Pharmacokinetics of Cefaclor in Normal Subjects and Patients with Chronic Renal Failure

We studied the pharmacokinetics of cefaclor, a new cephalosporin antibiotic, in normal subjects and subjects with chronic renal failure. Cefaclor was largely, but not entirely, eliminated by the kidneys. The cefaclor half-life in normal subjects was 40 to 60 min; in subjects with essentially no renal function, it increased to 3 h. In normal subjects, 50 to 70% of a 250-mg dose was excreted in the urine within 8 h. The linear relationship between the elimination constant and creatinine clearance allowed the construction of a useful dosage modification nomogram.     

Pharmacokinetics of Minocycline in Renal Failure

The pharmacokinetics of minocycline have been studied after single intravenous infusions and repeated oral doses to human subjects with varying degrees of renal impairment. There was no evidence of reduced drug clearance with reduced renal function after intravenous doses although there appeared to be an increase in the tissue distribution of antibiotic in the body in uremia. After identical multiple oral dosage regimens serum levels of antibiotic were comparable in normal and mildly uremic subjects. There was no evidence of renal toxicity in normal or uremic subjects with the repeated dosage regimen used.     

The Artificial Kidney in Chronic Renal Failure

Hemodialysis has proved valuable in improving and stabilizing patients in terminal chronic uremia.

In this analysis of 71 patients in whom hemodialysis was used, the diagnosis and therapeutic response were definitely correlated. The highest percentage of favorable responses was obtained in cases of polycystic renal disease; none of the patients with subacute glomerulonephritis responded favorably.

The prognosis was worse in chronic glomerulonephritis when hypertension or extensive glomerular destruction was present. Factors such as age, congestive heart failure and active infection were not significant in predicting a response.     

Myopathy in Chronic Renal Failure

A group of eleven patients in end-stage renal failure who developedproximal weakness is described. The muscle weakness in all caseswas shown to be myopathic in nature by quantitative electromyography.Four of the patients presented with muscle dysfunction and werefound to have severe osteomalacia secondary to renal disease.In these patients vitamin D in high doses produced some improvementin muscle weakness. In the other patients who were on maintenancedialysis, muscle weakness improved dramatically after renaltransplantation or dialysis with deionized water. There wereno quantitative differences between the two groups as far asmuscle weakness was concerned. However it is suggested thatmetabolic bone disease may be one pathogenic factor in the firstgroup and that some aspect of renal failure per se (or its treatmentby dialysis) may predominate in the second and contribute tothe first. ¹Present address: Medical School, Northwestern University, 303East Chicago Avenue, Chicago 60611, Illinois, U.S.A. ²Present address: Department of Neurology, Wayne State UniversityMedical School, Detroit, Michigan 48092, U.S.A.     

Pseudoclubbing in Chronic Renal Failure

Seven patients with chronic renal failure developed a peculiarabnormality of the fingers referred to as pseudoclubbing. Allhad radiological evidence of severe secondary hyperparathy roidismand elevated parathormone levels measured by C-terminal assay.Treatment with vitamin D and calcium, parathyroidectomy or renaltransplantation resulted in radiological healing but the deformityof the finger tips did not improve. Although these patientsrepresent a group with severe secondary hyperparathyroidism,autonomous secretion of parathormone is not a necessary accompanimentof this disorder.     

瘦素与慢性肾功能衰竭

瘦素是一种由肥胖基因（Obgene）编码的分子量为16.7kDa的多肽类激素,具有降低食欲、增加能量消耗等重要生理作用。瘦素与肾脏的关系密切,肾脏是瘦素的主要清除器官,同时瘦素又可对肾脏功能产生直接作用,影响慢性肾功能衰竭患者的疾病进程。因此,研究者希望通过调节血清中瘦素水平,达到缓解慢性肾功能衰竭进程的目的。     

Pharmacokinetics of Cefamandole in Patients with Renal Failure

The pharmacokinetics of cefamandole were studied in four patients with stable renal failure, two patients undergoing peritoneal dialysis, and four patients undergoing hemodialysis. Peak concentrations of cefamandole in serum were achieved 1 to 2 h after intramuscular injection in the patients with stable renal impairment, and the concentrations declined slowly, with half-life values of 12.3 to 18 h. Cefamandole was removed only very slowly by peritoneal dialysis. Hemodialysis was more efficient in removing cefamandole, with serum half-life values ranging from 3.8 to 7.9 h. The mean apparent volume of distribution of cefamandole in these 10 patients was 21.92 liters, or 31% of the body weight.     

