Departments of Endocrinology and Nephrology, University Hospital Groningen, The Netherlands. Email: m.n.kerstens{at}int.azg.nl
Sir,
In their interesting paper, Vogt et al. [1] studied the effects of puromycin aminonucleoside (PAN) and adriamycin-induced nephrotic syndrome on cortisol metabolism in rats. They observed a rise in the plasma ratio of corticosterone/11-dehydrocorticosterone as well as in the urinary ratio of (THB+allo-THB)/THA in nephrotic rats, and interpreted this change as a result of a decreased activity of 11ß-hydroxysteroid dehydrogenase type 2 (11ßHSD type 2). These experimental findings are in line with their previous study, in which they reported a decreased 11ßHSD type 2 activity in human nephrotic syndrome, based on an increase in the urinary ratio of (THF+allo-THF)/THE (i.e. the human equivalent of (THB+allo-THB)/THA) [2]. However, caution is warranted in ascribing the observed effects specifically to a decreased activity of 11ßHSD type 2. The plasma ratio of corticosterone/11-dehydrocorticosterone as well as the urinary ratio of (THB+allo-THB)/THA reflect the global setpoint of 11ßHSD, which is determined by the combined activities of 11ßHSD type 1 and 11ßHSD type 2 [3]. Accordingly, 11ßHSD type 1 contributes to the setpoint of the urinary ratio of (THF+allo-THF)/THE, as exemplified by its decrease in the rare syndrome of genetic 11ßHSD type 1 deficiency in humans [4]. It should be noted that several authors consider the ratio of urinary free cortisol to free cortisone (UFF/UFE) to be a more specific in vivo measurement of 11ßHSD type 2 activity [5,6]. Indeed, Kasuya et al. [7] have recently corroborated the diagnostic value of the UFF/UFE ratio for in vivo assessment of the 11ßHSD type 2 activity in humans by studying the metabolism of deuterium-labelled cortisol in healthy subjects. This ratio was, however, not assessed in the studies by Vogt et al. [1,2].
Therefore, we have measured the UFF/UFE ratio in proteinuric patients for evaluation of their renal 11ßHSD type 2 activity [8]. Interestingly, we found a decrease in the UFF/UFE ratio in untreated patients with nephrotic-range proteinuria. In our study, there was only a minor, non-significant increase in the urinary (THF+allo-THF)/THE ratio. Thus, our findings are compatible with an enhanced rather than an inhibited renal 11ßHSD type 2 activity, together with a possible increase in 11ßHSD type 1 activity. Furthermore, it should be noted that, in contrast to human kidney, rat kidney also expresses 11ßHSD type 1, which might have also been affected by the toxins applied in the rodent study by Vogt et al. [1]. These considerations draw attention to the difficulties in extrapolating the observed alterations in cortisol metabolism in rodents to the human situation. In our opinion, an abnormal 11ßHSD type 2 activity does not contribute to sodium and fluid retention in the human nephrotic syndrome.
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