related to the risk of osteoporosis. The aim of this review was to summarize the evidence for such relationship and to discuss possible mechanisms.We performed a review of the scientific literature on osteoporosis, particularly its etiology, and then focussed on studies addressing the relation between salt intake on the one hand, and calcium balance, bone resorption, bone mineral density and fractures on the other. Although a relation between high salt intake and increased bone loss is biologically plausible, the most pertinent studies relating salt intake to bone mineral density are only suggestive of high salt consumption as a risk factor for osteoporosis. Unfortunately, studies on fracture risk and salt intake are lacking.The relationship between salt intake and osteoporosis is still controversial. A possible relation between salt intake and fracture risk should be addressed in future studies.

The objective of this cross-sectional study in a population of 1472 dialysis patients was to identify the main factors involved in the choice of a specific option for dialysis therapy, taking into account three different types of criteria such as medical dependence (DM), nurse care requirement (SI) and independence for dialysis therapy (CA).Each patient has been analysed, independently of present treatment modality, according to the above three criteria, namely DM, SI and CA. For each type of parameter, patients have been allocated to one of three levels, each level being established to evaluate whether dialytic treatment should be undertaken as hospital centre dialysis (HDC) or in a facility off the hospital. Level 3 of any one category corresponded to the inability of doing haemodialysis at home (HHD) or in self-care unit (AD). Level 2 included patients who could be treated in AD or by peritoneal dialysis (PD) with the assistance of a nurse. CAPD or HHD were considered as potential treatment modalities only in patients qualifying for level 1 of each criterion.In the patient population as a whole, the following treatment options were observed: HHD 3.6%, CAPD 6%, PD 1.8%, AD 16.3% and HDC 72.2%. For medical dependence (DM) there was a relatively even distribution for the three levels in six centres. In contrast, two centres were characterized by a predominance of DM level 3. Differences in DM levels between centres were greatly reduced when considering separately only those patients who were actually treated by CAPD, HDC and AD. SI levels were more uniformly distributed within all centres, and this was true for HCD and AD patients. When considering CA levels in HDC patients, a large predominance of CA level 3 was observed in all centres whereas CA level 1 was nearly in existent.The major finding of this study was that the inability or the refusal of dialysis patients to participate at treatment, independently of medical condition and nurse care requirement, was the main factor in the choice of hospital centre dialysis.

The administration of recombinant erythropoietin (rHuEpo) to anemic chronic renal failure patients may be associated with an increase in blood pressure, possibly by direct effects on peripheral blood vessels. In the present study, experiments were designed to explore the hypothesis that rHuEpo could enhance vascular resistance through mitogenic effect on vascular smooth muscle cells (VSMCs), and that preexisting hypertension might be a predisposing condition. Cultured VSMCs from the thoracic aortae of spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats were studied for DNA synthesis, phospholipase C activity, and cell growth related proto-oncogene expression in the presence of rHuEpo. In cells from both strains, rHuEpo dose-dependently increased DNA synthesis and stimulated phospholipase C activity, as indicated by 3H-thymidine incorporation and 3H-inositol phosphate formation, respectively (EC50 approximately 4 U/ml). Exposure of VSMCs to rHuEpo for various times gradually increased the levels of c-myc and junB and transiently induced c-fos expression, as determined by Northern analysis. rHuEpo-induced DNA synthesis was markedly enhanced in VSMCs from SHR compared to those from WKY. In contrast, rHuEpo-induced phospholipase C activity and proto-oncogene expression did not differ between the two strains. Taken together, these results suggest that rHuEpo may function as a vascular smooth muscle cell growth promoting factor through activation of the phospholipase C cascade and modulation of proto-oncogene expression. It could thereby contribute to vascular hypertrophy and arterial hypertension.

Using the technique of Accelerator Mass Spectrometry (AMS), 26Al has been measured in plasma, liver, urine and bone of normal rats at 8, 24 and 48 hours after ingestion of trace amounts of Al (3.8 ng of 26Al and 63 ng of stable 27Al), both in citrate-free and citrate-containing solutions. Our data show that under physiological conditions, namely at normal levels of dietary intake, intestinal Al absorption is approximately 0.04%, and is not significantly enhanced by the presence of citrate. Interestingly, the amount of Al retained by bone (0.02%) is comparable to that excreted in urine during 48 h (0.02%). Our estimate of gastrointestinal absorption is more than two orders of magnitude smaller than that estimated by Day et al. [1991], also using 26Al, for a single human subject.

