EFFECT OF CYPROTERONE ACETATE (CA) ON GROWTH AND ENDOCRINE FUNCTION IN PRECOCIOUS PUBERTY

Abstract. Stahnke, N., Ilicki, A. and Willig, R. P. (Department of Paediatrics, University Hospital, Hamburg, West Germany). Effect of cyproterone acetate (CA) on growth and endocrine function in precocious puberty. Acta Paediatr Scand, Suppl. 277: 32, 1979.–16 girls with precocious puberty have been studied. Following low dosage cyproterone acetate (CA) therapy (mean daily dosage 65 mg/m² BSA) a beneficial effect on growth and skeletal maturation was observed. During high dosage therapy (150 mg/m² per day) endocrinological studies were performed in 10 of these patients. There was no significant difference in HGH levels (insulin-and arginine-test), T₃ and TSH values (TRH-test) between patients and controls, T₄ concentration was significantly increased. Basal prolactin levels and prolactin response to TRH was definitely elevated. Oral glucose load and arginine infusion resulted in a significantly enhanced insulin release. There was a significant reduction in basal LH levels and an increase in FSH response to LH-RH. Basal and diurnal plasma cortisol values were markedly reduced and the cortisol release due to corticotrophin injection, (lsinevasopressin (LVP) injection and insulin-hypoglycemia as well. A definite increase in basal ACTH levels was observed, during LVP-and insulin-hypoglycemia test ACTH concentrations were within or significantly above normal range. In our patients a primary adrenocortical insufficiency due to CA treatment was evident.     

Benefits of conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in pediatric renal transplant patients with stable graft function

Abstract:  Conversion from MMF to EC-MPS may reduce GI complications and permit increased MPA dosing with a concomitant reduction in CNI dose. In a prospective trial, paediatric renal transplant patients with stable graft function were converted from MMF to EC-MPS and followed-up for 12 months. Data from 28 patients (mean age 13.9 ± 3.1 yr) were available for analysis. Mean EC-MPS dose increased significantly from conversion to month 12 (668 ± 81 mg/m²/day vs. 747 ± 98 mg/m²/day, p < 0.001). CsA-ME dose (n = 23) decreased from 5.3 ± 1.7 mg/kg/day at conversion to 4.6 ± 1.4 mg/kg/day at month 12 (p = 0.010). cGFR increased from 69.5 ± 23.3 mL/min/1.73 m² at the time of conversion to 80.7 ± 30.7 mL/min/1.73 m² at month 12 (p = 0.007). The number of patients reporting at least one GI event during six months prior to conversion was 15/28 (53.6%), declining to 8/28 (28.6%) at month 6 post-conversion and 5/28 (17.8%) at month 12. This single-arm study suggests that conversion of paediatric renal transplant patients from MMF to EC-MPS does not compromise efficacy and leads to improved GI tolerability. MPA dose increased and CsA-ME dose decreased significantly, with an associated improvement in calculated GFR. A large-scale controlled trial is required to confirm these promising findings.     

Large Interindividual Variations in the Pharmacokinetics of Oral 6-Mercaptopurine in Maintenance Therapy of Children with Acute Leukaemia and Non-Hodgkin Lymphoma

ABSTRACT. The concentrations of 6-mercaptopurine were studied in plasma and red blood cells from 10 children with acute leukaemia or non-Hodgkin lymphoma receiving oral maintenance therapy. The doses varied between 25 and 79 mg/m² body surface once daily. Large interindividual differences were found in the concentrations both in plasma and in red blood cells. There was no clear relationship between the dose administered and the concentrations obtained. However, in each patient the concentrations in plasma and in red blood cells were very similar. In most patients, the peak concentrations were reached 1-2 hours after dose intake and the concentrations then declined with half-lives less than 1 hour. Further studies are necessary to evaluate the potential value of drug level monitoring in optimizing treatment with oral 6-mercaptopurine.     

