Plasma Nitrate and Nitrite Kinetics after Single Intake of Beetroot Juice in Adult Patients on Chronic Hemodialysis and in Healthy Volunteers: A Randomized, Single-Blind, Placebo-Controlled, Crossover Study.

Nitric oxide (NO) contributes to maintaining normal cardiovascular and renal function. This bioactive signalling molecule is generally formed enzymatically by NO synthase in the vascular endothelium. NO bioactivity can also be attributed to dietary intake of inorganic nitrate, which is abundant in our diet, especially in green leafy vegetables and beets. Ingested nitrate is reduced to nitrite by oral commensal bacteria and further to NO systemically. Previous studies have shown that dialysis, by means of removing nitrate and nitrite from the body, can reduce NO bioactivity. Hence, dietary intervention approaches aimed to boost the nitrate-nitrite-NO pathway may be of benefit in dialysis patients. The purpose of this study was to examine the kinetics of plasma nitrate and nitrite after a single intake of nitrate-rich concentrated beetroot juice (BJ) in adult hemodialysis (HD) patients and in age-matched healthy volunteers (HV). Eight HD patients and seven HV participated in this single center, randomized, single-blind, placebo-controlled, crossover study. Each participant received a sequential single administration of active BJ (70 mL, 400 mg nitrate) and placebo BJ (70 mL, 0 mg nitrate) in a random order separated by a washout period of seven days. For the kinetic analysis, blood samples were collected at different time-points before and up to 44 h after BJ intake. Compared with placebo, active BJ significantly increased plasma nitrate and nitrite levels both in HD patients and HV. The area under the curve and the maximal concentration of plasma nitrate, but not of nitrite, were significantly higher in HD patients as compared with HV. In both groups, active BJ ingestion did not affect blood pressure or plasma potassium levels. Both BJs were well tolerated in all participants with no adverse events reported. Our data provide useful information in planning dietary nitrate supplementation efficacy studies in patients with reduced NO bioactivity.

Impacto presente y consecuencias futuras de la pandemia en la salud de niños, niñas y adolescentes / Current impact and future consequences of the pandemic on children's and adolescents' health

Existe abundante bibliografía relacionada con el impacto de la pandemia de la enfermedad por el coronavirus 2019 (COVID-19) en la salud mental y social de niños, niñas, adolescentes y jóvenes. Un altísimo porcentaje de esta población tuvo síntomas emocionales y el nivel de ansiedad, depresión y pensamientos suicidas aumentaron considerablemente. Los adultos responsables de generar una red de soporte sufrieron el impacto con síntomas emocionales, inseguridad laboral y económica. En muchos niños, sin un entorno contenedor, aumentó la exposición a experiencias adversas, por lo que la pandemia puede considerarse como una experiencia adversa en sí misma. Se revisó el efecto a futuro de estas experiencias desfavorables en la infancia y cómo, con adecuado soporte familiar y social, podría disminuirse la sensibilidad al estrés generando mecanismos de resiliencia.La responsabilidad como ciudadanos y profesionales de la salud es reflexionar, discutir y desarrollar estrategias para mitigar estos daños que pueden tener graves consecuencias en la salud mental y física durante la niñez y la adultez.

There is plenty bibliography about the impact of the coronavirus disease 2019 (COVID-19) pandemic on the mental and social health of children, adolescents, and youth. A very high percentage of this population developed emotional symptoms and their levels of anxiety, depression, and suicidal ideatio increased considerably. The adults who were responsible for generating a support network were impacted and suffered emotional symptoms and job and economic uncertainty. In many children, without a supportive context, exposure to adverse experiences increased, so the pandemic may be considered an adverse experience itself. The future effect of such unfavorable experience on childhood and how family and social support may help to reduce stress through the development of resilience were reviewed. As citizens and health care providers, our responsibility is to reflect, discuss, and develop strategies to mitigate such damage that may have severe consequences on the mental and physical health of children and adults.

Current impact and future consequences of the pandemic on children's and adolescents' health. / Impacto presente y consecuencias futuras de la pandemia en la salud de niños, niñas y adolescentes.

There is plenty bibliography about the impact of the coronavirus disease 2019 (COVID-19) pandemic on the mental and social health of children, adolescents, and youth. A very high percentage of this population developed emotional symptoms and their levels of anxiety, depression, and suicidal ideation increased considerably. The adults who were responsible for generating a support network were impacted and suffered emotional symptoms and job and economic uncertainty. In many children, without a supportive context, exposure to adverse experiences increased, so the pandemic may be considered an adverse experience itself. The future effect of such unfavorable experience on childhood and how family and social support may help to reduce stress through the development of resilience were reviewed. As citizens and health care providers, our responsibility is to reflect, discuss, and develop strategies to mitigate such damage that may have severe consequences on the mental and physical health of children and adults.

