Activation of the alternative pathway of complement during the acute phase of typical haemolytic uraemic syndrome.

Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. We studied the activation state of classical and alternative pathways of complement during the acute phase of Shiga toxin-associated HUS by performing a prospective study of 18 patients and 17 age-matched healthy controls to evaluate C3, C3c, C4, C4d, Bb and SC5b-9 levels. SC5b-9 levels were increased significantly in all patients at admission compared to healthy and end-stage renal disease controls, but were significantly higher in patients presenting with oliguria compared to those with preserved diuresis. C3 and C4 levels were elevated significantly at admission in the non-oliguric group when compared to controls. No significant differences were found for C4d values, whereas factor Bb was elevated in all patients and significantly higher in oliguric patients when compared to both controls and non-oliguric individuals. A positive and significant association was detected when Bb formation was plotted as a function of plasma SC5b-9 at admission. Bb levels declined rapidly during the first week, with values not significantly different from controls by days 3 and 5 for non-oligurics and oligurics, respectively. Our data demonstrate the activation of the alternative pathway of complement during the acute phase of Stx-associated HUS. This finding suggests that complement activation may represent an important trigger for the cell damage that occurs during the syndrome.

Citoquinas reguladoras de la respuesta al trasplante renal alogénico / Regulatory cytokines in the response to the allogeneic renal transplant

The outcome of the kidney allograft mainly depends on the immune response and on its complex regulation, where the cytokine network and other mediators play an important role. At present, kidney biopsy is the most useful tool for monitoring the transplant rejection and the diagnosis of the associated nephropathies, in spite of the invasiveness of the procedure. Thus, it is of great interest to find alternative tools for diagnosis. The evaluation of regulatory cytokines is a simple procedure of low cost that could be useful to increase the sensitivity of the detection of polymorphic differences, to predict the graft acceptance and for the early detection of rejection. Recent studies suggest that the high production of pro-inflammatory mediators, such as Th1 cytokines, could be detrimental, whereas the production of anti-inflammatory regulatory cytokines, such as interleukin (IL)-10 and tumor necrosis factor (TGF)-beta, could be beneficial for graft survival. In the early stages, the cellular cytotoxicity is activated by the Th1 response and the detection of cytotoxic molecules is associated to the acute rejection. Later, the balance between pro and anti-inflammatory mediators and the regulation of their levels could be more important. In this regard, TGF-beta is also fibrogenic and a high local production can contribute to kidney damage. On the other hand, the increased production of IL-10 in response to the allogeneic stimuli could be, in most cases, an important marker of long-term acceptance.

La aceptación o el rechazo del riñón alogénico dependen principalmente de la respuesta inmune y de su compleja regulación en la cual la red de citoquinas y otros mediadores juegan un importantepapel. Actualmente, la biopsia renal es, a pesar de lo invasor del procedimiento, la herramienta de mayor utilidadpara el control del rechazo al trasplante y el diagnóstico de las nefropatías asociadas. Por ello, es de graninterés encontrar métodos alternativos para el diagnóstico. La evaluación de citoquinas reguladoras de la respuestainmune es un procedimiento sencillo y de bajo costo que podría ser de utilidad para incrementar la sensibilidadde la detección de diferencias polimórficas, para pronosticar la aceptación del trasplante y para ladetección precoz del rechazo. Los estudios recientes sugieren que la producción exagerada de mediadores proinflamatorios, incluyendo a citoquinas Th1, sería desventajosa para la sobrevida del trasplante, mientras que la producción de citoquinas reguladoras anti-inflamatorias, como la interleuquina (IL)-10 y el factor de crecimiento tumoral (TGF)-β, sería beneficiosa. En las primeras etapas, la respuesta Th1 puede incrementar la actividad citotóxica y la detección de moléculas citotóxicas está asociada al rechazo agudo. Luego podría ser más importante considerar el balance entre la producción de mediadores pro- y anti-inflamatorios y la regulación desus niveles. Así, el TGF-β es también fibrogénico y su excesiva producción local puede contribuir al daño renal.Por otro lado, el incremento de la producción de IL-10 en respuesta al estímulo alogénico sería, en la mayoríade los casos, un marcador importante para pronosticar la aceptación prolongada.

