Comparative nephrotoxicity of gentamicin and tobramycin: pharmacokinetic and clinical studies in 201 patients.

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.     

原发性高血压病对早期肾功能的影响

目的 探讨原发性高血压病对早期肾功能影响的临床意义.方法 通过肾动脉造影、内生肌酐清除率排除肾性高血压,检测入选的原发性高血压病患者的肾小球滤过功能指标和肾小管功能指标.结果 高血压1、2、3组尿β2-微球蛋白(β2-MG)/肌酐(Cr)均高于对照组(P＜0.05),尿N-乙酰β-D-氨基葡萄糖苷酶(NAG)/Cr在高血压2、3组明显增高(P＜0.01).高血压1、2、3组尿渗透压均低于对照组(P＜0.01).在3 h尿微量白蛋白检测中,高血压3组高于对照组(P＜0.01).结论 原发性高血压病在对早期肾功能的影响中,肾小管近端重吸收功能、远端浓缩功能较肾小球滤过功能更易受损.     

A Longitudinal Assessment of Renal Function during Treatment with Lithium

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.     

Evaluation of cefoxitin nephrotoxicity in experimentally induced renal failure.

The nephrotoxicity of cefoxitin was studied in a rat model of impaired renal function. Two levels of renal impairment were produced: "moderate," with blood urea concentrations of 100 to 150 mg/100 ml (16.7 to 25.1 mmol/liter) and glomerular filtration rates 25 to 35% of normal, and "severe," with blood urea concentrations greater than 150 mg/100 ml (greater than 25.1 mmol/liter) and glomerular filtration rates 10 to 20% of normal. Sham-operated animals were used as controls. Three dose schedules of cefoxitin were administered to these controls--500, 1,000, and 2,500 mg/kg per day administered as a divided dose for 5 days. Doses given to the moderately and severely uremic animals were adjusted so that serum levels of cefoxitin were similar to those attained in the sham-operated control animals. Concentrations of urea and creatinine in blood, glomerular filtration rates, and the urinary concentrating capacities of the experimental animals were monitored before and after cefoxitin treatment. There was no evidence of nephrotoxicity in even the most challenging experiment, in which blood serum levels of cefoxitin reached 2,000 microgram/ml in animals, with 15% renal function. These findings support available clinical data, suggesting that cefoxitin can be administered safely to patients with compromised renal function.     

A longitudinal assessment of renal function during treatment with lithium

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.     

Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis.

Forty-six patients with cystic fibrosis and chronic bronchopulmonary Pseudomonas aeruginosa infection entered a study of tobramycin-related chronic and acute nephro- and acousticovestibular toxicity. The patients (mean age, 15.7 years) had previously received 2-week courses of tobramycin therapy, for a mean cumulative total of 279 days each. The cumulative tobramycin dose ranged from 632 to 7,644 mg/kg. The patients were studied before and at the end of a 2-week course of treatment with tobramycin (10 to 20 mg/kg per day) to discriminate between acute and chronic toxicity. In patients studied at the beginning of the present course of treatment, the glomerular filtration rate, measured as 24-h creatinine clearance, did not correlate with the cumulative dose of tobramycin received during previous courses. Eighteen patients (39%) had a reduced glomerular filtration rate compared with normal values (mean, 12.5% reduction) but normal serum creatinine values. Two patients (5%) had a high-frequency hearing deficit (above 8 kHz), but only one deficit was possibly related to tobramycin. No chronic vestibular toxicity was observed. During the course of treatment, no patients developed acute nephrotoxicity. After 2 weeks of treatment 32% had a slightly reduced hearing threshold (15 to 30 dB) in two or more high frequencies, and 28% had a fall in vestibular response greater than 25% of the initial value but remained within normal limits. Thus, the acute and chronic toxicity of repeated high-dose tobramycin treatment in cystic fibrosis patients seems to be very mild.     

Serum cystatin C level for better assessment of glomerular filtration rate in cystic fibrosis patients treated by amikacin

