Subacute infusion of physiological doses of parathyroid hormone raises blood pressure in humans

Background. Acute administration of parathyroid hormone (PTH) causes vasodilation and blood pressure decrease in experimental animals. This effect contrasts with the putative role of secondary hyperparathyroidism in the pathogenesis of hypertension of patients with renal failure. Uraemia is characterized by insulin resistance and hyperinsulinaemia. We therefore investigated whether subacute administration of physiological doses of human 1,34-PTH affects blood pressure under conditions of controlled insulin levels (euglycaemic clamp technique) in humans. Methods. In a double-blind cross-over design 10 healthy male subjects received, on two occasions, in random order, for 2 h, either a sham infusion or an infusion of 200 units of 1,34-PTH. Results. Mean ionized calcium concentration increased significantly (P <0.01) within the normal range during euglycaemic hyperinsulinaemia, both with sham infusion (from 1.25 ± 0.04 to 1.29 ± 0.02 mmol/l) and with infusion of 1,34-PTH, but the increase was more marked with 1,34-PTH administration (from 1.26 ± 0.05 to 1.33 ± 0.07). In addition, mean platelet intracellular calcium concentration (by fluorescence spectroscopy) was unchanged with sham infusion (49.9 ± 4.1 versus 50.3 ± 5.0 nmol), but increased significantly (P <0.05; paired t-test) after 1,34-PTH infusion (from 49.8 ± 5.0 to 52.8 ± 5.8). The infusion of 1,34-PTH resulted in a significant (P <0.01) increase in mean MAP (from 84 ± 5 to 88 ± 5 mmHg) as compared with sham infusion (85 ± 4 versus 86 ± 4). The intra-individual changes in intracellular calcium concentration (&Dgr;[Ca²⁺]I) were significantly correlated to the changes in mean MAP (&Dgr;MAP) (r = 0.87, P <0.001). In contrast to blood pressure, insulin sensitivity was not affected by 1,34-PTH infusion (M-value: 7.2 ± 1.6 mg/kg per min) as compared with sham infusion (7.3 ± 1.4). Conclusion. Subacute administration of physiological doses of parathyroid hormone under hyperinsulinaemic conditions significantly affects intracellular calcium and blood pressure in healthy subjects, but does not affect the action of insulin.     

Hydrochlorothiazide treatment of children with hypercalciuria: effects and side effects

Urinary excretion of calcium and the changes in serum cholesterol fractions were investigated in 15 children with renal hypercalciuria, following 3-month hydrochlorothiazide (HCT) treatment (daily dose 1 mg/kg). Urinary calcium excretion (expressed as the ratio of calcium to creatinine) reached its lowest value after 2 weeks. It was still below the initial value at the end of the 3rd month of treatment (0.84±0.06, 0.29±0.03 and 0.6±0.09 mmol/mmol, respectively). A significant rise in the total serum cholesterol level (4.64±0.23 vs. 4.25±0.18 mmol/l before treatment,P<0.01) and the lowdensity lipoprotein (LDL)-cholesterol fraction (2.6±0.24 vs. 2.31±0.31 before treatment,P<0.01) was observed at the end of the 3rd month, while high-density lipoprotein (HDL)-cholesterol was slightly decreased. A significant elevation of the LDL/HDL ratio was also observed (from 1.76±0.17 to 2.2±0.17,P<0.001), indicating an increase in the atherogenic cholesterol fractions. The risks and benefits of the thiazide therapy should be considered before starting long-term treatment of children with hypercalciuria and haematuria or renal stone disease.     

The influence of low calcium dialysate on left ventricular diastolic function in peritoneal dialysis patients

Left ventricular (LV) diastolic function was found to be a significant predictor of cardiovascular events and general mortality in dialysis. Studies have indicated that dialysate calcium concentrations were significantly associated with cardiac function. However, the relationship between low calcium dialysate and LV diastolic function has not been clear. The aim of this study was to investigate the influence of low calcium dialysate on cardiac function in peritoneal dialysis (PD) patients. A total of 60 PD patients were enrolled in this study, with a calcium content of the PD solution of 1.25?mmol/L in 30 patients (low-calcium group) and 1.75?mmol/L in 30 patients (standard-calcium group). Standard M-mode and two-dimensional ultrasound measurements were applied to detect the cardiac function. After 12-month follow-up, we found no significant difference in blood pressure, calcium, phosphorus, parathyroid hormone (PTH), etc., between the two groups. Residual renal function (RRF), which is associated with LV cardiac function, was significantly decreased in the standard-calcium group compared with the low-calcium group (5.64?±?3.23 vs. 9.38?±?3.17, p?=?.001). Compared with the low-calcium group, E_max (peak early diastolic velocity) and A_max (peak late diastolic velocity) were significantly decreased (p?p?相似文献   