Citoquinas reguladoras de la respuesta al trasplante renal alogénico / Regulatory cytokines in the response to the allogeneic renal transplant

The outcome of the kidney allograft mainly depends on the immune response and on its complex regulation, where the cytokine network and other mediators play an important role. At present, kidney biopsy is the most useful tool for monitoring the transplant rejection and the diagnosis of the associated nephropathies, in spite of the invasiveness of the procedure. Thus, it is of great interest to find alternative tools for diagnosis. The evaluation of regulatory cytokines is a simple procedure of low cost that could be useful to increase the sensitivity of the detection of polymorphic differences, to predict the graft acceptance and for the early detection of rejection. Recent studies suggest that the high production of pro-inflammatory mediators, such as Th1 cytokines, could be detrimental, whereas the production of anti-inflammatory regulatory cytokines, such as interleukin (IL)-10 and tumor necrosis factor (TGF)-beta, could be beneficial for graft survival. In the early stages, the cellular cytotoxicity is activated by the Th1 response and the detection of cytotoxic molecules is associated to the acute rejection. Later, the balance between pro and anti-inflammatory mediators and the regulation of their levels could be more important. In this regard, TGF-beta is also fibrogenic and a high local production can contribute to kidney damage. On the other hand, the increased production of IL-10 in response to the allogeneic stimuli could be, in most cases, an important marker of long-term acceptance.(AU)

La aceptación o el rechazo del riñón alogénico dependen principalmente de la respuesta inmune y de su compleja regulación en la cual la red de citoquinas y otros mediadores juegan un importantepapel. Actualmente, la biopsia renal es, a pesar de lo invasor del procedimiento, la herramienta de mayor utilidadpara el control del rechazo al trasplante y el diagnóstico de las nefropatías asociadas. Por ello, es de graninterés encontrar métodos alternativos para el diagnóstico. La evaluación de citoquinas reguladoras de la respuestainmune es un procedimiento sencillo y de bajo costo que podría ser de utilidad para incrementar la sensibilidadde la detección de diferencias polimórficas, para pronosticar la aceptación del trasplante y para ladetección precoz del rechazo. Los estudios recientes sugieren que la producción exagerada de mediadores proinflamatorios, incluyendo a citoquinas Th1, sería desventajosa para la sobrevida del trasplante, mientras que la producción de citoquinas reguladoras anti-inflamatorias, como la interleuquina (IL)-10 y el factor de crecimiento tumoral (TGF)-β, sería beneficiosa. En las primeras etapas, la respuesta Th1 puede incrementar la actividad citotóxica y la detección de moléculas citotóxicas está asociada al rechazo agudo. Luego podría ser más importante considerar el balance entre la producción de mediadores pro- y anti-inflamatorios y la regulación desus niveles. Así, el TGF-β es también fibrogénico y su excesiva producción local puede contribuir al daño renal.Por otro lado, el incremento de la producción de IL-10 en respuesta al estímulo alogénico sería, en la mayoríade los casos, un marcador importante para pronosticar la aceptación prolongada.(AU)

Ambulatory blood pressure monitoring after recovery from hemolytic uremic syndrome.