Background and objective: Monitoring of renal function in cystic fibrosis (CF) patients is essential. The dosage regimen of amikacin is regularly modified according to the patient’s glomerular filtration rate (GFR). The aim of the study was to evaluate the use of cystatin C (CyC) for monitoring amikacin therapy along with other markers of renal tubular and glomerular function, and damage [N‐acetyl‐β‐ d glucosaminidase (NAG), creatinine level and creatinine clearance]. Methods: We compared the GFR, estimated from the serum concentrations of creatinine (Cockcroft–Gault formula) and CyC (Grubb’s formula). Seventy‐one patients (mean age 12 years; range 4–28 years) with CF were treated by intermittent intravenous infusion of amikacin. Tubular nephrotoxicity was investigated by measurement of urine NAG/urine creatinine ratio (U‐NAG/U‐creatinine). Concentrations of all markers were measured before starting amikacin therapy and at days 3, 5, 7, 10 and 12. Fluorescence polarization analysis, turbidimetry, enzymatic phototometric creatinine deaminase method and fluorimetry were used for determination of serum amikacin, serum CyC, creatinine and urine NAG activity. Receiver operating characteristic (ROC) analysis was performed to assess the influence of GFR estimated from serum creatinine and serum CyC for the prediction of amikacin clearance during aminoglycoside therapy. Results: Significant differences in the rate of U‐NAG/U‐creatinine were noted before and after treatment with amikacin (P < 0·001). Serum creatinine levels and creatinine clearance at the end of amikacin therapy (12th day) did not show any significant differences in comparison with the levels measured before the start of therapy (0th day). At days 5, 7, 10 and 12, serum CyC levels showed a significant elevation (P < 0·001), and CyC clearance showed a significant decrease (P < 0·001) in comparison with the levels measured at day 0. The ratio of amikacin clearance/creatinine clearance decreased with therapy whereas the amikacin clearance/CyC and amikacin clearance/CyC clearance increased. Conclusion: We showed that the rate of U‐NAG/U‐creatinine is a suitable marker for monitoring tubular nephrotoxicity in CF patients. Serum creatinine and estimated creatinine clearance are modest predictors of GFR in CF patients. CyC appears to be a better marker of GFR than serum creatinine concentration or creatinine clearance in our study. Serum CyC levels and CyC clearance showed greater ability to predict amikacin clearance during therapy than creatinine clearance.     

Serum hepatocyte growth factor levels in patients with chronic renal disease--effect of GFR and pathogenesis.

Hepatocyte growth factor (HGF) is a growth-promoting peptide that appears to act in a renotropic and nephroprotective manner during acute renal damage. Recent studies suggest that HGF is also of importance in chronic renal diseases. The serum HGF level is correlated with serum creatinine, and it has been suggested that glomerular and tubular diseases affect serum HGF differently. In the present study. levels of serum HGF were determined and correlated to glomerular filtration rate (GFR) in 118 patients with various chronic renal diseases. GFR was determined by 99mTc-DTPA clearance, and the GFR values were evenly distributed in the interval 5-155 mL/min/1.73 m2. Serum HGF levels increased slightly with decreasing GFR: the Pearson correlation coefficient being 0.49 (p<0.0001). In 21 additional patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis, there was a more marked increase in the serum levels of HGF. The effect of glomerular and tubular diseases on serum HGF was examined by comparing the HGF levels in two groups of patients with similar GFR values: 57 patients with mainly glomerular disorders (diabetic nephropathy with micro- or macroalbuminuria or glomerulonephritis) and 14 patients with mainly tubular disorders (polycystic kidney disease). There was no significant difference between the HGF levels of the two groups (p=0.30). In conclusion: Serum HGF levels are correlated with GFR (for GFR > or = 5 mL/min/1.73 m2) in patients with chronic renal diseases, and glomerular and tubular disorders seem to affect the HGF level similarly.     

Serum hepatocyte growth factor levels in patients with chronic renal disease - effect of GFR and pathogenesis

Hepatocyte growth factor (HGF) is a growth-promoting peptide that appears to act in a renotropic and nephroprotective manner during acute renal damage. Recent studies suggest that HGF is also of importance in chronic renal diseases. The serum HGF level is correlated with serum creatinine, and it has been suggested that glomerular and tubular diseases affect serum HGF differently. In the present study, levels of serum HGF were determined and correlated to glomerular filtration rate (GFR) in 118 patients with various chronic renal diseases. GFR was determined by 99m Tc-DTPA clearance, and the GFR values were evenly distributed in the interval 5-155 mL/min/1.73 m 2 . Serum HGF levels increased slightly with decreasing GFR; the Pearson correlation coefficient being 0.49 (p < 0.0001). In 21 additional patients with end-stage renal disease treated with continuous ambulatory peritoneal dialysis, there was a more marked increase in the serum levels of HGF. The effect of glomerular and tubular diseases on serum HGF was examined by comparing the HGF levels in two groups of patients with similar GFR values: 57 patients with mainly glomerular disorders (diabetic nephropathy with micro- or macroalbuminuria or glomerulonephritis) and 14 patients with mainly tubular disorders (polycystic kidney disease). There was no significant difference between the HGF levels of the two groups (p = 0.30). In conclusion: Serum HGF levels are correlated with GFR (for GFR &#85 5 mL/min/1.73 m 2 ) in patients with chronic renal diseases, and glomerular and tubular disorders seem to affect the HGF level similarly.     

