Experimental findings indicate that sirolimus (SRL) inhibits longitudinal growth by mechanisms potentially related to its inhibitory effects on both cell proliferation and expression of vascular endothelial growth factor (VEGF). The aim of this study was to investigate the growth pattern of kidney-transplanted children treated with SRL in a multicenter observational clinical study. Height, change in height SD (Δ height) and growth velocity of pediatric patients with renal transplant were calculated at 0, 6, 12, and 24 months after starting SRL. Controls of kidney-transplanted children not treated with SRL were matched by age, gender, renal function, and dose of corticosteroids. Sixty-eight children (34 SRL, 34 controls) were enrolled in the study. Nephrotoxicity was the most frequent indication to start therapy with SRL. SRL exerted an adverse effect on growth as demonstrated by significantly lower (p < 0.05) growth velocity (cm/year) and smaller change in height SD in the SRL group after 6 (4.08 vs. 6.56 and -0.05 vs. 0.14), 12 (4.44 vs. 6.11 and -0.03 vs. 0.28) and 24 (4.53 vs. 6.03 and -0.04 vs. 0.53) months of treatment. This study suggests that SRL therapy may interfere with growth of kidney-transplanted children. This undesirable effect needs to be taken into account when considering a switch to SRL and confirmed in further prospective trials including larger number of patients.
Background and objectives: Our aim was to evaluate the growth-promoting effect of growth hormone (GH) treatment in infants with chronic renal failure (CRF) and persistent growth retardation despite adequate nutritional and metabolic management.Design, setting, participants, & measurements: The study design included randomized, parallel groups in an open, multicenter trial comparing GH (0.33 mg/kg per wk) with nontreatment with GH during 12 months. Sixteen infants who had growth retardation, were aged 12 ؎ 3 months, had CRF (GFR <60 ml/min per 1.73 m 2 ), and had adequate nutritional intake and good metabolic control were recruited from eight pediatric nephrology departments from Spain and Portugal. Main outcome measures were body length, body weight, bone age, biochemical and hormonal analyses, renal function, bone mass, and adverse effects.Results: Length gain in infants who were treated with GH was statistically greater (P < 0.05) than that of nontreated children (14.5 versus 9.5 cm/yr; SD score 1.43 versus ؊0.11). The GH-induced stimulation of growth was associated with no undesirable effects on bone maturation, renal failure progression, or metabolic control. In addition, GH treatment improved forearm bone mass and increased serum concentrations of total and free IGF-I and IGF-binding protein 3 (IGFBP-3), whereas IGF-II, IGFBP-1, IGFBP-2, GH-binding protein, ghrelin, and leptin were not modified.Conclusions: Infants with CRF and growth retardation despite good metabolic and nutritional control benefit from GH treatment without adverse effects during 12 months of therapy.
We present a retrospective study of 30 children of mean age 3.02 +/- 1.81 years with steroid-resistant nephrotic syndrome (SRNS) treated with intravenous injection of methylprednisolone plus orally administered prednisone; 24 children also received cyclophosphamide (CP). Sixteen were resistant to steroids from the beginning, and 14 after a mean of 11.26 +/- 16.61 months. The initial histological diagnosis was: 18 minimal change disease (MCD), 11 focal segmental glomerulosclerosis (FSGS) and one diffuse mesangial proliferative glomerulonephritis (DMPG). Total remission was achieved in 22 patients (73.3%), partial response in three (10%) and no response in five (16.6%), two of whom were brothers carrying an NPHS2 gene double mutation. There was no difference in response between the MCD and FSGS patients; the only patient with DMPG did not respond. Only initial resistance was a sign of bad prognosis. At follow-up (6.4 +/- 3.6 years from last pulse), 21/22 were still in remission, 14/21 were without treatment. Six patients required cyclosporine or mycophenolate mofetil because of steroid dependence. Two non-responders developed end-stage renal failure (ESRF); the remaining patients maintained normal glomerular filtration. The treatment was well tolerated. In conclusion, most of the patients treated with sequential therapy consisting of methylprednisolone (MP) (100%) and CP (80%) showed remission and preserved renal function, but 20% developed steroid dependence.
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