Existe abundante bibliografía relacionada con el impacto de la pandemia de la enfermedad por el coronavirus 2019 (COVID-19) en la salud mental y social de niños, niñas, adolescentes y jóvenes. Un altísimo porcentaje de esta población tuvo síntomas emocionales y el nivel de ansiedad, depresión y pensamientos suicidas aumentaron considerablemente. Los adultos responsables de generar una red de soporte sufrieron el impacto con síntomas emocionales, inseguridad laboral y económica. En muchos niños, sin un entorno contenedor, aumentó la exposición a experiencias adversas, por lo que la pandemia puede considerarse como una experiencia adversa en sí misma. Se revisó el efecto a futuro de estas experiencias desfavorables en la infancia y cómo, con adecuado soporte familiar y social, podría disminuirse la sensibilidad al estrés generando mecanismos de resiliencia. La responsabilidad como ciudadanos y profesionales de la salud es reflexionar, discutir y desarrollar estrategias para mitigar estos daños que pueden tener graves consecuencias en la salud mental y física durante la niñez y la adultez.

Prematurity and Low Birth Weight in Neonates as a Risk Factor for Obesity, Hypertension, and Chronic Kidney Disease in Pediatric and Adult Age.

Low weight at birth may be due to intrauterine growth restriction or premature birth. Preterm birth is more common in low- and middle-income countries: 60% of preterm birth occur in sub-Saharan African or South Asian countries. However, in some higher-income countries, preterm birth rates appear to be increasing in relation to a reduction in the lower threshold of fetal viability. The cutoff is at 22-23 weeks, with a birth weight of approximately 500 g, although in developed countries such as Japan, the viability cutoff described is 21-22 weeks. There is evidence of the long-term consequences of prenatal programming of organ function and its relationship among adult diseases, such as hypertension (HT), central obesity, diabetes, metabolic syndrome, and chronic kidney disease (CKD). Premature delivery before the completion of nephrogenesis and intrauterine growth restriction leads to a reduction in the number of nephrons that are larger due to compensatory hyperfiltration and hypertrophy, which predisposes to the development of CKD in adulthood. In these patients, the long-term strategies are early evaluation and therapeutic interventions to decrease the described complications, by screening for HT, microalbuminuria and proteinuria, ultrasound monitoring, and renal function, with the emphasis on preventive measures. This review describes the effects of fetal programming on renal development and the risk of obesity, HT, and CKD in the future in patients with low birth weight (LBW), and the follow-up and therapeutic interventions to reduce these complications.

Calidad de vida de los hermanos de pacientes con enfermedad crónica / Quality of life among siblings of patients with chronic conditions

Introducción. La calidad de vida relacionada con la salud (CVRS) es una medida de resultado de salud. Evalúa el impacto subjetivo y global de las enfermedades en la vida cotidiana. Brinda información multidimensional sobre el bienestar físico, relación familiar y sus pares. Los estudios de CVRS de hermanos son limitados.Objetivo. Comparar CVRS de los hermanos de pacientes pediátricos con patologías reumáticas crónicas, trasplante renal o hepático con la de niños sanos con hermanos sin enfermedades crónicas.Resultados. Se compararon hermanos de niños con trasplante renal (n: 65), trasplante hepático (n: 35) y patologías reumáticas crónicas (n: 36) con el grupo control de niños sanos (n: 51). El grupo total de hermanos tuvieron puntuación más baja, estadísticamente significativa, en las dimensiones bienestar físico, amigos-apoyo social y recursos económicos. Los hermanos de trasplante renal tuvieron baja puntuación en las dimensiones de bienestar físico (p < 0,02; tamaño del efecto ­TE­: 0,66) y recursos económicos (p < 0,01; TE: 0,66). Los hermanos de trasplante hepático percibieron menor bienestar físico (p = 0,04), tenían menos amigos y apoyo social (p < 0,01), dificultades en el entorno escolar (p < 0,02) y recursos económicos (p < 0,01). Los hermanos de patologías reumáticas crónicas tuvieron menor bienestar físico (p < 0,05; TE: 0,44) y apoyo social-amigos (p < 0,01; TE: 0,58).Conclusión. La CVRS de niños/as sanos de hermanos con patologías crónicas es menor en bienestar físico, amigos-apoyo social y recursos económicos comparada con el grupo de niños sanos.