Iopentol in patients with chronic renal failure: its effects on renal function and its use as glomerular filtration rate parameter.

Iopentol (mean dose 0.42 g I kg-1) was administered for abdominal aortography and pelvic angiography in 10 patients with advanced non-diabetic chronic renal failure (S-creatinine 672 +/- 259 mumol l-1, mean +/- SD). Renal glomerular function measured as creatinine clearance and plasma clearance of [99Tcm]-diethyl-enetriaminepentaacetic acid (DTPA) was unchanged by iopentol, as also was urinary excretion of the renal tubular enzymes N-acetyl-beta-glucosaminidase (NAG) and alkaline phosphatase (ALP). The elimination of iopentol from serum and urine was delayed, and detectable serum and urine concentrations were found 5 days after administration of the contrast medium. Creatine clearance was 47% higher than the corresponding renal iopentol clearance. Plasma iopentol clearance, measured as the total area under the plasma concentration curve, was 40% higher than renal iopentol clearance because of extrarenal elimination of iopentol. We conclude that abdominal aortography with iopentol can be performed without effects on renal glomerular or tubular function parameters in patients with advanced renal failure. If iopentol is used for measurement of glomerular filtration rate (GFR) in this group of patients, one should measure renal clearance, as plasma clearance overestimates GFR.     

Pharmacokinetics of Cefamandole in Patients with Normal and Impaired Renal Function

The pharmacokinetics of cefamandole, a new cephalosporin, were investigated in 23 patients with urinary tract infections and normal or varying degrees of impairment of renal function. A daily dose of 1.5 to 3.0 g administered intramuscularly was tolerated well and resulted in very high urine concentrations. The pharmacokinetics of the antibiotic were compared with isotopically labeled [¹³¹I]hippurate and [¹²⁵I]iothalamate, which were used for determination of effective renal plasma flow and glomerular filtration rate, respectively. It was shown that cefamandole was excreted by glomerular filtration as well as by active tubular secretion. Probenecid inhibited the tubular secretion of cefamandole. The serum half-life of cefamandole in patients with normal renal function was approximately 1.5 h and increased in patients along with increasing impairment of renal function. Our studies indicate that a dosage regimen of 1 g of cefamandole every 8 h in patients with normal renal function results in urine concentrations sufficiently high for treatment of most common urinary tract infections. In patients with impaired renal function, the dosage interval should be increased or the dosage lowered according to the serum creatinine values.     

Increased homocysteine in heart failure: a result of renal impairment?

BACKGROUND: Hyperhomocysteinemia may constitute a risk factor for patients with severe heart failure. This study examines the relationship between plasma homocysteine concentration and left ventricular ejection fraction with renal function in heart failure patients free of coronary artery disease. METHODS: Left ventricular ejection fraction was documented in 62 patients with advanced heart failure who had no proven significant coronary artery stenosis. Glomerular filtration rate was measured using the Cockroft-Gault equation. RESULTS: Elevated homocysteine levels (>or=15 micromol/L) were detected in 22 patients. Low glomerular filtration rate was observed in patients who had normal serum creatinine concentration. Homocysteine was strongly correlated with age, duration of disease, left ventricular ejection fraction, serum creatinine, and glomerular filtration rate. Statistically significant trends were observed across respective homocysteine quartiles. However, by multivariate regression, the strongest predictor of homocysteine was the glomerular filtration rate. CONCLUSIONS: Impaired renal function leads to a diminished clearance rate, which can be a prominent pathophysiological mechanism in the elevation of homocysteine concentration in heart failure.     

Tissue lipid peroxidation and antioxidant status in patients with adenocarcinoma of the breast

