Isolation, assay, and secretion of individual human neurophysins.

Human neurophysin was isolated from acetone-dried human posterior pituitaries and separated into two major neurophysin peptides by ion exchange chromatography and into four major peptides by preparative disk gel electrophoresis. Antisera raised in rabbits distinguished only two specific antigenic sites on the isolated neurophysin peptides. Individual sensitive and specific radioimmunoassays for two human neurophysins were developed. These assays were used to measure each neurophysin in unextracted human plasma. The two neurophysins are secreted independently in man. One assay measures a neurphysin that is specifically secreted in response to estrogen administration, estrogen-stimulated neurophysin (ESN). The other assay measures a neurophysin that is specifically secreted in response to cigarette smoking, nicotine-stimulated neurophysin (NSN). The mean ESN is 1.1 ng/ml plus or minus 0.7 SD in women and 1.0 ng/ml plus or minus 0.7 SD in men. The mean NSN is 0.9 ng/ml plus or minus 0.2 SD in women and 0.6 ng/ml plus or minus 0.3 SD in men. It is proposed that these may prove to be a specific human "oxytocinneurophysin," ESN, and a human "vasopressin-neurophysin," NSN.     

QT dispersion and signal-averaged electrocardiogram in hemodialysis and CAPD patients.

OBJECTIVE: The aim of this study was to compare QT dispersion (QTd) and signal-averaged electrocardiogram (SA-ECG) parameters that may predict risk of malignant arrhythmias in patients on hemodialysis (HD), on continuous ambulatory peritoneal dialysis (CAPD), and in controls. SETTING: Controlled cross-sectional study in a tertiary-care setting. PATIENTS: 28 HD (M/F 18/10; mean age 32 +/- 9 years), 29 CAPD (M/F 17/12; mean age 34 +/- 10 years), and 29 healthy controls (M/F 17/12; mean age 32 +/- 8 years) were included. INTERVENTIONS: On ECG, minimum (QTmin) and maximum (QTmax) QT duration and their difference (QTd) were measured. In SA-ECG, duration of filtered QRS, HFLA signals less than 40 microV, and RMS voltage (40 ms) were also measured. RESULTS: Higher serum Ca2+ and lower K+ levels were found in CAPD compared to HD. All QT parameters were increased in HD and CAPD compared to controls. QT dispersion was significantly prolonged in HD compared to CAPD. In HD, QTd was correlated with left ventricular (LV) mass index (r = 0.53, p = 0.004), but not in CAPD (r = -0.09, p = 0.63). QT dispersion was significantly prolonged in patients with LV hypertrophy compared to patients without hypertrophy on HD (68 +/- 18 ms vs 49 +/- 18 ms, p = 0.008). In the analysis of SA-ECG, 3 of the 28 (11%) HD and 2 of the 29 (7%) CAPD patients had abnormal late potentials. Patients on HD and CAPD had significantly higher filtered-QRS duration compared to controls (105 +/- 15 ms and 104 +/- 12 ms vs 95 +/- 5 ms, respectively, p = 0.04). Patients with LV hypertrophy had higher filtered-QRS duration compared to patients without hypertrophy (109 +/- 12 ms vs 95 +/- 8 ms, p < 0.001). CONCLUSION: Dialysis patients had prolonged QTd and increased filtered-QRS duration in SA-ECG compared to controls. Patients on HD had longer QTd than patients on CAPD. QTd has been correlated to LV mass index in HD, but not in CAPD. This difference might be due to the effect of different dialysis modalities on electrolytes, especially the higher serum Ca2+ levels.     

Comparative study between intact PTH and fragments of PTH in patients on hemodialysis and CAPD.

Twenty-nine patients on hemodialysis (HD) and 29 patients on continuous ambulatory peritoneal dialysis (CAPD) were studied. Serum calcium and phosphorous levels were similar in the 2 groups. Serum parathyroid hormone (PTH) levels were determined by 4 different methods. Mid-molecule PTH levels were higher in HD (1099.5 +/- 876.8 pmol/L) than in CAPD patients (541.0 +/- 138.8 pmol/L), p less than 0.001, while intact PTH levels were similar. The ratio MM-PTH/Intact PTH was higher in HD (55.2 +/- 29.0) than in CAPD patients (39.0 +/- 20.0), where p less than 0.01. In patients with similar C-PTH, those on CAPD had higher levels of intact PTH (46.0 +/- 27.0 pmol/L) than those in HD (29.3 +/- 29.0 pmol/L), p less than 0.01. The ratio C-PTH/intact PTH was higher in HD (104.9 +/- 39.6) than in CAPD patients (59.3 +/- 32.3), p less than 0.001. The Peritoneal Saturation Index (PSI) of MM-PTH was 23.4 +/- 12%, and it showed a hyperbolic correlation in respect to MM-PTH serum levels. We concluded that CAPD can modify the plasma C-PTH and MM-PTH serum levels by peritoneal losses of these fragments.     

