Carnitine status of pediatric patients on continuous ambulatory peritoneal dialysis

Plasma carnitine and the effect of oral carnitine supplementation on serum triglycerides was studied in 12 pediatric patients receiving continuous ambulatory peritoneal dialysis (CAPD). Baseline evaluation of all patients included plasma carnitine and serum triglyceride values. Following randomization into two groups, only group 2 patients received oral L-carnitine supplementation, 100 mg/kg/day, for 2 months. The initial laboratory evaluation was repeated at the conclusion of the study. Plasma carnitine values were also determined from a control population. Mean baseline plasma carnitine concentrations of group 1 (39.8 +/- 8.0 nmol/ml) and group 2 (45.2 +/- 10.3 nmol/ml) patients were not significantly different from each other or from the control population. Serum triglyceride values were elevated in both groups (group 1 - 206.5 +/- 100.0 mg/dl; group 2 - 279.3 +/- 74.5 mg/dl). After 2 months, the mean plasma carnitine concentration of group 2 patients increased to 147.7 +/- 84.1 nmol/ml, significantly greater than the value of group 1, 32.8 +/- 8.0 nmol/ml (p less than 0.004). However, no significant change in the serum triglyceride level was noted in either group. We conclude that the plasma carnitine status of pediatric patients receiving CAPD is normal and that oral carnitine supplementation does not lead to the resolution of hypertriglyceridemia.     

Renal handling of silicon in normals and patients with renal insufficiency.

We have compared the renal handling of silicon in 16 patients with renal insufficiency to 14 normal individuals. Silicon, phosphate and creatinine were measured in plasma and urine samples. The renal insufficiency group showed significant increases in plasma silicon (1.28 +/- 0.19 vs. 0.17 +/- 0.03 mg/liter), creatinine (5.19 +/- 0.85 vs. 0.89 +/- 0.03 mg/dl) and phosphate (1.33 +2- 0.11 vs. 1.07 +/- 0.4 mmol/liter). Fractional phosphate excretion was increased in the renal insufficiency group (0.55 +/- 0.07 vs. 0.14 +/- 0.01). In contrast, the fractional excretion of ultrafiltrable silicon was not significantly different between groups (0.78 +/- 0.07 vs. 0.87 +/- 0.06). It is concluded that renal insufficiency does not alter the tubular handling of silicon and that regulatory control of silicon excretion is unlikely.     

Effect of chronic theophylline administration on amphotericin B nephrotoxicity in rats

The effect of chronic theophylline administration on amphotericin B nephrotoxicity was investigated in rats. A 7-day treatment of amphotericin B (5 mg/kg/day i.p.) significantly reduced the glomerular filtration rate (GFR) measured as inuline clearance and creatinine clearance (0.74 +/- 0.29 and 0.16 +/- 0.04 ml/min, respectively) in comparison to vehicle-treated rats (2.04 +/- 0.23 and 1.29 +/- 0.19 ml/min, respectively). The reduced GFR led to evaluations in serum creatinine and BUN concentrations (0.94 +/- 0.09 and 78 +/- 11 mg/dl) in comparison to their own values before treatment (0.45 +/- 0.11 and 19 +/- 3 mg/dl). In addition amphotericin B induced an increase in sodium and a decrease in potassium excretion, the fractional sodium excretion was elevated 50-fold. The methylxanthine, theophylline, had a beneficial effect on the outcome of amphotericin-B-induced renal failure. The inuline clearance was 1.17 +/- 0.04 ml/min, the creatinine clearance 0.43 +/- 0.03 ml/min, the serum creatinine concentration 0.76 +/- 0.05 mg/dl and the BUN concentration 40 +/- 6 mg/dl. Theophylline had no effect on total sodium excretion and potassium excretion. The fractional sodium excretion, however, improved significantly. Theophylline as well as sodium deoxycholate, the detergent of amphotericin B, given alone had no effect on renal hemodynamics measured after 7 days.     

Growth hormone secretion from pituitary cells in chronic renal insufficiency.

To examine whether growth hormone (GH) secretion is adversely affected by chronic renal insufficiency (CRI), the GH secretory response of dispersed anterior pituitary cells perifused with GH-releasing hormone (GHRH) was investigated in 5/6 nephrectomized (CRI, N = 18) and sham-operated (N = 18) rats. Two weeks after nephrectomy, during a period of stable uremia, CRI rats had significantly higher serum concentrations (mean +/- SEM) of urea nitrogen and creatinine than sham rats, 16.8 +/- 1.4 mmol/liter (47 +/- 4 mg/dl) and 79.6 +/- 0.0 mumol/liter (0.9 +/- 0.0 mg/dl) versus 6.1 +/- 0.4 mmol/liter (17 +/- 1 mg/dl) and 35.4 +/- 0.0 mumol/liter (0.4 +/- 0.0 mg/dl), respectively (P less than 0.0001). Incremental gains in body weight and nose to tail-tip length of CRI rats over two weeks were also significantly depressed, 53.3 +/- 5.38 g (CRI) versus 87.0 +/- 3.78 g (sham; P less than 0.0001) and 3.2 +/- 0.2 cm (CRI) versus 3.6 +/- 0.1 cm (sham; P less than 0.05). The cumulative food intake as well as food efficiency (g food consumed/g weight gain) were also adversely influenced by the uremic state: food intake 304 +/- 1 g (CRI) versus 397 +/- 6 g (sham; P less than 0.0001) and food efficiency 0.173 +/- 0.013 g/g of weight gain (CRI) versus 0.219 +/- 0.008 g/g of weight gain (sham). No significant difference in GH secretory rate (ng/min/10(7) cells) was found between the uremic and sham animals under basal conditions, 65.2 +/- 2.1 (CRI) and 67.9 +/- 2.2 (sham) or in response to GH-releasing hormone, 282.8 +/- 42.4 (CRI) versus 306.2 +/- 42.6 (sham).(ABSTRACT TRUNCATED AT 250 WORDS)     

