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1.
The renal function of 15 patients receiving cis-platinum (II) dichlorodiammine (CPDD) was examined prospectively in detail to elucidate early evidence of nephrotoxicity. Patients were given a total of 49 couses of CPDD at 20 mg/m2/day for 5 days with 1,000 ml of saline prehydration. Renal function was monitored by serial determinations of serum creatinine and glomerular filtration rate (measured as 125I-iothalamate clearance) and by measurement of parameters of tubular function, including tubular reabsorption of phosphorus, urine-to-serum glucose ratio, total protein, and total free immunoglobulin light chain excretion, serum electrolytes, and urine pH and specific gravity. There was no significant change in mean serum creatinine within a course of treatment, nor was there a cumulative increase in the serum creatinine. In 9 of 19 evaluable courses there was a small transient fall in glomerular filtration rate with prompt recovery. There was no cumulative decrease in glomerular filtration rate through 3 courses of treatment. Four of the patients with preexisting renal insufficiency suffered no significant additional nephrotoxicity. There was no tubular dysfunction demonstrable in any of the patients. This study represents the first prospective detailed examination of multiple parameters of renal function in patients treated with CPDD and reveals that the only parameter to show any change with this schedule of drug administration was the glomerular filtration rate.  相似文献   

2.
The pharmacokinetics, distribution, and plasma and renal clearance of a new aminoglycoside antibiotic, tobramycin, was studied in the treatment of 18 elderly male patients (average age, 69 years) with urinary tract infections. Ten of these patients had normal renal function and eight had impaired renal function of various degrees. After administration of 1 mg of tobramycin/kg of body weight every 6 to 8 h (two to three times the half-life), urine concentrations were found to be sufficient in the treatment of urinary tract infections caused by susceptible organisms. The renal clearance of tobramycin during constant intravenous infusion was also studied in eight patients. Good correlation was found between the patients serum creatinine and the half-life of tobramycin. The half-life of tobramycin in patients with normal renal function (serum creatine [Formula: see text] to 1.5 mg/100) was on the average 3 h. For practical purposes, therefore, the dosage of tobramycin in the treatment of urinary tract infections should be 1 mg/kg of body weight every 6 to 8 h in patients with normal renal function. For patients with impaired renal function, the dosage interval is calculated by multiplying the patients' serum creatinine by six. If the dosage intervals are kept unchanged, the dosage must be divided by the patients' serum creatinine. The initial loading dose should always be 1 mg/kg. The total renal clearance of tobramycin (92% of the glomerular filtration rate) was not influenced by the administration of probenecid, which indicates that tobramycin is excreted only by glomerular filtration.  相似文献   

3.
A total of 201 critically ill patients were studied during 267 courses of gentamicin or tobramycin treatment (139 gentamicin courses and 128 tobramycin courses). Of these 267 courses, pharmacokinetic and clinical data were obtained for 240 (120 gentamicin and 120 tobramycin). The data collected for pharmacokinetic analysis included measurements of serial blood and urine levels, urinary excretion of beta 2-microglobulin, protein levels, and granular casts. A two-compartment model was used to assess tissue accumulation, and in 89 courses the predicted accumulation was confirmed by cumulative urine collection or postmortem tissue analysis. As groups, the patients given gentamicin and tobramycin did not differ in age, weight, creatine clearance, total dose given, duration of treatment, initial aminoglycoside through serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Previous aminoglycoside treatment (usually gentamicin) had occurred more frequently in the tobramycin treated patients (P less than 0.01), and more males than females received tobramycin (P less than 0.05). Pharmacokinetic assessments of renal damage were based on both changes in glomerular filtration rate (serum creatinine levels, creatinine clearance) and renal tubular damage (beta 2-microglobin, casts), but only patients with elevated aminoglycoside tissue levels leading to renal tubular damage and subsequent creatinine clearance decreases were considered to have experienced aminoglycoside nephrotoxicity. In the pharmacokinetic analysis of nephrotoxicity, 29 gentamicin courses (24%) and 12 tobramycin courses (10%) were complicated by nephrotoxicity (P less than 0.01). The 201 study patients were also evaluated independently for clinical nephrotoxicity (defined as a serum creatinine level increase of 0.5 mg/dl or more). Clinical nephrotoxicity occurred at rates of 37% in the gentamicin-treated group and 22% in the tobramycin-treated group (P less than 0.02). In these similar groups of critically ill patients, tobramycin was less nephrotic than gentamicin.  相似文献   