Inadequate aldosterone response to hyperkalemia during angiotensin converting enzyme inhibition in chronic renal failure

To assess the mechanism involved in hyperkalemia during angiotensin converting enzyme inhibition with captopril in chronic renal failure, captopril, 150 mg/day, was administered to 16 patients with hypertension with plasma creatinine levels between 1.6 and 12.4 mg/dl. After 4 weeks of therapy, plasma potassium levels increased from 3.9 +/- 0.1 to 5.5 +/- 0.2 mEq/L (P less than 0.001) and the final plasma potassium levels correlated with plasma creatinine levels (r = 0.67; P less than 0.01). In six patients with plasma creatinine levels greater than or equal to 3 mg/dl, aldosterone excretion decreased after 4 weeks of captopril, from 7.5 +/- 3.1 to 1.8 +/- 0.5 micrograms/24 hr, whereas plasma renin activity increased from 0.6 +/- 0.2 to 4.4 +/- 1.1 ng/ml/hr (P less than 0.05). This was associated with increases in plasma potassium levels from 3.9 +/- 0.2 to 5.4 +/- 0.4 mEq/L (P less than 0.005) and a significant reduction in fractional excretion of potassium from an average of 34% to 25%. No significant changes in plasma creatinine levels were observed during therapy. There was a significant positive correlation between aldosterone excretion and the potassium excretion fraction (r = 0.53; P less than 0.01). Increases in plasma potassium levels were not able to increase aldosterone excretion, although the greater the plasma potassium level attained, the smaller the reduction in aldosterone excretion (r = 0.47; P less than 0.05). Our results indicate that adequate aldosterone production is essential to preserve potassium homeostasis in chronic renal failure. Moreover, angiotensin II appears necessary for an adequate aldosterone response to potassium stimulation.     

Increased elastase-alpha 1-antitrypsin complex in fulminant hepatic failure: relationship to bacterial infection and activation of coagulation.

To study the effect of infection, a frequent complication of fulminant hepatic failure (FHF), on the release of elastase from polymorphonuclear leucocytes and its inhibition in circulation we have measured the concentrations of alpha 1-antitrypsin, which binds and inhibits elastase in the circulation, and of elastase-alpha 1-antitrypsin complex, in 30 patients with FHF. Elastase-alpha 1-antitrypsin complex was significantly increased in FHF as compared to controls (303 +/- 51 micrograms/l compared to 37 +/- 5 micrograms/l; n = 10; P less than 0.001) demonstrating activation of leucocytes in FHF. Infection caused greater release of leucocyte elastase, complex levels were significantly greater in patients who were infected when compared to those who were not (463 +/- 84 micrograms/l; n = 13 compared to 180 +/- 46 micrograms/l; n = 17; P less than 0.01). Also patients who survived had significantly lower complex levels than those who did not (212 +/- 49 micrograms/l; n = 18 compared to 440 +/- 94 micrograms/l; n = 12; P less than 0.02). alpha 1-Antitrypsin activity was not significantly different from control subjects (0.99 +/- 0.06 U/ml compared to 0.97 +/- 0.05 U/ml). However alpha 1-antitrypsin activity was significantly higher in patients who survived (1.17 +/- 0.05 U/ml; n = 18) compared to those who did not (0.71 +/- 0.03 U/ml; n = 12; P less than 0.001) and patients who died had significantly lower levels than control subjects (P less than 0.01) indicating the importance of maintenance of normal inhibitor levels in patients with FHF. The leucocyte activation and release of elastase in FHF was linked to activation of the coagulation system; elastase--alpha 1-antitrypsin complex levels correlated significantly with thrombin-antithrombin III complex levels (r = 0.68; P less than 0.001) and inversely with fibrinogen (r = -0.71; P less than 0.001).     

Continuous ambulatory peritoneal dialysis is responsible for an increase in plasma norepinephrine.

