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Monitoring of Urea and Potassium by Reverse Iontophoresis In Vitro

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Abstract

Purpose

Reverse iontophoresis is an alternative to blood sampling for the monitoring of endogenous molecules. Here, the potential of the technique to measure urea and potassium levels non-invasively, and to track their concentrations during hemodialysis, has been examined.

Materials and Methods

In vitro experiments were performed to test (a) a series of subdermal urea and potassium concentrations typical of the pathophysiologic range, and (b) a decreasing profile of urea and potassium subdermal concentrations to mimic those which are observed during hemodialysis.

Results

(a) After 60–120 min of iontophoresis, linear relationships (p < 0.05) were established between both urea and potassium fluxes and their respective subdermal concentrations. The determination coefficients were above 0.9 after 1 h of current passage using sodium as an internal standard. (b) Reverse iontophoretic fluxes of urea and K+ closely paralleled the decay of the respective concentrations in the subdermal compartment, as would occur during a hemodialysis session.

Conclusions

These in vitro experiments demonstrate that urea and potassium can be quantitatively and proportionately extracted by reverse iontophoresis, even when the subdermal concentrations of the analytes are varying with time. These results suggest the non-invasive monitoring of urea and potassium to diagnose renal failure and during hemodialysis is feasible, and that in vivo measurements are warranted.

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Abbreviations

BUN:

Blood Urea Nitrogen

I :

current

IS:

internal standard

J :

flux

r 2 :

determination coefficient

T :

transport number

References

  1. B. Leboulanger, R. H. Guy, and M. B. Delgado-Charro. Reverse iontophoresis for non-invasive transdermal monitoring. Physiol. Meas. 25:R35–R50 (2004).

    Article  PubMed  Google Scholar 

  2. Y. N. Kalia, A. Naik, J. Garrison, and R. H. Guy. Iontophoretic drug delivery. Adv. Drug Deliv. Rev. 56:619–658 (2004).

    Article  PubMed  CAS  Google Scholar 

  3. P. G. Green, M. Flanagan, B. Shroot, and R. H. Guy. Iontophoretic drug delivery. In K. A. Walters and J. Hadgraft (eds), Pharmaceutical Skin Penetration Enhancement, Dekker, New York, 1993, pp. 311–332.

    Google Scholar 

  4. D. Marro, Y. N. Kalia, M. B. Delgado-Charro, and R. H. Guy. Contributions of electromigration and electroosmosis to iontophoretic drug delivery. Pharm. Res. 18:1701–1708 (2001).

    Article  PubMed  CAS  Google Scholar 

  5. A. Sieg, R. H. Guy, and M. B. Delgado-Charro. Electroosmosis in transdermal iontophoresis: implications for noninvasive and calibration-free glucose monitoring. Biophys. J. 87:3344–3350 (2004).

    Article  PubMed  CAS  Google Scholar 

  6. J. B. Phipps and J. R. Gyory. Trandermal ion migration. Adv. Drug Deliv. Rev. 9:137–176 (1992).

    Article  CAS  Google Scholar 

  7. R. R. Burnette and B. Ongpipattanakul. Characterization of the permselective properties of excised human skin during iontophoresis. J. Pharm. Sci. 76:765–773 (1987).

    Article  PubMed  CAS  Google Scholar 

  8. M. J. Tierney, J. A. Tamada, R. O. Potts, R. C. Eastman, K. Pitzer, N. R. Ackerman, and S. J. Fermi. The GlucoWatch biographer: a frequent automatic and noninvasive glucose monitor. Ann. Med. 32:632–641 (2000).

    Article  PubMed  CAS  Google Scholar 

  9. B. Leboulanger, J. M. Aubry, G. Bondolfi, R. H. Guy, and M. B. Delgado-Charro. Lithium monitoring by reverse iontophoresis in vivo. Clin. Chem. 50:2091–2100 (2004).

    Article  PubMed  CAS  Google Scholar 

  10. I. T. Degim, S. Ilbasmis, R. Dundaroz, and Y. Oguz. Reverse iontophoresis: a non-invasive technique for measuring blood urea level. Pediatr. Nephrol. 18:1032–1037 (2003).

    Article  PubMed  Google Scholar 

  11. N. K. Man, M. Touam, and P. Jungers. Causes et conséquences de l’urémie chronique, indications de la dialyse de suppléance. In L’Hémodialyse de Suppléance, Médecine-Sciences, Flammarion, Paris, 2003, pp. 1–15.

  12. A. Farkas, R. Vamos, T. Bajor, N. Mullner, A. Lazar, and A. Hraba. Utilization of lacrimal urea assay in the monitoring of hemodialysis: conditions, limitations and lacrimal arginase characterization. Exp. Eye Res. 76:183–192 (2003).

    Article  PubMed  CAS  Google Scholar 

  13. R. Koncki, A. Radomska, and S. Glab. Bioanalytical flow-injection system for control of hemodialysis adequacy. Anal. Chim. Acta 418:213–224 (2000).

    Article  CAS  Google Scholar 

  14. T. A. Depner, P. R. Keshaviah, J. P. Ebben, P. F. Emerson, A. J. Collins, K. K. Jindal, A. R. Nissenson, J. M. Lazarus, and K. Pu. Multicenter clinical validation of an on-line monitor of dialysis adequacy. J. Am. Soc. Nephrol. 7:464–471 (1996).

    PubMed  CAS  Google Scholar 

  15. S. Alloatti, A. Molino, M. Manes, and G. M. Bosticardo. Urea rebound and effectively delivered dialysis dose. Nephrol. Dial. Transplant. 13(Suppl 6):25–30 (1998).