4.
We undertook assessment of hearing in patients with cystic fibrosis who were taking part in a large randomized controlled trial of once- versus three-times-daily tobramycin for pulmonary exacerbations of cystic fibrosis (the TOPIC study). All patients were eligible to have standard pure tone audiometry performed across the frequency range of 0.25 to 8 kHz. High-frequency pure tone audiometry over 10 to 16 kHz was also performed with a subset of patients. Audiometry was undertaken at the start of tobramycin treatment, at the end of a 14-day course of treatment, and at follow-up 6 to 8 weeks later. We enrolled 244 patients, of whom 219 (125 children and 94 adults) completed treatment. Nineteen patients were excluded from analysis due to abnormal baseline audiometry. Complete pre- and posttreatment standard audiological data were obtained for 168/219 patients. We found no significant differences in hearing thresholds when they were assessed at the baseline, at the end of treatment, and at follow-up 6 to 8 weeks later were compared. In addition, no significant differences in hearing thresholds were detected between treatment regimens. Similar results were obtained for the subset of 63/168 patients who underwent high-frequency audiometry. We conclude that for a single 14-day course of tobramycin treatment in patients with cystic fibrosis with no preexisiting auditory deficit, no measurable effect on hearing was apparent with either once- or three-times-daily treatment. Estimation of the cumulative cochleotoxic risk in cystic fibrosis patients due to repeated aminoglycoside therapy, as evidenced by the patients excluded from this study due to hearing loss, also requires further characterization.  相似文献   

5.
In 40 CAPD patients treated for peritonitis, the authors did a prospective study of ototoxic effects of intraperitoneal tobramycin. They evaluated cochlear function in pure-tone threshold audiograms over a range of frequencies from 250-10,000 Hz, in the speech-reception threshold test and in the speech-discrimination test. These tests were performed within 48 hours of initiation of tobramycin treatment and within 2 or 3 weeks of the drug's discontinuation. With the aminoglycoside doses used in this study, no statistical difference between the mean baseline and mean follow-up hearing levels was seen in these 40 patients. However, according to the standard criteria of ototoxicity, the hearing in 10 of 40 patients (25%) deteriorated after tobramycin, while it improved in seven patients (17.5%). In the remaining 23 (57.5%), hearing remained stable. With respect to the risk factors for ototoxicity such as advanced age, increased duration of treatment, elevated plasma aminoglycoside levels, concomitant treatment with other ototoxic drugs, pre-existing hearing loss, renal dysfunction and hyperthermia, no statistically significant difference was demonstrated between the patients with deteriorated, stable or improved hearing. The results of this study do not confirm that tobramycin given intraperitoneally to CAPD patients produces auditory toxicity. The hearing deterioration observed in 10 patients may be due to synergistic factors. The improvement observed in 7 patients could not be explained.  相似文献   

6.
INTRODUCTION: The effects of protein-enriched diets on glomerular filtration have been described in normal subjects and in patients with chronic renal failure. In acute renal failure, the effects of administration of high rates of protein on renal function and nitrogen balance have not been studied in critically ill patients. The present study examines the effects of large doses of amino acids on the glomerular filtration rate and nitrogen balance in critically ill patients with acute renal failure. METHODS: Fourteen critically ill patients with a creatinine clearance below 50 ml/min and conserved diuresis above 2,000 ml/day received 2000 non-protein kcal/day and either 75 g (Group 1) or 150 g (Group 2) of amino acids parenterally. Renal function tests, fluid balance, sodium and nitrogen balances, and furosemide administration were assessed on day 1 (baseline day when dextrose 5% was administered) and days 2, 3 and 4. RESULTS: The two groups were comparable in terms of severity indices, sex and creatinine clearance. Group 2 was significantly older (p < 0.05). Blood urea nitrogen increased significantly in Group 1 but not in Group 2; creatinine clearance remained unchanged in the two groups. Group 2 patients had a significantly more positive cumulative nitrogen balance (-10.5 +/- 17 g/day vs. 9 +/- 8.3 g/day) (p < 0.01), less positive fluid balance (2003 +/- 1336 ml vs. -2407 +/- 1990 ml) and lower furosemide requirement (1003 +/- 288 mg vs. 649 +/- 293 mg) (p < 0.05). CONCLUSION: A high amino acid regimen administered as a part of parenteral nutrition improves nitrogen balance, reduces furosemide requirements and ameliorates water balance in acute renal failure patients with conserved diuresis.  相似文献   

