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Pediatric renal allograft transplantation does not normalize the increased cortisol/cortisone ratios of chronic renal failure

Department of Pediatrics, Friedrich-Alexander-University Erlangen-Nürnberg, Loschgestraße 15, D-91054 Erlangen, Germany

(Correspondence should be addressed to M Schroth, Kinder-und Jugendklinik, Universitätsklinikum Erlangen, Loschgestraße 15, D-91054 Erlangen, Germany; Email: michael_schroth{at}yahoo.de)

Objective: The conversion of cortisol (F) to cortisone (E) is catalyzed by 11beta-hydroxysteroid dehydrogenase type 2 (11ß-HSD2). Children suffering from chronic renal failure (CRF) have a decreased activity of 11ß-HSD2 contributing to increased arterial blood pressure. The objective was to investigate whether a normal conversion of F to E is achieved after renal transplantation (TX) in children.

Methods: Fifteen children with CRF, 17 children with steroid-free immunosuppression after TX, and 18 healthy controls (CO) were enrolled. The activity of 11ß-HSD2 in plasma was calculated using the ratio of F/E determined by tandem mass spectrometry, the ratio of tetrahydrocortisol (THF) +5-tetrahydrocortisol (5THF) in urine determined by gas chromatography/mass spectrometry, and the ratio of (THF +5THF)/tetrahydrocortisone (THE) in urine determined by tandem mass spectrometry.

Results: The F/E ratio (mean ± S.D./S.E.M.) was significantly higher in CRF and TX (5.6 ± 1.9/0.6, 7.12 ± 3.1/0.9) than in CO (1.18 ± 0.2/0.03, P < 0.0001) groups. The (THF + 5THF)/THE ratio in CRF (1.19 ± 1.1/0.5) and TX (1.19 ± 0.1/0.5) groups was significantly higher than in controls (0.21 ± 0.05/0.18, P < 0.0001). Positive correlations between plasma and urinary ratios (P = 0.0004. R² = 0.73 in CRF, P = 0.0013, R² = 0.56 in TX, P < 0.0001, R² = 0.66 in CO) were found, whereas significant correlations between F/E or (THF + 5THF)/THE ratios and blood pressure, the number of antihypertensive drugs taken or creatinine clearance could not be found.

Conclusions: In all children with chronic renal failure plasma and urinary cortisol/cortisone ratios are elevated and do not return to normal levels after renal allograft transplantation. This suggests that renal transplantation does not normalize 11ß-HSD2 activity.