Steroids have been a cornerstone in renal transplant immunosuppression. New immunosuppressive drugs have led to protocols using early steroid withdrawal or complete avoidance. A prospective protocol in 23 pediatric renal transplant (ages 2-14 yr) who received decreasing steroid doses stopping at day 7 post-Tx, FK, and MMF were compared with a CsA, AZT, historically matched steroid-based control group. Basiliximab was used in two doses. Anthropometric, biochemical variables, AR rates, and CMV infection were evaluated and compared using Student's t-test and regression analysis. A better growth pattern was seen in steroid withdrawal group. GFR rate and serum glucose were similar in both groups. Total serum cholesterol levels were significantly lower in steroid withdrawal group. The incidence of AR at 12 months was 4.3% in steroid withdrawal group vs. 8.6% in steroid-based group (p = ns). No difference in CMV infection was observed. Hemoglobin levels were low during the first months in both groups; reached normal values after six months. SBP became higher at 12 months in steroid-based group. Patient and graft survival was 98% in both groups at one-yr post-transplant. Early steroid withdrawal was efficacious, safe, and did not increase risk of rejection, preserving optimal growth, renal function, and reducing cardiovascular risk factors.

This prospective, comparative trial investigated the impact on mean change in height standard deviation score (SDS), acute rejection rate, and renal function of early steroid withdrawal in 96 recipients with 5 years of follow-up. Recipients under basiliximab induction and steroid withdrawal (SW: TAC/MMF; n = 55) were compared with a matched steroid control group (SC: TAC/MMF/STEROID, n = 41). SW received steroids until Day 6, SC decreased to 10 mg/m(2) within 2 months post-transplant. Five years after SW, the longitudinal growth (SDS) gain was 1.4 ± 0.4 vs. 1.1 ± 0.3 for SC group (p < 0.02). Height benefits in prepubertal and pubertal status in both groups were demonstrated in the delta growth trends (mixed model; p < 0.01). Biopsy-proven acute rejection in SW was 11% and 17.5%, SC (p: ns). Mean eGFR (ml/min/1.73 m(2)) at 5 years post-transplant was SW 80.6 ± 27.8 vs. 82.6 ± 25.1 for SC (p: ns). The death-censored graft survival rate at 1 and 5 years was 99 and 90% for SW; 98 and 96% for SC (p = ns). PTLD incidence in SW 3.3 vs. 2.5% in SC (p: ns). Five years post-transplant, early steroid withdrawal showed positive impacts on growth, stable renal function without increased acute rejection risk, and PTLD incidence.

Between 1989 and 2003, 100 transplants were performed in 96 patients at the pediatric nephrology unit of the Calvo Mackenna Children's Hospital. Mean age 10.9 +/- 3.9 yr (1-17.6), 30% from LD. Donors were younger than 5 yr in five patients and all recipients received an 'en bloc' graft. Original disease was hypo/dysplasia 27%, reflux nephropathy 22 and 17% chronic glomerulonephritis. The immunosuppressive protocol during the first period (n = 56, 1989-2000): Cyclosporine, steroids and azathioprine, and during the second period (n = 44, 2001-2003): FK, steroids, MMF and anti-CD25 antibody (mAbs). AR was reported in 22 patients, 11% in LD, 31% in DD (p < 0.01). The AR rate decreased from 40 to 8% after anti-CD25 monoclonal induction. Patient actuarial survival rate at 1, 3 and 5 yr was 100% for LD and 96% for DD. The overall actuarial graft survival at 1,3, and 5 yr was 96.7, 96.7 and 71% for LD and 89, 76 and 73% for DD donors. Graft survival rate improved from the first period (1989-2000) to the second period (2001-2003; p = 0.05). No difference in graft survival rate with HLA-A,B,DR matching was found. Graft survival rate was better when cold ischemia time was <24 h (p < 0.01). CMV infections increased from 19 to 40% when MMF and anti-CD25 Ab were introduced (p < 0.01). The height/age Z score at 1, 3 and 5 yr post-transplant was -2.2, -2.1, -2.2, respectively, for children older than 7 yr and -1.8, -1.9, -2.1 for those transplanted younger than 7 yr of age who were switched to alternate day steroids (p < 0.01). The cause of graft lost was: chronic rejection eight, non-adherence four, AR four and vascular thrombosis two. The cause of death in two patients was fungus septicemia and accelerated rejection. Pediatric renal transplantation can be performed in our group with acceptable morbidity, low mortality and graft survival rates similar to other reports in North America and Western Europe. Graft survival rate improved with newer immunosuppression and greater experience at the center. Management of non-adherence and chronic rejection remain the major challenges.

BackgroundFibroblast Growth Factor-23 (FGF23) and cofactor Klotho are key regulators of mineral metabolism in chronic kidney disease (CKD), but little is known about the mechanisms that regulate their production. This study evaluates longitudinal changes of FGF23 and Klotho levels and their regulatory factors in children on chronic peritoneal dialysis (PD).MethodsFGF23, Klotho, 25(OH) vitamin D, 1,25-dihydroxyvitamin D and parathyroid hormone (PTH) plasma concentrations were measured during 1 year of follow-up in PD children. Anthropometric and dialytical parameters were evaluated in addition to mineral metabolism variables.ResultsThirty-one patients under chronic PD were followed for 12 months. FGF23 mean plasma levels at Month 1 were significantly increased compared with controls, 215.1 ± 303.6 versus 9.4 ± 5.7 pg/mL, respectively (P < 0.001). Baseline Klotho levels were 41% lower in patients compared with controls, 132.1 ± 58 versus 320 ± 119.4 pg/mL, respectively (P < 0.001), and did not correlate with FGF23 and phosphorus levels. At Month 12, FGF23 (195 ± 300 pg/mL) and Klotho levels (130 ± 34 pg/mL) remained similar to baseline values. Log-FGF23 correlated significantly with height/age Z score (r= −0.38) and residual renal function (r = −0.44), but no correlation was found with serum phosphorus, phosphate intake, PTH and vitamin D levels. The log-FGF23 strongly correlated with calcium levels at Months 1, 6 and 12, however, this relationship was blunted if serum phosphorus was >6 mg/dL. By multiple regression analysis, calcium was the strongest variable determining FGF23 levels.ConclusionsIn this longitudinal study, FGF23 levels are markedly increased, and Klotho levels are reduced in PD children compared with controls. FGF23 levels appeared to be regulated primarily by serum calcium, showing a significant correlation at each time of measurement. This relationship was lost in patients with phosphorus >6 mg/dL. These observations may have important consequences to the therapeutic management of phosphate homeostasis in CKD patients.