METHOTREXATE IN THE PLASMA AND CEREBROSPINAL FLUID OF CHILDREN TREATED WITH INTERMEDIATE DOSE METHOTREXATE

ABSTRACT. Rechnitzer, C, Scheibel, E. and Hendel, J. (University Clinic of Paediatrics, Rigshospitalet and Department of Clinical Chemistry, Finsen Institute, Copenhagen, Denmark). Methotrexate in the plasma and cerebrospinal fluid of children treated with intermediate dose methotrexate. Acta Paediatr Scand, 70:615,.–Serious complications can follow treatment with intermediate dose methotrexate of acute lymphoblastic leukemia in childhood. Toxicity has been shown to be correlated to plasma methotrexate concentrations. During intravenous infusions of methotrexate (500 mg/m²) the mean concentrations achieved 1 to 4¹/₂ hours after the start of infusion were 1.3×10^-7 mol/l in cerebrospinal fluid and 1.7×10^-5 mol/1 in plasma. At 72 hours after start of methotrexate infusion, plasma methotrexate concentrations were significantly higher in cases with symptoms of toxicity. In all the children who developed toxic symptoms 72-hour plasma methotrexate concentration was above 1×10^-7 mol/l. Assuming that leucovorin is given 48 hours after the start of methotrexate infusion, 72-hour plasma methotrexate is suitable for detection of patients at risk for toxicity. In children treated with intermediate dose methotrexate we therefore recommend estimating plasma methotrexate concentration 72 hours after the start of infusion, and instituting supplementary leucovorin when plasma methotrexate concentration exceeds 1×10^-7 mol/l.     

Dosing considerations for oral acyclovir following neonatal herpes disease

Herpes simplex virus lesions recur in 8–30% of infants who receive a course of parenteral antiviral therapy for an initial infection. Long-term acyclovir is used by some clinicians to prevent recurrent Herpes simplex disease. We describe nine infants who were treated with doses of oral acyclovir which were chosen to achieve 2-h post-plasma concentrations of ≥2 μg/ml. Eight infants had Herpes simplex encephalitis and one had multiple recurrences of dermal and ocular disease. The target plasma concentration was chosen in order to attain acyclovir cerebrospinal fluid distribution (≤50% plasma) for an estimated ID₃₀ of Herpes simplex II strains of 0.1–0.5μg/ml. One of nine patients failed to achieve the target plasma acyclovir concentration. One of nine patients developed symptomatic recurrence of the central nervous system disease and none of the remaining eight patients experienced recognized dermal or neurologic recurrence of Herpes simplex disease. Renal and neurologic status were routinely monitored and no signs of acyclovir toxicity were observed. Plasma concentration of acyclovir ≥2μg/ml may be achieved with average oral doses of 1340mg/m²/dose (1000–1740 mg/m²/dose) given at 12-h intervals.     

Growth hormone treatment regimens in girls with Turner syndrome

To optimize growth hormone (GH) treatment in girls with Turner syndrome, two multicentre studies were carried out in The Netherlands: a frequency-response study (study 2) and a dose-response study (study 2). In study 1, 19 girls with Turner syndrome, aged 11 years or older, were treated with one or two daily injections of GH at a total dose of IU/m²/day (0.067 mg/kg/day) and ethinyloestradiol given orally at a dose of 0.05 μg/kg/day. All the girls reached final height. The mean (±SD) gain in final height was not significantly different between the once- or twice-daily regimens (7.6 ± 2.3 versus 5.1 ± 3.2 cm, respectively). The mean final height attained was 155.5 ± 5.4 cm. All the girls exceeded their adult height prediction. In study 2, 68 girls with Turner syndrome, aged 2-11 years, were randomized into three dosage groups: A, B and C. During the first year, the girls in all the groups received GH at a dose of 4 IU/m²/day (0.045 mg/kg/day), which group A continued to receive throughout the study. At the start of the second year groups B and C were switched to a dose of 6 IU/m²/day, which the girls in group B continued to receive for the reminder of the study. At the start of the third year, the girls in group C were switched to a dose of 8 IU/m²/day (0.090 mg/kg/day) for the remainder of the study. After 7 years of GH treatment, height SDS (based on Turner syndrome and normal population references) increased significantly in all three groups, but significantly more in groups B and C compared with group A ( p = 0.02 and p =0.001, respectively). Predicted adult height increased significantly, without a significant difference between the three groups. The mean final heights of 25 of the girls were 159.1, 161.8 and 162.7 cm for groups A, B and C, respectively.     

