Renal transplant rejection and graft versus host reactions between HLA genetically-identical sibling (HLAgi) donor/recipient (D/R) pairs are thought to result from minor histocompatibility antigen (mHAg) disparities. We have compared two methods of measuring HLAgi D/R T lymphocyte responses to "matured" dendritic cells: 1.) a modified Cylex assay of CD4+ ATP levels (MLDC-ATP) versus 2.) 3H-thymidine uptake (MLDC-3H). The MLDC-ATP kinetics peaked at 48 hours versus the MLDC-3H at 7 days, and appeared more sensitive. We tested HLAgi (normal) volunteer siblings (NLs), and D/R sibling pairs before and after renal transplantation (pre-Tx and post-Tx). The overall frequencies of positive responses in the MLDC-ATP for HLAgi NLs, pre-Tx, and post-Tx D/R pairs were 63%, 50%, and 42%, respectively. The percentage with reciprocal responses was 37.5%, 20%, and 22.22%, respectively. In one set of three HLAgi (NLs) siblings (two males and one female), there was a nongender-associated differential response. There was no MLDC correlation with class I MHC-associated mHAg (SSP) incompatibility, nor could some MLDC positive reactive pairs theoretically process the necessary HLA-class I restriction molecules for presentation of known (nanomeric) mHAg peptides. Speculatively, the MLDC reflects class II MHC-restricted mHAg reactions (not yet definable), with possible effects of other polymorphic (nonhistocompatibility) immune response genes, and thereby may be a useful measurement of CD4+ T-cell HLAgi transplantation immunity.

Lymphocyte subsets and T cell activation markers were measured in ten children with renal transplants for up to 1 year before and during their 1st year of recombinant human growth hormone (rhGH) treatment. The number of lymphocytes, helper or cytotoxic T cells or natural killer cells, and the T cell expression of CD25, CD26 and HLA-DR antigens were not altered by rhGH. B cell numbers declined both before and during treatment. There was no difference in lymphocyte subset numbers between children with and without rejection episodes.

Aims-To evaluate the efficacy (height velocity (HV), change in height standard deviation score (Delta HSDS)), and safety (glomerular filtration rate (GFR), incidence of rejection, and calcium and glucose metabolism) of recombinant human growth hormone (rhGH) treatment after renal transplantation.Design-A two year randomised controlled trial. Subjects-Fifteen prepubertal and seven pubertal children: mean (SD) age, 13.0 (2.6) and 15.2 (2.4) years, respectively; mean (SD) GFR, 51 (30) and 48 (17) ml/min/1.73 m(2), respectively. Six prepubertal and three pubertal children were controls during the first year; all received rhGH in the second year.Results-In the first year, mean (SE) HV and Delta HSDS in the prepubertal treated group increased compared with controls: 8.1 (0.9) v 3.7 (0.6) cm/year and 0.6 (0.1) v -0.3 (0.2), respectively. In the pubertal. treated group, mean (SE) HV and Delta HSDS were also greater: 10.1 (0.6) v 3.9 (1.3) cm/year and 0.6 (0.1) v -0.1 (0.2), respectively. Comparing all treated and control children, there was no significant change in GFR: treated group, mean (SE) 9.9 (5.4) ml/min/1.73 ml v control group, -1.6 (7.6) ml/min/1.73 ml. There were also no differences in the incidence of rejection in the first year: eight episodes in 13 patients v five episodes in nine patients, respectively. Phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and fasting insulin concentrations rose during the first year of treatment, but not thereafter. In the second year of treatment, HV remained above baseline.Conclusion-Treatment with rhGH improves growth in prepubertal and pubertal children with renal transplants, with no significant change in GFR or the incidence of rejection. Phosphate, ALP, PTH, and insulin increased during the first year of treatment.

Objective: Assessment of growth after renal transplantation in children of pubertal age by analyzing the annual increment in height standard deviation score (Ht SDS) in all girls greater than or equal to 10 years and boys greater than or equal to 11 years of age at the time of transplantation until latest follow-up (minimum 2 years).Patients: A total of 59 grafts were placed in 54 recipients (30 boys) between December 1984 and January 1995. Mean (range) age at transplantation was 13.6 years (10.1 to 17.7 years). Fifty-one percent had congenital renal disease, 36% acquired renal disease, and 13% had hereditary nephropathies. Eighty-seven percent were first grafts; of these, 29% were performed pre-emptively, and 23% were from living related donors.Results: Mean (SD) Ht SDS at transplantation was -1.8 (0.2) and increased significantly thereafter such that it was -1.6 (0.2) at 1 year, n = 52; -1.5 (0.2) at 2 years, n = 47; -1.0 (0.2) at 3 years, n = 27; -0.7 (0.3) at 4 years, n = 19; and -0.6 (0.3), n = 13, at 5 years after transplantation (analysis of variance, P < .001). The greatest improvement in Ht SDS in the first year was seen in children with the highest glomerular filtration rate (r = 0.429, P = .002) and in those who were shortest at the time of transplantation (r = -0.356, P = .009).Conclusion: Catch-up growth occurs in children receiving renal transplants during the expected time of puberty.