Treatment of the anaemia of predialysis patients with recombinant human erythropoietin (rHuEpo) is likely to become a widely accepted practice during the coming years. We estimated the impact on health care expenditures with the example of the French population of end-stage renal disease patients. Using retrospective data, we calculated the percentage of predialysis patients with advanced chronic renal failure who would be eligible for treatment according to two different criteria based on haemoglobin and clinical condition, the total duration of treatment, and the total amount of rHuEpo delivered. We estimate that the total cost of treating French predialysis patients could vary between 2.2 and 6.5 million Swiss francs, or 50,000 to 140,000 Swiss francs per million population, using rHuEpo dosage from 50 to 150 IU/kg week.

Treatment of the anaemia of predialysis patients with recombinant human erythropoietin (rHuEpo) is likely to become a widely accepted practice during the coming years. We estimated the impact on health care expenditures with the example of the French population of end-stage renal disease patients. Using retrospective data, we calculated the percentage of predialysis patients with advanced chronic renal failure who would be eligible for treatment according to two different criteria based on haemoglobin and clinical condition, the total duration of treatment, and the total amount of rHuEpo delivered. We estimate that the total cost of treating French predialysis patients could vary between 2.2 and 6.5 million Swiss francs, or 50,000 to 140,000 Swiss francs per million population, using rHuEpo dosage from 50 to 150 IU/kg week.

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.

Arterial hypertension in the SHR is associated with disturbances of calcium homeostasis, compared with its normotensive control, the WKY. In order to study intestinal Ca2+ handling at the subcellular level, we examined 45Ca2+ uptake kinetics in isolated brush-border membrane vesicles (BBMV). Experiments were conducted in male, 12- to 14-week-old rats on a 1% Ca diet. BBMV were purified by the method of Forstner et al. No difference in BBMV enrichment was observed between SHR and WKY. Ca2+ uptake was studied at various Ca2+ concentrations in the incubation medium (0.025-1.0 mM) and could be separated into a nonsaturable and a saturable component. The saturable component followed Michaelis-Menten kinetics. Vmax in the SHR was greater than in the WKY: 0.576 +/- 0.186 (n = 6) vs. 0.346 +/- 0.10 nmol/mg protein x 10 s (n = 6), mean +/- SD, p less than 0.05. However, Km was not different in the two animal strains. In conclusion, mediated Ca2+ transport into duodenal BBMV was increased in the adolescent SHR. When considering that the transcellular duodenal Ca2+ flux is decreased in the SHR at this age, the rate-limiting step of perturbed transeptithelial Ca2+ transport is probably localized at the site of the basolateral membrane.

The incidence of beta 2-microglobulin deposits appears to increase with time on dialysis. However, the precise prevalence of the disease is not known at present because adequate, noninvasive diagnostic procedures are still lacking. We performed systematic synovial biopsies of the sternoclavicular joint during surgical parathyroidectomy in 22 chronic hemodialysis patients with severe hyperparathyroidism. Nine of the patients proved to have beta 2-microglobulin amyloid deposits as demonstrated by Congo red staining and by immunofluorescence. They had undergone dialysis for longer time periods (12.6 vs 8.5 years, p less than 0.02) and tended to be older than the 13 amyloid-negative patients. They also had a significantly higher body aluminum overload, as demonstrated by a higher increase of plasma aluminum after desferrioxamine infusion. Finally, the presence of Congo-red-positive deposits correlated well with clinical and x-ray findings suggestive of dialysis amyloidosis.