The influence of hyperinsulinaemia on calcium-phosphate metabolism in renal failure

Background. Patients with renal failure are characterized by impaired insulin-mediated glucose uptake. Insulin plays a major role in the maintenance of phosphate homeostasis but it remains to be determined whether in uraemia insulin-dependent renal and extrarenal phosphate disposal is also affected. Methods. The effects of hyperinsulinaemia on serum concentrations of phosphate, ionized calcium and intact PTH as well as renal excretion of calcium and phosphate was studied under euglycaemic conditions (glucose clamp technique) in patients with advanced renal failure and in healthy subjects. Fifteen patients with renal failure (mean serum creatinine 917 &mgr;mol/l) and 12 control subjects were included. All subjects underwent a 3-h euglycaemic clamp with constant infusion of insulin (50 mU/m²/min) following a priming bolus. The urine was collected for 3 h before and throughout the clamp. Results. The tissue insulin sensitivity (M/I) was lower in patients with renal failure than in control subjects (5.3±2.4 vs 6.7±1.8 mg/kg/min per mU/ml, P=0.001) but the phosphate lowering action of insulin was larger in patients with renal failure than in control subjects. Urinary calcium excretion increased (P<0.05) and phosphate excretion did not change during the clamp in both groups. Despite a decrease of serum ionized calcium in the group of patients with renal failure and no change in the control group, plasma PTH fell significantly in both groups but this effect was still significant after 180 min only in the renal failure group. A significant correlation was observed between changes in serum phosphate and PTH induced by hyperinsulinaemia (r=0.48, P<0.01). Conclusions. Phosphate-lowering effect of insulin is well preserved in severe renal failure despite the resistance to insulin-stimulated glucose uptake. The decrease of serum PTH observed during hyperinsulinaemia appears to be independent of serum ionized calcium.     

Regulation of renal calbindin-D28K: The role of calcitonin

Infusion of calcitonin lowers circulating calcium, but in the distal tubule of the kidney, pharmacological doses of calcitonin increase the active calcium reabsorption. Calbindin-D28k plays a significant role in the calcium reabsorption in the distal convoluted tubule of the kidney. The effect of calcitonin on renal calbindin-D28k in relation to calcium metabolic changes was therefore examined. In study 1, thyroparathyroidectomy followed by autotransplantation of the parathyroid glands (TX) was compared with a sham operation in rats. TX reduced plasma calcitonin from 54±2 to 9±1 pg/ml (P<0.001), whereas ionized calcium and parathyroid hormone were returned to the control value after an initial decrease, indicating a successful implantation of the parathyroid glands. No changes were seen in calbindin-D or plasma 1,25(OH)₂D. In study 2, subcutaneous infusion of salmon calcitonin 2.5 U/kg/hour via osmotic pumps was compared with infusion of vehicle in rats. Ionized calcium was reduced from 1.37±0.01 to 1.33±0.02 mmol/liter (P<0.05), whereas no changes were seen in renal or intestinal calbindin-D or in plasma 1,25(OH)₂D. After TX, only calcitonin decreased whereas the other calcium metabolic parameters showed no change. This indicates that in rats, selective elimination of calcitonin does not influence other parameters of the calcium metabolism and that the effect of calcitonin on calcium transport in the distal tubule is not mediated via an increase in renal calbindin-D28k.     

Effect of menopause and aging on serum total and ionized calcium and protein concentrations

Summary The effects of menopause and aging on serum total and ionized calcium concentrations were evaluated in 402 healthy women (aged 18–71 years), of whom 83 were premenopausal and 319 postmenopausal. Serum albumin and globulin concentrations and serum pH were also measured in most of these women. Serum total but not ionized calcium concentration increased significantly at menopause. This increase in the protein-bound component of total calcium in postmenopausal women was associated with increases in mean serum globulin concentration (P=0.03) and in serum pH (P=0.03). Serum total calcium declined with age within the pre- and postmenopausal groups (r=−0.225,P=0.04 and r=−0.121,P=0.03, respectively). This was associated with an age-related decrease in serum albumin concentration in all women (r=−0.47,P<0.0001). Neither serum globulin concentration or pH varied with age. Thus, menopause and aging affect serum total, but not ionized calcium concentration.     