OBJECTIVE: To investigate the reason for increasing norepinephrine (NE) levels reported in continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: Norepinephrine was measured in the plasma and peritoneal dialysate of CAPD patients (n = 22) and in the plasma and the urine of healthy subjects (n = 20). It was also measured in the plasma of patients with chronic renal failure (CRF) (n = 15) and patients on hemodialysis (HD) (n = 15). RESULTS: It was found that NE was increased in CAPD patients compared with healthy individuals (687+/-221 pg/mL vs 199+/-25 pg/mL, p < 0.01).The daily removal of NE from the peritoneum of CAPD patients was lower compared with the amount of NE excreted in the urine of healthy subjects. Plasma NE increased after infusion of peritoneal dialysate. In 15 new patients on CAPD, it was found that NE plasma levels increased from 329+/-67 pg/mL before initiation of dialysis, to 584+/-173 pg/mL after 12 months of treatment (p < 0.01). Finally, plasma NE in CAPD patients (687+/-221 pg/mL) was significantly higher compared with the already increased levels in patients on HD or with CRF (406+/-143 pg/mL and 378+/-142 pg/mL, respectively). CONCLUSIONS: It is concluded that CAPD in patients with end-stage renal disease is responsible for a progressive increase of plasma norepinephrine.     

Evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D in man.

Recent studies provide evidence for extrarenal production of 1 alpha ,25-dihydroxyvitamin D [1 alpha ,25(OH)2D]. To investigate this possibility, serum vitamin D, 25-hydroxyvitamin D (25-OHD), 24,25-dihydroxyvitamin D [24,25(OH)2D], and 1 alpha ,25(OH)2D were measured in eight adult anephric subjects. All were undergoing hemodialysis and three of them were receiving vitamin D, 50,000 or 100,000 U/d. Serum vitamin D was elevated in two of the patients given vitamin D and was abnormally low in the others. Mean serum 25-OHD was increased in patients given vitamin D (94.0 +/- 7.6 ng/ml) and was normal in the others (16.4 +/- 0.9 ng/ml, P less than 0.001). Mean serum 24,25(OH)2D was normal in patients given vitamin D (1.38 +/- 0.27 ng/ml) and was low in the others (0.25 +/- 0.08 ng/ml, P less than 0.001). Serum 24,25(OH)2D correlated significantly with serum 25-OHD (r = 0.848, P less than 0.01). Mean serum 1 alpha ,25(OH)2D determined by receptor assay was 5.8 +/- 1.9 pg/ml in patients who were not given vitamin D and was 14.1 +/- 0.6 in those who were given vitamin D (P less than 0.001). Serum 1 alpha ,25(OH)2D correlated significantly with serum 25-OHD (r = 0.911, P less than 0.01). Mean serum 1 alpha ,25(OH)2D, measured by bioassay, was 8.3 +/- 1.9 pg/ml in patients who were given vitamin D and was 15.9 +/- 2.4 pg/ml in those who were given vitamin D (P less than 0.05). There was a significant correlation between the values for serum 1 alpha ,25(OH)2D obtained with the two methods (r = 0.728, P less than 0.01). The results (a) provide evidence in man for extrarenal production of both 24,25(OH)2D and, by two independent assays, of 1 alpha , 25(OH)2D, and (b) indicate that serum values of the two dihydroxy metabolites of vitamin D in anephric subjects vary with the serum concentration of the precursor 25-OHD.     

Erythrocyte glutathione peroxidase activity,plasma malondialdehyde and erythrocyte glutathione levels in hemodialysis and CAPD patients

