Jorge Ferraris

Effect of deflazacort versus methylprednisone on growth, body composition, lipid profile, and bone mass after renal transplantation

Abstract Kidney function, growth velocity, weight/ height ratio, body composition, lipid profile, and bone mass were studied in a randomized, multicenter trial of deflazacort versus methylprednisone in 27 prepubertal patients with kidney transplantation. Methylprednisone (0.20±0.03) was replaced by deflazacort (13 patients, 0.30±0.03 mg/kg per day). After 12 months, creatinine clearance decreased significantly only during methylprednisone therapy. Growth velocity increased only in patients treated with deflazacort from 3.3±0.6 to 5.6±0.5 cm/year. Serum levels of several components of the insulin-like growth factor axis did not change. Weight/height ratio was increased in methylprednisone-treated patients (P<0.05) and decreased in deflazacort-treated patients (P<0.005). Lean body mass increased in both groups (P<0.005). Fat body mass and serum leptin increased only in methylprednisone-treated patients (P<0.025). Total cholesterol and low-density lipoprotein-cholesterol increased in methylprednisone-treated patients by 9.9% (P<0.05) and 12.5% (P<0.025). High-density lipoprotein-cholesterol increased by 21% (P<0.005) and apolipoprotein B decreased by 11% (P<0.005) in deflazacort-treated patients. Total skeleton and lumbar spine bone mineral density decreased in both groups, but at 1 year methylprednisone-treated patients had lost 50% more bone. Bone mineral content decreased only in methylprednisone-treated patients (P<0.01). Our data suggest that substituting deflazacort for maintenance methylprednisone might prevent height loss, excessive bone loss, and fat accumulation; and leads to an improvement in the lipoproteins of these children.

Renal transplantation in patients with classical haemolytic-uraemic syndrome

Eighteen records from children with renal transplants (RT) and classical haemolytic-uraemic syndrome (HUS) were reviewed. The mean oliguric period was 17.9±7.5 days; the interval between acute phase and endstage renal disease (ESRD) was 9.3±5.2 years. HUS was the most frequent cause of renal transplantation (23.4%). There were no significant differences between patients with HUS and controls (children with RT but without HUS), regarding renal function, frequency of rejections, renal survival (HUS 65%, controls 57%) or patient survival (94.4% and 96.6%, respectively) after 9 years. None had clinical or histopathological evidence of HUS recurrence in the allograft. Of all children with living-related donors (LRD), renal survival after 3 years was longer for those who received cyclosporin A (CSA) (HUS and controls 86%) than for those who did not receive it (HUS 50%, controls 53%). Classical HUS is a frequent cause of ESRD in Argentina. The duration of the acute oliguric period is a good predictor of the likelihood of progression to chronicity. In the classical form of HUS there is no recurrence in the allograft. CSA and LRD can be used without risk in renal transplantation of children with classical HUS.

Effect of therapy with a new glucocorticoid, deflazacort, on linear growth and growth hormone secretion after renal transplantation

Deflazacort is an oxazoline compound derived from prednisolone with similar antiinflammatory effects but fewer side effects. We studied changes in kidney function, growth velocity, weight/height ratio, and growth hormone secretion before and a year after substitution of deflazacort for methylprednisone in nine patients aged 9 to 15 years, 4 years after renal transplantation; all were in Tanner pubertal stage 1. Methylprednisone (mean +/- SEM: 0.2 +/- 0.02 mg/kg per day) was replaced by deflazacort (0.3 +/- 0.03 mg/kg per day) for a mean period of 15 months. Serum creatinine and calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 1.5 +/- 0.3 to 3.2 +/- 0.5 cm/yr (p < 0.005) in the nine patients. Weight/height ratio decreased from 28.4% +/- 8.5% to 16% +/- 6.7% (p < 0.005). Cushingoid appearance decreased in all patients. Mean spontaneous growth hormone secretion increased from 2.5 +/- 0.4 to 4.4 +/- 1.2 ng/ml (p < 0.05). Our findings indicate that immunosuppressive treatment with deflazacort is as effective as methylprednisone and is associated with fewer side effects.

