Arising from: Acott PD (2006) Nat Clin Pract Nephrol 2: 304–305

Philip Acott reviewed the work of Webb and colleagues1 in a Practice Point commentary in Nature Clinical Practice Nephrology.2 The study by Webb et al. demonstrated the use of fingerprick blood samples as a novel method of therapeutic drug monitoring for pediatric renal transplant management. As mentioned by Webb, one of his co-workers, Keevil, had established earlier that ciclosporin A and creatinine concentrations could be monitored by fingerprick (capillary) blood samples analyzed by liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS).3 Subsequently, this same group confirmed the utility of fingerprick blood samples for monitoring immunosuppression in adult transplant recipients by LC-MS/MS.4 Repeating immunosuppressant drug level quantification is required to individualize dosage for maintenance immunosuppression.5 Therefore, under the standard testing paradigm, patients and their families must dedicate a substantial portion of their time to having venous samples obtained by phlebotomy at a clinical facility. In order to assist patients and their families to avoid loss of school time and employment time, the alternate testing strategy proposed by Webb and his group allows patients the option of at-home blood sampling by fingerprick for therapeutic monitoring of immunosuppressants (TDM-IS). The authors established that levels of the drugs in fingerprick samples and venous blood assessed by the LC-MS/MS correlated strongly with venous blood levels determined with a more widely used immunoassay (IMx®, Abbott Laboratories, Abbott Park, IL, USA). The confirmation of the close correlation of capillary versus venous blood sample analysis in TDM-IS by LC-MS/MS is important since small sample volume requirements (4 drops of blood) for tandem mass spectrometry are realistically obtainable by at-home fingerprick sampling. These findings form the basis of a feasible alternative for therapeutic drug monitoring of organ transplant patients.

We have pursued the development of at-home sampling as an option for routine TDM-IS in organ transplant patients. Utilizing LC-MS/MS analysis, widely recognized as the superior method of TDM-IS,5 we have validated the ability to provide clinically useful immunosuppressant whole blood concentration results from fingerprick blood samples obtained at home and shipped to a central laboratory. We applied the method to a group of postoperative renal allograft recipients upon their discharge to home. Our initial experiences indicate that the process is easily adopted by patients and that the samples provided are acceptable for analysis with sufficient volume and low rates of sample rejection (data on file with TMS BioScience). As Acott suggests, if an at-home sample based monitoring program is to be especially beneficial, other critical parameters, such as serum creatinine level, should be included in sample analysis reports. Accordingly, by use of our proprietary sample preparation techniques, we have incorporated traditional clinical chemistry analysis of the same samples to report serum creatinine and blood urea nitrogen concentrations. Additional clinical chemistry tests are under development and further study of sample collection and sample handling effects on analysis are in progress. We intend to fully explore the capabilities and limitations of a system combining at-home blood sampling and multiple testing methodologies to produce meaningful and reliable clinical information for managing transplant patients. We also are examining the impact on a patient's quality of life, the potential effect on medication adherence, and issues relating to access to health care for transplant patients. Data concerning rejection rates, incidence of adverse effects, morbidity & mortality, and other measures of outcome will be collected prospectively. We welcome communication from others interested in this unique approach to the management of maintenance immunosuppression.