Clinical Significance of Urinary C-Peptide Excretion in Children with Insulin-Dependent Diabetes Mellitus

ABSTRACT. In order to evaluate the accuracy of urinary C-peptide determination and the clinical significance of C-peptiduria for the early course of insulin-dependent diabetes (IDDM), the rate of urinary excretion of C-peptide was determined in 32 children and adolescents with IDDM and correlated with serum C-peptide concentration, urinary excretion of albumin and β-mic-rogloublin and with the glomerular filtration rate (GFR) measured in terms of the clearance of ⁹⁹mTc-DTPA. The age of the subjects ranged from 9.1 to 17.1 years (mean 13.1) and the duration of diabetes from 0.3 to 11.9 years (mean 4.6). There was a good correlation between postprandial serum C-peptide concentration and the 24-hour urinary C-peptide excretion rate ( r =0.81; p <0.001). GFR and urinary albumin excretion were slightly elevated in the diabetic patients as compared with non-diabetic subjects ( p <0.05 and p <0.001, respectively), but C-peptide excretion was unrelated to the degree of hyperfiltration or albuminuria, neither was there any correlation between the excretion rate of β₂-microglobulin and C-peptide. Glycaemic control was poorer in the diabetic children who had only trace amounts of C-peptide in their urine (<0.05 nmol/m²/24 h) than in those with minimal (0.05–1.0 nmol/m²) or moderate 24-hour urinary C-peptide excretion (>1.0 nmol/m²). It is concluded that urinary C-peptide excretion serves very well to reflect residual β-cell function and is unrelated to the slight renal hyperfunction and albuminuria often seen in diabetic subjects. Even minimal C-peptide excretion ranging from 0.05 to 1.0 nmol/m²/24 h still seems to indicate clinically significant insulin secretion.     

Rituximab for post-transplant recurrences of FSGS

Abstract:  A 14-yr-old boy whose primary kidney disease was FSGS developed severe recurrence of proteinuria immediately after a second living-related kidney transplant. Despite pre- and post-operative PP and immunosuppressive treatment consisting of steroids, CycA, daclizumab, and MMF, daily protein excretion and serum creatinine increased. We therefore administered rituximab on the fourth day of transplantation. He received four weekly doses of rituximab (375 mg/m²/dose), which resulted in a rapid clearing of circulating CD19-positive B cells, and remission of proteinuria was achieved six wk after the first rituximab treatment. Graft function was excellent six months after transplantation with proteinuria of 8 mg/m²/h. We conclude that rituximab may be an effective treatment for post-transplant recurrence of FSGS.     

Post-transplant lymphoproliferative disorders in children: The role of chemotherapy in the era of rituximab

Gallego S, Llort A, Gros L, Sanchez de Toledo Jr J, Bueno J, Moreno A, Nieto J, Sanchez de Toledo J. Post-transplant lymphoproliferative disorders in children: The role of chemotherapy in the era of rituximab.
Pediatr Transplantation 2010: 14: 61–66. © 2009 John Wiley & Sons A/S.
Abstract:  PTLD are the most frequent neoplasms in children postorgan transplantation. We describe our experience in the treatment of 14 children (three with early and 11 with late-onset disease) treated with a step-wise protocol developed at our institution. Treatment consisted of reducing immunosuppressants, followed by rituximab and chemotherapy if required. Rituximab, incorporated into the protocol in 2001, has been determinant for the total chemotherapy burden patients need to achieve remission. In seven patients who did not receive rituximab, anthracycline total dose ranged from 160 to 240 mg/m², while only one of the patients receiving rituximab required DOXO (range: 0–120 mg/m²) (p = 0.003). The use of alkylating agents was also notably lower in patients receiving rituximab (median dose = 1200 mg/m²) compared with those who did not receive rituximab (median dose = 5800 mg/m²) (p = 0.006). Twelve patients are in remission and two died, one from refractory disease and the other from septic shock. Two-year OS and EFS were 85.7% and 57%, respectively. In conclusion, our experience with the use of rituximab in children with PTLD after solid organ transplantation appeared to be associated with a lesser requirement for alkylating agents and anthracyclines compared with historical subjects, suggesting a reduction in the side effects of these agents.     

Failure of cortisone acetate therapy in 21-hydroxylase deficiency in early infancy