The outcome of acute renal failure due to diarrhea-associated hemolytic uremic syndrome (D+ HUS) is generally predicted to be good. However, there are only a few long-term observations with detailed reports on long-term sequelae. Specifically, adequate long-term blood pressure (BP) evaluations are scarce. The present study evaluated BP in pediatric patients after childhood D+ HUS. The study group comprised 28 patients (20 males) aged 6-23.5 years (median 10.1 years). All patients had a history of D+ HUS at a median age of 1.1 years (range 0.5-6 years). Based on the duration of oliguria and/or anuria, the primary disease was classified as mild (n=6), moderate (n=6), or severe (n=16). The BP in these patients was studied at a median time of 8.4 years (range 2.3-22.9 years) after manifestation of D+ HUS by means of office BP measurements and 24-h ambulatory BP monitoring (ABPM) using a Spacelabs 90207 oscillometric monitor. Measurements were compared with normal values of published standards for healthy children and adolescents. Conventional office BP measurements were above the 95th percentile in 1 patient. By ABPM, 2 patients were diagnosed to have mean systolic daytime and nighttime values in the hypertensive range, and systolic and diastolic hypertension was confirmed in the first patient. All these patients had a severe form of D+ HUS in the past. By applying ABPM, BP anomalies were detected in 5 additional patients. Elevated systolic BP loads were found in 4 patients, and daytime systolic and diastolic hypertension in the other 1. At the time of the study, 2 of them were classified as "recovered." The late outcome of D+ HUS may be worse than anticipated. BP anomalies as long-term sequelae of D+ HUS could be identified by ABPM but not by office BP measurements. These findings may represent an isolated sign of residual renal disturbance.

Hyperhomocysteinemia in stable pediatric, adolescents, and young adult renal transplant recipients.

BACKGROUND: High total plasma homocysteine (tHcy) levels are accompanied by an increased risk for premature development of atherosclerosis and atherothrombosis. Adult renal transplant recipients have elevated tHcy levels. Corresponding data in pediatric, adolescent, and young adult renal transplant recipients are scarce. We investigated whether tHcy levels were elevated in stable renal transplant recipients who received kidney grafts before age 18. METHODS: This cross-sectional study was conducted during routine posttransplantation follow-up. Fasting tHcy levels, serum creatinine, and lipoprotein profile were measured in 38 clinically stable renal transplant recipients with different degrees of renal function. No patient was receiving B vitamin or folic acid supplementation. Estimated glomerular filtration rate (GFR) was assessed according to Schwartz's formula. All patients followed a triple-drug immunosuppressive regimen, with the exception of three patients (deflazacort and azathioprine). Forty-one apparently healthy subjects constituted the control group. tHcy levels were determined by fluorescence polarization immunoassay in an IMx analyzer. RESULTS: Mean tHcy levels in transplant recipients were significantly higher than in controls (16.8+/-8.7 micromol/L and 9.5+/-2.3 micromol/L, respectively; P<0.01). A significant positive correlation between tHcy and serum creatinine levels was observed for both transplant recipients (rS=0.70, P<0.01) and controls (rS=0.54, P<0.01). In transplant recipients, tHcy correlated negatively with estimated GFR (rS=[minus]0.47, P<0.05). Fasting tHcy levels in excess of 14.6 micromol/L (>95th percentile in controls) were present in 19 (50%) patients; 14 of these patients had an estimated GFR<60 ml/min per 1.73 m2. When the renal transplant recipients were analyzed by renal function, mean tHcy was significantly higher in patients with an estimated GFR<60 ml/min per 1.73 m2 compared with patients with an estimated GFR> or =60 ml/min per 1.73 m2 (20.5+/-9.9 vs. 13.2+/-5.8 micromol/L, P<0.01). Both groups were significantly different from controls (P<0.01). No relationship was found between tHcy level and either cumulative cyclosporine or cumulative methylprednisone doses. No differences were observed in tHcy levels or lipoprotein profile between patients who were receiving deflazacort and those on methylprednisone. CONCLUSIONS: Hyperhomocysteinemia in renal transplant recipients is a common condition. Testing for fasting tHcy level might be a useful tool to identify patients at increased risk for development of vascular disease.

Differences in anthropometric parameters and the IFG-I-IGFBP3 axis between liver and renal transplant children.