Impact of long-term immunosuppression with cyclosporin A on serum lipids in stable renal transplant recipients

To determine the impact of long-term immunosuppression on serum lipids in stable renal graft recipients we measured serum lipids and apolipoprotein B concentrations in 20 patients receiving therapy with cyclosporin (CsA) and low-dose prednisolone (CsA/P) and in 18 patients on therapy with azathioprine and maintenance steroids (Aza/P). The patients were matched for age, body mass index, primary renal disease and dose of prednisolone, but not for the duration in transplantation and serum creatinine concentration. Triglyceride concentrations were significantly higher in the CsA/P group than in Aza/P-treated patients: 2.62±0.35 vs 1.62±0.23 mmol/l (P<0.05). Similarly, total cholesterol (C) levels were significantly more elevated in the CsA/P recipients than in the other group: 7.44±0.32 vs 5.84±0.25 (P<0.02). CsA/P patients had higher serum levels of LDL-C (4.79±0.20 vs 3.43±0.19 mmol/l P<0.001) and apolipoprotein B concentrations (191±13 vs 128±9 mg/dl; P<0.001). CsA/P and Aza/P recipients had similar concentrations of HDL-C (1.73±0.13 vs 1.52±0.09 mmol/l; NS). We conclude that in stable renal graft recipients with good transplant function long-term immunosuppression with CsA/P is associated with a more atherogenic lipid status than therapy with Aza/P.     

Correction of metabolic acidosis increases serum albumin concentrations and decreases kinetically evaluated protein intake in haemodialysis patients: a prospective study

Background: Metabolic acidosis in haemodialysis (HD) patients increases whole body protein degradation while the correction of acidosis reduces it. However, the effects of the correction of acidosis on nutrition have not been clearly demonstrated. Study design: In this study we have evaluated the effects of 3 months of correction of metabolic acidosis by oral sodium bicarbonate supplementation on protein catabolic rate (PCRn) and serum albumin concentrations in 12 uraemic patients on maintenance HD for at least 6 months (median 49 months; range 6-243 months). Pre-dialysis serum bicarbonate, arterial pH, serum albumin, total serum proteins, serum creatinine, plasma sodium, haemoglobin, PCRn, Kt/V, and TACurea, were evaluated before and after correction. Results: Serum bicarbonate levels and arterial pH increased respectively from 19.3±0.6 mmol/l to 24.4±1.2 mmol/l (P<0.0001) and 7.34±0.03 to 7.40±0.02 (P<0.0001). Serum albumin increased from 34.9±2.1 g/l to 37.9±2.9 g/l (P<0.01) while PCRn decreased from 1.11±0.17 g/kg/day to 1.03±0.17 g/kg/day (P<0.001). No changes in Kt/V, total serum proteins, serum creatinine, plasma sodium, haemoglobin, body weight, pre dialysis systolic and diastolic blood pressure, and intradialytic weight loss were observed. Conclusions: Our data demonstrate that correction of metabolic acidosis improves serum albumin concentration in HD patients. The correction of acidosis induced a decrease in PCRn values, as evaluated by kinetic criteria, suggesting that in the presence of moderate to severe acidosis this parameter does not reflect the real dietary protein intake of the patients probably as a result of increased catabolism of endogenous proteins. The correction of metabolic acidosis should be considered of paramount importance in HD patients.     

Endothelin-1 in children with chronic renal failure

Endothelin-1 (ET-1) was meansured after extraction from plasma of normal adults (5.9±1.9 pg/ml,n=22), normal children (7.1±1.86 pg/ml,n=29), nonhaemodialysed children with chronic renal failure (CRF) (11.1±1.8 pg/ml),n=10), renal graft recipients (9.5±3.4 pg/ml,n=37), haemodialysed children 24 h after a haemodialysis session (20.02±10.9 pg/ml,n=26) and haemodialysed children before and after a haemodialysis session (15.31±10.6 and 13.8±8.5 respectively,n=14). A sensitive and specific radioimmunoassay was used. ET-1 was significantly higher in non-haemodialysed CRF children and in renal graft recipients than in normal children (P<0.001 andP<0.01, respectively) and significantly higher in haemodialysed children when compared with normal children, non-haemodialysed CRF children and renal graft recipients (P<0.001). ET-1 concentrations were similar in normal children and normal adults. ET-1 was inversely correlated with glomerular filtration rate in non-haemodialysed CRF children (r=–0.39,P<0.01) and positively correlated with extracellular volume in haemodialysed children (r=0.435,P<0.03). After haemodialysis, ET-1 increased in 6 and decreased in 8 of the 14 children studied before and after a haemodialysis session.     