7.
We analyzed data from three prospective, controlled, randomized, double-blind clinical trails to determine whether furosemide increases the nephrotoxicity and auditory toxicity of aminoglycosides. All patients who received at least 72 h of treatment and who had no other cause for nephrotoxicity or auditory toxicity were included in the analysis. Nephrotoxicity developed in 10 of 50 (20.0%) patients given furosemide and in 38 of 222 (17.1%) patients not given furosemide (P greater than 0.3). Auditory toxicity developed in 5 of 23 patients (21.7%) given furosemide and in 28 of 119 patients (23.5%) not given furosemide (P greater than 0.3). In each case, the groups receiving and not receiving furosemide did not differ in mean age, initial creatinine, duration of aminoglycoside therapy, mean change in auditory acuity or creatinine, mean number of days to the development of toxicity, the frequency with which gentamicin, tobramycin, amikacin, or cephalothin was administered, or the mean predose and 1-h postdose plasma aminoglycoside levels. We conclude that furosemide use should not be considered a major risk factor for the development of aminoglycoside-induced nephrotoxicity or auditory toxicity.  相似文献   

8.
BACKGROUND: Cystatin C has recently been proposed as an alternative marker of glomerular filtration rate. The diagnostic value of plasma cystatin C for the longitudinal assessment of kidney function after renal transplantation, however, has not been addressed. METHODS: Renal function was evaluated in 30 adults receiving renal transplants (46 +/- 9 years, mean +/- SD) and in 56 healthy controls (38 +/- 10 years) using cystatin C. Plasma cystatin C was determined daily starting the day of surgery and for 3 weeks after surgery by an immunonephelometric assay. RESULTS: Plasma concentration significantly decreased during the first week (-44% vs -29% for creatinine). Plasma cystatin C correlated with plasma creatinine (r = 0.741; P <0.0001) and the reciprocal of the creatinine clearance estimated by the Cockcroft-Gault formula (r = 0.882; P <0.001). In all three cases of acute renal impairment, the increase in plasma cystatin C values was more prominent than that of creatinine. CONCLUSIONS: Plasma cystatin C is an alternative and accurate marker of allograft function in adult transplant patients. Increased sensitivity compared with creatinine for the detection of acute reduction in glomerular filtration rate allows in some cases a more rapid diagnosis of acute rejection or treatment nephrotoxicity.  相似文献   

9.
AIM: A retrospective analysis of a clinical course of mesangioproliferative glomerulonephritis (MPGN) in patients with glomerular deposition of IgA (IgA nephropathy--IgA-N), with glomerular deposition of other Ig to determine prognostic factors of MpGN progression including IgA-N and to examine the patients' sensitivity to immunodepressive therapy. MATERIAL AND METHODS: 2000 patients with primary MPGN followed up from 1980 to 1999 from the disease onset to development of chronic renal failure (creatinine > 2.5 mg%). Factors affecting kidney survival were studied using the Cox regression model, factors predicting sensitivity to immunodepressive therapy--using multiple logistic regression. RESULTS: IgA-N differed by the course and prognosis from other forms of MPGN. In IgA-N urinary syndrome and macrohematuria were encountered more frequently, in other forms of MPGN more frequent was nephrotic syndrome. Prognosis of patients with IgA-N was worse than in MPGN patients without IgA deposition: 10-year "renal survival" (creatinine < 2.5 mg%) was 64 and 97% (p < 0.05), respectively. Prognosis-deteriorating factors for MPGN patients were the following: male sex, nephritis onset in 40-year-olds and older subjects, acute nephritic syndrome (creatinine > 1.5 mg%), high proteinuria, hematuria (> 50 in sight), the presence of synechia and TIC in renal biopsy, location of immune deposits both in the mesangium and basal glomerular membranes. The responders to the immunodepressive therapy had 10-year renal survival 100%. Positive results of immunodepressive therapy were observed significantly more frequently in patients with normal level of creatinine, moderate hematuria, absence of synechias and TIC in renal biopsy, given large total course dose of corticosteroids and cytostatics. Efficiency of oral cyclophosphamide and its intravenous pulse-therapy did not differ significantly. In pulse therapy an average cumulative dose was lower 6 times, side effects occurred 3 times less frequently. CONCLUSION: The importance of morphological information for prognosis and predicting sensitivity of MPGN patients to immunosuppressive therapy necessitates renal biopsy before therapy. Intravenous pulse therapy with cyclophosphamide is preferable as an active treatment in patients with sclerosis in renal biopsy.  相似文献   

