Pharmacokinetics of teicoplanin in subjects with varying degrees of renal function

The pharmacokinetics of teicoplanin were studied in 20 subjects with varying degrees of renal function after administration of a single 200 mg intravenous dose. Pharmacokinetic parameters were calculated with a three compartment open model and by non-compartmental analysis. The elimination half-life increased as creatinine clearance decreased (rs = -0.87, P less than 0.001). The distribution volume was 1.0 (+/- 0.3) 1/kg of actual body weight and did not vary with changes in creatinine clearance. In normal subjects the main route of elimination was renal. The plasma clearance of teicoplanin correlated with creatinine clearance (rs = 0.91, P less than 0.001). At lower levels of creatinine clearance the variation in elimination half-life was such that we recommend individualization of the teicoplanin dosage following the measurement of the drug concentration in plasma.     

Population Pharmacokinetics of Isavuconazole in Subjects with Mild or Moderate Hepatic Impairment

Isavuconazole, administered as the prodrug isavuconazonium sulfate, was recently approved by the U.S. Food and Drug Administration and the European Medicines Agency for the treatment of adults with invasive aspergillosis and mucormycosis. The objective of this analysis was to develop a population pharmacokinetic model using NONMEM (version 7.2) for subjects with hepatic impairment, using intravenous and oral administration data from two hepatic studies, and to simulate concentration profiles to steady state, thus evaluating the need for dose adjustment. A two-compartment model with Weibull absorption function and first-order elimination process adequately described plasma isavuconazole concentrations. The population mean clearance in healthy subjects was 2.5 liters/h (5th and 95th percentiles: 2.0 and 3.1). The mean clearance values for subjects with mild and moderate hepatic impairment decreased approximately to 1.55 liters/h (5th and 95th percentiles: 1.3 and 1.8 liters/h) and 1.32 liters/h (5th and 95th percentiles: 1.05 and 1.35), respectively. Peripheral volume of distribution increased with body mass index. Simulations of mean concentration time profiles to steady state showed less than a 2-fold increase in mean trough concentrations for subjects with mild and moderate hepatic impairment compared with healthy subjects. After administration of the single dose, safety data for subjects with mild and moderate hepatic impairment were generally comparable to those for healthy subjects in both studies. Due to the <2-fold increase in trough concentrations and the established safety margin, dose adjustment appears to be unnecessary in subjects with mild or moderate hepatic impairment.     

Kidney volume in type 1 (insulin-dependent) diabetic patients with normal or increased urinary albumin excretion: effect of long-term improved metabolic control

Forty-seven patients with type 1 (insulin-dependent) diabetes mellitus and 14 normal subjects had renal volume determined by an ultrasonic technique. Renal volume of 299 +/- 49 ml/1.73 m2 (mean +/- SD) in type 1 diabetic patients with normal urinary albumin excretion exceeded that in the normal subjects (245 +/- 53 ml/1.73 m2, p less than 0.05). Compared with diabetic patients with normal urinary albumin excretion, renal volume was significantly higher in patients with microalbuminuria (372 +/- 24 ml/1.73 m2, p less than 0.05) and patients with clinical nephropathy (352 +/- 48 ml/1.73 m2, p less than 0.05). In a multiple linear regression with HbA1c, urinary albumin excretion, age, diabetes duration and mean blood pressure as independent variables, variations in HbA1c could account for 33% of the variations in kidney volume (n = 47, r = 0.57, p less than 0.01). The other variables played no role. When only patients without clinical nephropathy were included, HbA1c and kidney volume remained significantly correlated (n = 34, r = 0.60, p less than 0.01). In those patients a strong correlation between kidney volume and function, i.e. the glomerular filtration rate was found (n = 34, r = 0.70, p less than 0.01); metabolic control and function were also correlated (n = 34, r = 0.62, p less than 0.01). The urinary albumin excretion accounted for only 6% of the variation of the kidney volume (NS). In nine patients with microalbuminuria the kidney volume could be reduced during 2 years of improved metabolic control by means of insulin infusion pumps.(ABSTRACT TRUNCATED AT 250 WORDS)     

Impaired growth hormone secretion in the adult population: relation to age and adiposity.