Sequential changes of biochemical bone parameters after kidney transplantation

Background. Persistant hyperparathyroidism after renal transplantation (Rtx) has been reported in several studies. However these studies evaluated biochemical bone parameters either only during a short time period (up to 6 months) or for a longer time period, but with long intervals in between. Therefore, we prospectively evaluated biochemical bone parameters of kidney transplant recipients at short intervals for 2 years after surgery. Methods. Biochemical bone parameters were prospectively investigated in 129 patients 2, 3, 5, 8, 12, 18 and 24 months after Rtx. All patients received prednisone and cyclosporin A as immunsuppressive therapy, and 75 patients was treated with calcium, phosphorus, or vitamin D preparations. Results. Serum creatinine levels decreased from 166.8±5.4 &mgr;mol/l to 140.0±4.9 two years after Rtx; (data are expressed as mean±s.e.m.). Serum phosphorus levels increased slightly from 0.9±0.022 mmol/l to 0.98±0.025 (12m), but remained within the lower normal range. We observed a rise in total and albumin adjusted calcium concentrations 3 months after Rtx. 52% of all patients had serum calcium levels above 2.62 mmol/l (upper normal limit in our laboratory) 3 months after renal transplantation with a gradual decrease thereafter. There was no correlation of calcium and PTH levels. We observed a significant rise in biochemical bone parameters from 2 to 5 months after renal transplantation (P<0.001): alkaline phosphatase (AP) increased from 164.3±9.4 to 236±12.7 U/l (normal 50-180), bone specific alkaline phosphatase (BAP) rose from 17.7±1.36 to 23.2±1.7 ng/ml (normal:4-20) and osteocalcin (OC) increased from 20.2±1.5 to 26.7±1.9 ng/ml (normal 4-12). AP and BAP levels values normalized 12 months after renal transplantation, whereas OC was still above normal throughout the study period. Patients were subdivided into two groups: those with good and those with impaired graft functions. Patients with good graft function had stable serum creatinine levels (⩽132 &mgr;mol/l or ⩽1.5 mg/dl) well below the mean serum creatinine concentration during the study period. The significant changes in AP, BAP, and OC occurred irrespective of renal function. However, patients with impaired graft function (n=65) had significantly higher PTH-levels (70 pg/ml higher) than patients with good graft function (n=64), P<0.01. PTH was positively correlated with serum creatinine (r=0.0.001). Moreover, patients with low 25(OH) vitamin D levels (n=63) had significantly higher PTH concentrations (between 40 and 80pg/ml, P<0.01) throughout the sudy period compared to patients (n=66) with a sufficient 25(OH)D supply irrespective of graft function. There was a negative correlation of 25(OH)D levels and PTH; (r=-0.49, P<).001). 1,25(OH)2D3 (evaluated in 24 patients) levels increased from 46.5±6.6 to 76.9±7.6pg/ml (normal: 35-90) at 12 months. Conclusion: Hypercalcaemia is a common phenomenon in the early period after kidney transplantation and occurs in the presence of low normal phosphorus levels. It is most probably related to improved PTH action and 1-hydroxylation of vitamin D. The rise in biochemical bone parameters between 3 and 5 months occurs irrespective of graft function and normalization is only achieved 1 year after transplantation. PTH is constantly elevated for up to 2 years after kidney transplantation and is most probably related (a)to impaired graft function and (b) to suboptimal 25 OH vitamin D supply. Keywords: hypercalcaemia; biochemical bone parameters; renal transplantatiom; secondary hyperparathyroidism; vitamin D      

IONIZED SERUM CALCIUM LEVELS DURING ACUTE RENAL FAILURE: INTERMITTENT HEMODIALYSIS VS. CONTINUOUS HEMODIAFILTRATION

Background: Achieving “adequacy of dialysis” includes the maintenance of normal serum ionized calcium concentrations and is an important therapeutic goal in the treatment of acute renal failure (ARF). It is unknown whether this goal is best achieved with intermittent or continuous renal replacement therapy. Methods: We compared the effects of continuous veno–venous hemodiafiltration (CVVHDF) and intermittent hemodialysis (IHD) on serum ionized calcium concentrations using daily morning blood tests in 88 consecutive intensive care patients of which half were treated with IHD and half with CRRT. Results: Mean patient age was 54 ± 14 years for IHD and 60 ± 14 years for CVVHDF (NS). However, patients who received CVVHDF were significantly more critically ill (mean APACHE II scores: 24.4 ± 5.1 for IHD vs. 29.2 ± 5.7 for CVVHDF, p<0.003). Before treatment, the mean ionized calcium concentration was 1.177 ± 0.03 mmol/l for IHD and 1.172 ± 0.04 mmol/l for CVVHDF (NS), with abnormal values in 51.6% of IHD patients and in 68% of CVVHDF patients (NS). During treatment, hypocalcemia was significantly more common among CVVHDF patients (24.5% vs. 14.9%; p<0.011) while hypercalcemia was more frequent during IHD (36.1% vs. 25.6%; p<0.019). Conclusions: Abnormal serum ionized calcium concentrations are frequent in ARF patients before and during renal replacement. Once dialytic therapy is applied, CVVHDF is more likely to lower serum calcium concentrations, while IHD is more likely to induce hypercalcemia. Appreciation of these different biochemical effects may assist clinicians in adjusting dialytic therapy in selected patients.     

