title: Creatinine generation is reduced in patients requiring continuous venovenous hemodialysis and independently predicts mortality.
abstract: BACKGROUND
  Existing systems for grading severity of acute kidney injury (AKI) rely on a change of serum creatinine concentration over a defined time interval. The rate of change in serum creatinine increases by degree of reduction in glomerular filtration rate, but is mitigated by low creatinine generation rate (CGR). Failure to appreciate variation in CGR may lead to erroneous conclusions regarding severity of AKI and distorted predictions regarding patient outcomes based on AKI severity.
  
  
  METHODS
  Cohort study of 103 patients who received continuous venovenous hemodialysis (CVVHD) over a 2-year period in a tertiary care hospital setting. Study participants entered the cohort when they were anuric, receiving a stable and uninterrupted dose of CVVHD with serum creatinine in steady state. They were followed until hospital discharge. CGR was measured based on dialyzate effluent volume and effluent creatinine concentration (prospective cohort) and via effluent volume and serum creatinine concentration (retrospective cohort).
  
  
  RESULTS
  CGR (mean 10.5, range 1.7-22.4 mg/kg/day) was substantially lower in this patient population than what would be predicted from existing equations. Correlates of CGR in multivariable analysis included the length of hospitalization prior to measurement and presence of an oncologic diagnosis. Lower CGR was independently associated with in-hospital mortality in unadjusted analysis and after multivariable adjustment for measures of severity of illness.
  
  
  CONCLUSIONS
  Grading systems for severity of AKI fail to account for variation in CGR, limiting their ability to predict relevant outcomes. Calculation of CGR is superior to other risk metrics in predicting hospital mortality in this population.
authors.affiliation: Renal Electrolyte and Hypertension Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. francis.wilson@uphs.upenn.edu
authors.forename: Francis P
authors.initials: FP
authors.lastname: Wilson
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Sheehan
authors.forename: Laura H
authors.initials: LH
authors.lastname: Mariani
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Berns
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000175:diagnosis / Q000401:mortality; D000368:Aged; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D005260:Female; D006440:Hemofiltration / Q000379:methods* / Q000401:mortality; D017052:Hospital Mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D010351:Patient Discharge; D011446:Prospective Studies; D006435:Renal Dialysis / Q000379:methods* / Q000401:mortality; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D003404:Creatinine