Growth hormone (GH) release was studied in adults of normal stature, ages 21-86 yr. The subjects were 85-115% of ideal body weight, between the 5th and 95th percentiles in height, and free of active or progressive disease. 9 to 12 individuals in each decade from thirds to ninth were evaluated. The following criteria of GH status were measured: serum GH concentration, analyzed by radioimmunoassay at half-hour intervals for 4 h after onset of sleep, and at 1-h intervals from 8 a.m. to 4 p.m. in 52 subjects; daily retention of N, P, and K in response to 0.168 U human (h)GH/kg body wt3/4/day in 18 subjects; and plasma somatomedin C (SmC) level before and during exogenous hGH treatment in 18 subjects. All 10 individuals, 20-29 yr old, released substantial amounts of endogenous GH during both day and night (average peak serum GH obtained during day and night was 7.3 and 20.3 ng/ml, respectively); average plasma SmC was 1.43 U/ml (95% tolerance limits, 0.64-2.22 U/ml). There was no significant effect of exogenous hGH on elemental balances or on plasma SmC. In contrast, 6 of 12 individuals 60-79 yr old showed the following evidences of impaired GH release; peak waking and sleeping serum GH less than 4 ng/ml; plasma SmC less than 0.38 U/ml; a significant retention in N, P, and K; and a significant rise in plasma SmC, in response to exogenous hGH. Plasma SmC, serum GH during sleep, serum GH during the day, retentions of N, P, and K in response to exogenous hGH, and rise in plasma SmC in response to hGH were all intercorrelated (P less than 0.05). Plasma SmC less than 0.38 U/ml corresponded to peak nocturnal serum GH less than 4 ng/ml. The prevalence of plasma SmC less than 0.38 U/ml increased progressively from age 20 to 90: third decade, 0%; fourth, 11%; fifth, 20%; sixth, 22%; seventh, 42%; eight, 55%; and ninth, 55%. Within each decade, plasma SmC was inversely related to adiposity.     

Serum adiponectin and renal dysfunction in men with type 2 diabetes

OBJECTIVE: Inflammation is associated with both chronic kidney dysfunction and type 2 diabetes. Adiponectin, a novel circulating anti-inflammatory protein made by adipocytes, has been reported to be lower in diabetic than nondiabetic subjects. In contrast, serum levels of adiponectin are elevated in end-stage renal disease. We sought to investigate the relation between adiponectin and mild to moderate renal dysfunction in men with type 2 diabetes. RESEARCH DESIGN AND METHODS: Multivariate logistic regression was used to evaluate the relation between serum adiponectin concentrations and the presence of renal dysfunction (estimated glomerular filtration rate [eGFR] <60 ml/min per 1.73 m(2) by the four-variable Modification of Diet in Renal Disease equation) in participants with type 2 diabetes in the Health Professionals' Follow-Up Study. A total of 733 men were included in this cross-sectional analysis. RESULTS: Adiponectin was positively correlated with age (Spearman coefficient, r = 0.19, P < 0.001) and negatively correlated with weight (Spearman coefficient, r = -0.18, P < 0.001). Those with adiponectin in the second quartile or higher (>10 microg/ml) compared with those in the first quartile had a reduced odds for renal dysfunction (multivariate odds ratio 0.48 [95% CI 0.28-0.81]). These results were unchanged when serum lipids were included in the multivariate model. CONCLUSIONS: We conclude that a higher serum adiponectin concentration is associated with reduced odds of moderate renal dysfunction in men with type 2 diabetes.     