Urinary calcium and oxalate excretion in children

We have established normal values for calcium/creatinine (Ca/Cr) and oxalate/creatinine (Ox/Cr) ratios in 25 infants (aged 1–7 days) and 391 children (aged 1 month to 14.5 years) and compared these with values obtained in 137 children with post-glomerular haematuria and 27 with nephrolithiasis. Oxalate was measured by ion chromatography. Nomograms of Marshall and Robertson were used to calculate urine saturation to calcium oxalate. The Ca/Cr ratio was normally distributed whereas the Ox/Cr ratio had a log-normal distribution. The molar ratio of Ca/Cr was the lowest in the first days of life and the highest between 7 month and 1.5 years (mean±SD=0.39±0.28 mmol/mmol). Following a slight decrease it stabilised by the age of 6 years (0.34±0.19 mmol/mmol). The highest Ox/Cr values were measured during the 1st month of life [geometric mean 133 (range 61–280) mol/mmol], followed by a gradual decrease until 11 years of age [mean 24 (range 6–82) mol/mmol]. Thirty-six haematuric children had hypercalciuria (26%), 23 had absorptive hypercalciuria, 13 renal type. Children with absorptive hypercalciuria on a calcium-restricted diet had significantly higher oxalate excretion than those with renal hypercalciuria and the control group [38 (range 28–49) vs. 22 (range 16–29) and 23 (range 22–27) mol/mol respectively,P<0.01]. Calcium oxalate urine saturation of stone patients was higher than that of patients with haematuria and the normal population (1.18±0.05 vs. 1.06±0.03,P<0.03 and 0.84±0.03,P<0.001 respectively). The measurement of Ca/Cr and Ox/Cr in first-morning urine samples is suitable for screening for hypercalciuria and hyperoxaluria. Interpretation of the values requires age-specific reference values. Both calcium and oxalate determinations should be part of the evaluation of patients with haematuria, hypercalciuria or nephrolithiasis.     

Cinacalcet impact on calcium homeostasis and bone remodeling in 13 renal transplanted patients with hyperparathyroidism and hypercalcaemia

The purpose of the study is to assess the impact of cinacalcet on calcium and bone remodeling, in post-renal transplanted patients with persistent hypercalcaemia secondary to hyperparathyroidism. Thirteen renal-transplanted adult recipients with a glomerular filtration rate over 30 ml/min/1.73 m², a total serum calcium > 2.60 mmol/l with ionized calcium > 1.31 mmol/l and a parathyroid hormone serum level over 70 pg/ml, were treated with cinacalcet for 4 months followed by a 15-day wash out. The results show that cinacalcet lowers significantly total and ionized calcium respectively from 2,73 (2,67-2,86) to 2,31 (2,26-2,37) mmol/l (P < 0.05) and from 1,39 (1,37-1,47) to 1,21 (1,15-1,22) mmol/l (P < 0.05) with no alteration of the 24-hour urine calcium/creatinine ratio and no significant expected PTH serum level suppression (153 [115-214,9] and 166 [122-174] pg/ml). On the other hand, fasting urine calcium was significantly decreased from 0,61 (0,27-1,02) to 0,22 (0,15-0,37) (P < 0.05) and bone-specific alkaline phosphatases increased from 20,5 (13-46,6) to 33,8 (12-58,9) ng/ml, upon cinacalcet treatment. After its discontinuation, all these effects were reversible. In conclusion, cinacalcet normalizes total and ionized calcium in renal-transplanted recipients with hypercalcemia secondary to hyperparathyroidism through a mechanism that could be independent of PTH serum level suppression. The increase in bone-specific alkaline phosphatases, biochemical markers of bone accretion and the significant decrease in fasting urine calcium suggest the possibility of a beneficial impact of cinacalcet on bone remodeling.     

The effect of uraemia, acidosis, and dialysis treatment on protein metabolism: a longitudinal leucine kinetic study