Improved long-term allograft function in pediatric renal transplantation with mycophenolate mofetil

Abstract:  MMF has been shown to decrease the incidence of acute rejection in children and adults at 1 and 3 yr. Other beneficial effects of MMF have been more difficult to demonstrate. Our open‐labeled study presents a 5‐yr data for patients and graft survival, allograft function, and growth in MMF‐treated patients. The trial included 29 patients who were treated with MMF in combination with cyclosporine and methylprednisone. Patients were compared with a preceding group of 29 patients treated with AZA instead of MMF. Patient and graft survival rate 5 yr after transplantation were 97 and 90% in the MMF group vs. 93 and 83% in the AZA group (p: NS). Acute rejection was 20.6% in the MMF group vs. 58.6% in the AZA group (p < 0.01). Chronic rejection was 10.3% in the MMF group and 25% in the AZA group (p: NS). The changes in the creatinine clearance from baseline to 5 yr (Δ) were different between groups (−6.0 ± 5.1 mL/min/1.73 m2 in the MMF group vs. −22.2 ± 7.6 mL/min/1.73 m2 in the AZA group, p < 0.05). Also, the slope of 1/Scr showed a significant lower incidence of worsening renal function after the second year of renal transplantation (p < 0.0001) in the MMF group compared with the AZA group. Δ Height SDS in prepubertal patients was 0.3 ± 0.4 SDS in the MMF group vs. −0.8 ± 0.2 SDS in the AZA group (p < 0.05).

Effects of deflazacort immunosuppression on long-term growth and growth factors after renal transplantation.

Abstract. Deflazacort is an oxazoline compound derived from prednisolone. We studied changes in kidney function, growth velocity, weight/height ratio, insulin-like growth factor (IGF-I), and IGF binding proteins before and after substitution of deflazacort for methylprednisone in 27 transplanted patients aged 3.1 – 20 years. Methylprednisone (mean±SEM 0.17±0.01 mg/kg per day) was replaced by deflazacort (0.29±0.01 mg/kg per day) for a period of 1 – 5 years. Calculated creatinine clearance did not change significantly during deflazacort treatment. Growth velocity increased from 2.6±0.5 cm/year to 5.2±0.7 cm/year (1st year) in 14 prepubertal patients. After 4 years of deflazacort treatment, height standard deviation score for chronological age did not change in 7 prepubertal patients. Mean weight/height ratio decreased by 50% (1st year) and remained reduced during follow-up. Serum IGF-I, IGF binding protein -3 (IGFBP3), IGF/IGFBP3 molar ratio, and IGF-I and -II binding capacities showed no significant change; however in 5 of 6 patients IGFBP2 decreased during deflazacort therapy. Our findings suggest that immunosuppressive treatment with deflazacort is as effective as methylprednisone and may lead to an improvement in the growth prognosis of children with renal transplantation.

Renal physiology in newborns and old people: Similar characteristics but different mechanisms

Five characteristics of neonate renal physiology, namely glomerular hypofiltration, low renal blood flow and alterations in water, sodium and potassium management, disappear during the first year of life but reoccur during senescence. However, the underlying mechanisms are different during the two periods.

Evidence of hypothalamic-pituitary thyroid abnormalities in children with end-stage renal disease*

Patients with end-stage renal disease may have abnormalities of growth and of gonadal and thyroid hormones, so we attempted to determine the mechanisms that may be involved in the altered thyroid function. We evaluated serum thyroid hormone levels, their changes immediately after hemodialysis, the serum thyrotropin (thyroid-stimulating hormone (TSH) response to thyrotropin releasing hormone, and the circadian pattern of serum TSH in nine children with end-stage renal disease who were between 7 1/2 years and 17 years 1 month of age. Seven patients had been receiving hemodialysis for a median of 3.3 years; the other two were receiving continuous ambulatory peritoneal dialysis. Four patients had low serum total thyroxine (T4) values, and all nine had low free T4 values. Mean concentrations of total T4, free T4, and total triiodothyronine (T3), which were significantly less than normal before hemodialysis, returned to normal levels immediately after dialysis. Postdialysis thyroid hormone increases did not correlate with the decrease in weight or the increase in hematocrit observed immediately after dialysis. All but one patient had basal TSH levels within the normal range. Three patients had a deficient TSH response to thyrotropin releasing hormone, and the TSH response was prolonged in all of them. The mean (+/- SD) nocturnal TSH surge was 50 +/- 68%. Five of the eight patients studied had a nocturnal TSH surge below the normal range (95% confidence limits 47% to 300%). Serum free T4 values correlated with the TSH nocturnal surge (r, 0.73; p less than 0.05). Our findings support the hypothesis that some patients with end-stage renal disease have central hypothyroidism.