OBJECTIVES: Cardiovascular disease is the major cause of mortality in patients receiving hemodialysis (HD) and continuous ambulatory peritoneal dialysis (CAPD) due to chronic renal failure. Increased lipid peroxidation and depletion of antioxidants may contribute to increased risk of atherosclerosis. We have therefore assessed the effect of hemodialysis and CAPD on oxidant and antioxidant status. DESIGN AND METHODS: Plasma malondialdehyde (MDA), Glutathione (GSH) levels and glutathione peroxidase (Gpx) activities were determined in 20 healthy persons (control), 20 patients on HD, 16 patients on CAPD. RESULTS: MDA was elevated in posthemodialysis and CAPD patients in comparison to prehemodialysis and control groups (posthemodialysis 1.39 +/- 0.38 nmol/mL, CAPD 1.26 +/- 0.27 nmol/mL, prehemodilaysis 0.83 +/- 0.22 nmol/mL, controls 0.72 +/- 0.21 nmol/mL p < 0.0001). With respect to antioxidants, glutathione levels were significantly lower in prehemodialysis, posthemodialysis and CAPD groups than those in control group (prehemodialysis 16.82 +/- 6.73 mg/dL RBC, posthemodialysis 31.43 +/- 11.88 mg/dL RBC, CAPD 40 +/- 12.72 mg/dL RBC, controls 62.26 +/- 24.01 mg/dL RBC, p < 0.0001). While erythrocyte GSH levels were significantly lower in the prehemodialysis patients than those in posthemodialysis and CAPD patients (p < 0.0001), it was significantly lower in posthemodialysis patients than those in CAPD patients (p < 0.05). There were no significant differences with respect to erythrocyte Gpx levels among the groups (p > 0.05). CONCLUSIONS: These findings indicate oxidative stress in patients with chronic renal failure which is further exacerbated by hemodialysis and CAPD, as evidenced by increased lipid peroxidation and low antioxidant levels.     

Plasma concentrations of atrial natriuretic peptide in various diseases

Using a radioimmunoassay for atrial natriuretic peptide (ANP) we studied plasma concentrations of immunoreactive ANP in order to investigate the pathophysiological role of ANP in patients with various diseases. Plasma ANP levels were elevated in patients with congestive heart failure (394 +/- 260 pg/ml, n = 8) and chronic renal failure (219 +/- 86 pg/ml, n = 11). In patients undergoing hemodialysis plasma ANP levels were markedly high and decreased after hemodialysis from 433 +/- 166 pg/ml to 204 +/- 92 pg/ml (n = 11). ANP was removed from blood to dialysate (21 +/- 13 pg/ml of dialysate, n = 6, dialysate flow: 500 ml/min). Plasma ANP level was conversely correlated with creatinine clearance (r = -0.812, p less than 0.001) in patients with renal diseases (n = 29). In patients with atrial fibrillation, pace maker implantation, lung disease, chronic glomerulonephritis, nephrotic syndrome, essential hypertension, liver disease and cerebrovascular disease, plasma ANP levels were not significantly different from those in normal subjects (70 +/- 32 pg/ml, n = 28). These results suggest that ANP may be a circulating hormone playing pathophysiological roles in congestive heart failure and chronic renal failure.     

Pharmacokinetics of esmolol and ASL-8123 in renal failure

The effect of renal function on the pharmacokinetics of esmolol, an ultra-short-acting beta-adrenergic blocker, and its major metabolite, ASL-8123, was examined in six healthy control subjects, six patients maintained on hemodialysis, and six patients on continuous ambulatory peritoneal dialysis (CAPD). In addition, the impact of hemodialysis and CAPD on removal of esmolol and ASL-8123 was determined. Multiple blood, urine, and dialysate samples were collected during a 72-hour period and assayed for esmolol and ASL-8123 by HPLC. The pharmacokinetic disposition of esmolol was not significantly altered by renal failure. Mean (+/- SD) total body clearance for esmolol was 171.4 +/- 69.8, 249.8 +/- 176.3, and 265.3 +/- 143.1 ml/min/kg for the control, hemodialysis, and CAPD patients, respectively. Mean elimination half-life (t1/2) was 7.2 minutes in control subjects compared with 7.1 and 8.0 minutes for the hemodialysis and CAPD groups, respectively. The apparent volume of distribution of esmolol did not differ significantly among the three groups. ASL-8123 was shown to accumulate in patients with renal failure, as evidenced by a mean maximum blood concentration of 42.8 +/- 12.2 micrograms/ml in the control group compared with 76.1 +/- 23.9 and 87.1 +/- 20.4 micrograms/ml in the hemodialysis and CAPD groups, respectively (p less than 0.05). The elimination t1/2 of ASL-8123 was prolonged in patients with renal failure, averaging more than 42 hours compared with only 4 hours in the control subjects. Approximately 20% of the esmolol dose as ASL-8123, was removed by either hemodialysis or CAPD, contributing minimally to the elimination of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of hemostatic disturbances between patients on CAPD and patients on hemodialysis.