Renal handling of cathodic trypsin-like immunoreactivity in man

The renal handling of cathodic trypsin-like immunoreactivity (TLI) was examined in 60 healthy persons (group I), 59 patients with proteinuria (group II), 7 healthy men receiving intravenous lysine to partially inhibit renal tubular protein reabsorption (group III) and 20 patients who underwent diagnostic renal vein catheterization (group IV). The urinary TLI concentration and TLI ratio (TLI clearance divided with creatinine clearance) were higher in group II than group I (p less than 0.001, Mann-Whitney test). In group II negative correlations were present between serum TLI and creatinine clearance (Spearman's rho = -0.84, p less than 0.001) and between TLI ratio and creatinine clearance (rho = -0.76, p less than 0.001). In group III the renal TLI clearance was undetectable before lysine but increased to a maximal median value of 4.00 ml/min per 1.73 m2 (range: 2.44-9.25 ml/min per 1.73 m2) after lysine. In group IV, the renal arterio-venous extraction of TLI was correlated to inulin extraction (rho = 0.85, p less than 0.001). The glomerular filtrability (the ratio between TLI and inulin extractions) was median 0.53 (range: 0.13-0.94). In conclusion, TLI has a high glomerular filtration and an almost complete tubular reabsorption and catabolism (with normal kidney function).     

Trazodone kinetics: effect of age, gender, and obesity

Single 25 mg intravenous and 50 mg oral doses of trazodone were given to 43 healthy subjects, divided into young men and women (aged 18 to 40 years) and elderly men and women (aged 60 to 76 years). Among men, trazodone volume of distribution (Varea) was increased in elderly vs. young subjects (1.15 vs. 0.89 L/kg; P less than 0.05), and clearance decreased (1.65 vs. 2.31 ml/min/kg; P less than 0.05), thereby increasing elimination half-life (t1/2) in elderly men (8.2 vs. 4.7 hours; P less than 0.001). Varea in women was also increased in the elderly (1.5 vs. 1.27 L/kg; P less than 0.02), causing increased t1/2 (7.6 vs. 5.9 hours; P less than 0.05), but clearance was unrelated to age. Absolute bioavailability of oral trazodone averaged 70% to 90% and was unrelated to age or sex. In 23 obese subjects (mean weight 112 kg) vs. 23 matched control subjects of normal weight (mean 65 kg), Varea was greatly increased (162 vs. 67 L; 1.43 vs. 1.04 L/kg; P less than 0.001) and was highly correlated with body weight (r = 0.91). Clearance was unchanged between groups (146 vs. 136 ml/min), but the increased Varea caused prolonged t1/2 in obese subjects (13.3 vs. 5.9 hours; P less than 0.001). Reduced clearance of trazodone among elderly men may indicate a need for dosage reduction during chronic therapy. In obese individuals, choice of dosage during chronic treatment should be based on ideal rather than total body weight.     

Study of the cadmium level of the population of the Augsburg area (Southern Germany)

Cadmium concentrations in liver and kidney were determined in 68 deceased patients (41 male, 27 female) from the Augsburg area. The following concentrations were found: liver 2.2-77.3 (median 16.0) nmol/g dry weight; renal cortex 87.2-2120.0 (median 315.4) nmol/g dry weight; renal medulla 34.7-913.7 (median 186.4) nmol/g dry weight. On average, the values for the renal medullas were 0.56 times the values for the renal cortex. Females showed lower values in liver, renal cortex and renal medulla than males. The total bodily burden with cadmium was determined to be 13.2-303.9 (median 51.6) mumol. A moderate, but significant correlation was found between the cadmium concentrations in the liver and the kidney (rs = 0.3), a stronger correlation between the concentrations in the renal cortex and renal medulla (rs = 0.6). The problematic conversion of the results obtained with wet samples into values for dry samples is discussed, as well as the possible influence of different diseases of the liver and/or the kidney on the concentrations found.     

Pharmacokinetics and metabolism of intravenous and oral fleroxacin in subjects with normal and impaired renal function and in patients on continuous ambulatory peritoneal dialysis.