Pharmacokinetics of Nafcillin in Patients with Renal Failure

Nafcillin, a pencillinase-resistant penicillin, is frequently used for treatment of staphylococcal infections in hemodialysis patients. Despite its widespread use, there is a paucity of available data regarding the pharmacokinetics of nafcillin in hemodialysis patients. Therefore, sodium nafcillin, 25 mg/kg, was given intravenously over a 5- to 15-min period to 12 hemodialysis patients. Eleven patients were studied during dialysis, and eight of these were studied again during the interdialysis period. The initial serum half-life for nafcillin was 0.208 h during dialyses and 0.278 h between dialyses. The terminal half-life was 1.48 h during dialyses and 1.89 h between dialyses. There was no statistically significant difference between these values. These data indicate that renal failure does not appreciably affect the serum half-life of nafcillin, and hemodialysis does not accelerate the rate of clearance of nafcillin from the blood. Therefore, no modification of the usual nafcillin dosage is necessary when using this drug in hemodialysis patients.     

Urea Metabolism in Chronic Renal Failure

Urea degradation was measured during 16 experiments in 13 chronic uremic patients being treated with essential amino acids or their analogues. [(14)C]Urea was injected i.v. and the clearance of labeled urea from its volume of distribution was compared with the simultaneous renal clearance of ordinary urea, which averaged 2.0 liters/day. The difference, extrarenal clearance of urea, averaged 3.1 liters/day as compared with a previously reported mean of 18 liters/day in normal subjects. Thus urea-splitting activity in the gut of uremic subjects expressed in these terms is far less than in normal individuals. Nevertheless, the amount of ammonia N formed from urea in these patients, 3.5 g/day, is not significantly different from normal, owing to their elevated plasma urea. In the same subjects, urea appearance rate was measured as the sum of urea excretion and the daily change in the urea pool. No negative correlation was noted between urea appearance and urea degradation, as might be expected if portal ammonia were being utilized for protein synthesis. However, urea production was positively correlated (r = 0.76) with urea degradation, suggesting that most of the resulting portal ammonia is converted back to urea. The results fail to support the view that degradation of urea in the gut promotes N conservation in uremic subjects maintained on low protein diets.     

Body Composition in Chronic Renal Failure

In severe chronic renal failure loss of weight is common dueto a reduction in body fat and fat-free solids. The lean bodymass forms an increased proportion of body weight. Body wateris relatively increased largely due to an excess extracellularfluid. Intracellular fluid is reduced relative to standard weightin the majority of patients. The exchangeable sodium is increased. The changes are not confined to patients with terminal uraemiabut are most marked in those who have received prolonged treatmentwith low-protein diets. After the start of regular haemodialysis body weight falls becauseof losses of body water from both extracellular and intracellularspaces. Thereafter body weight increases, due to gains in bodyfat and fat-free solids. Changes in exchangeable sodium arevariable. Intercurrent illness, poor dialysis, or fluid indiscretionsrapidly induce a return of the original abnormalities and recoveryis slow. Similar changes in body composition are observed after renaltransplantation though these may be modified by large dosesof prednisone. In general, transplantation is more effectivein restoring body composition to normal than haemodialysis. These changes closely resemble those found in malnutrition andit is suggested that the abnormalities of body composition foundin chronic renal failure are attributable to protein-caloriedeficiency. ¹This work forms part of a thesis approved by the Universityof London for the degree of Doctor of Medicine.     

The Ventilatory Cost of Exercise Compared in Chronic Heart Failure and Chronic Renal Anaemia

The cardiorespiratory responses to maximal treadmill exercisewere compared in matched groups of patients with chronic renalanaemia or treated chronic heart failure, and in normal controls.Exercise capacity was similarly reduced in both patient groupscompared to normal controls, the raised respiratory exchangeratio at peak exercise implying anaerobic metabolism due tolimited oxygen delivery in heart failure and limited oxygencarrying capacity in anaemia. Minute ventilation (V_F) was relatedlinearly to minute CO₂ production (VCO₂) in all subjects (eachr>0.92) from all three groups. The slope of the V_E/VCO₂ relationshipwas normal in anaemia but steeper in heart failure, reflectingventilation/perfusion mismatching in chronic heart failure.     

Influence of Renal Failure on Ciprofloxacin Pharmacokinetics in Rats

Ciprofloxacin pharmacokinetics have been shown to be modified in patients with renal failure (e.g., the intestinal secretion of ciprofloxacin is increased). This study investigated the influence of renal failure on the pharmacokinetics of ciprofloxacin following oral and parenteral administration to rats of a dose of 50 mg/kg of body weight. After parenteral administration, only renal clearance (CL_R) was reduced in nephrectomized rats (5.3 ± 1.4 versus 17.8 ± 4.7 ml/min/kg, P < 0.01, nephrectomized versus control rats). However, nonrenal clearance was increased in nephrectomized rats (32 ± 4 versus 15 ± 5 ml/min/kg, P < 0.01, nephrectomized versus control rats), suggesting compensatory mechanisms for reduced renal function. After oral administration, apparent total clearance and CL_R were reduced (P < 0.01) in nephrectomized rats (117 ± 25 and 6.8 ± 4.4 ml/min/kg, respectively) compared with the values for control rats (185 ± 9 and 22.6 ± 5.3 ml/min/kg, respectively) and the area under the concentration-time curve was higher (P < 0.01) for nephrectomized rats (436.3 ± 90.5 mg · min/liter) than for control rats (271.3 ± 14.3 mg · min/liter). Terminal elimination half lives in the two groups remained constant after oral and parenteral administration. These results suggest an increased bioavailability of ciprofloxacin in nephrectomized rats, which was confirmed by a nonlinear mixed-effect model.     

