title: Influence of co-morbidity on renal function assessment by Cockcroft-Gault calculation in lung cancer and mesothelioma patients receiving platinum-based chemotherapy.
abstract: BACKGROUND
  Creatinine clearance (CrCl) estimation by Cockcroft-Gault calculation (CG) often replaces measurement of glomerular filtration rate (GFR) by [(51)Cr]-ethylenediaminetetraacetic acid clearance (EDTA). Co-morbidity, age, and renal impairment influence the accuracy of CG, whilst the relationship between CG and EDTA has been poorly assessed in lung cancer patients, a population significantly affected by these covariates.
  
  
  METHODS
  Retrospective analysis of co-morbidity, nephrotoxic drug use, chemotherapy toxicity, and correlation between paired CG and EDTA, in 388 lung cancer and mesothelioma patients receiving platinum-based chemotherapy.
  
  
  RESULTS
  Potentially nephrotoxic co-morbidity or medication use occurred in 47% of patients, and was twice as likely in those aged >70 years (OR=2.07; 95%CI: 1.25-3.44, p=0.003). Patients with co-morbidity or nephrotoxic medication use had a lower EDTA compared to those without these baseline factors (p=0.02), but were not significantly more likely to experience chemotherapy toxicity. CG and EDTA correlation was high (r(2)=0.68), but reduced in patients with ETDA<50 ml/min (r(2)=0.26, p=0.02) or >120 ml/min (r(2)=0.32, p=0.09), and in those with CG>120 ml/min (r(2)=0.20, p=0.01). The correlation between CG and EDTA was not significantly altered in patients with co-morbidity or nephrotoxic medication use. CG bias (mean percentage error) and precision (mean absolute percentage error, MAPE) were 7% and 26%, respectively, and precision was impaired in patients with abnormally raised serum creatinine (MAPE 65%, p<0.0001).
  
  
  CONCLUSIONS
  CG estimation of CrCl is accurate and safe in lung cancer patients with potentially nephrotoxic co-morbidity or concomitant medication, but should not be used when values are outside the range 50-120 ml/min, or with abnormally elevated serum creatinine.
authors.affiliation: Dept Medical Oncology, Christie Hospital, Manchester M20 4BX, UK.
authors.forename: R A
authors.initials: RA
authors.lastname: Hubner
authors.forename: R
authors.initials: R
authors.lastname: Goldstein
authors.forename: S
authors.initials: S
authors.lastname: Mitchell
authors.forename: A
authors.initials: A
authors.lastname: Jones
authors.forename: S
authors.initials: S
authors.lastname: Ashley
authors.forename: M E R
authors.initials: ME
authors.lastname: O'Brien
authors.forename: S
authors.initials: S
authors.lastname: Popat
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015897:Comorbidity; D003404:Creatinine / Q000097:blood; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008175:Lung Neoplasms / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology* / Q000503:physiopathology; D008297:Male; D008654:Mesothelioma / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology* / Q000503:physiopathology; D008875:Middle Aged; D017671:Platinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011237:Predictive Value of Tests; D012016:Reference Values; D012189:Retrospective Studies; D012306:Risk; D012680:Sensitivity and Specificity
chemical_list: D017671:Platinum Compounds; D003404:Creatinine