The pharmacokinetics of fleroxacin, including the formation of N-demethyl and N-oxide fleroxacin after the administration of single intravenous (100-mg) and oral (400-mg) doses, was investigated in 26 subjects with various levels of renal function, including 7 patients on continuous ambulatory peritoneal dialysis. Fleroxacin was well tolerated by all subjects. The volume of distribution, systemic availability, and peak concentration after the administration of oral fleroxacin were independent of the glomerular filtration rate. As a consequence of a declining renal clearance but not nonrenal clearance, the total body clearance of fleroxacin declined with decreasing glomerular filtration rate from 1.41 +/- 0.23 ml/min per kg in subjects with normal renal function to 0.58 +/- 0.13 ml/min per kg in patients with end-stage renal disease (r = 0.84, P less than 0.001). The analysis revealed that the N-oxide metabolite exhibited formation-limited kinetics and the N-demethyl metabolite exhibited elimination-limited kinetics. The areas under the curve of both metabolites increased with declining renal function. In patients on continuous ambulatory peritoneal dialysis the mean dialysate/plasma concentration ratio of fleroxacin increased from 0.52 +/- 0.11 to 0.71 +/- 0.13 (P less than 0.001) with increasing dwell time, resulting in a 7.8 +/- 3.6% recovery of unchanged fleroxacin in peritoneal dialysate. In conclusion, (i) a 50% reduction of the maintenance dose is recommended in patients with a renal function below 20 to 30 ml/min per 1.73 m2, and (ii) therapeutic concentrations of fleroxacin in the peritoneal dialysate should be achievable after oral administration in patients on continuous ambulatory peritoneal dialysis.     

Lomefloxacin pharmacokinetics in subjects with normal and impaired renal function.

Lomefloxacin pharmacokinetics were investigated in 6 normal subjects and 24 uremic patients after a single oral dose of 400 mg. In subjects with normal renal function, the peak level in plasma averaged 3.5 +/- 0.9 micrograms/ml (mean +/- standard deviation) and was obtained at 1.3 +/- 0.9 h. The absorption rate constant was 3.8 +/- 1.6 h-1. The terminal half-life was 7.77 +/- 0.95 h. The apparent volume of distribution was 2.54 +/- 0.66 liters/kg. Total body and renal clearances were 259 +/- 83 and 200 +/- 55 ml/min per 1.73 m2, respectively. The percentage of the dose recovered unchanged in 48-h urine was 80.6 +/- 2.8. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 38 h in severely uremic patients (glomerular filtration rate, less than 10 ml/min). Renal insufficiency did not significantly modify the peak level in plasma, the time to peak, the apparent volume of distribution, or the nonrenal clearance of lomefloxacin. The dialysis clearance of lomefloxacin was 54 +/- 13 ml/min. Linear relationships were found between lomefloxacin pharmacokinetic parameters and glomerular filtration rate data. Dosage adjustments are necessary in uremic patients.     

Cefmenoxime pharmacokinetics in patients with renal insufficiency.

The pharmacokinetics of cefmenoxime were determined after a 30-min intravenous infusion of 15 mg/kg of total body weight to 33 adult subjects with normal renal function (CLCR, greater than 80 ml/min per 1.73 m2, group I), mild renal insufficiency (CLCR, 40 to 79 ml/min per 1.73 m2, group II), moderate renal insufficiency (CLCR, 10 to 39 ml/min per 1.73 m2, group III), or severe renal impairment, (CLCR, less than 10 ml/min per 1.73 m2, group IV) or to patients between hemodialysis (CLCR, less than 10 ml/min per 1.73 m2, group V). Concentrations of cefmenoxime in serum and urine were determined by high-pressure liquid chromatography, and serum concentrations were fit to a two-compartment model. There was no significant relationship between creatinine clearance and either peak serum concentrations or volume of distribution at steady state. Patients in group I excreted 81% of the dose into the urine within 24 h; recovery decreased with worsening renal function. The mean terminal half-lives in groups I to V were 1.06, 1.50, 3.55, 4.60, and 11.4 h, respectively. There were good linear relationships between creatinine clearance, and the elimination rate and total body clearance of cefmenoxime. Dosage recommendations for subjects with renal insufficiency are proposed.     

