Impaired phosphate handling of renal allografts is aggravated under rapamycin-based immunosuppression.
BACKGROUND
Impaired phosphate handling of the renal allograft is a common problem and of multifactorial origin. The aim of the study was to elucidate whether a rapamycin- or a mycophenolate-based immunosuppressive therapy aggravates the renal phosphate leak in kidney transplant recipients.


METHODS
Renal phosphate handling was determined in thirty-eight cadaveric allograft recipients, with good renal function at 8, 12, 20 and 28 weeks after transplantation. Nineteen patients (group 1) received triple immunosuppression with rapamycin, cyclosporine and prednisolone, nineteen other transplant recipients received mycophenolate mofetil, cyclosporine and prednisolone immunosuppression (group 2), and six healthy subjects (group 3) served as controls. After 12 weeks of stable graft function, group 1 patients were divided further into two subgroups. Ten patients were kept on their immunosuppressive regimen (group 1A), whereas the remaining nine randomly chosen subjects had their cyclosporine withdrawn; they were thus maintained on a dual immunosuppression regimen with prednisolone and a higher dosage of rapamycin (group 1B).


RESULTS
Renal phosphate reabsorption was significantly lower in group 1 at 8 and 12 weeks after transplantation as compared with groups 2 and 3. At 20 weeks after transplantation, patients with rapamycin-based immunosuppression (groups 1A and 1B) continued to exhibit hypophosphataemia and impaired renal phosphate handling. Group 1B had the lowest TmP/ GFR compared with all groups. At 28 weeks, renal phosphate reabsorption and plasma phosphate levels were no longer different between patient groups and controls.


CONCLUSIONS
These data suggest that rapamycin-based immunosuppression prolongs the phosphate leak of the allografted kidney, leading to low serum phosphate levels during the first weeks after transplantation.
Schwarz
C
C
Department of Internal Medicine III, Division of Nephrology and Dialysis, University of Vienna, Vienna, Austria.
Böhmig
G A
GA
Steininger
R
R
Mayer
G
G
Oberbauer
R
R
D000328:Adult; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D017674:Hypophosphatemia / Q000097:blood / Q000139:chemically induced; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism*; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D010710:Phosphates / Q000378:metabolism*; D020123:Sirolimus / Q000009:adverse effects* / Q000627:therapeutic use; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D010710:Phosphates; D009173:Mycophenolic Acid; D020123:Sirolimus