Growth during puberty in renal failure and following renal transplantation is often poor. Treatment with rhGH improved height SDS in 13 pubertal children with renal disease.

Objective: To provide accurate measurement of renal function during treatment with recombinant human growth hormone (rhGH).Methods: We measured glomerular filtration rate and effective renal plasma flow by clearance of inulin and para-aminohippuric acid before rhGH therapy, after 1 week, and then at 6-month intervals for up to 2 years of treatment in 16 children (mean (SD) age = 13.1 (2.2) years; glomerular filtration rate = 52 (27) ml/min per 1.73 m(2)). The mean (SD) time from transplantation was 6.5 (3.6) years.Results: Linear growth velocity during rhGH therapy increased from 4.0 (1.8) to 8.8 (2.6) cm/yr (p < 0.0001). One child was withdrawn after 9 months because of abnormal glucose tolerance, and another child received a second renal transplant after 18 months. Glomerular filtration rate increased to 57 (29) ml/min per 1.73 m(2) at 1 week (p = 0.004), remained improved at 6 months (63 (30); p = 0.013), but was not significantly better at 1 year (59 (33)). Effective renal plasma flow on day 1 was 237 (127) ml/min per 1.73m(2) and was unchanged on day 8 (244 (123)), at 6 months (271 (149)), and after 1 year (269 (157)). During the study there was no significant change in filtration fraction, blood pressure, or kidney volume, and excretion of microalbumin and N-acetylglucosaminidase was unaltered. There was one rejection episode per 14.8 patient-months in the year before treatment, 1 per 18.9 patient-months during the first year of treatment, and 1 per 13 patient-months during the second year of rhGH therapy.Conclusion: Treatment with rhGH improves growth in children with renal transplants. Glomerular filtration rate was increased after 1 week and 6 months of rhGH therapy but returned to baseline values thereafter. The data indicate the need for long-term follow-up of children with renal transplants who are receiving rhGH.

Infants with chronic renal failure often grow badly despite medical management. rhGH treatment results in good catch-up growth and should be used in infants who do not respond to conservative management.

The effects of age, height velocity over the preceding year, glomerular filtration rate (GFR) and prednisolone dose on growth response have been assessed by single and multiple linear regression analysis in 23 prepubertal children [age, mean (SD), 8.2 (2.5) years] with chronic renal failure (CRF) and 16 prepubertal children [12.1 (2.3) years] with renal transplants treated for 1 year with recombinant human growth hormone (rhGH), 30 U/m2 per week. Height velocity [mean (SD), cm/year] increased from 4.7 (1.3) to 9.7 (2.1) (P < 0.0001) in the CRF group and 3.1 (1.6) to 7.3 (2.8) (P < 0.0001) in the transplant group. In the CRF group, there was a correlation between age and height velocity, both in the pretreatment year (r = -0.755, P < 0.0001) and during treatment (r = -0.421, P = 0.045). There was no correlation between pretreatment height velocity or GFR and response to rhGH. In the transplanted children height velocity during the treatment year correlated with age (r = -0.647, P = 0.007), prednisolone dose (r = -0.689, P = 0.003), GFR (r = 0.542, P = 0.030) and pretreatment height velocity (r = 0.655, P = 0.006). Multiple regression analysis showed prednisolone dose and age to be the most important predictors of response.

In normal subjects recombinant human growth hormone (rhGH) increases glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) through the action of insulin-like growth factor-I (IGF-I). We have measured clearance of inulin and para-aminohippuric acid in 18 children with chronic renal failure (CRF) during their 1st year of rhGH treatment to look at the immediate (first 3 h), short-term (1 week) and long-term (1 year) effects of treatment. On day 1 mean (range) age was 9.1 (4.9–13.9) years, GFR 19 (9–58) and ERPF 77 (34–271) ml/min per 1.73 m2. During treatment height velocity increased from 4.5 (1.7–6.5) to 9.5 (4.8–12.7) cm/year (P<0.0001). Two children required dialysis after 0.75 years and 1 child was electively transplanted after 0.5 years. There were no other serious adverse events. GFR and ERPF were unchanged in the 3 h following rhGH. GFR remained constant on day 8, 22 (6–56) and after 1 year, 20 (9–59) ml/min per 1.73 m2. ERPF increased to 96 (33–276) ml/min per 1.73 m2 on day 8P=0.005), and remained elevated, but not significantly so, at 99 (24–428) ml/min per 1.73 m2 at 1 year. Fasting IGF-I increased from 147 (46–315) ng/ml to 291 (61–673) by day 8P<0.003), and to 341 (101–786) ng/ml at 1 year. There was no correlation between the change in IGF-I and renal function. Blood pressure, albumin excretion and dietary protein intake were unchanged by treatment. The significance of increased ERPF after 1 week of rhGH in CRF is unclear, but long-term follow-up of renal function is indicated.