Oxidative stress status during the acute phase of haemolytic uraemic syndrome

BACKGROUND Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopaenia and acute renal failure. The aim of this study was to investigate the levels of oxidative stress (OS) during the acute phase of HUS. METHODS This prospective study included 18 patients diagnosed with D + HUS, 6 age-matched healthy controls and 29 children with end-stage renal disease (ESRD) not caused by HUS under regular haemodialysis. Plasma lipid peroxidation and non-enzymatic antioxidant defences were measured as thiobarbituric acid-reactive substances (TBARs) and total reactive antioxidant potential (TRAP), respectively, during hospitalization and in control individuals. RESULTS TBARs were significantly higher in both oliguric and non-oliguric patients at admission (1.8 ± 0.1; 1.7 ± 0.2 μM) and discharge (1.5 ± 0.1; 1.0 ± 0.1 μM) vs controls (0.5 ± 0.1 μM, P < 0.01) following disease progression. Maximal TBARs values differed significantly between oliguric and non-oliguric groups (4.5 ± 0.9 vs 2.4 ± 0.3 μM, P < 0.01) and were significantly higher (P < 0.05) than those found in ESRD patients (1.63 ± 0.1). TRAP values were significantly higher at admission and when the disease was fully established (measured here as highest TBARs record) vs controls (675 ± 51, 657 ± 60 and 317 ± 30 μM Trolox, P < 0.01), and were similar to control values at discharge (325 ± 33 μM Trolox). CONCLUSIONS We demonstrate here increased levels of OS during the acute phase of HUS, with peak plasma lipid peroxidation values well above those registered in ESRD individuals, and suggest a connection between OS and the clinical course of HUS.

Kidney transplantation in small children with live related donors: 20 years of experience

OBJECTIVES Kidney transplantation (Tx) with a live related donor is the best option available for the treatment of end-stage renal disease at any age. Modern dialysis has allowed many very young and small children to receive a renal transplant with good results in spite of the limitations of space and the size of the adult kidney. Here, we report our experience with renal Tx with live related donors in this complex group of pediatric patients. MATERIAL AND METHODS From 1978 to 2004 a kidney transplantation was performed in 211 pediatric patients. Of this group, 23 patients between 1 and 10 years of age (16 males and seven females) of less than 17 kg (8.9-16.9 kg) received their first live related donor transplantation between 1985 and 2004. Renal insufficiency was secondary to nephropathy in 11 patients, infravesical obstruction in six and renal dysplasia or renal infarcts in six. RESULTS Patient and graft survival was 100% and 95.6% with an average follow up of 89.6 months (6-231). There were no vascular or urological complications. Urinary infection in five (21.7%) and acute rejection in three (13%) were the most common complications. One patient has returned to dialysis 11 years after Tx. CONCLUSIONS Young pediatric patients with a low body weight did not suffer a higher percentage of postoperative surgical complications, and the follow-up results are similar to those in older patients. A complex urological malformation has not prevented a living related Tx. These results encourage us to perform this procedure more frequently in younger patients when a live donor is available.

Syndrome of inappropriate secretion of antidiuretic hormone in nasopharynx carcinoma

Abstract. The syndrome of inappropriate secretion of antidiuretic hormone (ADH) or SIADH has been reported in various disorders. We report a pediatric patient with nasopharynx carcinoma who may have developed a clinical SIADH with severe hyponatremia and generalized seizure during the administration of intravenous hydration. We propose that the inappropriately high plasma level of ADH led to the inability to excrete sufficient amounts of free water during a hyperhydration protocol with a relatively hypotonic fluid, which resulted in acute hyponatremia and central nervous system involvement. To avoid this complication, intravenous hydration before chemotherapy in children with nasopharynx carcinoma should be performed at a slower infusion rate and with a sodium chloride concentration of more than half isotonic.