The metabolic effects of oral L-carnitine administration in infants receiving total parenteral nutrition with fat

beta-Oxidation, an important pathway in the metabolism of free fatty acids, occurs within the mitochondria in mammals. L-Carnitine is an essential cofactor in the transfer of long-chain fatty acids across the inner mitochondrial membrane. Maintenance of normal carnitine concentrations in whole blood and tissues, either through diet or biosynthesis, would appear necessary for adequate utilization of fat as an energy source. Infants, especially premature ones, without an exogenous dietary source of carnitine, have decreased plasma carnitine levels compared with infants receiving carnitine-supplemented feedings. To determine the importance of carnitine supplementation in a total parenteral nutrition program in infants in which a fat emulsion serves as a major calorie source, the following study was undertaken. Twelve infants receiving total parenteral nutrition (TPN) with fat for seven days were divided into two treatment groups. Group 1 was orally supplemented for seven days with carnitine (70 mumol/l/kg/24 h in 24 mL of 5% dextrose), while the second group received seven days of placebo supplementation (dextrose 5%, 24 cc/24 h). Plasma carnitine levels in the carnitine-supplemented group were significantly higher (29 +/- 8 nmol/mL) than in the control group (12.4 +/- 3.5 nmol/mL) after seven days of treatment. However, clearance of serum triglycerides and free fatty acids was not significantly different between the two groups. Baseline triglyceride levels in the carnitine-supplemented group were 96 +/- 42 mg/dL, increased to 242 +/- 101 mg/dL after the lipid challenge and decreased to 121 +/- 47 mg/dL two hours after the lipid infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

A single-day treatment of tumor-induced hypercalcemia by intravenous amino-hydroxypropylidene bisphosphonate

Twenty patients with malignant hypercalcemia were treated with amino-hydroxypropylidene bisphosphonate (AHPrBP, previously APD), a potent inhibitor of osteoclast-mediated bone resorption. To assess the efficacy of a single-day treatment and determine the optimal dose of this compound, all patients received AHPrBP intravenously over 24 h, but they were divided into two subsequent groups of 10 patients: Group A received a single dose of 60 mg AHPrBP and group B received a single dose of 30 mg. In both groups all patients responded to AHPrBP with a decrease in plasma calcium concentration after a mean time lag of 1 day. Within 6 days, plasma calcium (corrected for serum proteins) fell from 3.24 +/- 0.14 to 2.24 +/- 0.06 mmol/liter in group A (p less than .001), but only from 3.22 +/- 0.15 to 2.49 +/- 0.10 mmol/liter in group B (p less than .005). Whereas in all patients from group A plasma calcium was within the normal range at days 9 and 14, in 4 patients of group B it was still above the normal range at day 9, and in 5 patients at day 14. There was a significant difference in plasma calcium between group A and group B from days 5 to 14 (p less than .005). In both groups, urinary calcium excretion fell dramatically and similarly, and plasma phosphate concentration decreased significantly (p less than .01) to values slightly below the normal range from days 4 to 6.(ABSTRACT TRUNCATED AT 250 WORDS)     

Postoperative hypophosphataemia.

The possible mechanisms of postoperative hypophosphataemia were studied in women undergoing uncomplicated cholecystectomy. Six patients were allocated to each of three groups. Group I received no intravenous fluids, group II received dextrose/saline solution alone and group III received dextrose/saline solution with phosphorus supplementation. The serum concentration of inorganic phosphorus fell in all three groups, the greatest fall being in the group receiving dextrose/saline solution. However, the lowest level reached (0.82 mmol/l) was within the normal range for our laboratory. Concentrations of red blood cell adenosine triphosphate and 2,3-diphosphoglycerate showed similar changes. The operations were not associated with a large catabolic response nor with an increase in urinary phosphorus excretion. The postoperative reduction in serum concentration of inorganic phosphorus appeared to be due mainly to haemodilution. There is no indication for routine phosphorus supplementation following uncomplicated elective surgery.     