OBJECTIVE: Disturbances in hemostasis are common findings in uremic patients. Both bleeding diathesis and thrombosis are observed. The purpose of this study was to assess whether renal replacement therapy in the form of hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) affects coagulation and fibrinolysis in patients with end-stage renal failure. DESIGN: Comparison of hemostatic measures in patients on CAPD, HD, and matched healthy controls. SETTING: Department of Nephrology and Internal Medicine, Bialystok University School of Medicine. PATIENTS AND METHODS: Twenty-four HD patients and 23 CAPD patients were evaluated with respect to platelet aggregation, hemostatic parameters, serum lipids, lipoprotein(a), and cytokines [tumor necrosis factor alpha (TNFalpha) and interleukin-1 (IL-1)]. INTERVENTIONS: Four exchanges of CAPD per day, using 2.0 L dialysate over a period of 25 +/- 31 months; or 4-5 hours of HD 3 times per week for a period of 31 +/- 22 months. RESULTS: Platelet aggregation in whole blood and platelet-rich plasma was significantly impaired in both groups of dialyzed patients compared to healthy volunteers. Markers of endothelial cell injury (thrombomodulin and von Willebrand factor) were significantly higher in HD and CAPD patients compared to the control group. A similar pattern of changes was observed for lipoprotein(a), fibrinogen, tissue factor pathway activity, and factor VII activity. Activity of factor X was significantly enhanced in CAPD compared to HD patients and controls. Euglobulin clot lysis time was significantly prolonged in HD and CAPD patients over controls, being more prolonged in CAPD patients. Markers of ongoing coagulation (thrombin-antithrombin complexes and prothrombin fragments 1+2) were higher in uremic patients, significantly higher in CAPD than in HD. A marker of ongoing fibrinolysis (plasmin-antiplasmin complexes) was higher in uremic patients but was lower in CAPD than in HD patients. Concentrations of TNFalpha and IL-1 were higher in HD than in CAPD patients. CONCLUSION: Patients on CAPD showed evidence of a higher degree of hypercoagulation than HD patients.Thus, hemostatic abnormalities in end-stage renal failure may be affected to some extent by the choice of renal replacement therapy.     

Plasma bone Gla protein concentrations in healthy adults. Dependence on sex, age, and glomerular filtration

Plasma bone Gla protein (BGP) was determined by radio-immunoassay in 266 healthy adults, men (n = 132) and women (n = 134), aged 20-79 years. In the women aged 30-69 years, plasma BGP increased significantly with age (r = 0.44, p less than 0.001), and a particularly steep increase was seen from 1.1 +/- 0.5 (mean +/- 1 SD) in the fifth decade to 2.0 +/- 1.4 nmol/l in the seventh decade. In men, aged 30-69 years, no correlation was found between plasma BGP and age (r = -0.07, NS). Plasma bone Gla protein is removed from the circulation mainly by the kidneys and the increased plasma BGP in the women could be caused by decreased renal clearance. The interrelationship was analysed by means of partial correlation. When creatinine clearance was held constant in women, BGP still correlated positively with age (r = 0.40, p less than 0.001), but not with creatinine clearance (r = 0.003, NS) when age was fixed. Plasma BGP was significantly increased above normal in 35 patients with chronic renal failure (10.2 +/- 14.6 nmol/l). Non-linear regression analysis showed that plasma BGP was within the normal range when 24-h creatinine clearance was greater than 30 ml/min, and large increases in plasma BGP did not occur until the 24-h creatinine clearance was below 20 ml/min. We conclude that, in normal subjects and patients with mild to moderate renal failure, plasma elevations of BGP reflect increased bone turnover rather than decreased renal clearance.     

Pharmacokinetics of cefodizime in normal individuals and in patients with renal failure

The pharmacokinetics of cefodizime (HR 221) were studied in 6 healthy male individuals and 12 male patients with various degrees of chronic renal failure following intravenous bolus injection of 1 g of the drug. Serum pharmacokinetics were described by an open two-compartment kinetic model. The serum levels of cefodizime exceeded the MIC90 for Enterobacteriaceae, Haemophilus influenzae and Neisseria gonorrhoeae for more than 12 h in healthy individuals and 24 h in renal failure patients. The half-life of elimination was significantly prolonged (p less than 0.001) from 2.7 +/- 0.2 h in healthy volunteers to 7.7 +/- 1.5 h in renal failure patients. The total systemic clearance decreased significantly (p less than 0.001) from 43.3 +/- 5.8 ml/h/kg in healthy volunteers to 23.2 +/- 5.6 ml/h/kg in renal failure patients. A linear correlation (r = 0.9; p less than 0.001) was found between creatinine clearance and the total systemic clearance of cefodizime. The AUC0-infinity in patients with renal failure was more than double the value in healthy volunteers. An equation to calculate the 1-gram dose interval of cefodizime in patients with compromised renal function is provided.     