Background: Uraemia and dialysis are viewed as catabolic processes resulting in malnutrition in chronic renal failure (CRF) patients. To sort out the effects of uraemia, acidosis, and dialysis on protein metabolism, we measured leucine flux in CRF patients before and after initiation of maintenance dialysis. Subjects and methods: Whole-body leucine flux was measured by primed-constant infusion of L[1-¹³C]leucine in nine CRF patients longitudinally; twice before and once after initiation of maintenance dialysis (D). Before dialysis, one leucine flux was measured when the patients were acidotic (A), and the other, when acidosis was corrected with NaHCO, (NA). Five normal subjects underwent one single leucine flux measurement to serve as control (N). Both patients and normal subjects consumed a constant diet for 6 days and leucine flux was measured on the 7th day 12 h post-absorption. Diet for the CRF patients was identical during the three periods. Plasma L[1-¹³C]leucine and L[1-¹³C]KIC were measured by gas chromatography/mass spectrometry and expired ¹³CO2 by isotope ratio spectrometry. Leucine kinetics were calculated using standard equations. Results: Plasma CO2 levels were 19, 26 and 31 mmol/l in A, NA and D periods respectively. All kinetic results (&mgr;mol/kg/h) are presented as means±SD in the order of A, NA, D, and N, and CRF values that are statistically different from N are identified (*). The amounts of leucine release from endogenous protein breakdown (Ra or Q) were 101±12* 95±9* 113±22 and 117±6. Leucine oxidation (C), quantities of leucine irreversibly oxidized to CO2, were 16.5±5.4, 9.7±3.7*, 12.3±3.0*, and 23.2±3.1. Leucine protein incorporation levels (S) were 85±10, 85±8, 101±19 and 94±6. The S of 101 in CRF patients at period D was statistically higher than those during A and NA periods. Conclusions: These data indicate that when acidosis was corrected, CRF patients adapted to lower protein intake by reducing amino-acid oxidation and protein degradation, and maintained protein synthesis at normal levels. Metabolic acidosis impaired the downregulation of amino-acid oxidation. Maintenance dialysis treatment longitudinally restored protein flux to normal and increased protein synthesis. The general notion that uraemia and dialysis are protein catabolic is not supported by this work.     

Protein and lipid metabolism in nephrotic infants on peritoneal dialysis after nephrectomy

Congenital nephrotic syndrome of the Finnish type (CNF) is associated with protein deficiency despite substantial protein supplementation in the nephrotic state before nephrectomy. Different protein intakes (2.5 vs. 3.7 g/kg per day) in hypoproteinaemic children on continuous cycling peritoneal dialysis (CCPD) were studied. Lipids were also measured to determine whether severe atherogenic abnormalities seen during nephrosis improved after nephrectomy. Growth was normal or became normal with both protein intakes. Serum pre-albumin and transferrin concentrations became normal. Total protein (57±3.0 vs. reference limits 60–75 g/l) and albumin (28±5.0 vs. reference limits 30–50 g/l) concentrations improved but remained below normal, even with the higher protein intake. Muscle mass determined by measuring femoral quadriceps muscle thickness using ultrasound was markedly reduced in all patients at nephrectomy. It improved (P<0.05) in all but 2 patients who had several bacterial infections, but reached normal level in only 3 patients within 6 months. Plasma total, very low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) triglyceride concentrations decreased (P<0.05,P<0.05 andP<0.01, respectively) and VLDL, LDL and high-density lipoprotein (HDL) particles contained less triglyceride than in the nephrotic state. HDL cholesterol concentrations increased by 28% [0.58±0.22 mmol/l during nephrosis, 0.81±0.21 mmol/l on CCPD after nephrectomy (P<0.05)] but remained below the level of 1.38±0.75 mmol/l in normal controls (P<0.001). If compared with controls there were still significant abnormalities in lipoprotein concentrations on CCPD. Hence, a protein intake of 2.5 g/kg per day representing 140% of the recommended dietary allowance is sufficient to maintain normal growth and improve nutritional and protein status in CNF patients on CCPD. Although lipid levels improved they remained abnormal.     

Parathyroid hormone decreases in vivo insulin effect on glucose utilization

Hyperparathyroidism is associated with impaired glucose tolerance, and parathyroidectomy may improve carbohydrate homeostasis. It has been suggested that parathyroid hormone (PTH) suppresses insulin secretion but it is unclear whether it also interferes with the peripheral action of insulin. To evaluate in vivo effects of PTH on insulinmediated glucose utilization, 15 male Sprague Dawley rats were continuously infused with rat PTH (1–34) using an Alzet miniosmotic pump at a rate of 0.03 nm/hour. Controls were infused with the vehicle alone. Following 5 days of PTH infusion, plasma calcium (Ca) levels were higher in the PTH-infused rats (12.3±0.2 versus 9.9±0.1 mg/dl, P<0.01). On the 5th day, glucose (700 mg/kg) and insulin (0.175 U/kg) were given as a bolus infusion through the left femoral vein, blood samples were obtained from the right femoral vein, and plasma glucose and insulin were measured at basal (0 minutes) and at 2, 5, 10, and 20 minutes postinfusion. Basal, nonfasting glucose levels were higher (166±4 versus 155±4 mg/dL, P<0.04) in the PTH-infused rats but their insulin levels were similar to those of controls (6.5±0.6 versus 5.6 ±0.5 ng/ml). Postinfusions and maximal (2 minutes) glucose and insulin levels were similar in both groups. However, although insulin levels were similar in both groups at all measured time points, glucose levels at 20 minutes were higher in the PTH-treated rats (205±13 versus 173±9; P<0.03). Also, calculated glucose disappearance rates (Kg) were decreased in the PTH-infused rats (4.05±0.3 versus 4.63±0.8; P=0.054), suggesting an impaired peripheral effect of insulin on glucose utilization. To gain insight into the potential contribution of the hypercalcemia or the PTH to these abnormalities, correlation evaluations were performed. Only in PTH-infused rats did plasma Ca correlate with plasma glucose at 0 and 20 minutes (r=0.6, P=0.02; r=0.7, P=0.01) and with the area under the glucose curve (r=0.6, P=0.03) during the glucose-insulin infusion. Also only in PTH-infused rats did PTH correlate with 0 (P=0.07) and 20-minute (P=0.02) plasma glucose levels. There was no correlation between either Ca or PTH and basal insulin levels or the area under the insulin curve in either group. Consequently, we suggest that in the rat, PTH infusion associated with hypercalcemia impairs insulin effect on glucose utilization in vivo and this defect may be induced by the Ca, PTH, or both.This study was presented in part at the 76th Annual Meeting of the Endocrine Society, Anaheim, CA, USA, June 1994.     