Twenty men and 23 women aged from 18 to 65 years, who had been under maintenance haemodialysis for 2 to 16 years and whose haematocrit had been below 30 percent for at least 3 months received recombinant human erythropoietin intravenously at the end of each session for one year. Anaemia was corrected in all patients, the delay in response to each dosage variation being about 4 weeks. The necessary maintenance dosage ranged from 96 to 240 u/kg/week. The number of leucocytes increased significantly until the 4th month, from 5880 +/- 1760 to 6600 +/- 1920 per cubic mm (P less than 0.01). During treatment, pre-dialysis blood creatinine concentrations and potassium and phosphate levels rose, while blood calcium levels fell significantly from 2.45 +/- 0.16 to 2.36 +/- 0.19 mmol/l (P less than 0.01). A nonsignificant increase in systolic and diastolic pressures was also observed, from 129 +/- 16 to 134 +/- 18 mmHg (P = 0.06) and from 75 +/- 9 to 78 +/- 10 mmHg (P = 0.07) respectively. Eight patients (18 percent) required antihypertensive drugs or a higher dose of those previously prescribed. There were 7 cases of vascular thrombosis on pre-existing stenosis, and the dosage of heparin during dialysis had to be increased in most patients. This study confirms that erythropoietin plays a major role in the genesis of the anaemia associated with renal failure. The absence of severe complications in this series was probably due to the criteria of inclusion in the study.

Alterations in intestinal transport and absorption of calcium have been described for the spontaneously hypertensive rat (SHR) as compared to the normotensive Wistar-Kyoto rat (WKY). Several in vitro studies of intestinal calcium transport done with everted gut sacs and the Ussing chamber found that calcium transport was lower in the SHR than the WKY. Calcium uptake by isolated enterocytes was also lower in SHR than WKY. However, net intestinal calcium absorption measurements by the balance method are variable in the literature with findings of decreased, increased, and no difference in absorption reported for the SHR. Study differences in age of the animals and diets may explain some of the disparate findings. The possible relationship between systemic alterations in calcium metabolism, including intestinal transport and absorption, and the pathogenesis of hypertension is discussed.

Parathyroid hormone (PTH) has been shown to modify Ca2+ and Na+ transport in several epithelia. The molecular mechanisms of these effects are poorly understood. We investigated here whether PTH may modify Na+ and K+ transport across the human red blood cell membrane in vitro and ex vivo. Fourteen patients with severe primary or secondary hyperparathyroidism and hypercalcemia were studied before and 5-7 days after surgical parathyroidectomy. Erythrocyte ouabain-sensitive as well as furosemide-sensitive Na+ efflux rates of the patients were comparable to that of healthy volunteers and remained unchanged after parathyroidectomy. Moreover, erythrocyte Na+ fluxes of control subjects remained unchanged when red blood cells were incubated in the presence of 1.0 IU/ml of bovine PTH (1-85). However, erythrocytes from hyperparathyroid patients showed a significant increase in passive K+ permeability when compared to that of healthy controls (p less than 0.05). This abnormality could be corrected in vivo after parathyroidectomy and in vitro using quinine, respectively. It is concluded that hyperparathyroidism induces a moderate increase in Ca2+ dependent K+ permeability of erythrocytes ("Gardos effect") which is reversible after parathyroidectomy.

The study reports an aluminium-intoxicated haemodialysis patient who had encephalopathy, osteomalacia and congestive cardiomyopathy prior to his death. Detailed light and electron microscope examination revealed the presence of aluminium deposits within lysosomes of cells from many organs, including the kidney, liver, brain and heart. The heavy aluminium deposits in myocardial lysosomes favor a possible role of the trace element in the patient's congestive cardiomyopathy.

In long-term haemodialysis patients a new type of amyloidosis composed of beta 2-microglobulin (beta 2-M) has recently been described. The amyloid deposition has a particular predilection for articular structures. In the pathogenesis of this complication markedly elevated plasma beta 2-M concentrations, such as those observed in anuric patients, have a role. However, other as yet ill-defined factors must also be implicated, possible candidates being aluminium intoxication and the widely used regenerated cellulose (cuprophan) membrane. In the present experimental study, we examined tissue distribution of exogenous beta 2-M after i.v. injection of 125I-beta 2-M to bilaterally nephrectomised rats. One hundred and twenty minutes after injection, most radioactivity remained in the vascular compartment. The accumulation in tissues was weak, and no predilection for a particular tissue became apparent. Interestingly, chronically aluminium-overloaded, acutely anephric rats accumulated a significantly greater amount of 125I-beta 2-M in their spleens than anephric rats without prior aluminium intoxication. We then attempted to induce beta 2-M amyloid deposition in rats and mice, some of whom had undergone chronic aluminium intoxication and subcutaneous implantation of regenerated cellulose fragments for various periods of time. They were subsequently made anephric to obtain high plasma beta 2-M concentrations. None of the animals developed beta 2-M amyloidosis in spleen, liver, skin and mechanically altered joint synovium. In conclusion, chronic aluminium intoxication enhances splenic accumulation of exogenous 125I-beta 2-M in anephric rats. The factors required to form beta 2-M-amyloidosis in vivo have still to be defined.