BACKGROUND: Pediatric endocrinologists initially treat congenital adrenal hyperplasia with either cortisone acetate (CA) or hydrocortisone (HC). Despite high doses of CA, we noted that 17-hydroxyprogesterone (17-OHP) and corticotropin were not fully suppressed in serum from neonates with 21-hydroxylase deficiency (21-OHD) until they were 40- to 80-days-old. In contrast, serum concentrations of 17-OHP were suppressed immediately by oral treatment with HC. METHODS: We sought to understand the reason for this discrepancy. Serum cortisol (F), cortisone (E), and 17-OHP were measured by radioimmunoassay or high-performance liquid chromatography in seven neonates with 21-OHD and in 118 normal subjects. From the time of diagnosis, CA was administered to four of the neonates with 21-OHD, while HC was given to the other three. RESULTS: In normal subjects serum E concentrations were greater than F during the first 2 months after birth, whereas F concentrations exceeded E after 2 months of age. Although infants receiving CA initially were given a high dose, serum F concentrations were extremely low, while 17-OHP concentrations were high until about 2 months of age. Then serum F exceeded E, and 17-OHP became fully suppressed even though infants received only a moderate dose of CA. In contrast, HC administration successfully normalized serum 17-OHP in the neonatal period. With temporary switching of neonates from HC to CA, serum F concentrations immediately decreased and 17-OHP concentrations increased. CONCLUSION: Conversion of E to F may be limited during early infancy, adversely affecting treatment with CA. Cortisone acetate may be inappropriate as a glucocorticoid replacement during early infancy in patients with 21-OHD.     

DOSAGE OF SALICYLATES FOR CHILDREN WITH JUVENILE RHEUMATOID ARTHRITIS A Prospective Clinical Trial with Three Different Preparations of Acetylsalicylic Acid

Abstract. 41 children with juvenile rheumatoid arthritis (JRA) and 6 with postinfectious arthropathies, aged 3–15 years, were treated with acetylsalicylic acid for 14 days during which time the patients were hospitalized. Three different acetylsalicylic acid preparations were used: a microencapsulated form, an enteric-coated form and standard acetylsalicylic acid tablets. Serum salicylate concentrations were measured by Trinder's photometric method. With doses of 90–120 mg/kg/day symptoms of salicylism appeared in about 50% of the cases. Daily doses of 2 g/m² (not exceeding 70 mg/kg) proved relatively safe in this study, whereas symptoms and signs of intoxication appeared at doses exceeding 3 g/m²/day. In this respect there were no significant differences between the three acetylsalicylic acid preparations used. The results of this study also suggest that the serum salicylate concentrations should not exceed 2000 μmol/1 (about 27 mg/100 ml). The symptoms of salicylism correlated closely with serum salicylate levels, which, in turn, correlated well with the dosage in g/m². Elevation of serum aspartate aminotransferase was noted in 1/3 of the cases. All of these had a dose exceeding 2 g/m², and the frequency of elevated enzyme activities increased with increasing dosage. In the group receiving enteric-coated form of acetylsalicylic acid, there were fewer positive benzidine tests (12%) than in the two other groups (22–28%).     

Renal Involvement in Patients with Congenital Cyanotic Heart Disease

ABSTRACT. Patients with congenital cyanotic heart disease may develop a glomerulopathy with proteinuria and impaired renal function. In order to investigate this problem we conducted a study on 27 patients with uncorrected cyanotic heart disease who were between 1 day and 25 years old. As a consequence of hypoxaemia haematocrit was elevated to 57%. Proteinuria was above 150 mg/day/1.73 m² body surface in 12 patients. Only one of 9 children under 10 years of age had pathological proteinuria presenting as isolated albuminuria. Seven out of 10 patients between 11 and 20 years had an elevated proteinuria with a glomerular pattern. Creatinine clearance was normal in these patients. All four patients above 20 years of age had a considerable glomerular proteinuria with a mean excretion of 5.7 g/24 h/1.73 m² body surface. These patients suffered additionally from chronic cardiac failure and creatinine clearance was below the normal range. There was a clear relationship between pathological proteinuria and age of the patients and thus duration of hypoxaemia. Patients with pathological proteinuria had a significant higher erythrocyte count (7.3±2 1.3 vs. 5.6±1.4 10¹²/l p <0.01) and a lower mean corpuscular haemoglobin. In summary, children with persistent congenital cyanotic heart disease have substantial risk of developing a glomerulopathy if the cyanosis remains unchanged for more than ten years.     

Effects on Control and Growth

ABSTRACT. Jansen, M., Wit, J. M. and Van den Brande, J. L. (Departments of Paediatrics, Universities of Rotterdam and Utrecht, the Netherlands). Reinstitution of mineralo-corticoid therapy in congenital adrenal hyperplasia. Effects on control and growth. Acta Paediatr Scand, 70:229, 1981. –The results of reintroduction of mineralocorticoid substitution therapy (9-α-fluorohydrocortisone) in five children with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency are described. All children had shown a salt-losing syndrome in infancy, but were off mineralocorticoids during several years; at the start of this study they all had elevated plasma renin activity (PRA). Four of them had increased and fluctuating pregnanetriol excretion during the year preceding reintroduction of mineralocorticoids, indicating poor control despite substantial substitution with hydrocortisone: 26±1.9 mg/m²/day (mean±S.E.M.). Reintroduction of mineralocorticoid therapy at ages 5.0–9.4 years resulted in a marked improvement of control, significant reduction in hydrocortisone requirements (to 17.6±1.4 mg/m²/day) and improvement in linear growth. The data suggest that, in all children with CAH and elevated PRA, continuation throughout childhood of mineralocorticoid therapy in addition to glucocorticoid therapy is necessary for optimal control and linear growth.     