BACKGROUND: Growth can be differently altered after liver and renal transplantation (Tx) in childhood. METHODS: We compared graft function, linear growth, immunosuppression and serum IGF-I (RIA) and IGFBP3 (IRMA) concentrations in 15 liver (5.6+/-1.1 years old) and 17 renal (7.4+/-0.1 years old) Tx patients who were followed for 4-6 years. RESULTS: Graft function was normal post-liver Tx, although in renal recipients creatinine clearance decreased significantly during follow-up. Liver Tx children presented an increase in mean height of 0.92+/-0.2 SDS (P<0.01) beyond the 2nd year post-Tx, although in renal Tx patients height SDS did not improve. Immunosuppressive corticoid dosage could be decreased and discontinued in liver Tx patients, while in renal recipients it was maintained between 0.18+/-0.01 and 0.16+/-0.02 mg/kg/day. At 3.7+/-0.4 years post Tx, liver Tx patients presented higher mean serum IGF-I level, lower mean serum IGFBP3 value, leading to a higher mean IGF-I/IGFBP3 molar ratio, P<0.001. CONCLUSIONS: We found that while catch up growth coud be achieved after liver Tx, height SDS did not improve after renal Tx. This may be related to a reduced renal graft function and/or to differences in immunosuppressive corticoid dosage. In children with renal transplants a challenge for the future will reside in making it possible to substitute steroid therapy without altering graft function.

Conversion from azathioprine [correction of azathioprina] to mycophenolate mofetil in pediatric renal transplant recipients with chronic rejection.

BACKGROUND: Chronic rejection is the leading cause of graft failure. Both nonimmunological and immunological mechanisms contribute to this pathology. METHODS: We studied changes in kidney function, mixed lymphocyte culture, cell-mediated lympholysis, serum HLA class I antigens, cytotoxic antibodies, and lymphocyte population before and after 6 months of follow-up in 22 pediatric renal transplanted patients. The immunosuppressive protocol used was: cyclosporine, azathioprine, and corticosteroids. Eight patients demonstrated chronic graft rejection (by biopsy), group I; and eight patients had no clinical evidence of chronic and/or acute rejection, group II. Substitution of mycophenolate mofetil (MMF) (600 mg/m2 bid for azathioprine was done in patients of groups I and II. Another six patients with chronic rejection, did not receive MMF, group III. RESULTS: Creatinine clearance increased in group I (44+/-5 vs. 51.1+/- ml/min/1.73 m2, P<0.03) but it decreased in group III (30+/-3 vs. 25+/-2, P<0.01). Urinary protein excretion decreased only in group I (0.3+/-0.03 to 0.06+/-0.03 g/24 hr, P<0.03). During MMF therapy antidonor mixed lymphocyte culture decreased 62 and 70% (P<0.05) in group I and II. Cell-mediated lympholysis against lymphocyte of the donor decreased 65% (P<0.05) in group I. Cell-mediated lympholysis toward control cells decreased 54% (P<0.01) in group II. Serum HLA class I antigens, only decreased from 0.7+/-0.1 to 0.5+/-0.1 microl/ml, P<0.05, in group I. CD19+ decreased from 7.9+/-1.1 to 5.6+/-0.8%, P<0.05, and 7.8+/-1.2 to 5.5+/-0.9%, P<0.05, in groups I and II, respectively. CD16+ increased from 5.7+/-1.1 to 8.6+/-1.3 (P<0.05) only in group I. CONCLUSIONS: Our data suggest that substituting MMF for azathioprine therapy leads to an improvement in the immunosuppression and renal function in children with on-going chronic rejection.

Effect of deflazacort versus methylprednisone on growth, body composition, lipid profile, and bone mass after renal transplantation. The Deflazacort Study Group.

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.

A randomized, double-blind, placebo-controlled trial of the effects of prophylactic theophylline on renal function in term neonates with perinatal asphyxia.