Abnormalities of calcium metabolism and of its two principal regulating hormones, parathyroid hormone and 1,25-dihydroxyvitamin D3 (calcitriol), have been reported in the spontaneously hypertensive rat (SHR). Reports of abnormal calcitriol metabolism in the SHR by several groups have not provided measurements of tissue calcitriol receptors. Similarly, few data are available as to the parathyroid status of the SHR. In the present study, circulating calcitriol levels and intestinal and parathyroid gland calcitriol receptor status were determined in male SHR and in Wistar-Kyoto (WKY) rats. Parathyroid status was investigated by determination of parathyroid gland mass together with tissue micromorphometry and by quantitative histology of bone as a measure of the biological action of parathyroid hormone. Circulating calcitriol levels were reduced in the 11-week-old SHR compared with the WKY rat (165 +/- 23 vs. 194 +/- 28 pmol/l, p less than 0.01, mean +/- SD). Calcitriol-free ratio was diminished and maximal specific binding capacity for calcitriol was increased in the SHR in parathyroid tissue (172 +/- 4.9 vs. 123 +/- 6.6 fmol/mg protein, p less than 0.01) and in intestinal mucosa with no change of receptor affinity. Plasma ionized calcium (1.29 +/- 0.05 vs. 1.45 +/- 0.35 mmol/l, p less than 0.05) and phosphate (1.5 +/- 0.26 vs. 2.4 +/- 0.03 mmol/l, p less than 0.05) were significantly lower in the SHR. Parathyroid gland mass was increased in the SHR (59 +/- 12 vs. 17 +/- 7 micrograms/100 g body wt, p less than 0.001) as a result of hyperplasia and not hypertrophy. Higher osteoclast numbers were observed in SHR bone (27.6 +/- 0.79 vs. 23.9 +/- 0.66 osteoclasts/mm2, p less than 0.01), suggesting increased parathyroid hormone activity. In summary, in the 11-week-old SHR we observed reduced circulating calcitriol levels together with increased tissue calcitriol receptor numbers, increased parathyroid gland mass, and histological evidence of hyperparathyroidism. It is possible that these abnormalities influence the development of hypertension in the SHR.

In the present study, lipid and apolipoprotein composition of very low density lipoprotein (VLDL) was analyzed in 39 patients with end-stage renal failure by comparison with 41 healthy subjects. Uremic patients had an increase of serum triglycerides (TG) concentration by comparison with control values. This increase of serum TG was associated with an increase of VLDL which had a normal percent amount of main components. Furthermore a mid-band between VLDL and low density lipoproteins (LDL) on polyacrylamide gel was observed in 22 out of 39 uremic patients but in only 1 out of 41 control subjects. In uremic VLDL Apo B48 was more frequently observed than in control VLDL (p less than 0.05). Furthermore, the content of Apo CII expressed as percent of total Apo C was significantly (p less than 0.001) decreased in uremic VLDL (19.13 +/- 4.54 p. cent) as compared to normal VLDL (23.57 +/- 4.40 p. cent). Apo CIII-O was significantly (p less than 0.001) increased (9.58 +/- 7.19 p. cent vs 5.55 +/- 6.12 p. cent, whereas Apo CIII-1 and Apo CIII-2 distribution was not modified in uremic VLDL. These anomalies were present in uremic patients even when no elevation of fasting serum TG was present. No significant change was observed in uremic patients before their fifth as compared to their first hemodialysis (HD) session, respectively, for any of the parameters studied. Advanced chronic renal failure is associated with a variety of anomalies of TG-rich lipoproteins isolated at d less than 1.006 g/ml which are not reflected by the degree of hypertriglyceridemia and are not corrected by the first four HD sessions.