The profile of renal function over time in a cohort of pediatric heart transplant recipients

Abstract:  To assess the burden over time of renal dysfunction in pediatric heart transplant patients using an objective measure on an annual basis for serial comparison. GFR was measured at regular interval by nuclear medicine scintigraphy. Results were analyzed in relation to age, time post-transplantation, gender, and average calcineurin-inhibitor dose for the first two months post-transplantation. Results were compared with cGFR using the Schwartz equation. A total of 91 patients (56 males) transplanted between 1990 and 2004 underwent 373 GFR measurements. Median age at transplantation was 3.3 yr (birth – 17.8). Median first GFR at 0.7 yr (0.1–4.1) post-transplant was normal (94 mL/kg/1.73 m²). Freedom from at least mild renal insufficiency was 84% and 33% at one and five years post-transplant. Females had better renal function early post-transplant (GFR 105 mL/min/1.73 m²) but an increased probability of an abnormal GFR over time. Higher calcineurin inhibitor dose in the first two months post-transplantation was associated with an increasing probability of an abnormal GFR over time. The cGFR overestimated the measured GFR by 33 ± 26 mL/kg/1.73 m². Renal insufficiency is an important morbidity after pediatric transplantation with the majority of patients experiencing at least mild renal dysfunction. Calculated GFR significantly underestimates the burden of renal insufficiency in this patient population.     

Physical effects of growth hormone treatment in children with Prader-Willi syndrome

A randomized, controlled study of 54 children (age, 4-16 years) with Prader-Willi syndrome was conducted to assess the potential beneficial effects of growth hormone (GH) treatment. After observation for 6 months, the children were randomized to receive GH at a dose of 3 IU/m²/day (1 mg/m²/day) ( n = 35) or no intervention ( n = 19). The effects of GH treatment on linear growth, body composition, muscle strength, pulmonary function and resting energy expenditure were assessed. The levels of GH secreted in resonse to clonidine stimulation were universally low, and mean (± SD) insulin-like growth factor I SDS was -1.2 ± 0.8 pretreatment. In children treated for 1 year, mean height velocity SDS significantly increased from -1.0 ± 2.5 to 4.6 ± 2.9 ( p < 0.0001), mean percentage body fat decreased from 46.3 ± 8.4% to 38.4 ± 10.7% ( p < 0.001), mean lean body mass increased from 20.5 ± 6.3 kg to 25.6 ± 4.3 kg ( p <0.01) and respiratory muscle function and physical strength imporved. Mean respiratory quotients significantly decreased from 0.81 to 0.77 ( p < 0.001); however, resting energy expenditure did not change. Therefore, GH therapy appears to reduce some of the physical disabilities experienced by children with Prader-Willi syndrome.     

Short-Term Effect of Low and High Protein Intake on Renal Function in Children with Renal Disease

ABSTRACT. The short-term effect of different levels of protein intake on renal function was investigated in 18 children with moderately (51–85 ml/min/1.73 m² BSA) or severely (9–50 ml/min/1.73 m² BSA) reduced glomerular filtration rates (GFR). The GFR and effective renal plasma flow (ERPF), estimated as the clearances of respectively inulin and para-aminohippuric acid during uncontrolled (2-2.5 g/kg bw), low (1.2 g/kg bw for 12 days) and high (3–5 g/kg bw for 24 h) protein intake were determined by a standard clearance method employing continuous infusion and spontaneous voiding. There were no significant differences in GFR or ERPF during uncontrolled and low protein intake. During high protein intake the GFR and ERPF increased significantly in patients with GFRs above 50 ml/min/1.73 m² BSA and ERPFs above 150 ml/min/1.73 m² BSA. It is concluded that these findings might indicate a functional reserve capacity in children with only moderately reduced renal function.     