BACKGROUND: The results obtained for serum cystatin C, which has been proposed as a novel marker of glomerular filtration rate (GFR), in kidney and liver transplant are still very limited. In our study, the relationship between serum cystatin C and creatinine in kidney and liver transplant patients was investigated. METHODS: Serum cystatin C and creatinine concentrations were determined in 182 samples from 52 kidney transplant patients and 71 samples from 28 liver transplant patients at 1-9870 days post-transplantation time. Eighty-seven serum samples from 66 patients with different types of chronic kidney disease were also analysed. RESULTS: The serum creatinine (r=-0.517, p<0.001) and cystatin C (r=-0.409, p<0.001) concentrations were negatively correlated with the post-transplantation time in the kidney transplant patients. In the liver transplant patients, the correlation between these variables is not statistically significant. The creatinine/cystatin C ratio in the liver transplant group is significantly lower than in the other group of patients (p<0.001). This ratio in the kidney transplant patients groups is significantly lower than in the kidney disease group (p<0.001). In the kidney transplant patients the creatinine/cystatin C ratio and the post-transplantation time were negatively correlated (r=-0.523, p<0.001); however, in the liver transplant patients the correlation between these variables was not significant. CONCLUSIONS: In the groups of kidney disease and kidney transplant patients, as renal function decreases, there is an increase in the creatinine/cystatin C ratio. This may be due to the fact that, since creatinine is eliminated by glomerular filtration and tubular secretion, as renal function is impaired, its serum concentration increases to a greater extent than that of cystatin C, which is only eliminated by glomerular filtration. In the liver transplant patients, the creatinine/cystatin C ratio is lower than in the other groups. This may be due to better preserved renal function, lower muscular mass and a reduced rate of creatine formation and creatinine production in some of these patients. The serum cystatin C would be a better GFR marker than the widely used creatinine in liver transplant patients.     

Methodology for assessment of renal function

A variety of methods for evaluation of renal function have been discovered, among which glomerular filtration rate (GFR) attracts much attention because of the major determinant of renal function. Recently, novel technique to evaluate glomerular filtration has been developed, including cystatin C, which reflects the changes in GFR at the earlier stage than serum creatinine. Furthermore, a progress has been made in evaluating tubular damage, with the discovery of N-acetyl glucosaminidase and liver-type fatty acid binding protein. More convenient and sensitive methods will be required to assess the changes in renal function in a clinical setting.     

水化治疗预防不同肾功能水平病人造影剂相关肾损伤的临床观察

[目的]探讨水化治疗预防不同肾小球滤过率（GFR）病人行冠状动脉介入术后造影剂相关肾损伤的效果,以便指导临床工作。[方法]将血肌酐正常的冠状动脉介入术后139例病人,根据GFR不同分为正常组和异常组,两组病人术后行常规水化治疗。比较两组术前、术后血肌酐、肾小球滤过率、血尿素氮、血清β2-微球蛋白、尿微量白蛋白、24 h出入量情况。[结果]两组术后均未发生造影剂肾病,术后6 h、12 h尿量差异有统计学意义（P〈0.05）;两组血尿素氮、β2-微球蛋白水平比较差异有统计学意义（P〈0.05）;术后第2天尿微量白蛋白与术前差值比较,差异有统计学意义（P〈0.05）。[结论]血肌酐正常的病人中有一部分潜在或已存在肾功能异常,术前应常规计算肾小球滤过率,临床可通过加强水化治疗预防不同肾小球滤过率的冠状动脉介入术后病人造影剂相关肾损伤。     

Chronic tubulointerstitial nephritis and renal insufficiency associated with long-term "subtherapeutic" gentamicin

To determine whether long-term "subtherapeutic" concentrations of aminoglycoside produce chronic tubulointerstitial nephropathy, Fisher rats were given gentamicin, 20 mg/kg/day, for up to 6 months via indwelling osmotic infusion pumps. Studies included renal histology, autoradiographic quantitation of renal cell tritiated thymidine uptake, renal function and renal cortical gentamicin assay. Acute proximal tubular injury, without tubular necrosis, followed by recovery, occurred during the first month. Subsequently only mild, nonprogressive tubulointerstitial changes and a twofold increase in tubular cell turnover were observed. Inulin clearance fell more than 50% during the 6 months of treatment compared with 10% in age-matched controls. Serum creatinine and creatinine clearance overestimated glomerular filtration rate during treatment and did not distinguish treated animals from controls. During the month after 6 months of gentamicin, tubular microcystic changes and active tubulointerstitial nephritis developed, with a continued fall in inulin clearance. In summary, gentamicin, in "subtherapeutic" doses, produces mild chronic tubulointerstitial nephritis with progressive renal failure. Cessation of treatment is associated with microcystic and inflammatory changes, suggesting that the renal response to tubular injury can be dissociated from the amount of toxin in the renal cortex. Keeping serum aminoglycoside levels below accepted therapeutic range for 6 months did not preclude nephrotoxicity.     