Ofloxacin pharmacokinetics in renal failure.

The pharmacokinetics of ofloxacin were investigated in 12 normal subjects and 21 uremic patients after the administration of a single oral 200-mg dose. An open three-compartment body model was used to calculate ofloxacin pharmacokinetic parameters. In healthy subjects, the peak plasma level averaged 2.24 +/- 0.90 micrograms/ml and was obtained at 0.83 +/- 0.31 h. The absorption rate constant was 4.22 +/- 1.64 h-1. The terminal half-life was 7.86 +/- 1.81 h. The apparent volume of distribution was 2.53 +/- 0.78 liters/kg. Total body and renal clearances were 241.4 +/- 53.8 and 196.5 +/- 42.9 ml/min per 1.73 m2, respectively. A total of 68.4 +/- 11.9% of the dose was recovered unchanged in 24-h urine. In uremic patients, the terminal half-life increased in relation to the degree of renal failure: from 8 h in normal subjects to 37 h in severely uremic patients. Renal insufficiency did not significantly modify the peak plasma level, the apparent volume of distribution, the fractional clearance, or the nonrenal clearance of ofloxacin. However, the time to peak level was delayed in patients with creatinine clearance of less than 30 ml/min. Linear relationships were found between ofloxacin pharmacokinetic parameters and glomerular filtration rate data. Ofloxacin is only very slightly removed by hemodialysis. Dosage adjustments of ofloxacin in uremic patients are proposed.     

Pharmacokinetics of lomefloxacin in renally compromised patients

The single-dose pharmacokinetics of orally administered lomefloxacin (400 mg) were studied in normal subjects and in patients with various degrees of renal function. The subjects were classified by creatinine clearance (CLCR) normalized for body surface area: group 1, CLCR of greater than 80 ml/min/1.73 m2; group 2, CLCR of 80 to greater than 40 ml/min/1.73 m2; group 3, CLCR of 40 to greater than 10 ml/min/1.73 m2; and group 4, CLCR of less than or equal to 10 ml/min/1.73 m2. Each group consisted of eight subjects. The pharmacokinetics of lomefloxacin were significantly influenced by renal function. There were significant differences in the elimination rate constant, half-life, area under the concentration-time curve from 0 h to infinity, apparent total drug clearance, renal clearance, and apparent nonrenal drug clearance between the four renal function groups. Mean half-lives for groups 1, 2, 3, and 4 were 8.09, 9.11, 20.90, and 44.25 h, respectively. There were no significant differences between the renal groups for maximum concentration of the drug in serum and apparent volume of distribution. Age had no apparent effect on lomefloxacin disposition. There was a significant relationship between CLCR and lomefloxacin total body clearance (r = 0.92, P = 0.001) and renal clearance (r = 0.94, P = 0.001). Despite a predominate renal route of elimination, nonrenal lomefloxacin clearance significantly decreased with decreasing renal function (r = 0.72, P = 0.001). Mean lomefloxacin excretion rates over 48 h were 60.7, 56.0, 29.1, and 1.0% of the administered dose for groups 1, 2, 3, and 4, respectively. Mean glucuronide excretion rates over 48 h were 7.8, 6.3, 10.0, and 0.6% of the administered dose for groups 1, 2, 3, and 4, respectively. Hemodialysis had no effect on lomefloxacin concentrations in plasma. In patients with normal to moderate renal function, 400 mg of lomefloxacin per day should provide therapeutic concentrations in blood. The lomefloxacin dose should be reduced to 200 mg/day as the CL(CR) falls below 30 ml/min/1.73 m2. No additional dosage adjustments appear to be necessary for hemodialysis patients.     

