Klinische Wochenschrift

Klin. Wschr. 54, 187-188 (1976)

© by Springer-Verlag 1976

Radioimmunoassay of Plasma Digoxin in Nephrotic Syndrome P. Kramer, R.P. Buckesfeld, C. McIntosh and F. Scheler Medizinische Klinik und Poliklinik der Universit/it G6ttingen

Radioimmunologische Bestimmung von Digoxin bei nephrotischem Syndrom

PLASMA- DIGOXIN 5 [ngtml]

Zusammenfassung. Mit drei verschiedenen Radioimmunoassays wurde die Digoxin-Konzentration im Plasma von 12 Patienten mit Hypoalbuminfimie vor und nach Erh6hung der Atbumin- und TBG-Konzentration bestimmt. Die Messungen mit dem ClinicalAssays-[12sI]-Kit und dem Schwarz/Mann-[3H]-Kit ergaben auch bei Patienten mit schwerem nephrotischem Sydrom zuverlfissige Werte.

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Summary. Plasma digoxin was determined by three different radioimmunoassays in btood samples from 12 patients with hypoalbuminemia before and after increasing the concentration of albumin and TBG. With the Clinical-Assays-[lzsI]-Kit and the Schwarz/Mann-[BH]-Kit reliable digoxin values were obtained even in patients with severe nephrotic syndrome. Key words: Radioimmunoassay - Digoxin - Nephrotic syndrome - Hypoalbuminemia.

Introduction

In patients with nephrotic syndrome the plasma concentration of albumine and thyroxin binding globulin (TBG) are decreased because of the high renal excretion of these plasma proteins. According to Holtzmann et al. [5] plasma from patients with tow albumin concentration will increase the binding of the labelled digoxin to the radioimmunoassay antibody and thus produce erroneously low values for plasma digoxin. We have investigated this problem using three different commercial radioimmunoassay kits. The results of this study present evidence that interference of low albumin or low TBG concentration with the radioimmunological determination of digoxin is of Iittle practical significance. Materials and Methods

The plasma digoxin was determined by three different commercial radioimmunoassay kits: * Mit Unterstiitzung der deutschen Forschungsgemeinschaft im Rahmen des SFB 89 Kardiologie G6ttingen.

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Fig, I. The effect of increasing aIbnmin concentration on the determination of digoxin by three different methods in plasma samples from patients with severe nephrotic syndrome. Increase in albumin concentrations was achieved by stepwise addition of concentrated human albumin

I. Digoxin-Radioimmunoassay-[3H] (dextran coated charcoal separation) Schwarz/Mann, Becton Dickinson & Co. 2. Digoxin-Radioimmunoassay-[125 I] (dextran coated charcoal separation) Schwarz/Mann, Becton Dickinson & Co, 3. Digoxin-Radioimmunoassay-[1251] (coated tube) Clinical Assays, Inc. The first two procedures were performed by strict adherence to the operational instruction delivered with the kits. The performance of the Gamma-Coat-method has been described recently in detail [7]. Blood samples were obtained from 12 patients with nephrotic syndrome or hypoalbuminemia of other aetiology. Seven patients had been treated with digoxin; in 5 patients digoxin was added to the plasma samples. In 2 patients with a very low albumin concentration of 1.5 g/100 ml (Fig. t) digoxin was determined with all three methods as the albumin concentration was increased stepwise by adding concentrated human albumin (20 g/100 ml, BehringWerke AG, Marburg/Lahn). In the 10 other plasma samples (albumin concentration of 2.5 g/100 ml) digoxin was determined only with the [125I]-kits before and after increasing the albumin concentration by 2 g/100 ml. The influence of TGB on the determination of digoxin by the different radioimmunoIogical methods was tested by measurement before and after addition of 10 gg of purified TBG (Clinical Assays, Inc., Cambridge, Massachusetts) to

188 1 ml of the plasma from the two patients H.T. and R.B. who showed a very tow albumin concentration. The number of these investigations was limited because of the extremly high costs of purified TBG. Tritium samples were counted in a Packard Tri-Carb Model 3380 using the commercial liquid scintillation solubilizer InstagelO. Quenching correction was performed by internal standardisation. [t25I]-samples were counted in an Auto-Gamma-Packard Model 5220.

Results

As demonstrated in Fig. 1 the determination of plasma digoxin by the Schwarz/Mann-[3H]-kit and the Clinical-Assays-[lzsI]-kit was not influenced by a change in albumin concentration. The slight decrease of digoxin concentration (Schwarz/Mann-[3H]-kit: R.B. p