Effects of Renal Failure and Dialysis on Cefazolin Pharmacokinetics

Serum and urinary levels of cefazolin were determined after a 500-mg parenteral dose in eight azotemic volunteers. The mean peak serum concentration was 1.5 to 5 times the levels obtained in nonazotemic patients. The serum half-life of cefazolin was increased significantly. In patients on dialysis, the mean serum half-life of cefazolin was 4.05 h during (or after) hemodialysis, and 32.1 h during (or after) peritoneal dialysis. There was a significant decrease in cefazolin removal when dialysate flow or membrane surface area of the dialyzer were decreased. It was also shown that one circuit through the dialysis unit caused measurable decrease in cefazolin concentration. These data and previously published reports suggest: (i) the maintenance dose of cefazolin can be decreased in azotemic patients; (ii) patients on hemodialysis will require an additional half dose after dialysis because of efficient removal during hemodialysis; and (iii) patients on peritoneal dialysis do not require an extra dose.     

Plasma 25-Hydroxycholecalciferol in Chronic Renal Failure

Abstract. 47 patients with chronic renal failure were investigated for plasma 25-hydroxycholecalciferol (25-OH D₃) concentration, serum calcium, phosphorus, alkaline phosphatase. 22 patients had chronic haemodialysis twice weekly. There is a highly significant positive coefficient of correlation between calcaemia and 25-OH D₃ plasma concentration. Levels of serum calcium had previously been shown to correlate well with the presence and type of osteodystrophies in chronic renal failure. Since these patients may be unable to synthesize 1,25 dihydroxy D₃, the metabolite of vitamin D₃ considered to be active on intestine and bone, a direct role of 25-OH D₃ in the regulation of calcium metabolism may have to be considered.     

老年慢性肾功能衰竭并发急性左心功能衰竭的早期诊断

目的为老年慢性肾功能衰竭(CRF)患者并发急性左心功能衰竭(AHF)的早期诊断和处理提供帮助。方法50例60岁以上CRF患者分为两组,I组为CRF并发AHF31例,Ⅱ组为同期其他疾病并发AHF19例,采用临床调查法对其常见的临床早期症状进行对比分析。结果老年CRF并发AHF时早期症状不典型,更容易延误病情。结论在临床上准确及时诊治可阻止病情的发展,挽救患者的生命。     

The Influence of Misoprostol on the Adverse Renal Effects and Stereospecific Pharmacokinetics of Ibuprofen in Chronic Renal Insufficiency

The use of nonsteroidal anti-inflammatory drugs in patients with chronic renal insufficiency (CRI) may be complicated by renal functional abnormalities due to the inhibition of renal prostaglandins. We tested the hypothesis that administration of the oral PGE1 analog, misoprostol, could attenuate the adverse renal effects of ibuprofen in patients with CRI. Because the metabolism of misoprostol and the stereoinversion of R- to S-ibuprofen involve the same metabolic pathway, the stereospecific pharmacokinetics of ibuprofen were also evaluated. In a randomized, crossover trial of six stable CRI patients (Clcr 25--67 ml min(minus sign1)), in sodium balance on a 150 mEq Na(+) per day metabolic diet, we compared the effects of ibuprofen 600 mg qid with and without misoprostol 200 &mgr;g qid upon Clcr, Clinulin, Clpah, Na(+), and K(+) excretion during 4-h clearance studies. We also assessed stereospecific ibuprofen kinetics following single dose (acute) and after 7 days on drug(s) (chronic). Daily weights, supine blood pressures, electrolytes, osmolality, BUN, creatinine and 24-h urine collections for Clcr and Na(+) and K(+) excretions were obtained during chronic dosing. Supine and upright plasma renin activities were obtained prior to dosing and during chronic dosing for both treatment limbs. Ibuprofen alone resulted in an approximately 20% transient reduction in GFR, occurring 2--2.5 h following dosing in both the acute and chronic clearance studies. This was not affected by misoprostol. There was a greater degree of stimulation of PRA with the upright posture with misoprostol plus ibuprofen than with ibuprofen alone. There was a significant weight gain in both study limbs, but no effect of misoprostol (1.2 plus minus 0.2 kg ibuprofen alone and 1.0 plus minus 0.2 kg ibuprofen plus misoprostol, p = 0.13). Otherwise no clinically significant alteration in renal function occurred in either treatment limb. The presence of misoprostol did not alter the stereospecific pharmacokinetics of ibuprofen. We conclude that misoprostol does not significantly alter the renal effects of ibuprofen in patients with mild to moderate CRI.     