Acidosis increases magnesiuria in children with distal renal tubular acidosis

In experimental animals, metabolic acidosis increases renal magnesium (Mg) excretion, whereas metabolic alkalosis reduces it. The objective of this study was to examine renal magnesium handling (U_Mg) in children with primary distal renal tubular acidosis (DRTA). We measured U_Mg in 11 children (3 females, 8 males, aged 6.9±4.9 years) with primary DRTA. They were studied either during spontaneous acidosis post treatment removal (3 patients) or after ammonium chloride (100 mmol/m²) induced acidosis (8 patients), and then following oral sodium bicarbonate load (4 g/1.73 m²). During acidosis (plasma pH 7.28±0.09, bicarbonate 13.2±4.3 mEq/l), U_Mg was elevated (U_Mg/Cr 0.18±0.06 mg/mg, normal values 0.1±0.06, P =0.003) although plasma Mg (P_Mg) was in the normal range (1.93±0.31 mg/dl, controls 1.77±0.19, P =NS). After acute correction of metabolic acidosis (plasma pH 7.44±0.05, bicarbonate 25.6±1.6 mEq/l, P <0.001; urine pH 7.52±0.28, bicarbonate 86.9±39.1 mEq/l), U_Mg decreased significantly ( P =0.003), returning to control values after about 2 h (U_Mg/Cr 0.09±0.06 mg/mg). Bicarbonate load resulted not only in reduction in U_Mg but also in a decrease in urinary calcium excretion (U_Ca/Cr) from 0.46±0.17 mg/mg to 0.14±0.12 mg/mg ( P <0.001). We conclude that in children with primary DRTA, urinary Mg excretion is markedly increased and that this defect, like the hypercalciuric defect, is correctable by sodium bicarbonate administration.     

Prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women

Hypovitaminosis D can result in low bone mass. The prevalence of hypovitaminosis D has public health implications, especially where data are lacking. Since diet and sunlight are the two souces of vitamin D, the results obtained in one geographical region may not be universally applicable. The aim of this study is to characterize the prevalence and seasonal variation of hypovitaminosis D and its relationship to bone metabolism in community dwelling postmenopausal Hungarian women. We determined serum levels of 25-hydroxyvitamin D (25-OH-D), PTH, osteocalcin (OC), degradation products of C-terminal telopeptides of type-I collagen (CTx), dietary calcium intake and BMD at L2–L4 lumbar spine (LS) and femur neck (FN) in 319 randomly selected ambulatory postmenopausal women. The prevalence of hypovitaminosis D (serum 25-OH-D50 nmol/l) was 56.7%. On comparing patients with normal and low 25-OH-D, a significant difference was found in age (61.6±8.5 years versus 67.3±9.9 years; P<0.001), PTH (3.9±1.9 pmol/l versus 4.3±2.7 pmol/l; P<0.05), FN BMD (0.802±0.123 g/cm² versus 0.744±0.125 g/cm²; P<0.001) and dietary calcium intake (714.4±199.4 g/day versus 607.9±233 g/day; P<0.001). Osteoporotic patients had a significantly lower 25-OH-D (37.6±19.8 nmol/l versus 56.4±24 nmol/l; P<0.001) and dietary calcium intake (519.2±244.5 mg/day versus 718.2±164.3 mg/day; P<0.001). After controlling for all other variables, 25-OH-D was found to be significantly associated with age, the average hours of sunshine in the 3 months prior to 25-OH-D level determination and dietary calcium intake (r ²=0.190; P<0.001). For FN BMD, significant independent predictors were age, body mass index, 25-OH-D and dietary calcium intake (r ²=0.435; P<0.001). The prevalence of hypovitaminosis D during spring, summer, autumn and winter was 71%, 46.3%, 49.4% and 56.7%, respectively. There was significant seasonal variation in 25-OH-D, PTH, OC, calcium intake and FN BMD. There is a high prevalence of hypovitaminosis D in healthy postmenopausal Hungarian women, and FN BMD is associated with serum 25-OH-D and dietary calcium intake.     