    Article  PubMed  CAS  Google Scholar 

  16. L. R. Narasimhan, W. Goodman, and C. K. Patel. Correlation of breath ammonia with blood urea nitrogen and creatinine during hemodialysis. Proc. Natl. Acad. Sci. U. S. A. 98:4617–4621 (2001).

    Article  PubMed  CAS  Google Scholar 

  17. Reviewing the draft NKF-DOQI guidelines. 1. National Kidney Foundation-Dialysis Outcome Quality Initiative. Nephrol. News Issues 11:10–11 (2000).

    Google Scholar 

  18. G. S. Metry, P. O. Attman, P. Lonnroth, S. N. Beshara, and M. Aurell. Urea kinetics during hemodialysis measured by microdialysis—a novel technique. Kidney Int. 44:622–629 (1993).

    Article  PubMed  CAS  Google Scholar 

  19. M. Capdevila, I. Martinez Ruiz, C. Ferrer, F. Monllor, C. Ludjvick, N. H. Garcia, and L. I. Juncos. The efficiency of potassium removal during bicarbonate hemodialysis. Hemodial. Int. 9:296–302 (2005).

    Article  PubMed  CAS  Google Scholar 

  20. B. Redaelli, G. Bonoldi, G. Di Philippo, M. R. Vigano, and A. Malnati. Behaviour of potassium removal in different dialytic schedules. Nephrol. Dial. Transplant. 13:35–38 (1998).

    Article  PubMed  CAS  Google Scholar 

  21. J. Ahmed and L. S. Weisberg. Hyperkaliemia in dialysis patients. Sem. Dial. 14:348–356 (2001).

    Article  CAS  Google Scholar 

  22. S. H. Pai and M. Cyr-Manthey. Effects of hemolysis on chemistry tests. Lab. Med. 22:408–410 (1991).

    Google Scholar 

  23. D. Yücel and K. Dalva. Effect of in vitro hemolysis on 25 common biochemical tests. Clin. Chem. 38:575–577 (1992).

    PubMed  Google Scholar 

  24. M. J. Tierney, J. A. Tamada, R. O. Potts, L. Jovanovic, and S. Garg. Clinical evaluation of the GlucoWatch biographer: a continual, non-invasive glucose monitor for patients with diabetes. Biosens Bioelectron. 16:621–629 (2001).

    Article  PubMed  CAS  Google Scholar 

  25. A. Sieg, R. H. Guy, and M. B. Delgado-Charro. Reverse iontophoresis for noninvasive glucose monitoring: the internal standard concept. J. Pharm. Sci. 92:2295–2302 (2003).

    Article  PubMed  CAS  Google Scholar 

  26. A. Sieg, R. H. Guy, and M. B. Delgado-Charro. Simultaneous extraction of urea and glucose by reverse iontophoresis in vivo. Pharm. Res. 21:1805–1810 (2004).

    Article  PubMed  CAS  Google Scholar 

  27. N. G. Levinsky. Fluides et Electrolytes. In J. D. Wilson, E. Braunwald, K. J. Isselbacher, R. G. Petersdorf, J. B. Martin, A. S. Fauci, and R. K. Root (eds), T.R. Harrison, Principes de Médecine Interne, Médecine-Sciences, Flammarion, Paris, 1992, pp. 278–295.

    Google Scholar 

  28. B. Kirschbaum. The effect of hemodialysis on electrolytes and acid-base parameters. Clin. Chim. Acta 336:109–113 (2003).

    Article  PubMed  CAS  Google Scholar 

  29. B. Canaud. Adequacy target in hemodialysis. J. Nephrol. 17:77–86 (2004).

    Article  CAS  Google Scholar 

  30. R. van der Geest, M. Danhof, and H. Boddé. Validation and testing of a new iontophoretic continuous flow through transport cell. J. Control. Release 51:85–91 (1998).

    Article  PubMed  Google Scholar 

  31. P. F. Mulvenna and G. Savidge. A modified manual method for the determination of urea in seawater using diacetylmonoxime reagent. Estuar., Coast. Shelf Sci. 34:429–438 (1992).

    Article  CAS  Google Scholar 

  32. E. Rozet, V. Wascotte, N. Lecouturier, V. Préat, W. Dewé, B. Boulanger, and P. Hubert. Improvement of the decision efficiency of the accuracy profile by means of indexes for analytical methods validation. Application to a diacetyl-monoxime colorimetric assay used for the determination of urea in transdermal iontophoretic extracts. Anal. Chim. Acta (2006).

  33. C. R. Harding. The stratum corneum: structure and function in health and disease. Dermatol. Ther. 17(Suppl 1):6–15 (2004).

    Article  PubMed  Google Scholar 

  34. M. Loden. Role of topical emollients and moisturizers in the treatment of dry skin barrier disorders. Am. J. Clin. Dermatol. 4:771–788 (2003).

    Article  PubMed  Google Scholar 

  35. B. Mudry, R. H. Guy, and M. B. Delgado-Charro. Electromigration of ions across the skin: determination and prediction of transport numbers. J. Pharm. Sci., 95:561–569(2006).

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

Funded in part by the FRSM (Fonds de Recherche Scientifique Medical) (Belgium) and by the U.S. National Institutes of Health (EB-001420). Valentine Wascotte is a research fellow of the FNRS (Fonds National de la Recherche Scientifique) (Belgium) and thanks Denis Dufrane, Nathalie Lecouturier and Bernard Ucakar for their helpful contributions.

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Correspondence to Véronique Préat.

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Wascotte, V., Delgado-Charro, M.B., Rozet, E. et al. Monitoring of Urea and Potassium by Reverse Iontophoresis In Vitro . Pharm Res 24, 1131–1137 (2007). https://doi.org/10.1007/s11095-007-9237-0

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  • DOI: https://doi.org/10.1007/s11095-007-9237-0

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