Relationship of proximal fixation to renal dysfunction in patients undergoing endovascular aneurysm repair

Technological advancements have lead to dramatic improvements in stentgraft device design resulting in more trackable delivery systems and transrenal uncovered stents and barbs for better fixation. Transrenal bare-stents may limit stentgraft migration, particularly in patients with short or flared proximal aortic necks. However, potential disadvantages might be in worsening renal function, particularly in patients with preexisting renal insufficiency. We retrospectively analyzed our recent 7 year experience of patients undergoing endovascular aneurysm repair (EVAR) using a variety of stentgrafts with and without transrenal bare-stent fixation. Patients were divided into 2 groups; infrarenal fixation (IRF) vs transrenal fixation (TRF), or patients with preoperative serum Cr values that were normal (= or <1.5 mg/dl) vs slightly elevated (1.6-2 mg/dl), vs markedly elevated (2.1- 3.5 mg/dl). The exclusion criteria included patients with chronic renal insufficiency (CRI) on hemodialysis, and preoperative high-grade renal artery stenoses requiring angioplasty and stenting. Of 705 patients that underwent EVAR, 496 (IRF: 385 [78%], and TRF: 111 [22%]) were available with routine evaluations of serum Cr and CT scans. Preexisting comorbidities, mean procedure contrast volume, and postprocedure follow-up were similar in both groups. In the immediate postoperative period, mean serum Cr did not change significantly in either the IRF group (1.3+/-0.7 mg/dl to 1.2+/-0.9 mg/dl) or the TRF group (1.3+/-0.5 mg/dl to 1.3+/-0.6 mg/dl). Mean serum Cr did, however, significantly increase over longer follow-up in both groups: 1.4+/-0.8 mg/dl for IRF (P<0.03), and 1.5 +/- 0.8 mg/dl for TRF (P<0.01). Cr clearance was similarly unchanged in the immediate postoperative period (58+/-23 to 61+/-25 ml/min/1.73 m2 for IRF group, 53+/-17 to 55+/-17 ml/min/1.73 m2 for TRF group), but was significantly decreased in longer follow-up (53+/-23 ml/min/1.73 m2 for IRF, p<0.02: and 48+/-16 ml/min/1.73 m2 for TRF, P<0.01). There were no significant differences in serum Cr increase (p=0.19) or Cr clearance decrease (p=0.68) between the IRF and TRF groups. Small renal infarcts were noted in 6 patients (1.6%) in the IRF group, and in 8 patients (7%) in the TRF group (p=0.37). Of patients with normal preoperative renal function, renal dysfunction developed in 7.7% of IRF group and 6.1% of TRF group (p=0.76). In patients with preexisting CRI, renal dysfunction developed in 18.2% of IRF group, and 17.1% of TRF group (p=0.95). Eight patients with postoperative renal dysfunction, 5 (1.3%) from IRF group and 3 (2.7%) from TRF group subsequently required hemodialysis, and this difference was not statistically significant (p=0.91). We also analyzed 200 consecutive patients undergoing EVAR with intra-arterial contrast agents with and without preexisting CRI not on dialysis. The groups were identified on the basis of preprocedure serum Cr: group 1 (n=108), Cr less than 1.5 mg/dL (normal range); group 2 (n=65), Cr 1.5 to 2.0 mg/dL; group 3 (n=27), Cr 2.1 to 3.5 mg/dL. Routine precautions in patients with CRI included preoperative intravenous hydration with 2 L of normal saline solution, discontinuation of all nephrotoxic drugs, intraoperative administration of mannitol (0.5 g/kg intravenously), and use of nonionic, low osmolar intra-arterial contrast agent (Omnipaque 350). One-hundred and eight patients had normal renal function (group 1), and 92 patients had preexisting CRI with baseline Cr 1.5 to 2.0 mg/dL (group 2, n=65) or 2.1 to 3.5 mg/dL (group 3, n=27). Comorbid conditions included coronary artery disease (group 1, 51%; group 2, 49%; group 3, 59%), hypertension (group 1, 39%; group 2, 46%; group 3, 52%), and diabetes mellitus (group 1, 25%; group 2, 35%; group 3, 48%). In groups 1, 2, and 3, the mean volume of low osmolar contrast agent used was 210 cc, 160 cc, 130 cc, respectively; hemodynamic instability developed in 3, 1, and 1 patient, respectively. The incidence of postoperative complications between the 3 study groups was not statistically different. In grications between the 3 study groups was not statistically different. In group 1 a transient increase in serum Cr (>30% over baseline and >1.4 mg/dL) was noted in 3 patients (2.7%), 2 of whom (1.9%) required temporary hemodialysis and 1 (0.9%) who died of renal failure. In group 2 a transient increase in serum Cr was noted in 2 patients (3.1%); both patients (3.1%) required temporary hemodialysis, and 1 patient (1.5%) died of renal failure. In group 3 a transient increase in serum Cr was noted in 2 patients (7.4%); 1 patient (3.7%) required temporary hemodialysis, and 1 patient (3.7%) died of renal failure. Perioperative hypotension significantly increased the risk for elevated serum Cr and death (p<0.05), and larger contrast volume was associated with an increase in serum Cr (p<0.05) during the postoperative period. Following EVAR renal function declines slightly with both IRF and TRF. Our data show no overall difference between patients with IRF and TRF with respect to infarcts, decline in renal function, or onset of dialysis. There were a slightly greater number of renal infarcts in the TRF group, but these infarcts were clinically inconsequential. In patients with CRI, EVAR with intra-arterial radiographic contrast agents is believed to impair renal function, and CRI is considered a relative contraindication to the procedure. Results of our investigation indicate that risk for worsening renal insufficiency, dialysis, and death is only slightly and not significantly greater in patients with CRI compared with patients with normal renal function. With appropriate precautions of avoiding perioperative hypotension and limiting the volume of nonionic contrast agents, CRI need not be a contraindication for EVAR with intra-arterial contrast agents.     