An Attempt to Assess the Replacement Dose of Human Growth Hormone in the Treatment of Growth Hormone Deficient Children

Hibi, I., Tanaka, T., Yano, H., Umezawa, S., Kagawa, J., Tanae, A. and Ishikawa, E. (National Children's Medical Research Center, Tokyo, the National Children's Hospital, Tokyo and the Department of Biochemistry, Miyazaki Medical College, Miyazaki, Japan). Acta Paediatr Scand [Suppl] 337:87, 1987.
In 25 patients with hGH deficiency, who had been treated long-term with hGH, the mode of hGH administration was switched from the conventional method (0.3–0.5 IU/kg/week, in two or three divided doses, intramuscularly) to daily subcutaneous injection at 1900–2100 hours with a dose of 0.46 ± 0.07 IU/kg/week (equivalent to 14.7 ± 2.0 IU/m²/week). After 1–3 months of this new mode of hGH administration, blood and urine were sampled at 0900 hours after overnight fasting. Blood glucose, plasma insulin, plasma IGF-1 and plasma total IGF (after extraction) were analysed in blood samples. IGF-1 and hGH were measured in urine samples. These measurements indicated that the dose studied was close to a replacement one, but might be slightly higher than the exact replacement dose.     

Umbilical cord-blood transplantations from unrelated donors in patients with inherited metabolic diseases: Single-institute experience

Abstract:  We evaluated the feasibility of UCBT from unrelated donors and a myeloablative preparative regimen that did not involve anti-thymocyte globulin in five children with lysosomal and peroxisomal diseases. Patients with MPS II (n = 1), adrenoleukodystrophy (n = 1), metachromatic leukodystrophy (n = 2), and Krabbe disease (n = 1) received UCBT between December 2001 and September 2005. All patients received oral Bu (600 mg/m²), CY (200 mg/kg IV), and fludarabine (180 mg/m² IV). Prophylaxis for GVHD consisted of a combination of tacrolimus and a short methotrexate course. Neutrophil engraftment occurred a median of 24 days (range, 21–25) after transplantation. None had graft rejection. One patient developed grade III acute GVHD and the other four patients had grade I acute GVHD; none had extensive chronic GVHD. One patient developed hemorrhagic cystitis. There were no treatment-related deaths. Although one child with MPS II died of PTLD 10 months after the UCBT, four of the five children are alive 14, 20, 31, and 55 months after transplantation with complete donor chimerism. These results suggest the feasibility of the UCBT with Bu, fludarabine, and CY-preparative regimen for patients with inherited metabolic diseases.     

Comparison of Different Regimens of Prednisone Therapy in Frequently Relapsing Nephrotic Syndrome

Abstract. The long-term results of four different regimens of prednisone therapy were compared in 32 children with steroid sensitive, frequently relapsing idiopathic nephrotic syndrome with minimal glomerular lesions on renal biopsy. Prednisone was adminstered according to the following dosage schedules: 1) long-term daily, 2) standard intermittent, 3) standard alternate-day, and 4) short-term daily. Over a mean observation period of 7 years patients without steroid dependency received a cumulative dosage of prednisone of 10 mg/m²/day and those with steroid dependency received 19 mg/m²/day. Relapse free intervals were the longest with long-term daily prednisone therapy compared to the other three regimens. In frequently relapsing patients without steroid dependency the relapse free intervals were similar with either intermittent or alternate-day prednisone therapy (median 75 d); however, they were significantly shorter with short-term prednisone therapy (median 33 d). In frequently relapsing patients with steroid dependency the time of remission was generally shorter than in patients without steroid dependency (median 25d vs. 69d) with no benefit of any of the different forms of short-term treatment.     

Pulse Methylprednisolone Therapy in Severe Idiopathic Childhood Nephrotic Syndrome

ABSTRACT. The effect of methyl prednisolone therapy (PM) was studied in 18 children with severe idiopathic nephrotic syndrome (NS). Eight patients were defined as "corticosteroid-resistant" because there was no response to treatment after a minimum of 4 weeks of 2 mg/kg/day of prednisone; 10 patients had a corticosteroid-dependent NS with frequent relapses which occurred under a high threshold dose of prednisone (1 mg/kg/day). Each patient received 4–6 pulses of 1 g/1.73 m² methylprednisolone. Tolerance was generally good. PM therapy permitted a more rapid remission than oral prednisone (average 9±4 days vs. 22±9 days). Remission occurred in 5 of the 8 corticosteroid-resistant patients three of these 5 patients developed corticosteroid-dependent NS. For the children with a corticosteroid-dependent nephrotic syndrome, PM therapy did not affect the threshold dose of prednisone.