Vitamin K promotes the formation of gamma-carboxylated glutamic acid (Gla) residues within different protein classes such as vitamin K-dependent clotting factors, bone Gla-protein (BGP or osteocalcin), and atherocalcin. Gla-containing proteins have a high affinity for the Ca2+ ion. In addition to bone and atheromatous plaques they are also regularly found in ectopic calcifications, but not in uncalcified soft tissue. In the present study we investigate the possibility that vitamin K and BGP, in addition to previously recognized factors, may play a role in soft tissue calcification of chronic hemodialysis patients. Patients without radiovisible ectopic calcifications (group A) are compared to patients with such Ca deposits (group B). Both patient groups have comparable values of predialysis plasma Ca, P, alkaline phosphatases, parathyroid hormone (PTH) and 25 hydroxyvitamin D. The CaxP product is slightly higher in group B than in group A patients. Plasma vitamin K1 levels of group B patients are increased to more than twice the values observed in group A patients. Plasma BGP, even though not significantly different, shows a trend towards decreased levels in group B patients. A positive correlation exists between plasma vitamin K1 and BGP for patient group A alone, but not for group B alone. A correlation is also observed between plasma PTH and BGP (all patients) and between serum alkaline phosphatases and plasma BGP (all patients). Taken together, these results favor the hypothesis that in addition to an increased CaxP product a vitamin K excess may induce soft tissue calcification in hemodialysis patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia has been recognized recently as a possible complication of primary hyperparathyroidism. If the hyperparathyroid state can induce anemia in patients with normal kidney function, the extremely high levels of circulating parathyroid hormone usually observed in hyperparathyroidism secondary to chronic renal failure may have an unfavorable influence on the anemia of uremic patients. We investigated the influence of subtotal parathyroidectomy on the severity of the anemia of 18 uremic subjects undergoing long-term hemodialysis therapy. Subtotal parathyroidectomy resulted in a significant increase of mean hematocrit value. RBC count, and hemoglobin level. Serial bone biopsies suggested a relationship between the amount of marrow fibrosis and the improvement of anemia after surgery, but the precise mechanism of this phenomenon is still unknown.

Red blood cell (RBC) production has been explored in hyperparathyroid as compared to normal rats. The hyperparathyroid state was obtained by feeding the rats a calcium-deficient diet during 30 days. A significant decrease (p less than 0.001) in reticulocyte count and in erythrocyte 59Fe incorporation was observed in hyperparathyroid rats when compared to control animals. A comparable inhibition of erythrocyte 59Fe incorporation in hyperparathyroid rats was found when the study was performed after stimulating bone marrow activity by acute arterial hemorrhage. These results of decreased RBC production using a model of endogenous hyperparathyroidism could be confirmed in additional experiments using a model of exogenous hyperparathyroidism. In this model, the rats received either parathyroid extract (3 x 10 USP/day during 8 days) or vehicle only. Again, a decrease in erythrocyte 59Fe incorporation was observed in hyperparathyroid animals when compared to control animals. It is concluded that the hyperparathyroid state is accompanied by a decrease of RBC production in the rat. It is probable that a similar pathogenesis underlies the anemia of patients with primary or secondary hyperparathyroidism.

A hemodialyzed woman with radiologically and histologically proven osteomalacia presents a spontaneous fracture that is associated with aluminium intoxication. The hyperalbuminemia (16,6 mumol/1) was not caused by the aluminium contained in the dialysate fluid but by oral ingestion of aluminium gel in a patient presenting hyperabsorption of this metal. Increased absorption could be demonstrated by oral administration of aluminium hydroxide (2 x 12 g A1 (OH)3 spread over 48 hrs) whereas the same test failed to reveal hyperabsorption in two other hemodialyzed patients. The precise mechanism of increased absorption of aluminium is not known. It is concluded that increased digestive absorption of aluminium should be investigated in patients with kidney failure treated with aluminium gel and presenting high blood levels of this metal.