Calcium citrate, a nonaluminum-containing phosphate-binding agent for treatment of CRF

Calcium citrate was evaluated as a dietary phosphate binder in 81 patients with end-stage renal disease. These patients were grouped as follows: Group 1, 43 patients who were treated with calcium citrate; and Group 2 (the control group), 38 patients who were treated with aluminum-containing compounds. Blood chemistries were measured monthly and medications adjusted to maintain the following levels: serum calcium, greater than 9 mg/dl; serum phosphorus, less than 5.5 mg/dl; and total CO2 content, greater than 22 mmol/liter. At the end of the treatment period, the following serum values were obtained in Groups 1 and 2, respectively: calcium, 9.6 +/- 1.2 mg/dl (mean +/- SD) versus 8.9 +/- 0.8 mg/dl (P less than 0.001); phosphorus 5.5 +/- 1.9 mg/dl versus 7.0 +/- 2.3 mg/dl (P less than 0.005); and calcium-phosphate product, 52 +/- 18 versus 61 +/- 21 (P less than 0.05). Differences in alkaline phosphatase, total CO2 content, and C-terminal parathyroid hormone (C-PTH) values were not statistically significant between the two groups. Fifteen patients in Group 1 were then switched to aluminum-containing compounds and chemistries were compared one month later. During calcium citrate therapy, serum calcium was significantly higher, while C-PTH and serum alkaline phosphatase were significantly reduced. No difference was noted in serum phosphorous and total CO2 content. A questionnaire completed by 17 patients in Group 1 documented excellent patient tolerance to calcium citrate. Hypercalcemia (greater than 10.5 mg/dl) was the only significant complication, but only one patient became symptomatic. We conclude that, as a phosphate binder, calcium citrate is at least as effective as aluminum-containing compounds.     

Aminohydroxypropylidene bisphosphonate (APD) treatment for tumor-associated hypercalcemia: a randomized comparison between a 3-day treatment and single 24-hour infusions

Intravenous aminohydroxypropylidene bisphosphonate (APD) normalizes serum calcium in most hypercalcemic cancer patients, however the optimal therapeutic scheme has not been established. We compared in a randomized prospective trial the efficacy and the tolerance of APD given as a 3-day treatment of daily 2-h infusions of 0.5 mg/k.d in 250 ml of saline (group A) with single 24-h infusions of 1.5 mg/kg (group B) or of 0.5 mg/kg in 1 liter of saline (group C). Thirty-three cancer patients remaining hypercalcemic after a 48-h rehydration period were included and monitored daily until normocalcemia or treatment failure was documented. Serum calcium became normal in all but 1 patient (in group C) but remained normal for only 1 or 2 days in 4 other patients (1 in A, 1 in B, 2 in C). The decline in total or ionized serum calcium was slightly less marked in group C than in the two other groups, but the differences were not significant. The fall of fasting urinary calcium excretion was however significantly less rapid in group C (p less than 0.05 from day 1 to day 4). Serum concentrations of iPTH and 1,25-dihydroxyvitamin D [1,25-(OH)2D] increased significantly in the three groups. Serum magnesium concentrations fell slightly from 1.41 +/- 0.05 to 1.28 +/- 0.04 mEq/liter (p less than 0.001) after rehydration but returned to normal after APD administration (day 5, 1.52 +/- 0.04 mEq/liter, p less than 0.001 versus day 0).(ABSTRACT TRUNCATED AT 250 WORDS)     

Enhanced clinical utility of de novo cyclosporine C2 monitoring after lung transplantation.

