Urinary casts as an indicator of renal tubular damage in patients receiving aminoglycosides

Schentag, Jerome J.; Gengo, Francis M.; Plaut, Martin E.; Danner, David B.; Mangione, Antoinette; Jusko, W J

doi:10.1128/aac.16.4.468

Cited by 60 publications

(32 citation statements)

References 13 publications

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“…Previous studies showed that the identification of granular casts and RTEC in the urine sediment analysis correlates well with ATN (17,18). Schentag et al (17) demonstrated that the increase in urinary cast excretion provides information about kidney injury that allows one to adjust aminoglycoside dosages 5 to 9 d before a rise in serum creatinine concentration develops in patients with aminoglycoside nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Diagnostic Value of Urine Microscopy for Differential Diagnosis of Acute Kidney Injury in Hospitalized Patients

Perazella

Coca

Kanbay

et al. 2008

Clinical Journal of the American Society of Nephrology

163

132

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Background and objectives: Urine microscopy is the oldest and one of the most commonly used tests for differential diagnosis of acute kidney injury (AKI), but its performance has not been adequately studied in the setting of AKI.Design, setting, participants, & measurements: Fresh urine samples were obtained from 267 consecutive patients with AKI, and urinary sediment was examined. The cause of AKI was assessed at two time points: (1) Before urine microscopy diagnosis and (2) after patient discharge or death (final diagnosis). A urinary scoring system also was created on the basis of casts and renal tubular epithelial cells (RTEC) to differentiate acute tubular necrosis (ATN) from prerenal AKI.Results: The urinary sediment scoring system was highly predictive of the final diagnosis of ATN. In patients with a high pretest probability of ATN (initial diagnosis of ATN), any casts or RTEC (score >2) resulted in very high positive predictive value and low negative predictive value for a final diagnosis of ATN. In patients with a low pretest probability of ATN (initial diagnosis of prerenal AKI), lack of casts or RTEC on urinary sediment examination had a sensitivity of 0.73 and specificity of 0.75 for a final diagnosis of prerenal AKI. The negative predictive value of lack of casts or RTEC in patients with low pretest probability of disease was 91%.Conclusions: Urine sediment examination is a valuable diagnostic tool for confirming the diagnosis of ATN. A score of >2 on an ATN urinary sediment scoring system is an extremely strong predictor of ATN.

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Section: Discussionmentioning

confidence: 99%

Diagnostic Value of Urine Microscopy for Differential Diagnosis of Acute Kidney Injury in Hospitalized Patients

Perazella

Coca

Kanbay

et al. 2008

Clinical Journal of the American Society of Nephrology

163

132

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“…Serum creatinine levels and 24-h creatinine clearance values were determined by autoanalyzer methods; 24-h urinary excretion of 82-microglobulin was determined by the radioimmunoassay, and values of more than 50 mg/24 h were associated with nephrotoxicity (4). Quantitative cast counts were performed daily on random urine samples, and values of more than 500 casts per mil on 3 consecutive days were associated with nephrotoxicity (10 on April 27, 2019 by guest http://aac.asm.org/ Downloaded from increase in the creatinine level. These abnormal values were more than 200 mg for gentamicin and more than 175 mg for tobramycin (15).…”

Section: Methodsmentioning

confidence: 99%

“…Rates of aminoglycoside administration were determined individually for all patients according to nomograms and measured peak and trough serum concentrations. Blood for assays was obtained throughout treatment and in most patients for 10 to 20 days after aminoglycoside treatment was stopped (to quantitate the terminal halflife), as previously described (9,10,(11)(12)(13)15 Assays. Serum, urine, and postmortem tissue aminoglycoside concentrations were measured by both a microbiological assay and a radioimmunoassay, as previously described (12,13).…”

Section: Methodsmentioning

confidence: 99%

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

Schentag¹,

Plaut²,

Cerra³

1981

Antimicrob Agents Chemother

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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 fl2-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, creatinine clearance, total dose given, duration of treatment, initial aminoglycoside trough serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Previous aminoglycoside treatment (usually gentamicin) had occurred more frequently in the tobramycintreated patients (P < 0.01), and more males than females received tobramycin (P < 0.05). Pharmnacokinetic assessments of renal damage were based on both changes in glomerular filtration rate (serum creatinine levels, creatinine clearance) and renal tubular damage (,82-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 pharnacokinetic analysis of nephrotoxicity, 29 gentamicin courses (24%) and 12 tobramycin courses (10%) were complicated by nephrotoxicity (P < 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 < 0.02). In these similar groups of critically ill patients, tobramycin was less nephrotoxic than gentamicin.