Effect of hemodialysis on left ventricular function. Dissociation of changes in filling volume and in contractile state

Prior studies of the effect of hemodialysis on left ventricular function have not distinguished between the removal of uremic toxins and the change in cardiac filling volume. To separate these effects, left ventricular function was examined by serial echocardiography in five stable hemodialysis patients before and after three different dialysis procedures: (a) hemodialysis with volume Loss, (b) ultrafiltration (volume loss only), and (c) hemodialysis without volume loss. The patients were similarly studied under control conditions and after increased (5 degrees of head-down tilt for 90 min) and decreased (lower body negative pressure) cardiac filling volume. After hemodialysis with volume loss, end-diastolic volume (EDV) decreased from 167 to 128 ml (P less than 0.001) and end-systolic volume (ESV) decreased from 97 to 51 ml (P less than 0.001) without a change in stroke volume (SV). Ejection fraction increased from 42 to 52% (P less than 0.001) and mean velocity of circumferential fiber shortening (VCF) increased from 0.61 to 1.04 circumferences (circ)/s (P less than 0.001). After ultrafiltration, EDV decreased from 167 ml to 124 ml (P less than 0.001) and SV from 73 ml to 39 ml (P less than 0.001), without significant changes in ESV or VCF. In contrast to the maneuvers in which volume loss occurred, after hemodialysis without volume loss ESV decreased from 95 to 66 ml (P less than 0.001) and SV increased from 74 ml to 97 ml (P less than 0.001) without changes in EDV. EF increased from 44 to 59% (P less than 0.001) and VCF increased from 0.64 to 1.26 circ/s (P less than 0.001). Ventricular function curves plotted from data obtained under conditions of altered cardiac filling volume before and after the three dialysis maneuvers demonstrate that ultrafiltration produced a pure Frank-Starling effect, while hemodialysis with or without volume loss produced a shift in the ventricular function curves, which demonstrated an increase in the contractile state of the left ventricle. The changes in left ventricular function produced by regular hemodialysis are the combined effects of a decrease in EDV and an increase in the contractile state of the left ventricle.     

Hepatic and renal extraction of circulating type I procollagen aminopropeptide in patients with normal liver function and in patients with alcoholic cirrhosis

The circulating level and splanchnic and renal extraction of serum type I procollagen aminoterminal propeptide (PINP) was studied in 20 patients with normal liver function and in 15 patients with alcoholic liver cirrhosis. In patients with alcoholic cirrhosis, the concentration of PINP in the femoral artery blood was significantly higher than in the group of patients with normal liver function (median 145 microg/l, 95% CI 98-195 versus 57 microg/l, 95% CI 42-92, p<0.001). A significant decrease in the concentration of PINP between the femoral artery (median 57 microg/l, 95% CI 42-92) and the hepatic vein (median 45 microg/l, 95% CI 40-70, p<0.001) was found in patients with normal liver function. In this group we also observed a significantly higher concentration of PINP in femoral artery blood (median 60 microg/l, 95% CI 45-87) as compared with that in renal vein (median 50 microg/l, 95% CI 40-65, p<0.001). In contrast, serum-PINP did not differ between arterial and hepatic or venous venous blood in patients with alcoholic cirrhosis. Size-chromatography revealed no significant change in the ratio of the high and low molecular forms of PINP following extraction in liver and kidney. It is concluded that circulating PINP is extracted in the normal liver and kidney, and that the serum concentration of PINP is significantly higher in patients with alcoholic cirrhosis than in patients with normal liver function. Both the hepatic and the renal clearance of PINP are seriously impaired/reduced in patients with alcoholic cirrhosis.     