BACKGROUND: The 2-hour post-cyclosporine (CyA) dose concentration (C2) is favored as the best single-point correlate of CyA area-under-the-concentration curve. CyA nephrotoxicity is a prominent cause of renal dysfunction that affects 38% of lung transplant (LTx) recipients at 5 years. METHODS: We assessed the utility of de novo C2 monitoring after LTx by comparing 2 sequential groups of 18 bilateral LTx recipients followed with traditional de novo trough CyA (C0) monitoring and de novo C2 monitoring, respectively. Target C0 levels were 450 microg/liter and 250 microg/liter at 1 week and 3 months (3/12). Target C2 levels were 1,200 microg/liter and 800 microg/liter. Groups were matched for anthropometrics and diagnoses. Baseline serum creatinine (Cr) was lower in the C0 group than in the C2 group (65 +/- 17 vs 81 +/- 21 micromol/liter, p = 0.02). RESULTS: At 3 months, survival for both groups was 100%, but the C0 group had a greater increase in Cr from baseline (90 +/- 54% vs 33 +/- 23%, p < 0.001) despite similar CyA dosage (6.6 +/- 3.8 vs 6.5 +/- 2.9 mg/kg/day, p = 0.94). There was no difference in forced expiratory volume in 1 second (% predicted) (71 +/- 16 vs 69 +/- 14, p = 0.68), mean acute vascular rejection score per patient (2.61 +/- 2.12 vs 1.44 +/- 1.72, p = 0.079), mean bronchial rejection score per patient (3.72 +/- 1.81 vs 2.83 +/- 1.58, p = 0.126) or rate of infection (1.85 vs 1.79 events per 100 patient-days). CONCLUSIONS: De novo C2 monitoring, which reduces both the risk of CyA toxicity and the risk of sub-therapeutic dosing, is a safe and effective technique for short-term preservation of renal function after LTx.     

Effective treatment of hyperhomocysteinemia in heart transplant recipients with and without renal failure.

BACKGROUND: Elevated total plasma homocysteine (tHcy) levels have been associated with vascular disease and higher mortality in patients with coronary artery disease. Graft coronary disease is a major cause of mortality in long-term survivors of heart transplantation, and hyperhomocysteinemia may be one of its causes. The objectives of our study were to establish the effectiveness of a 3 stage homocysteine-lowering algorithm in a group of 84 heart transplant (HTx) patients and to evaluate the effect of renal function on the response to homocysteine-lowering therapy. METHODS: Prospective treatment of 84 Htx patients (64 male; mean age, 48 +/- 13 years) with tHcy > 75th percentile consisted of a 3-stage treatment algorithm: Stage 1, folic acid (FA) 2 mg + vitamin (vit) B(12) 500 mcg daily; Stage 2, addition of vit B(6) 100 mg daily; Stage 3, increase FA to 15 mg daily. Serum creatinine (Cr) and tHcy levels were measured before treatment and 21 +/- 19 weeks after each stage of treatment. RESULTS: All 3 stages of treatment significantly lowered mean tHcy from 22.4 +/- 16.3 (mean +/- SD) micromol/liter to 16.3 +/- 6.7 micromol/liter (p < 0.00001), from 17.6 +/- 6.1 micromol/liter to 15.2 +/- 5.3 micromol/liter (p < 0.0001), and from 16.8 +/- 5.2 micromol/liter to 15.6 +/- 5.3 micromol/liter (p < 0.05), respectively. The average reduction from baseline was 38%. Creatinine levels did not change significantly during the study period. Total plasma homocysteine levels decreased below the 75th percentile in 55% of patients, with Cr levels significantly lower in this group of patients (126 +/- 36 micromol/liter vs 182 +/- 65 micromol/liter, p < 0.00001). However, we found no significant relationship between % change in tHcy and baseline Cr. CONCLUSIONS: In a group of 84 heart transplant patients with tHcy levels >75th percentile, treatment with FA and vit B(6) and B(12) according to a 3-stage algorithm resulted in statistically significant declines in mean tHcy levels. Overall, tHcy levels decreased 38%, with target tHcy levels <75th percentile achieved in 55% of the patients. The % change in tHcy was not related to Cr. Further studies are needed to correlate treatment of hyperhomocysteinemia with clinical endpoints, such as the time to development of transplant vasculopathy and long-term survival, and to define the most appropriate targets for therapy.     

Long-term effects of calcium carbonate and 2.5 mEq/liter calcium dialysate on mineral metabolism

Many investigators have shown that calcium carbonate (CaCO3) is an effective phosphate binder which also prevents the potential disabling effects of aluminum (Al) accumulation. However, hypercalcemia may develop in a substantial numbers of patients. Thus, to control serum phosphate (PO4) and prevent hypercalcemia, we performed studies in 21 patients on maintenance hemodialysis in which, in addition to the oral administration of CaCO3, the concentration of calcium (Ca) in the dialysate was reduced from 3.25 to 2.5 mEq/liter. The studies were divided in three periods: I. control, on Al-binders (one month); II. no Al-binders (one month); III. CaCO3 (seven months). Blood was obtained three times/week before dialysis for the first five months of the study and once a week for the remaining four months. During the control period, the mean serum calcium was 8.86 +/- 0.08 mg/dl. The value decreased to 8.65 +/- 0.07 mg/dl when phosphate binders containing aluminum were discontinued, and increased to 9.19 +/- 0.07 mg/dl (P less than 0.001 compared to period II) during oral supplementation with calcium carbonate. The mean serum phosphorus was 5.03 +/- 0.07 mg/dl during the control period, and increased to 7.29 +/- 0.91 mg/dl (P less than 0.001) after phosphate binders were discontinued. It decreased to 4.95 +/- 0.06 mg/dl (P less than 0.001) with the administration of calcium carbonate. During CaCO3 administration, serum Al decreased from 64.2 +/- 8.5 to 37.1 +/- 3.6 and 25.1 +/- 3.0 micrograms/liter (P less than 0.001) at three and seven months, respectively. Serum parathyroid hormone (PTH) decreased by 20%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Contrast nephropathy with a non-ionic iodide medium in patients with normal and mildly impaired renal function