10.
Renal function in rats with essential fatty acid deficiency   总被引:2,自引:0,他引:2  
1. Renal function was studied in 50-, 70-, 90- and 200-day-old rats with essential fatty acid deficiency. The pharmacokinetics of tobramycin was investigated in 90-day-old essential fatty acid-deficient rats. 2. A higher glomerular filtration rate and a higher serum concentration of urea were seen in 50-day-old essential fatty acid-deficient rats compared with age-matched controls. Later, the glomerular filtration rate progressively deteriorated in parallel with a decline in effective renal plasma flow and with a concomittant rise in serum levels of urea and creatinine. The serum concentration of protein was lower in the rats with essential fatty acid deficiency and that of sodium was higher than in the control rats. The non-renal clearance of tobramycin was increased in the rats with essential fatty acid deficiency. 3. The early hyperfiltration in essential fatty acid-deficient rats with the subsequent fall in glomerular filtration rate, which was paralleled by a rise in serum levels of urea and creatinine, as well as the increased non-renal clearance of tobramycin, are in accordance with the clinical manifestations of cystic fibrosis. Rats with essential fatty acid deficiency might be a useful model with which to study the pathophysiological renal changes in cystic fibrosis related to the progressive essential fatty acid deficiency in this disease.  相似文献   

11.
目的:探讨血清胱抑素C在重症患者伴有急性肾损伤早期诊断中的价值。方法:对ICU中39例发生AKI者(观察组)及32例未发生AKI者(对照组),采用酶法测血清肌酐水平,透射比浊法测血清胱抑素C水平,采用ROC评价血清胱抑素C的诊断价值,应用Cockroft-Gault公式估算肾小球滤过率。结果:观察组患者血清胱抑素C较对照组明显升高(P〈0.05),观察组血清胱抑素C与血清肌酐呈正相关关系(r=0.683,P〈0.05),与肾小球滤过率呈负相关关系(r=-0.346,P〈0.05)。ROC得出血清胱抑素C最佳截断值为1.65mg/L,肌酐最佳截断值为128.8μmol/L。急性肾损伤1期患者血清胱抑素C灵敏度(85%),高于血清肌酐灵敏度(70%),且出现异常的时间要早于肌酐。急性肾损伤2、3期患者间灵敏度比较差异无统计学意义(P〉0.05)。结论:在危重患者中血清胱抑素C可作为急性肾损伤肾小球滤过率的内源性标志物,对急性肾损伤患者早期诊断有重要作用。  相似文献   

12.
Renal function was studied during lithium treatment in 28 patientson two occasions separated by a mean interval of 4.7 years.Glomerular filtration rate, assessed by creatinine clearanceand serum creatinine concentrations, showed no impairment. Albuminexcretion rate, a marker of glomerular permeability, showedno consistent change. In contrast, a decline in urine concentratingability (mean 140 mOsm/kg) was found in all patients, exceedingthe reduction to be expected from ageing in all but three. Theseresults support the view that treatment with lithium long-termdoes not damage renal glomerular function, but that progressiveimpairment of the distal tubular responsiveness to arginineisvasopressin is common.  相似文献   