Dialysis efficacy during acetate-free biofiltration

Background. Acetate-free biofiltration (AFB) is a haemodiafiltration technique based on continuous post-dilution infusion of a sterile isotonic bicarbonate solution. We performed a long-term randomized prospective trial to compare dialysis efficacy and metabolic control of AFB versus bicarbonate haemodialysis (HD). Methods. The AFB group consisted of 11 and the HD group of nine patients, matched for age, sex and urea reduction rate. Biochemical parameters were obtained every 3 months for 1 year (haemoglobin, calcium, phosphate, urea, pre- and post-dialysis bicarbonate, and parathormone (PTH)) and medication was updated. Efficacy of dialysis calculated by KT/V using the dialysate sampling method was determined every 3 months. In AFB patients, the infusion rate of bicarbonate solution was adjusted individually to obtain bicarbonate values of ⩾22 mmol/l before dialysis and ⩽32 mmol/l after dialysis. In the HD group, bicarbonate was added as oral medication to match these bicarbonate concentrations. Statistical analysis was performed using ANOVA for repeated measurements. Results. Pre-dialysis serum bicarbonate levels had risen to the same extent in both groups at the end of the study period (AFB from 21.8 to 26.1 mmol/l, P<0.001, and HD from 20.8 to 24.9 mmol/l, P<0.001). Post-dialysis bicarbonate level was higher in the AFB than in the HD group (P<0.01). Calcium and phosphate levels remained stable in both groups. PTH increased in both groups (AFB from 10.6 to 23.7 pmol/l, and HD from 24.6 to 32.8 pmol/l), with a significant rise only in the AFB patients (P<0.013). Finally, haemoglobin levels and erythropoietin dosage did not change in either group. No significant differences between the two groups were observed. Conclusions. Acidosis was better corrected in AFB without the need for oral supplementation of bicarbonate. However, neither serum calcium nor phosphate levels changed. The observed increase in PTH in the AFB group remains to be clarified. Dialysis efficacy, measured as KT/V, improved during AFB.     

Suramin administration is associated with a decrease in serum calcium levels

Suramin has been shown to have an effect on bone resorption in in vitro models. It is not clear if a similar effect is seen in patients treated with suramin. The clinical effect of suramin treatment on total serum calcium was examined in two groups of patients with hormone-refractory prostate cancer. In all, 28 patients in group 1 were examined within 2 weeks before and 2 weeks after suramin treatment and 72 patients in group 2 were examined within 2 weeks before, during, and after treatment with suramin. In addition, calcium controls spiked with suramin were run in three different commercially available assays for evaluation of the effect of suramin dose on calcium determination. Group 1 patients showed a decrease in serum calcium after treatment with suramin. The mean uncorrected serum calcium level was 2.29 ± 0.025 mmol/l before treatment and 2.09 ± 0.025 mmol/l after treatment (P < 0.0001, paired Wilcoxon test). The mean serum calcium value corrected for albumin was 2.33 ± 0.02 mmol/l before treatment and 2.24 ± 0.02 mmol/l after treatment (P=0.0022, paired Wilcoxon test). Group 2 patients also displayed a decrease in serum calcium after treatment with suramin. The mean baseline value was 2.23 mmol/l (median 2.26 mmol/l, range 1.20–2.54 mmol/l). The mean level of serum calcium corrected for albumin as determined at the end of treatment was 2.14 mmol/l (median 2.16 mmol/l, range 0.98–2.46 mmol/l). In all, 48 patients for whom pre- and posttreatment values were available for analysis displayed a median calcium decrease of 0.09 mmol/l (P=0.0005, Wilcoxon signed-rank test for the null hypothesis of no change). For 68 patients in group 2, data on serial serum calcium measurements during treatment were available for analysis. A projected median decrease in serum calcium of 0.06 mmol/l (range –0.43 to 0.72 mmol/l) over an 8-week interval of suramin therapy was found. Overall, 47 of the 68 slopes were negative (P=0.0022, Wilcoxon signed-rank test). Nine patients were treated with suramin for less than 6 weeks. These patients' calcium levels were significantly higher than those of 50 patients treated for longer periods (median value 2.24 versus 2.16 mmol/l, P=0.035, Wilcoxon rank-sum test). No correlation was found between suramin dose and calcium level using the Kodak Ektachem, Hitachi 914, or Synchron Clinical System CX3 method. In conclusion, suramin treatment was consistently associated with decreases in serum calcium in two groups of patients with hormone-refractory cancer. Suramin placed in calcium controls did not affect calcium determination using three commercially available methods.