Cefotaxime and desacetyl cefotaxime kinetics in renal impairment

Cefotaxime and desacetyl cefotaxime kinetics after a single, 1 gm intravenous dose were evaluated in five groups of subjects: group I, normal creatinine clearance (CLCR greater than 90 ml/min); group II, mild renal insufficiency (CLCR 30 to 89 ml/min); group III, moderate renal insufficiency (CLCR 16 to 29 ml/min); group IV, severe renal insufficiency (CLCR 4 to 15 ml/min); and group V, end-stage renal disease requiring maintenance hemodialysis (CLCR less than 6 ml/min). The steady-state volume of distribution (Vss) ranged from 10% to 55% of body weight but was not related to CLCR. The terminal t1/2 values of cefotaxime and desacetyl cefotaxime were 0.79 and 0.70, 1.09 and 3.95, 1.55 and 5.65, 2.54 and 14.23, and 1.63 and 23.15 hours in groups I to V, respectively. There were no significant changes in Vss or t1/2 after multiple dosing, but there were significant correlations between CLCR and cefotaxime total body clearance, cefotaxime and desacetyl cefotaxime renal clearance, and cefotaxime nonrenal clearance. Dosage regimens for the use of cefotaxime in patients with renal impairment are proposed.     

Circulating endogenous vasoactive intestinal polypeptide (VIP) in patients with uraemia and liver cirrhosis

The concentration of vasoactive intestinal polypeptide (VIP) in peripheral venous plasma was median 6.0 pmol l-1 (range 0-20) in 112 normal subjects. In fifty-three patients with decreased kidney function plasma VIP was significantly increased (median 15.0 pmol l-1, range 0.5-70, P less than 0.0001) and positively correlated to serum creatinine concentration (r = 0.51, P less than 0.001). In 133 patients with liver cirrhosis peripheral venous VIP was slightly elevated (median 7.0 pmol l-1 range 0-86, P less than 0.01). Samples obtained during a central venous catheterization showed significant renal extraction of circulating VIP in control subjects (median extraction fraction 23%, P less than 0.05, n = 6) and in patients with cirrhosis (median 60%, P less than 0.02, n = 8), but not in uraemic patients (median 0%, NS n = 5). In control subjects and patients with cirrhosis the concentration of VIP in the hepatic vein was significantly below that of systemic plasma (-42%, P less than 0.05, n = 6 and -45%, P less than 0.01, n = 10, respectively). On the contrary, in uraemic patients hepatic venous VIP was almost similar to systemic VIP (-4%, NS, n = 7). The results indicate that in normal subjects and patients with cirrhosis both the liver and kidneys are involved in the biodegradation of VIP. The elevated level of circulating VIP in uraemic patients may in part be due to decreased renal and hepatic biodegradation but increased neuronal release of VIP, especially in the splanchnic system, may also contribute to the increased plasma VIP in this condition.     

肾动态显像前位采集测定肾脏前移患者肾小球滤过率的可行性

目的探讨单侧肾脏前移患者肾动态显像前位采集测定肾小球滤过率(glomerular filtration rate,GFR)的可行性和准确性。方法选择2017年8月至2021年12月于复旦大学附属中山医院核医学科行肾动态显像，并通过Gates法测定GFR的单侧肾脏前移患者22例，同时进行前位和后位图像采集，并使用后位图像处理双肾数据，使用前位图像处理前移单肾数据，计算相应GFR值。健侧肾后位采集测定的GFR值与前移肾前位采集测定的GFR值之和记作GFR_优化；常规后位采集测定的双肾GFR值之和记作GFR_常规。采用慢性肾脏病流行病学协作组(Chronic Kidney Disease Epidemiology Collaboration,CKD-EPI)推荐的基于血清肌酐(serum creatinine,sCr)方程计算的估算GFR(estimated GFR,eGFR)作为参照值，比较GFR_优化、GFR_常规与eGFR的差异，并进行Pearson相关性分析。结果22例患者前移单肾的前位肾脏深度显著小于后...     

Evidence for two distinct and functionally important sites of enhanced thromboxane production after bilateral ureteral obstruction in the rat.