血清半胱氨酸蛋白酶抑制剂C检测对肿瘤化疗患者早期肾损伤的诊断意义

目的探讨血清半胱氨酸蛋白酶抑制剂C(CysC)在肿瘤化疗患者早期肾功能损伤诊断的临床应用价值。方法以56例健康体检人员为对照,比较96例不同肾功能损伤的肿瘤化疗患者CysC、肌酐(Cr)的检测情况,并进行统计学分析。结果肾小球滤过率(GFR)、CysC,肿瘤中各组与对照组比较均有统计学差异(P<0.05);肾功能轻度受损组、肾功能不全组与肿瘤肾功能正常组比较均有统计学差异(P<0.05);Cr肿瘤肾功能正常组与对照组比较无统计学差异(P>0.05),肾功能轻度受损组与肾功能正常组比较无统计学差异(P>0.05);CysC(r=-0.835,P<0.001)、Cr(r=-0.642,P<0.001)与GFR均呈负相关;方法学指标评价CysC各项指标[灵敏度、特异度、正确诊断指数、符合率、阴(阳)性预测值]均优于Cr。结论 CysC对肿瘤化疗患者早期肾功能损伤的监测更具参考价值。     

The changing face of newborn screening: diagnosis of inborn errors of metabolism by tandem mass spectrometry

BACKGROUND: The concentration of serum cystatin-C (Cys-C) is highly correlated with creatinine (Cr), and is mainly determined by glomerular filtration; thus, Cys-C may be an index of the glomerular filtration rate (GFR). However, the kinetics of urinary Cys-C and Cr excretions are unclear. Thus, we investigated the kinetics of urinary Cys-C and Cr excretions, and examined whether the urinary Cys-C concentration can be used as a marker of renal function. METHODS: The urinary excretion of Cys-C and Cr was evaluated in 1670 healthy subjects and 217 patients with proteinuria. We also investigated the urinary Cys-C concentration in 52 patients with chronic renal failure. RESULTS: There was a good correlation between the urinary concentrations of Cys-C and Cr in the healthy group. This relation was also observed in patients showing persistent proteinuria without tubular cell damage. The mean urinary Cr concentration increased with age, and it was affected by the muscle mass. In contrast, the urinary Cys-C concentration was not affected by the muscle mass, and the concentration remained constant for all ages. We further found that the ratio of Cys-C to Cr (CCR) is a good index of the state of Cys-C reabsorption in the proximal tubules. CONCLUSIONS: The urinary CCR can be a marker of renal tubular dysfunction. In addition, when CCR was in the normal range, the urinary Cys-C concentration accurately reflected the glomerular filtration function.     

零点肾穿活检:对供者临床资料与组织学异常情况的相关性分析

背景:目前,活体肾脏捐赠的数量在全国乃至全世界范围内增长,因此,保障供者安全在亲体肾移植中占有重要地位.如何准确诊断移植供者可能存在的肾脏疾病,以指导供者手术后潜在肾脏病治疗和肾功能保护成为亲体肾移植后保障供者安全的重要课题.目的:建立一种对供者捐肾前的临床资料与组织学异常情况间相关性的评价方法.方法:对解放军南京军区福州总医院2008-02/2009-11所有亲属肾移植的相关数据做回顾件分析,于供肾血管离断并灌注完成后进行穿刺.用零点肾穿的方法评估下列病变:间质纤维化,小管萎缩,微小动脉透明变性,肾小球系膜增生和肾小球硬化.移植前的统计数据包括:体质量,体质量指数,收缩压,舒张压,血清肌酸酐,肾小球滤过率和蛋白尿.结果与结论:62例供者术前检查均未发现明显肾脏疾病征象,零点肾穿活检发现肾脏病理改变28例,其中间质纤维化与收缩压和肌酐清除率,肾小管萎缩与舒张压和尿蛋白,小动脉透明样变与肌酐和肾小球滤过率,肾小球系膜增生和体质量指数具有弱相关性,肾小球硬化与其他变量均无相关性.     

Assessment of renal function by serum creatinine and creatinine clearance: glomerular filtration rate estimated by four procedures

We compared creatinine concentrations in serum and urine and creatinine clearances determined by two Jaffé (Beckman's "Astra," Boehringer Mannheim Diagnostics) and two enzymatic (Kodak, Boehringer Mannheim Diagnostics) methods. Serum creatinine and creatinine clearances determined by each method were also compared with the glomerular filtration rate as measured with use of sodium [125I]iothalamate in patients with a wide range of renal function. Results between methods correlated excellently, but we saw clear method-dependent biases of up to 2.9 mg/L for serum. The highest serum creatinine values and the lowest creatinine clearances were obtained with Boehringer Mannheim Diagnostics' Jaffé method. The reciprocal of the serum creatinine and the creatinine clearance also correlated well with the glomerular filtration rate, but all methods over-estimated the glomerular filtration rates to varying degrees. Appropriate standardization of methods appears to be as important as method principle for establishing an accurate relationship between creatinine determinations and glomerular filtration rate.