Improvement of glycemic control by 1 year of insulin therapy leads to a sustained decrease in sE-selectin concentrations in type 2 diabetes

OBJECTIVE: To examine whether and how improvement of glycemic control by long-term insulin therapy decreases endothelial activation as measured by serum levels of the soluble adhesion molecules sE-selectin and vascular cell adhesion molecule (VCAM-1) and whether the drug used to lower blood glucose in addition to insulin influences such a response. RESEARCH DESIGN AND METHODS: Circulating adhesion molecules were measured before and after 3 and 12 months of therapy in 81 patients with type 2 diabetes and 41 subjects without diabetes. The patients were treated with bedtime administration of NPH insulin combined with either glibenclamide (n = 19), metformin (n = 17), glibenclamide and metformin (n = 17), or morning administration of NPH insulin (n = 23). RESULTS: Before insulin therapy, serum sE-selectin level was 71% higher in the patients with type 2 diabetes (77 +/- 4 ng/ml) than in the normal subjects (45 +/- 3 ng/ml, P < 0.001), whereas levels of sVCAM-1 were comparable (420 +/- 25 vs. 400 +/- 11 ng/ml, respectively). Glycemic control in all patients improved as judged from a decrease in HbA1c from 9.7 +/- 0.2 to 7.6 +/- 0.1% (P < 0.001). sE-selectin decreased to 67 +/- 4 ng/ml by 3 months (P < 0.001 vs. 0 months) and then remained unchanged until 12 months (70 +/- 4 ng/ml P < 0.001 vs 0 months). sVCnM-1 levels at 12 months was similar to those at 0 months (416 +/- 25 ng/ml). The change in glycemic control, measured by HbA1c, but not in other parameters, was correlated with the change of sE-selectin (r = 0.41, P < 0.001) within the patients with type 2 diabetes. The decreases in sE-selectin were not different between the various treatment groups. CONCLUSIONS: We conclude that improvement in glycemic control by administration of insulin alone or insulin combined with either glibenclamide, metformin, or both agents induces a sustained decrease in sE-selectin, the magnitude of which seems to be dependent on the degree of improvement in glycemia. These data suggest that sE-selectin might provide a marker of effects of treatment of chronic hyperglycemia on endothelial activation.     

Plasma aluminum levels in pediatric dialysis patients: comparison of hemodialysis and continuous ambulatory peritoneal dialysis

Accumulation of aluminum occurs in children with renal failure and can cause anemia, disabling osteodystrophy, and encephalopathy. Effects on bone mineralization are of particular concern in pediatric patients with growth potential. We measured plasma aluminum levels in 36 patients on continuous ambulatory peritoneal dialysis (CAPD) and 22 on hemodialysis under surveillance at a single pediatric center. The levels were above normal in 35 and 21 patients, respectively, and the values correlated with the oral dose of aluminum-containing phosphate-binding medications (r = 0.57; P less than 0.001). Younger and smaller children had higher plasma aluminum levels and also received larger doses of oral aluminum-containing compounds. Mean plasma aluminum levels (57.2 +/- 52.8 and 48.7 +/- 32.1 micrograms/liter, respectively) and the daily oral doses of elemental aluminum (47.3 +/- 37.6 and 39.2 +/- 26.7 mg/kg, respectively) were not statistically different in patients on CAPD and those on hemodialysis. Plasma aluminum levels did not correlate with estimated cumulative oral intake of aluminum, total duration of dialysis, serum calcium and phosphorus concentrations, N-terminal parathyroid hormone levels, or transfusion requirements. Retention of aluminum is common in children undergoing dialysis, correlates with the amount of aluminum administered orally, and results in similar elevations of plasma aluminum with CAPD and hemodialysis. Younger and smaller children are at increased risk for accumulation of aluminum. Alternative methods for control of serum phosphorus are needed in children with end-stage renal disease.     