1. After bilateral ureteral obstruction there is an enhanced production of thromboxane A2 by the kidney which contributes to a decline in renal function. An acute interstitial macrophage infiltrate also occurs. 2. The relative contribution of infiltrating cells and intrinsic renal cells to the enhanced production of thromboxane A2 by the hydronephrotic kidney were determined. The effects of both irradiation and subsequent administration of the thromboxane synthesis inhibitor OKY-046 on both thromboxane B2 excretion and renal function were examined in rats with 24 h bilateral ureteral obstruction. 3. Irradiation effectively prevented the leucocyte infiltrate after bilateral ureteral obstruction (1.2 +/- 0.8 x 10(5) versus 27.1 +/- 0.1 x 10(5) cells/g of cortex, n = 4 in each group), resulted in a significantly higher inulin clearance (2.78 +/- 0.27 versus 1.49 +/- 0.17 ml min-1 kg-1 body weight, n = 7 and n = 8, respectively, P less than 0.001) and reduced thromboxane B2 excretion to 39% of non-irradiated values. Subsequent administration of OKY-046 to previously irradiated animals further reduced thromboxane B2 excretion to 20% of the value in non-irradiated rats with bilateral obstruction and further increased inulin clearance to 3.34 +/- 0.26 ml min-1 kg-1 body weight. 4. Glomerular macrophage numbers were decreased after bilateral ureteral obstruction (in contrast to the interstitium). However, glomeruli isolated from rats with 24 h bilateral ureteral obstruction exhibited enhanced production of thromboxane B2 compared with sham-operated control rats (855.6 +/- 31.1 versus 392.2 +/- 25.5 pg 60 min-1 mg-1 of protein, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

基于三维超声构建糖尿病肾病诊断预测模型的初步研究

目的应用三维超声获得肾脏体积参数,结合临床资料指标建立诊断糖尿病肾病的预测模型方程。 方法选取2型糖尿病合并肾损害的研究对象62例,根据肾脏穿刺活检病理结果将其分为糖尿病肾病（DN）组和非糖尿病肾病（NDRD）组,其中DN组35例,NDRD组27例,通过三维超声得出肾脏体积,并用其体表面积进行校正得出肾脏体积指数,比较分析两组研究对象的性别、年龄、体重、身高、体重指数、体表面积、收缩压/舒张压、尿蛋白、肾小球滤过率、血浆尿素氮、血肌酐、尿肌酐、空腹血糖、糖尿病病史、是否进行糖尿病治疗、是否有糖尿病视网膜病变、是否有血尿以及双肾体积、肾脏体积指数是否存在差异,选取临床资料指标与肾脏体积指数用Logistic回归进行预测模型的建立。 结果DN组与NDRD组比较,收缩压、尿蛋白、肾小球滤过率、血浆尿素氮、血肌酐、糖尿病病史、是否有糖尿病视网膜病变、是否有血尿临床资料,差异均有统计学意义（t=4.8056、2.3748、5.0350、4.0205、4.3821、5.9283,χ²=2.9606、3.1691,P均<0.05）,右肾肾脏体积指数两组间的比较,差异有统计学意义（t=2.7166,P<0.05）,性别、年龄、体重、身高、体重指数、体表面积、舒张压、尿肌酐、空腹血糖、是否进行糖尿病治疗、右肾体积、左肾体积和左肾体积指数,差异均无统计学意义（P均>0.05）;通过双肾肾脏体积指数和主要临床资料参数构建诊断预测模型方程,预测模型方程判断DN的ROC曲线下面积为0.9217,95%置信区间（0.8557~0.9877）,最佳阈值0.2069,特异度85.19%,敏感度85.71%,准确性85.48%,阳性预测值0.8824,阴性预测值0.8214,阳性似然比5.7857,阴性似然比0.1677。 结论基于三维超声建立的DN诊断的预测模型方程,可为临床诊断DN提供了一种新的诊断手段,对今后的临床诊断和治疗有重要的意义。