BACKGROUND: The kidney is the most damaged organ in asphyxiated full-term infants. Experiments in rabbits and rats have shown that renal adenosine acts as a vasoconstrictive metabolite in the kidney after hypoxemia and/or ischemia, contributing to the fall in glomerular filtration rate (GFR) and filtration fraction. Vasoconstriction produced by adenosine can be inhibited by the nonspecific adenosine receptor antagonist, theophylline. Gouyon and Guignard performed studies in newborn and adult rabbits subjected to normocapnic hypoxemia. Their results clearly showed that the hypoxemia-induced drop in GFR could be avoided by the administration of low doses of theophylline. OBJECTIVE: This study was designed to determine whether theophylline could prevent and/or ameliorate renal dysfunction in term neonates with perinatal asphyxia. SETTING: Buenos Aires, Argentina. STUDY DESIGN: We randomized 51 severe asphyxiated term infants to receive intravenously a single dose of either theophylline (8 mg/kg; study group: n = 24) or placebo (control group: n = 27) during the first 60 minutes of life. The 24-hour fluid intake and the urine volumes formed were recorded during the first 5 days of life. Daily volume balances (water output/input ratio and weights) were determined. Severe renal dysfunction was defined as serum creatinine elevated above 1.50 mg/dL, for at least 2 consecutive days after a fluid challenge, or rising levels of serum creatinine (.3 mg/dL/day). The GFR was estimated during the second to third days of life by endogenous creatinine clearance (mL/minute/1.73 m2) and using Schwartz's formula: GFR (mL/minute/1.73 m2) =.45 x length (cm)/plasma creatinine (mg/100 mL) during the first 5 days of life. Tubular performance was assessed as the concentration of beta2-microglobulin (beta2M) determined by enzyme immunoassay, on the first voided urine 12 hours after theophylline administration. The statistical analysis for the evaluation of the differences between the groups was performed with Student's t and chi(2) tests as appropriate. RESULTS: During the first day of life, the 24-hour fluid balance was significantly more positive in the infants receiving placebo compared with the infants receiving theophyline. Over the next few days, the change in fluid balance favored the theophyline group. Significantly higher mean plasma values were recorded in the placebo group from the second to the fifth days of life. Severe renal dysfunction was present in 4 of 24 (17%) infants of the theophylline group and in 15 of 27 (55%) infants of the control group (relative risk:.30; 95% confidence interval:.12-.78). Mean endogenous creatinine clearance of the theophylline group was significantly increased compared with the creatinine clearance in infants receiving placebo (21.84 +/- 7.96 vs 6.42 +/- 4.16). The GFR (estimated by Schwartz's formula) was markedly decreased in the placebo group. Urinary beta2M concentrations were significantly reduced in the theophylline group (5.01 +/- 2.3 mg/L vs 11.5 +/- 7.1 mg/L). Moreover, 9 (33%) patients of the theophylline group versus 20 (63%) infants of the control group had urinary beta2M above the normal limit (<.018). There was no difference in the severity of the asphyxia between infants belonging to the theophylline and control groups in regards of Portman's score. Except for renal involvement, a similar frequency of multiorganic dysfunction, including neurologic impairment, was observed in both groups. The theophylline group achieved an average serum level of 12.7 microg/mL (range: 7.5-18.9 microg/mL) at 36 to 48 hours of live versus traces (an average serum level of .87 microg/mg) in the placebo group. CONCLUSIONS: Our data suggest that prophylactic theophylline, given early after birth, has beneficial effects on reducing the renal dysfunction in asphyxiated full-term infants. (ABSTRACT TRUNCATED)

Effect of therapy with deflazacort on dyslipoproteinemia after pediatric renal transplantation.

Deflazacort is an oxazolone compound derived from prednisolone, with similar immunosuppressive action but fewer side effects. Kidney function, weight/height ratio, serum triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, very-low-density lipoprotein cholesterol, low-density lipoprotein (LDL) cholesterol, apolipoprotein A, apolipoprotein B, and lipoprotein (a) were studied before and 6 months after substitution of deflazacort (mean +/- SEM, 0.3 +/- 0.1 mg/kg per day) for methylprednisone (0.2 +/- 0.1 mg/kg per day) in 14 patients treated with cyclosporine, aged 3.1 to 20.3 years, 3 years after renal transplantation. Serum creatinine and calculated creatinine clearance did not change significantly, and weight/height ratio decreased from 20.0% +/- 7.1% to 12.5% +/- 6.5% (P < .005) during deflazacort therapy. Total cholesterol was reduced by 15.9% (from 233 +/- 15 mg/dL to 196 +/- 13 mg/dL, P < .01), LDL cholesterol by 25.5% (from 153 +/- 14 mg/dL to 114 +/- 12 mg/dL, P < .01), and TC/HDL cholesterol ratio by 28.3% (from 5.3 +/- 0.4 to 3.8 +/- 0.4, P < .01), whereas HDL cholesterol increased 18% (from 45 +/- 2 mg/dL to 53 +/- 2 mg/dL) and apolipoprotein A by 8.3% (from 122 +/- 5 mg/dL to 132 +/- 5 mg/dL, P < .05) during deflazacort therapy. Our data suggest that substituting deflazacort for maintenance methylprednisone therapy leads to an improvement in the lipoprotein profile of children after renal transplantation.

