Pediatric renal allograft transplantation does not normalize the increased cortisol/cortisone ratios of chronic renal failure.
OBJECTIVE
The conversion of cortisol (F) to cortisone (E) is catalyzed by 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). Children suffering from chronic renal failure (CRF) have a decreased activity of 11beta-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 11beta-HSD2 in plasma was calculated using the ratio of F/E determined by tandem mass spectrometry, the ratio of tetrahydrocortisol (THF) +5alpha-tetrahydrocortisol (5alphaTHF) in urine determined by gas chromatography/mass spectrometry, and the ratio of (THF +5alphaTHF)/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 + 5alphaTHF)/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. R(2) = 0.73 in CRF, P = 0.0013, R(2) = 0.56 in TX, P < 0.0001, R(2) = 0.66 in CO) were found, whereas significant correlations between F/E or (THF + 5alphaTHF)/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 11beta-HSD2 activity.
Schroth
Michael
M
Department of Pediatrics, Friedrich-Alexander-University Erlangen-Nürnberg, Germany. michael_schroth@yahoo.de
Plank
Christian
C
Rauh
Manfred
M
Dörr
Helmuth-Günther
HG
Rascher
Wolfgang
W
Dötsch
Jörg
J
D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000097:blood; D000293:Adolescent; D001794:Blood Pressure; D002648:Child; D002675:Child, Preschool; D003348:Cortisone / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D007676:Kidney Failure, Chronic / Q000201:enzymology*; D016030:Kidney Transplantation; D008297:Male; D013760:Tetrahydrocortisol / Q000652:urine; D013761:Tetrahydrocortisone / Q000652:urine; D014184:Transplantation, Homologous
D013761:Tetrahydrocortisone; D013760:Tetrahydrocortisol; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003348:Cortisone; D006854:Hydrocortisone