Red blood cell calcium level in chronic renal failure: effect of continuous ambulatory peritoneal dialysis

Red blood cell (RBC) calcium, calcium 45 influx, and calcium extrusion as indicated by Ca-stimulated, Mg-dependent adenosine triphosphatase (CaATPase) was determined in patients with chronic renal failure (CRF), patients with CRF receiving continuous ambulatory peritoneal dialysis (CAPD) treatment, and controls. Cell calcium, which in the controls was 5.5 mumol/L of cells, was elevated in patients with CRF--30.6 +/- 6.8 mumol/L of cells (p less than 0.002)--and in patients receiving CAPD-23.6 +/- 6.7 mumol/L of cells (p less than 0.02). Basal CaATPase activity in controls was 850.7 +/- 66.7 nmol inorganic phosphate per milligram of protein per hour. It was suppressed in patients with CRF and patients receiving CAPD: 504.9 +/- 34.4 nmol inorganic phosphate per milligram of protein per hour and 618.2 +/- 47.3 nmol inorganic phosphate per milligram of protein per hour, respectively (p less than 0.01). Calmodulin-stimulated CaATPase revealed a pattern similar to that of CaATPase basal activity. RBC calcium showed an inverse correlation with CaATPase activity (r = -0.935, p less than 0.005) in patients with CRF. Calcium influx was increased in patients with CRF and in patients receiving CAPD: 12.00 +/- 1.34 mumol/L of cells per hour and 13.60 +/- 1.70, respectively, compared with 4.61 +/- 0.39 mumol/L of cells per hour in controls (p less than 0.001). Patients with CRF have elevated RBC calcium levels mainly related to decreased extrusion and to increased influx. CAPD fails to improve substantially these abnormalities. Plasma vanadium levels were markedly elevated in patients undergoing hemodialysis and marginally in patients receiving CAPD.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma free amino acids and their metabolites in Taiwanese patients on hemodialysis and continuous ambulatory peritoneal dialysis

BACKGROUND: The high prevalence of protein-energy malnutrition is a critical issue for patients with end stage renal disease (ESRD) on hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Levels of plasma and intracellular amino acids are significant indicators of protein metabolism and nutritional status assessment. We measured plasma FAAs in patients on maintenance dialysis and to provide information in monitoring the therapeutic strategy, particularly in AA supplementary therapy or protein restriction. METHODS: Fifty-five patients with ESRD were investigated, 25 on HD (male : female=14 : 11; 48-67 y) and 30 on CAPD (male : female=17 : 13; 45-64 y). The subjects had been on dialysis for an average of 13 months (range, 9 to 22 months). Their plasma FAAs (including their intermediate metabolites) were measured by ion exchange chromatography before and after HD or during CAPD and were compared with data obtained from 20 age- and sex-matched healthy controls. RESULTS: The total plasma FAA levels (urea and free ammonia, NH3 were excluded) in pre-HD samples (3911 +/- 709 micromol/l) was significantly higher than in the other groups (2570 +/- 378 in control, 3210 +/- 640 in post-HD, and 3468 +/- 271 in CAPD samples). The mean plasma FAA concentrations differed significantly between pre-HD and controls and between pre-HD and CAPD samples (p<0.05). No significant differences were found among the other group comparisons. Comparing individual FAA concentrations, only citrulline differed significantly among all groups (p<0.05), whereas serine, glutamine, beta-alanine, beta-aminoisobutyric acid, and gamma-aminobutyric acid were not different. Concentrations of some FAAs involved in the urea cycle, e.g., arginine, aspartic acid, citrulline, and ornithines, and solutes urea and NH3, were significantly increased. Ratios of tyrosine/phenylalanine and valine/glycine ratios were markedly reduced in all patients on dialysis compared with controls. CONCLUSION: FAAs either from dietary uptake or protein catabolism are substantially retained in the plasma of patients with ESRD, possibly producing higher levels of the waste products (urea and NH3) through the urea cycle and ammonia metabolism in liver. Maintenance dialysis can effectively eliminate excess FAAs in plasma, as there was a 17.9% reduction post-HD. The abnormalities in FAA metabolism found in patients with ESRD necessitate careful consideration of dialysis and dietary measures.     

Pharmacokinetics of cefoperazone (2.0 g) and sulbactam (1.0 g) coadministered to subjects with normal renal function, patients with decreased renal function, and patients with end-stage renal disease on hemodialysis.