Syndrome of inappropriate secretion of antidiuretic hormone in nasopharynx carcinoma.

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.

Quality of life after kidney transplantation in children.

We assessed the long-term rehabilitation and quality of life after kidney transplantation in 17 recipients of transplants during their childhood who had reached 10 years or more after grafting. We found that all recipients considered themselves to be in good to excellent health, and 59% were completely satisfied with their life. Ninety-four percent of the recipients did not report any interference of their health with their family life. Only one recipient was unemployed, and five recipients have to miss work (n=2) and school (n=3) a few days a year due to their health status. Health seldom or never interfered with social life in 11 recipients, and in 6 of 9 sexually active recipients, their health status was not an obstacle in their sexual relationships. Two recipients expressed concerns about their short stature, and three were concerned with their body appearance. In conclusion, we describe a group of young adult recipients who presented a highly satisfactory rehabilitation and quality of life after their successful transplantation.

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

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.

Soluble HLA class I antigens in pediatric patients with renal transplants from related living donors without acute rejection and treated with triple therapy.

All HLA class I Ag-expressing cells may be the source of serum Ag sHLA I. T and B lymphocytes secrete considerable amounts of Ag sHLA I in a variety of in vitro and in vivo activation systems. The purpose of this study was to evaluate the level of Ag sHLA I in serum of children with kidney transplants from related living donors without acute rejection and with triple therapy. We studied 25 patients (2-21 years) with first kidney transplant, 19 individuals (10-20 years) undergoing hemodialysis without transplant, and 25 normal children (4-21 years). The levels of Ag sHLA in transplant patients was 0.2-3.2 micrograms/ml (mean = 1.04). The hemodialyzed patients was 0.48-4.5 micrograms/ml (mean = 2.09), and the normal control was 0.30-4.38 micrograms/ml (mean = 2.04). A statistically significant reduction was observed in transplant patients compared to normal control and hemodialyzed patients (p < 0.05 in both cases), whereas between normal and hemodialyzed patients no significant difference was seen (p > 0.05). The reduced levels of Ag sHLA I in blood could be an expression of adequate immunosuppressive treatment.

Therapy with a new glucocorticoid: effect of deflazacort on linear growth and growth hormone secretion in renal transplantation.

In children who have undergone successful renal transplantation, the failure of linear growth, a cushingoid appearance and obesity decrease self-esteem and hamper rehabilitation. Changes in kidney function, growth velocity, weight to height ratio and growth hormone (GH) secretion were studied before, and 2 years after, replacement of methylprednisone (6 +/- 0.3 mg/day; mean +/- SEM) by deflazacort (9.6 +/- 0.5 mg/day) 4 years after renal transplantation in 10 patients aged 9-16 years with stable renal function. Serum creatinine and creatinine clearance did not change significantly during deflazacort treatment. In 8 patients at Tanner stage I, growth velocity increased significantly during the 1st and 2nd year of deflazacort therapy (p < 0.01 and p < 0.005, respectively). Weight to height ratio decreased significantly during the 1st and 2nd year of deflazacort treatment (p < 0.005, p < 0.02, respectively) though in 3 patients, this returned to base levels after 2 years of deflazacort therapy. The mean spontaneous GH secretion increased significantly (p < 0.05). There was a correlation between growth velocity and spontaneous GH secretion during deflazacort therapy. The cushingoid appearance decreased in the majority of patients. Renal function remained stable.

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.