title: Clinical Validation of Simultaneous Analysis of Tacrolimus, Cyclosporine A, and Creatinine in Dried Blood Spots in Kidney Transplant Patients.
abstract: Monitoring of creatinine and immunosuppressive drug concentrations, such as tacrolimus (TaC) and cyclosporin A (CsA), is important in the outpatient follow-up of kidney transplant recipients. Monitoring by dried blood spot (DBS) provides patients the opportunity to sample a drop of blood from a fingerprick at home, which can be sent to the laboratory by mail.
  
  
  
  We performed a clinical validation in which we compared measurements from whole-blood samples obtained by venapuncture with measurements from DBS samples simultaneously obtained by fingerprick. After exclusion of 10 DBS for poor quality, and 2 for other reasons, 199, 104, and 58 samples from a total of 172 patients were available for validation of creatinine, TaC and CsA, respectively. Validation was performed by means of Passing & Bablok regression, and bias was assessed by Bland-Altman analysis.
  
  
  
  For creatinine, we found y = 0.73x - 1.55 (95% confidence interval [95% CI] slope, 0.71-0.76), giving the conversion formula: (creatinine plasma concentration in μmol/L) = (creatinine concentration in DBS in μmol/L)/0.73, with a nonclinically relevant bias of -2.1 μmol/L (95% CI, -3.7 to -0.5 μmol/L). For TaC, we found y = 1.00x - 0.23 (95% CI slope, 0.91-1.08), with a nonclinically relevant bias of -0.28 μg/L (95% CI, -0.45 to -0.12 μg/L). For CsA, we found y = 0.99x - 1.86 (95% CI slope, 0.91-1.08) and no significant bias. Therefore, for neither TaC nor CsA, a conversion formula is required.
  
  
  
  DBS sampling for the simultaneous analysis of immunosuppressants and creatinine can replace conventional venous sampling in daily routine.
authors.affiliation: 1 Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 2 Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 3 Section Pharmacokinetics, Toxicology and Targeting, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Herman
authors.initials: H
authors.lastname: Veenhof
authors.forename: Remco A
authors.initials: RA
authors.lastname: Koster
authors.forename: Jan-Willem C
authors.initials: JC
authors.lastname: Alffenaar
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Berger
authors.forename: Stephan J L
authors.initials: SJL
authors.lastname: Bakker
authors.forename: Daan J
authors.initials: DJ
authors.lastname: Touw
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000553:Ambulatory Care; D015415:Biomarkers / Q000097:blood; D003404:Creatinine / Q000097:blood*; D016572:Cyclosporine / Q000009:adverse effects / Q000097:blood*; D059788:Dried Blood Spot Testing; D016903:Drug Monitoring / Q000379:methods*; D005240:Feasibility Studies; D005260:Female; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000097:blood*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000601:surgery*; D016030:Kidney Transplantation / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D016559:Tacrolimus / Q000009:adverse effects / Q000097:blood*; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine; D016559:Tacrolimus