The single-dose pharmacokinetics of intravenously administered cefoperazone (2.0 g) and sulbactam (1.0 g) were studied in normal subjects and in patients with various degrees of renal failure. In an open, parallel experimental design, six normal subjects (creatinine clearance, greater than 90 ml/min), two patients with mild renal failure (creatinine clearance, 31 to 60 ml/min), eight patients with moderate renal failure (creatinine clearance, 7 to 30 ml/min), and four functionally anephric patients (creatinine clearance, less than 7 ml/min) were studied. The functionally anephric patients were given two test doses to allow study of drug disposition both on and off hemodialysis. Serial blood and urine samples were collected from time zero to 12 h after dosing in normal subjects and from 0 to 72 h in renal patients. Serum concentrations of both drugs declined biexponentially. For cefoperazone, the terminal elimination half-lives averaged from 1.6 to 3.0 h and were similar in subjects and patients. No cefoperazone pharmacokinetic parameters were appreciably altered by renal failure or hemodialysis, and there was no correlation between the total body clearance of cefoperazone and estimated creatinine clearance. In contrast, the sulbactam total body clearance was highly correlated with estimated creatinine clearance (r = 0.92, P less than 0.01) and was significantly higher in normal volunteers than in the renally impaired groups (P less than 0.01). The sulbactam terminal elimination half-life in functionally anephric patients (9.7 +/- 5.3 h) differed significantly from that of normal volunteers (1.0 +/- 0.2 h) and patients with mild renal failure (1.7 +/- 0.7 h, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of active vitamin D3 and parathyroid hormone on the serum osteocalcin in idiopathic hypoparathyroidism and pseudohypoparathyroidism.

Serum osteocalcin was measured in patients with idiopathic hypoparathyroidism or pseudohypoparathyroidism, before or during the treatment with active vitamin D3 (1,25(OH)2D3 or 1 alpha OHD3). Serum osteocalcin and plasma 1,25(OH)2D were decreased in 11 patients with idiopathic hypoparathyroidism before treatment (2.8 +/- 1.27 ng/ml, P less than 0.001 and 14.3 +/- 4.27 pg/ml, P less than 0.001, respectively). In 24 patients with idiopathic hypoparathyroidism during the treatment, serum osteocalcin and plasma 1,25(OH)2D were within the normal range (4.5 +/- 0.74 ng/ml and 25.7 +/- 5.69 pg/ml, respectively). In five patients with pseudohypoparathyroidism before treatment, plasma 1,25(OH)2D was decreased (15.6 +/- 10.6 pg/ml, P less than 0.001) but serum osteocalcin was normal (7.8 +/- 1.66 ng/ml). In nine patients with pseudohypoparathyroidism during the treatment with active vitamin D3, serum osteocalcin and plasma 1,25(OH)2D were normal (6.8 +/- 1.47 ng/ml and 27.2 +/- 6.0 pg/ml, respectively). Serum PTH in pseudohypoparathyroidism was increased before treatment (0.70 +/- 0.34 ng/ml, P less than 0.05) and was normal during the treatment (0.50 +/- 0.13 ng/ml). In idiopathic hypoparathyroidism, the active vitamin D3 increased serum osteocalcin without PTH. In pseudohypoparathyroidism, PTH may increase serum osteocalcin or modulate the effect of active vitamin D3 on serum osteocalcin.     

Plasma levels of endothelin in chronic renal failure and after renal transplantation: impact on hypertension and cyclosporin A-associated nephrotoxicity.

1. Plasma levels of endothelin were measured in 30 patients with chronic renal failure, 32 patients on chronic haemodialysis treatment and 25 renal graft recipients with stable renal graft function. 2. In patients with chronic renal failure as well as in patients on regular haemodialysis treatment, mean plasma levels of endothelin were significantly increased (4.59 +/- 2.09 pg/ml, 10.08 +/- 3.12 pg/ml, respectively) when compared with normal subjects (1.88 +/- 0.6 pg/ml, P less than 0.01, P less than 0.001, respectively). 3. In the group with chronic renal failure a positive correlation between the plasma level of endothelin and the plasma concentration of creatinine was observed (P less than 0.003). 4. Renal graft recipients on cyclosporin A with stable renal graft function had a normal plasma level of endothelin suggesting that cyclosporin A nephrotoxicity is not mediated by endothelin. 5. Hypertensive patients with chronic renal failure or on regular haemodialysis and hypertensive renal graft recipients did not differ from the corresponding normotensive population with regard to the plasma level of endothelin, demonstrating that an increased plasma level of endothelin does not play a major role in the pathogenesis of renal hypertension.