Effects of infusion of a non-ionic contrast medium(iopamidol, 370 mg l/ml) on renal function in a normovolemic state were examined in patients with normal and mildly affected renal function who underwent coronary angiography(CAG). The patients were divided into three groups: group I (n = 69) with serum creatinine(S-Cr) level < 1.0 mg/dl; group II (n = 50) with S-Cr level of 1.0 to 1.3 mg/dl and group III(n = 17) with S-Cr level of 1.3 to 2.0 mg/dl. Patients with S-Cr > or = 2.0 mg/dl were subjected to 3-h hemodialysis immediately after CAG(group HD, n = 11). Serum(S) and urine(U) values of Cr, Na, K, Cl, beta 2-microglobulin(beta 2MG), and U-N-acetyl-beta-D-glucosaminidase(NAG) were measured before and 24 h after CAG. U-NAG and U-beta 2MG were corrected for U-Cr, and fractional excretion of beta 2MG(FE beta 2MG) was determined. Basal U-NAG/Cr, U-beta 2MG/Cr and FE beta 2MG were increased in groups III and HD, suggesting the preexistence of tubular dysfunction. S-Cr was increased significantly only in group I, but there was no change in S-beta 2MG. U-NAG/Cr after CAG was elevated in all the groups, whereas U-beta 2MG/Cr(or FE beta 2MG) was increased only in group III. Greater than two-fold increases of U-NAG/Cr were noted equally in groups I through III. In contrast, the greater than two-fold increase of U-beta 2MG/Cr(or FE beta 2MG) occurred more frequently in group III as compared to the other groups. The incidences of such cases in group HD were similar to those of group III. The half life of serum iodide concentration was significantly shortened by 3-h HD(1.8 +/- 0.3 h vs. 15.9 +/- 3.8 h without HD). In conclusion, patients presenting S-Cr > or = 1.3 mg/dl were at high risk of renal tubular dysfunction even when contrast media was administered in the absence of significant increase in S-Cr. Whether an increase in U-NAG/Cr indicates tubular damage or is merely the result of tubular reabsorption of the agent remains to be clarified. Post-CAG hemodialysis efficiently eliminates contrast medium from the circulation.     

Neurological and neuropathological sequelae of correction of chronic hyponatremia

The effect of correction of chronic hyponatremia at different rates was studied in 91 rats maintained at a plasma [Na+] of 112 +/- 1 mmol/liter for 19 +/- 1 days. Hyponatremia was corrected into normal ranges (140 to 145 mmol/liter) using three different methods. Rats corrected by water restriction achieved normal plasma [Na+] by 2.1 +/- 0.2 day and had a maximal (4 hr) correction rate of 1.0 +/- 0.1 mmol/liter.hr; rats corrected by water diuresis achieved normal plasma [Na+] by 1.6 +/- 0.1 day and had a maximal correction rate of 2.8 +/- 0.2 mmol/liter.hr; rats corrected by hypertonic saline infusion achieved normal plasma [Na+] by 5.4 +/- 0.3 hr and had a maximal correction rate of 5.7 +/- 0.4 mmol/liter.hr. A fourth control group was not corrected. No demyelinative lesions were found in the brains from the uncorrected rats, whereas the occurrence of such lesions in the brains of the corrected rats was highly correlated with the maximal rate of increase in plasma [Na+] (r = 0.68, P less than 0.001), and to a lesser degree with the magnitude of the increase in plasma [Na+] over the first 24 hours of correction (r = 0.41, P less than 0.001). Brain myelinolysis was first observed in animals whose maximal (4 hr) rate of correction exceeded 1.75 mmol/liter.hr, and the incidence of demyelination increased progressively in rats with more rapid rates of correction. Similarly, myelinolysis was first observed in rats whose magnitude of correction at 24 hours exceeded 16 mmol/liter and also increased in rats with larger 24 hour magnitudes of correction.(ABSTRACT TRUNCATED AT 250 WORDS)     