慢性肾功衰竭患者的糖代谢紊乱

本文测定了27例慢性肾功衰竭(CRF)患者口服葡萄糖耐量试验(OGTT)时的血清胰岛素,并以性别年龄匹配的27例正常人作为对照。结果显示CRF患者耐糖曲线及胰岛素释放曲线均高于正常对照组;耐糖异常(IGT)及耐糖正常(NGT)的CRF患者胰岛素释放曲线有明显差异。     

慢性肾功能衰竭患者血脂与颈动脉硬化的关系

【目的】研究慢性肾功能衰竭维持性血液透析患者与非透析患者血脂与颈动脉硬化的关系。【方法】收集27例慢性肾功能衰竭维持性血液透析患者（A组）、27例配时对照者及25例非透析患者（B组）、25例配时时照者．查血TC．TG，HDL-C．LDL-C，Apo-Al．ApoB及Lipoprotein（a）[LP（a）]；彩超观测双侧颈总动脉、颈动脉分叉处及颈内动脉的解剖及血流动力学情况，包括斑块，最大（Vmax）和最小血流速度（Vmin）（即收缩期和舒张期峰值血流速度），血管内皮厚度（即内膜-中膜厚度．IMT）．阻力指数（RI）。【结果】A组HDL-C较对照组显著降低，LP（a）显著增高（均P〈0．01）；B组Apo—B、TG、LDL-C、LP（a）显著增高（P〈0．01～0．05），HDL-C显著降低（P〈0．01），A组和B组血脂结果比较未见显著性差异（P〉0．05）；A组与其对照组相比平均IMT、最大IMT、RI、斑块发生率均显著增高（P〈0．01）；Vmin显著降低（P〈0．01）。B组与其时照组相比平均IMT、最大IMT、斑块发生率均显著增高（P〈0．01）．A组较B组Vmin显著降低（P〈0．01）；颈动脉斑块阴性组和阳性组患者血脂结果比较未见明显差异；斑块阳性组患者较阴性组平均IMT、最大IMT均有显著性增厚；A组和B组LDL-c、Lp（a）、Apo-B分别与平均IMT、最大IMT呈正相关（P〈0．05）。【结论】慢性肾功能衰竭维持性血液透析患者和非透析患者存在血脂异常和动脉硬化．并存在一定关系．纠正血脂异常有可能改善慢性肾功能衰竭维持性血液透析患者和非透析患者的生存率。     

彩色多普勒对慢性肾功衰竭肾动脉血流参数范围探讨

本文利用彩色多普勒成像技术对慢性肾功衰竭失代偿期患者４５例的肾动脉血流分布、频谱特征及血流参数进行检测。旨在对临床医师提供参考及疾病鉴别。结果：（１）、慢性肾衰双侧主肾动脉及分支血流信号分布有逐渐减弱甚至消失的趋势，主肾动脉显示率为１００％（４５／４５），段动脉显示率为９３％（４２／４５），叶间动脉显示率为５８％（２６／４５），弓形动脉显示率为０（０／４５）；（２）、各级动脉频谱波峰变钝，舒张充盈曲线低平、中断，曲线欠光滑，空心层流消失，弓形动脉频谱极难测得；（３）、肾动脉血流参数表明从主肾动脉至分支血流速度逐级明显降低，阻力指数较大，搏动指数增大。结论：本组结果表明，慢性肾衰失代偿期患者肾动脉及分支血流分布、频谱特征及血流参数与正常相差较大，从而以血流信号的分布、频谱形态的变化及血流参数的异常初步判断肾血流及肾功能状态，以迅速了解病情、监测治疗、估评预后，为慢性肾衰的快速判定和全面诊断提供更加完善的依据     

慢性肾衰竭患者血小板一氧化氮合酶活性的改变

目的 通过测定慢性肾衰竭(CRF)患者血小板一氧化氮合酶(NOS)的活性,探讨CRF患者血小板损伤的机制.方法 取12例CRF患者外周静脉血,利用凝胶色谱柱法收集血小板,同位素二步色谱法测定血小板NOS活性.健康成人10名作为对照.结果 CRF患者血小板NOS活性明显低于正常人(P＜0.01).组胺刺激后血小板NOS活性仍低于正常(P＜0.05).结论 CRF患者血小板功能异常与其血小板NOS活性降低有关.