13.
A total of 157 patients were treated with tobramycin or amikacin in a controlled prospective randomized trial. Dosages were adjusted to renal function according to a nomogram. Trough and peak aminoglycoside levels were available at the end of the trial. Of the above total, 113 recipients of nine or more doses of tobramycin or six or more doses of amikacin, without other apparent cause of renal failure, were evaluated for nephrotoxicity. Thirty-six patients were evaluated for auditory toxicity. The patients in groups evaluated for either nephrotoxicity or auditory toxicity were similar with respect to intensity and etiology of bacterial disease, concurrent exposure to other antimicrobial drugs, age and sex distribution, initial serum creatinine level, and total dose and duration of antimicrobial therapy. Nephrotoxicity of similar severity developed in 4 of 59 (6.8%) recipients of tobramycin and in 7 of 54 (13.1%) recipients of amikacin (P greater than 0.05). Mild auditory toxicity developed in 3 of 19 (15.7%) recipients of tobramycin and in 2 of 17 (11.7%) recipients of amikacin (P greater than 0.05). When patients with abnormally high mean trough or peak aminoglycoside levels were excluded from comparison, nephrotoxicity was 6.12 and 5.12% (P greater than 0.05) and auditory toxicity was 17.6 and 7.69% (P greater than 0.05) in the groups given tobramycin and amikacin, respectively. We conclude that the nephrotoxicity and auditory toxicity of amikacin and tobramycin are not significantly different and that such toxicities are indeed infrequent events when the dosages of these drugs are adjusted to hold blood levels within the safe boundaries suggested by the studies of others.  相似文献   

14.
Renal function was studied during lithium treatment in 28 patients on two occasions separated by a mean interval of 4.7 years. Glomerular filtration rate, assessed by creatinine clearance and serum creatinine concentrations, showed no impairment. Albumin excretion rate, a marker of glomerular permeability, showed no consistent change. In contrast, a decline in urine concentrating ability (mean 140 mOsm/kg) was found in all patients, exceeding the reduction to be expected from ageing in all but three. These results support the view that treatment with lithium long-term does not damage renal glomerular function, but that progressive impairment of the distal tubular responsiveness to arginine vasopressin is common.  相似文献   

15.
Netilmicin, a new semisynthetic aminoglycoside, was used in the treatment of 42 patients with serious gram-negative bacterial infections. Of the 40 evaluable patients, 24 (60%) were cured, and 8 (20%) had a favorable clinical response, for a total clinical response rate of 80%. Eight patients failed to respond; of these, three had undrained abscesses and two had severe granulocytopenia. Three of the patients who failed had organisms in which resistance to netilmicin developed during therapy, and in two of these three netilmicin was the only aminoglycoside to which resistance developed. Of the 37 patients evaluable for toxicity, 8 (22%) developed renal insufficiency. Two patients had mild but persistant elevation in serum creatinine. Three patients had nephrotoxicity while on gentamicin in the past. Pre- and posttherapy audiograms were done on 26 patients; none had hearing loss. Four patients had mild, transient asymptomatic elevations in alkaline phosphatase. The pretreatment clinical isolates were tested for in vitro susceptibility. The median minimal inhibitory concentration of netilmicin, gentamicin, and tobramycin ranged between 0.5 and 2 mug/ml. The median minimal inhibitory concentration of amikacin was approximately twofold higher. No clear in vitro superiority of one aminoglycoside over another was observed.  相似文献   

16.
The pharmacokinetics and dosage requirements of gentamicin were studied in 1,640 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine or normal creatinine clearance. The half-life ranged from 0.4 to 32.7 h in 331 patients who had normal creatinine clearance. The factors related to the elimination rate constant were creatinine clearance, age, distribution volume, weight, gender, and hematocrit. The daily dose necessary to obtain therapeutic serum concentrations ranged from 0.5 to 25.8 mg/kg in patients with normal serum creatinine and from 0.7 to 25.8 mg/kg in patients with normal creatinine clearance. In 13 patients (0.9%), a significant change in base-line serum creatinine (greater than or equal to 0.5 mg/dl) occurred during or after treatment, which may have been gentamicin-associated toxicity. Overt cochlear or vestibular toxicity did not occur in these patients. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough serum concentrations.  相似文献   

