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Comparison of Methods for Measurement of Na⁺/Li⁺ Countertransport Across the Erythrocyte Membrane

¹ Depts. of Biochem. and
³ Med. Informatics, Epidemiol., and Statistics, Univ. of Nijmegen, Nijmegen, The Netherlands,
² Dept. of Clin. Chem.,
⁴ Divs. of Gen. Intern. Med. and
⁵ Nephrol., University Hosp. Nijmegen, Nijmegen, The Netherlands
^a Address correspondence to this author at: P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.

To the Editor:

About 30% of patients with insulin-dependent diabetes mellitus develop diabetic nephropathy. Since diabetic nephropathy contributes to a large extent to the high mortality of these patients, a risk marker for the development of this condition is desirable. Increase in Na+/Li+ countertransport across the red cell membrane has been suggested as such an early marker (1)(2)(3)(4), although this was not uniformly confirmed (5)(6)(7). In this study, the three main methods to load erythrocytes with Li+ were compared and tested for their measuring error and intrasubject variation of V_max and K_0.5 for Na+.

The "classic" LiCl loading [8, 9] is the most "physiological" and noninvasive method. However, the loading procedure takes 3 h, which precludes the use of this method as a standard procedure. The Li₂CO₃ loading as described by Elving et al. (6) has the advantage that it takes only 30 min to load the cells with Li+. The Li+ enters the cell via the HCO₃^-/Cl^- exchanger as a LiCO₃^- ion in exchange for a Cl^- ion, which explains the fast Li+ loading. This method has been reported to give plots to which Michaelis–Menten kinetics apply (10). The nystatin method was developed by Canessa et al. (11) because at 150 mmol/L Na+ (the highest concentration that can be used at an osmolarity of 300 mosmol/L), the extracellular binding site for Na+ is often not saturated. With nystatin, an antifungal drug that penetrates the plasma membrane, the intra- and extracellular osmolarity can be raised to 600 mosmol/L, so extracellular concentrations of Na+ up to 300 mmol/L can be used. Because of this, K_0.5 values can in principle be measured more accurately than with the other methods. We found, . . . [Full Text of this Article]

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The following articles in journals at HighWire Press have cited this article:

				G. Zerbini, D. Gabellini, D. Ruggieri, and A. Maestroni Increased Sodium-Lithium Countertransport Activity: A Cellular Dysfunction Common to Essential Hypertension and Diabetic Nephropathy J. Am. Soc. Nephrol., January 1, 2004; 15(90010): S81 - 84. [Abstract] [Full Text]