Glomerular and tubular function following orthotopic liver transplantation in children.
Since its advent, cyclosporine nephrotoxicity has been a major concern to pediatricians attending to liver transplant recipients. The aims of this study were to examine glomerular and tubular function after orthotopic liver transplantation (OLT) in children, their correlation to CsA, and how they differed according to the underlying disease.


METHODS
Glomerular and tubular function was examined in 28 patients aged 7 months to 14 yr at the time of transplantation (mean 4.0 +/- 3.6), retrospectively examining creatinine clearance, tubular phosphate reabsorption (TRP), calcium/creatinine ratio, sodium excretion fraction, and protein/creatinine ratio. The group with metabolic disease and an underlying tubulopathy was compared with the group with liver disease only. The effect of CsA trough levels and cumulated dose on these indices was examined, as was the effect of antihypertensives on creatinine clearance. Both glomerular and tubular functions improved significantly following liver transplantation. In patients on CsA (n = 21), CrCl decreased significantly at 1 month post-OLT (42.6 +/- 26.6 mL/min/1.73 m(2)) when compared with pretransplantation, and 3, 12 and 60 months post-OLT (p < 0.05). It improved between 12 and 60 months post-OLT (p < 0.05). It was correlated with cyclosporine trough levels (p < 0.03), and with total dose of CsA at 12 months. This was not true for patients on tacrolimus (n = 7). Overall pretransplant TRP was below normal (73.7% +/- 19.6), which was significantly lower than the values at years 2, 3, and 5 post-OLT (p < 0.05), owing mainly to the metabolic group which recovered normal proximal tubular function by the end of the second week post-OLT. Calcium/creatinine ratio was significantly worse in the group with liver disease only (p < 0.01). Protein/creatinine ratio normalized rapidly in both groups. Urinary sodium excretion fraction (FENa) was very abnormal in the early postoperative phase, normalizing thereafter in both groups. Kidney function improved after liver transplantation in patients with and without pre-existing kidney dysfunction. Overall, creatinine clearance was correlated to CsA trough levels suggesting CsA did not have an irreversible 'sclerosing' effect in the medium term. Combined antihypertensive therapy using nifedipine and enalapril may be the optimal choice for patients requiring medical management of their hypertension, although the observed effect on creatinine clearance did not reach statistical significance in this study. Tubular dysfunction is frequent in both groups of patients, pre- and post-transplant, and may contribute to bone mineral density as well as to metabolic disturbances in this population.
McLin
Valérie A
VA
Department of Pediatrics, University of Geneva Hospital, Geneva, Switzerland. valérie.mclin@cchmc.org
Girardin
Eric
E
Lecoultre
Claude
C
Mentha
Gilles
G
Belli
Dominique C
DC
D000293:Adolescent; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000627:therapeutic use; D002118:Calcium / Q000652:urine; D002648:Child; D002675:Child, Preschool; D003404:Creatinine / Q000652:urine; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007223:Infant; D007684:Kidney Tubules / Q000503:physiopathology*; D016031:Liver Transplantation; D008297:Male; D011507:Proteinuria / Q000175:diagnosis; D012189:Retrospective Studies; D012964:Sodium / Q000652:urine; D015996:Survival Rate
D000959:Antihypertensive Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D012964:Sodium; D003404:Creatinine; D002118:Calcium