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“…Quantitative cast counts were performed daily on random urines collect-ed in the morning. Values exceeding 500 casts per ml for 3 days were defined as nephrotoxic damage (14).…”

Section: Methodsmentioning

confidence: 99%

Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients

Schentag¹,

Cerra²,

Plaut³

1982

Antimicrob Agents Chemother

Self Cite

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We studied 201 critically ill patients during 267 courses of gentamicin (139 courses) or tobramycin (128 courses) therapy. Clinical and pharmacokinetic data were obtained on 240 of 267 courses (120 courses each of gentamicin and tobramycin). Two judgments of nephrotoxicity and its cause were made independently in this study, using a clinical and a pharmacokinetic definition of nephrotoxicity. The two sets of criteria were generally in good agreement, as all but 10 of 41 patients who were judged nephrotoxic by pharmacokinetic criteria were independently judged nephrotoxic by the clinical definition. Groups of patients judged nontoxic did not differ from groups judged nephrotoxic in age, sex, weight, initial creatinine clearance, total dose given, duration of treatment, initial aminoglycoside trough serum levels, number of dosage adjustments, concurrent use of furosemide, or concurrent cephalosporins. Prior aminoglycosides (usually gentamicin) had been used more frequently in the nontoxic group (P < 0.05). Two major conclusions of this study are at variance with those of previous investigators: (i) we found no clinical parameters of value in predicting nephrotoxicity in critically ill patients; and (ii) aminoglycoside serum concentrations, once in the therapeutic range, were of limited value in prevention of aminoglycoside nephrotoxicity in our patients.We and others have previously shown that the various aminoglycosides differ in their intrinsic nephrotoxic potential in animals (1, 9, 11, 13) and humans (10,17,18,19). In such studies, both nontoxic and nephrotoxic patients must have precise control of the serum concentrations before the population can be analyzed for the factors predisposing to nephrotoxicity. We have treated 201 critically ill patients with suspected or proven infections, with aminoglycosides administered in regimens that were closely monitored by measured blood levels (17). Dosing adjustments were made as required to maintain the recommended concentration range. The judgment of nephrotoxicity was made independently by both clinical and pharmacokinetic criteria. Gentamicin was more frequently (24%) nephrotoxic than was tobramycin (12%). In this analysis, we compared all nontoxic patients with all nephrotoxic patients so as to use our large groups of nephrotoxic patients to define the characteristics of those who experienced renal damage when appropriately dosed with aminoglycosides. METHODSPatients. We gave 201 acutely ill patients 267 courses of aminoglycoside therapy. Pharmacokinetic and clinical data were available on 240 courses, which were used for analysis. The patients were older adults in critical care units, with serious infections complicating either major medical or surgical disorders. Most infections were intra-abdominal or pneumonic. Patients were entered into this study at the time of request for dosing and pharmacokinetic monitoring.Dosing and sample collection. Aminoglycosides were administered by intravenous infusion over 30 to 60 min. Dosing rates were determined initially by n...

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Urinary casts as an indicator of renal tubular damage in patients receiving aminoglycosides

Cited by 60 publications

References 13 publications

Diagnostic Value of Urine Microscopy for Differential Diagnosis of Acute Kidney Injury in Hospitalized Patients

Diagnostic Value of Urine Microscopy for Differential Diagnosis of Acute Kidney Injury in Hospitalized Patients

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

Clinical and pharmacokinetic characteristics of aminoglycoside nephrotoxicity in 201 critically ill patients

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