Outcome of renal transplantation in early childhood

............................................................................................................................................................. 6 LIST OF ORIGINAL PUBLICATIONS .............................................................................................................. 8 ABBREVIATIONS .................................................................................................................................................. 9 INTRODUCTION.................................................................................................................................................. 11 REVIEW OF THE LITERATURE ..................................................................................................................... 12 RENAL TRANSPLANTATION IN CHILDREN............................................................................................. 12 IMMUNOSUPPRESSION ................................................................................................................................. 13 Cyclosporine................................................................................................................................................... 13 Other immunosuppressants............................................................................................................................ 14 PATIENT AND GRAFT SURVIVAL............................................................................................................... 15 Patient survival ............................................................................................................................................... 15 Graft survival.................................................................................................................................................. 16 Causes of and risk factors for graft survival.................................................................................................. 18 LONG-TERM RENAL FUNCTION ................................................................................................................. 20 Glomerular function and renal plasma flow.................................................................................................. 20 Hypertension................................................................................................................................................... 22 Tubular function and handling of electrolytes .............................................................................................. 23 Functional adaptation of an adult kidney to a pediatric recipient................................................................. 25 LONG-TERM RENAL HISTOPATHOLOGY AND CHRONIC ALLOGRAFT NEPHROPATHY........... 26 Scoring of renal histopathology..................................................................................................................... 26 Chronic allograft nephropathy ....................................................................................................................... 28 Risk factors for the development of chronic allograft nephropathy............................................................. 30 GROWTH............................................................................................................................................................ 33 Growth in chronic renal failure...................................................................................................................... 33 Growth after renal transplantation ................................................................................................................. 35 Growth hormone treatment in chronic renal failure and after renal transplantation.................................... 37 NEURODEVELOPMENTAL OUTCOME....................................................................................................... 40 Complications and risk factors for an impaired neurodevelopmental outcome........................................... 41 School and cognitive performance ................................................................................................................ 43 AIMS OF THE STUDY......................................................................................................................................... 45 PATIENTS AND METHODS .............................................................................................................................. 46 ETHICAL CONSIDERATIONS........................................................................................................................ 46 PATIENTS .......................................................................................................................................................... 46 METHODS.......................................................................................................................................................... 48 Preoperative management and treatment protocol........................................................................................ 48 Immunosuppression ....................................................................................................................................... 48 Acute rejection................................................................................................................................................ 49 Renal function (I) ........................................................................................................................................... 49 Calculations ................................................................................................................................................................. 50 Renal histopathology (II) ............................................................................................................................... 50 Growth (III-V)................................................................................................................................................ 51 Neurodevelopmental assessment (IV-V)....................................................................................................... 52 Statistical analysis .......................................................................................................................................... 54 RESULTS................................................................................................................................................................ 55 PATIENT AND GRAFT SURVIVAL............................................................................................................... 55 Patient survival ............................................................................................................................................... 55 Graft survival.................................................................................................................................................. 56 Acute rejections (I)......................................................................................................................................... 57 RENAL FUNCTION (I AND II) ......................................................................................................................... 57 Glomerular function and renal plasma flow.................................................................................................. 57 Hypertension................................................................................................................................................... 61 Tubular function and handling of electrolytes .............................................................................................. 61 RENAL HISTOPATHOLOGY (II) ................................................................................................................... 62 Overall histology and lost grafts.................................................................................................................... 62 Acute rejection and cyclosporine toxicity ..................................................................................................... 65 Renal function and histology ......................................................................................................................... 66 Donor source and histology ........................................................................................................................... 66 Recipient age and histology ........................................................................................................................... 66 Growth hormone and histology ..................................................................................................................... 67 GROWTH (III).................................................................................................................................................... 68 Growth without growth hormone therapy ..................................................................................................... 68 Growth hormone therapy ............................................................................................................................... 69 Bone age ......................................................................................................................................................... 70 Weight............................................................................................................................................................. 70 NEURODEVELOPMENTAL OUTCOME (IV-V) .......................................................................................... 70 Major neurodevelopmental sequelae and neuroradiology ............................................................................ 70 EEG and anticonvulsive treatment ................................................................................................................ 73 Audiometry..................................................................................................................................................... 73 Cognitive performance................................................................................................................................... 73 School performance........................................................................................................................................ 74 Risk factors and events................................................................................................................................... 75 Neonatal ....................................................................................................................................................................... 75 Septic infections ........................................................................................................................................................... 75 Hypertension ................................................................................................................................................................ 75 Seizures......................................................................................................................................................................... 75 Aluminum toxicity ........................................................................................................................................................ 76 DISCUSSION.......................................................................................................................................................... 77 PATIENT AND GRAFT SURVIVAL............................................................................................................... 77 RENAL FUNCTION (I) ..................................................................................................................................... 78 RENAL HISTOPATHOLOGY (II) ................................................................................................................... 81 GROWTH (III).................................................................................................................................................... 83 NEURODEVELOPMENTAL OUTCOME (IV-V) .......................................................................................... 85 CONCLUSIONS..................................................................................................................................................... 89 ACKNOWLEDGMENTS ..................................................................................................................................... 90 REFERENCES ....................................................................................................................................................... 92 ORIGINAL PUBLICATIONS ........................................................................................................................... 103