17.
ObjectivesProton pump inhibitors (PPIs) are widely used for acid suppression therapy. Recently, PPI use was reported to be associated with chronic kidney disease (CKD); however, whether a low dose of PPIs is associated with CKD remains unknown.MethodsThis retrospective observational study included hypertensive patients who visited Kenwakai Hospital between 2017 and 2019. Renal parameters, such as the estimated glomerular filtration rate (eGFR) and serum creatinine (Scr), were extracted from medical records and compared between three years before treatment and the baseline. PPI use was assessed as cumulative exposure for three years.ResultsThe study population included 152 patients (57.9% men; mean age, 74.5 years). Of those, 35.5% were PPI users (low dose, 17.1%; high dose, 18.4%). A significant decrease in eGFR and an increase in Scr were observed between three years before treatment and the baseline in the high-dose PPI group but not the non-use or low-dose PPI groups.ConclusionsOur results suggest that a low dose of PPIs may be safe in clinical settings, but further prospective studies are needed to clarify our findings.  相似文献   

18.
In previous studies a high frequency of elevated plasma tHcy concentrations has been observed in psychogeriatric patients (40-50%), but the main cause of these increased concentrations could not be established with certainty. Impaired renal function could partly contribute to elevated plasma tHcy concentrations in psychogeriatric patients. Therefore, in the present study, cystatin C was used as a sensitive marker for glomerular filtration. A linear regression analysis including age, blood folate, serum cobalamin, serum cystatin C and serum creatinine showed that only serum creatinine (p<0.001) and blood folate (p<0.001) independently predicted plasma tHcy concentration. However, about 44% of the patients with elevated plasma tHcy concentrations had signs of reduced glomerular filtration rate, as judged by increased serum cystatin C, whereas only about 13% of the patients with normal concentrations of plasma tHcy had signs of reduced glomerular filtration rate. This finding indicates that renal impairment may to some extent contribute to the elevated plasma tHcy concentration, even though serum cystatin C did not independently predict plasma tHcy concentration.  相似文献   

19.
For persons with proteinuria, angiotensin-converting enzyme inhibitors (ACEis) and angiotensin II receptor blockers (ARBs) are treatment mainstays for reducing kidney disease progression. Guidelines for managing hypertension and chronic kidney disease recommend titrating to the maximum ACEi/ARB dose tolerated. Using deidentified national electronic health record data from the Optum Labs Data Warehouse, we examined ACEi/ARB dosing among adults with proteinuria—defined as either a urine albumin to creatinine ratio of 30 mg/g or greater or a protein to creatinine ratio of 150 mg/g or greater—who were prescribed an ACEi/ARB medication between January 1, 2017, and December 31, 2018. Among 100,238 included patients (mean age, 65.1 years; 49,523 [49.4%] female), 29,883 (29.8%) were taking maximal ACEi/ARB doses. Among 74,287 patients without potential contraindications to dose escalation (systolic blood pressure <120 mm Hg, estimated glomerular filtration rate <15 mL/min per 1.73 m2, serum potassium level greater than 5.0 mEq/L, or acute kidney injury within the prior year), the frequency of maximal ACEi/ARB dosing was 32.3% (24,025 patients). In adjusted analyses, age less than 40 years, female sex, Hispanic ethnicity, lower urine albumin to creatinine ratio, lack of diabetes, heart failure, lower blood pressure, higher serum potassium level, and prior acute kidney injury were associated with lower odds of maximal ACEi/ARB dosing. Having a prior nephrologist visit was not associated with maximal dosing. Our results suggest that greater attention toward optimizing the dose of ACEi/ARB therapy may represent an opportunity to improve chronic kidney disease care and reduce excess morbidity and mortality associated with disease progression.  相似文献   

20.
Nephrogenous cyclic AMP (NcAMP), total cyclic AMP excretion (UcAMP), and plasma immunoreactive parathyroid hormone (iPTH), determined with a multivalent antiserum, were prospectively measured in 55 control subjects, 57 patients with primary hyperparathyroidism (1 degrees HPT), and 10 patients with chronic hypoparathyroidism.In the group with 1 degrees HPT, NcAMP was elevated in 52 patients (91%), and similar elevations were noted in subgroups of 26 patients with mild (serum calcium 相似文献   

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