A kinetic study of cation transport in erythrocytes from uremic patients

We previously described in red blood cells (RBCs) from uremic patients on dialysis a reduction in sodium (Na) efflux through the Na, potassium (K) cotransport system (Na,K CoT) while Na efflux through the Na,K pump was normal. We then examined Na efflux in fresh cells and in cells loaded to obtain one level of intracellular sodium (Nai) concentration at about 25 mmol/liter cell. In the present study we used similar cation flux methodology to examine the kinetics of cation efflux through the Na,K pump and Na,K CoT in uremic patients on dialysis. RBCs were Na-loaded to attain five different levels of Nai concentration over a range of 5 to 50 mmol/liter cells using the ionophore nystatin. At each level of Na-loading, the Nai achieved was similar in RBCs from controls and patients. Ouabain-sensitive Na efflux through the Na,K pump showed no difference in rate between normals and dialysis patients. When the kinetic parameters of this transport pathway were considered, the apparent affinity (K0.5) for sodium was not significantly different between controls and patients (18.4 +/- 2.3 vs. 20.0 +/- 2.6 mmol/liter cell) and the maximal velocity of efflux (Vmax) was also not different between controls and patients (9.6 +/- 0.7 vs. 8.5 +/- 1.2 mmol/liter cell/hr). Comparison of Nai-activated Na versus K efflux rates through the Na,K CoT in normal subjects demonstrated similar saturation kinetics, (K0.5 15.8 +/- 3.3 vs. 12.2 +/- 2.8 mmol/liter cell, Vmax 0.81 +/- 0.1 vs. 0.78 +/- 0.1 mmol/liter cell/hr) consistent with the known stoichiometric ratio of 1 Na:1 K:2 Cl described for this mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)     

Amelioration of chronic renal allograft dysfunction in cyclosporine-treated patients by addition of azathioprine

Management of chronic renal allograft dysfunction in cyclosporine-prednisone treated renal allograft recipients remains problematic. We therefore initiated a protocol of azathioprine addition (1.0-1.5 mg/kg/day) to ongoing CsA/Pred therapy. Three groups were treated. Group A (n = 21) had chronic progressive renal dysfunction (serum creatinine greater than or equal to 2.5 mg/dl or more than 15% above baseline) four or more months after transplantation. Group B (n = 8) had frequent or severe rejection episodes occurring despite adequate CsA levels. Group C (n = 7) had constitutional side effects of CsA with or without renal dysfunction persisting despite drug taper or financial difficulty in affording CsA. Aza was initiated 17.8 +/- 2.8 months after transplantation in group A, the mean serum creatinine having risen from 2.55 +/- 27 mg/dl to 3.04 +/- .20 mg/dl (P = .07) over the six months preceding Aza initiation, despite stable and low therapeutic range HPLC whole-blood CsA levels (118 +/- 10 ng/ml vs. 133 +/- 11 ng/ml, P = NS). Renal function declined at a rate of -0.20 +/- .06 Cr1/year in the six-month period before addition of Aza, and then improved at a rate of 0.09 +/- .04 Cr-1/year after addition of Aza (P = .002). These changes in renal function occurred without a decrease in CsA levels (118 +/- 10 six months before Aza vs. 126 +/- 26 six months after Aza, P = NS). In group B Aza was initiated at 58 +/- 8 days after transplantation when mean sCr was 3.56 +/- .29 mg/dl and mean CsA level was 222 +/- 17 ng/ml. At least follow-up 12.7 +/- 2.0 months after addition of Aza, all group B grafts were functioning, mean sCr was 2.69 +/- .31 mg/dl (P = .09 compared with baseline), and mean CsA level was 128 +/- 34 ng/ml (P = .07 compared with baseline). Group C patients had addition of Aza at 43 +/- 19 months after transplantation when mean sCr was 2.97 +/- .60 and mean CsA level was 125 +/- 30 ng/ml; addition of Aza had no influence on the rate of decline in renal function in this group. Of these 36 patients, 6 received therapy for acute rejection over the entire follow-up period of 12.3 +/- 1.4 months after addition of Aza; 4 of these retain graft function. Infectious complications consisted of 2 urinary tract infections, 1 bacterial pneumonia, and one case of otitis media.(ABSTRACT TRUNCATED AT 400 WORDS)     

烧伤后早期应用不同液体复苏血钠和红细胞变化的临床研究

目的　观察烧伤后早期应用不同液体复苏患者血钠和红细胞的变化。方法　将 15 0例烧伤患者分为 3组 ,A组为中、小面积烧伤患者 5 0例 ,给予平衡盐溶液 (钠离子 130mmol/L)复苏 ;B组为大面积烧伤患者 5 0例 ,液体复苏方法同A组 ;C组为大面积烧伤患者 5 0例 ,给予高渗乳酸钠溶液 (钠离子 174mmol/L)复苏。观察伤后 1～ 3d患者的补液总量、血钠、红细胞数量及红细胞平均体积 (MCV)的变化。对A、B组患者的烧伤指数 (BI)与其伤后 1d的血钠值作相关性分析。　 结果　伤后 3d内A组患者补液总量、补钠量均低于其他两组 (P <0.0 1);C组补液总量低于B组 ,而补钠量多于B组 (P <0.0 1)。伤后 3d内B组血钠值接近正常值下限 ,C组血钠值接近正常值上限 ,前者明显低于后者 (P <0.0 5或 0 .0 1)。伤后 3d内B、C组的红细胞数量相近 (P >0.0 5 )。伤后 1dB、C组患者的MCV分别为 (95 .5± 5 .5 )、(92 .1± 4 .5 )fl,伤后 2d各为 (93.2± 6 .4 )、(90 .9± 5 .4 )fl,组间比较差异无显著性意义 (P >0.0 5 )。A、B组患者伤后 1d的血钠值与自身BI呈负相关 (r=- 0 84,P<0.0 1)。　 结论　大面积烧伤患者伤后早期采用高渗盐溶液复苏 ,血钠值平稳且红细胞的肿胀程度较轻     