The binding characteristics of chlorophenoxyisobutyric acid (CPIB) to serum proteins has been studied in 10 chronically uremic patients and 9 healthy subjects using the technique of equilibrium dialysis. Scatchard analysis of the results indicated a significant decrease in association constants for low as well as for high affinity sites. The number of binding sites however was not diminished thus suggesting the presence of competitive inhibitors. Such inhibitors were dializable, at least in part, as demonstrated by in vivo-hemodialysis and in vitro-dialysis experiments. The in vivo administration of 50 mg heparin intravenously led to a striking increase in the unbound fraction of serum CPIB whereas the addition of 10 IU/ml heparin in vitro induced no change of protein binding which is in favor of only an indirect effect of heparin. In conclusion, CPIB binding to serum proteins of chronically uremic patients as compared to normal volunteers was decreased leading to an increase of its unbound circulating fraction. The observed change of protein binding appeared to be due to the presence of competitive inhibitors in uremic serum.

The effects of PTH on jejunal calcium, sodium, and water transport were studied in the rat in situ. In TPTx rats, as well as in normal rats, bovine PTH induced a decrease in net calcium, sodium, and water absorption. Additionally, lumen-to-plasma calcium flux was found decreased in both groups. Stimulation of endogenous PTH secretion by calcium-poor hyperoncotic albumin resulted in a similar decrease in net calcium, sodium, and water absorption. It is suggested that PTH has a direct inhibitory effect on jejunal calcium, sodium, and water absorption.

It may sometimes be difficult to distinguish primary from secondary hyperparathyroidism when advanced renal failure coexists. We report here the case of a patient with end-stage renal failure who had severe hyperparathyroidism. Cervical exploration revealed only the presence of four parathyroid glands normal in size and histological appearance which were removed. Because the existence of severe hyperparathyroidism had been firmly established based on biochemical and radiological evidence, the diagnosis of primary hyperparathyroidism due to an ectopic adenoma became obvious. Digital angiography and computerized tomography were then carried out. The results of angiography were inconclusive but computerized tomography revealed and precisely localized a mediastinal adenoma which was subsequently removed via sternotomy. The existence of a hypoparathyroid state was confirmed over the following two months. Reimplantation of parathyroid fragments which had been cryopreserved during the first operation, was then performed with success.

Twenty-three uremic patients on intermittent hemodialysis for eight to eighteen years provided the material for the present pathological study. In all of them, there was evidence for dialysis related amyloidosis based on previous clinical or histological findings or both. The material examined consisted of nine skin biopsies, five abdominal fat aspirates, eight trans-iliac bone biopsies and numerous post-mortem specimens of various visceral organs from eight cases. None of the skin biopsies or fat aspirates showed amyloid deposits. In only one bone biopsy could a small Congo red positive area be recognized that showed characteristic birefringence under polarizing light. Autopsy material findings were negative except for one case: this patient had been dialyzed for 18 years. Very minute amyloid deposits with a positive immunofluorescence staining for beta 2-microglobulin (beta 2-M) were found in the walls of small vessels from her lung, heart, liver and intestine. Thus, in chronic hemodialysis patients the accumulation of beta 2-M amyloid fibrils in tissues other than joints and juxta-articular structures appears to have a low incidence, to occur lately and to be of limited size. Although extra-articular amyloid deposits may progressively occur and extend with increasing survival time on dialysis, tiny deposits such as those observed in only two of our patients will hardly lead to serious complications.

Sulphaemoglobin production, induced by an oxidative stress (ascorbate and cyanide) has been studied in uraemic patients. Results are expressed as the ratio of optic density of sulphaemoglobin (620nm) to optic density of total haemoglobin (540nm). The mean (+/- SEM) ratio found was 0.35 +/- 0.03 in 28 controls and 0.56 +/- 0,03 in 51 uraemic subjects (p less than 0.001). Cross incubation tests demonstrated that the anomaly was caused by a plasma factor. In vitro studies - guanidinic compounds added to control erythrocyte suspensions before incubation - suggest that this factor might be guanidinic propionic acid.

A closed loop closed batch dialysate delivery system was used to determine whether Na or K has an action on the renin-angiotensin system apart from volume changes. Twenty-eight patients on chronic haemodialysis were studied, 12 (group I) were normotensive and 16 (group II) had poorly controlled hypertension. Acute Na depletion or repletion (delta NA), AND K loss (delta K) were induced with or without net water loss. Net electrolyte and water movement across the dialysis membrane could be precisely quantitated.