Trimethoprim-sulfamethoxazole therapy in outpatients: is hyperkalemia a significant problem?

A prospective, randomized clinical study was undertaken to determine the effect of standard-dose trimethoprim-sulfamethoxazole combination treatment on serum potassium concentrations in outpatients treated in an ambulatory clinic. Ninety-seven patients were treated with oral antibiotics for a variety of infections. Fifty-one patients treated with trimethoprim-sulfamethoxazole (trimethoprim, 320 mg/day; sulfamethoxazole, 1,600 mg/day) constituted the treatment group, while 46 patients treated with other antibiotics served as controls. Serum potassium, sodium, and chloride concentrations, serum carbon dioxide content, blood urea nitrogen level, serum creatinine level, and serum glucose concentration were measured. The baseline serum potassium concentration in the treatment group was 4.30 +/- (SD) 0.36 mmol/l, and it increased significantly (p < 0.001) to 4.66 +/- 0.45 mmol/l on day 5 of therapy. Subgroup analysis of mean serum potassium concentration on day 5 of therapy failed to detect clinically relevant hyperkalemia. In patients with a serum creatinine level equal to or greater than 1.1 mg/dl (K+, 4.83 +/- 0.48 mmol/l), a nonsignificant difference (p = 0.3) in the potassium concentration was noted on day 5 as compared with patients with a serum creatinine level <1.1 mg/dl (K+, 4.63 +/- 0.44 mmol/l). Although diabetics had a higher serum potassium concentration (K+, 4.91 +/- 0.44 mmol/l) than nondiabetics (K+, 4.61 +/- 0.44 mmol/l), the difference was not statistically significant (p = 0.055). Patients aged >/=50 years (K+, 4.82 +/- 0.59 mmol/l) had a significantly different (p = 0.046) serum potassium concentration on day 5 than patients aged <50 years (K+, 4.55 +/- 0.28 mmol/l). In contrast, the baseline serum potassium concentration in the control group was 4.37 +/- 0.45 mmol/l, and it decreased (p = 0.1) to 4.22 +/- 0.4 mmol/l on 5 days of drug therapy. Trimethoprim-sulfamethoxazole therapy, when used to treat a variety of infections, leads to an increase in serum potassium concentration in most patients. After 5 days of therapy with this drug, the treatment group developed a statistically significant rise in the serum potassium concentration as compared with the control group. However, severe hyperkalemia (K+ >/=5.5 mmol/l) occurred in only 3 patients (6%) treated with trimethoprim-sulfamethoxazole. In addition, none of the subgroups of treated patients developed clinically important hyperkalemia. This suggests that outpatients, in contrast to acquired immunodeficiency syndrome patients and hospitalized patients with mild renal insufficiency, develop severe or life-threatening hyperkalemia less commonly when treated with this antimicrobial regimen. However, outpatients having risk factors which may predispose to the development of hyperkalemia should be carefully monitored when treated with trimethoprim-sulfamethoxazole.     

Impact of donor serum sodium levels on outcome after heart transplantation.

We investigated the impact of elevated donor serum sodium levels on outcome after heart transplantation in 336 consecutive heart transplantations. Mean donor serum sodium was 148.2+/-10.2 mmol/liter (range 116 to 180 mmol/liter). Recipients were divided into 4 groups with serum sodium levels of 141, 147 and 155 mmol/liter, resulting in sodium levels of: 133+/-6.1 mmol/liter for Quartile A; 144+/-4.2 mmol/liter for Quartile B; 151+/-4.3 mmol/liter for Quartile C; and 162+/-6.6 mmol/liter for Quartile D, respectively (mean+/- standard deviation). Mean occurrence of primary graft failure (PGF) was 3.6% with the following quartile breakdown: A, 3.6%; B, 4.8%; C, 3.6%; and D, 2.4% (p=non-significant [NS]). Mean 5-year survival was 81.32% with: A, 83.51%; B, 76.03%; C, 80.47%; and D, 85.25% (p=NS). Coronary allograft vasculopathy (CAV) occurred in 19% of patients with a quartile breakdown of: A, 16.5%; B, 21%; C, 20%; and D, 14.5% (p=NS). No impact of donor serum sodium levels was seen on early post-operative results or on long-term outcome, indicating that cardiac allografts from donors with elevated sodium levels may be transplanted successfully with favorable results.