Introduction. Health-related quality of life (HRQoL) is a measure of health outcomes. It assesses the subjective and overall impact of diseases on daily life. It also provides multidimensional data about physical well-being, family and peers relations. HRQoL studies on siblings are limited.Objective. To compare HRQoL among siblings of pediatric patients with chronic rheumatic diseases, kidney or liver transplant and healthy children whose siblings had no chronic conditions.Results. The siblings of children with kidney transplant (n: 65), liver transplant (n: 35), and chronic rheumatic diseases (n: 36) were compared to the healthy children group (n: 51). The total siblings group had a lower, statistically significant score in the physical well-being, social support and peers, and financial resources dimensions. The siblings of kidney transplant patients had a low score in the physical well-being (p < 0.02; effect size [ES]: 0.66) and financial resources (p < 0.01; ES: 0.66) dimensions. The siblings of liver transplant patients perceived a lower physical well-being (p = 0.04), less social support and peers(p < 0.01), and difficulties in relation to school environment (p < 0.02) and financial resources (p < 0.01). The siblings of those with chronic rheumatic diseases had a lower score in the physical well-being (p < 0.05; ES: 0.44) and social support and peers (p < 0.01; ES: 0.58) dimensions.Conclusion. HRQoL among healthy children whose siblings have a chronic disease was lower in the physical well-being, social support and peers, and financial resources dimensions compared to the healthy children group.

Quality of life among siblings of patients with chronic conditions. / Calidad de vida de los hermanos de pacientes con enfermedad crónica.

INTRODUCTION: Health-related quality of life (HRQoL) is a measure of health outcomes. It assesses the subjective and overall impact of diseases on daily life. It also provides multidimensional data about physical wellbeing, family and peers relations. HRQoL studies on siblings are limited. OBJECTIVE: To compare HRQoL among siblings of pediatric patients with chronic rheumatic diseases, kidney or liver transplant and healthy children whose siblings had no chronic conditions. RESULTS: The siblings of children with kidney transplant (n: 65), liver transplant (n: 35), and chronic rheumatic diseases (n: 36) were compared to the healthy children group (n: 51). The total siblings group had a lower, statistically significant score in the physical well-being, social support and peers, and financial resources dimensions. The siblings of kidney transplant patients had a low score in the physical wellbeing (p < 0.02; effect size [ES]: 0.66) andfinancial resources (p < 0.01; ES: 0.66) dimensions. The siblings of liver transplant patients perceived a lower physical well-being (p = 0.04), less social support and peers (p < 0.01), and difficulties in relation to school environment (p < 0.02) and financial resources (p <0.01). The siblings of those with chronic rheumatic diseases had a lower score in the physical well-being (p < 0.05; ES: 0.44) and social support and peers (p <0.01; ES: 0.58) dimensions. CONCLUSION: HRQoL among healthy children whose siblings have a chronic disease was lower in the physical well-being, social support and peers, and financial resources dimensions compared to the healthy children group.

Introducción. La calidad de vida relacionada con la salud (CVRS) es una medida de resultado de salud. Evalúa el impacto subjetivo y global de las enfermedades en la vida cotidiana. Brinda información multidimensional sobre el bienestar físico, relación familiar y sus pares. Los estudios de CVRS de hermanos son limitados. Objetivo. Comparar CVRS de los hermanos de pacientes pediátricos con patologías reumáticas crónicas, trasplante renal o hepático con la de niños sanos con hermanos sin enfermedades crónicas. Resultados. Se compararon hermanos de niños con trasplante renal (n: 65), trasplante hepático (n: 35) y patologías reumáticas crónicas (n: 36) con el grupo control de niños sanos (n: 51). El grupo total de hermanos tuvieron puntuación más baj a, estadísticamente significativa, enlas dimensiones bienestar físico, amigos-apoyo social y recursos económicos. Los hermanos de trasplante renal tuvieron baja puntuación en las dimensiones de bienestar físico (p < 0,02; tamaño del efecto -TE-: 0,66) y recursos económicos (p < 0,01; TE: 0,66). Los hermanos de trasplante hepático percibieron menor bienestar físico (p = 0,04), tenían menos amigos y apoyo social (p < 0,01), dificultades en el entorno escolar (p < 0,02) y recursos económicos (p < 0,01). Los hermanos de patologías reumáticas crónicas tuvieron menor bienestar físico (p < 0,05; TE: 0,44) y apoyo social-amigos (p < 0,01; TE: 0,58). Conclusión. La CVRS de niños/as sanos de hermanos con patologías crónicas es menor en bienestar físico, amigos-apoyo social y recursos económicos comparada con el grupo de niños sanos.

"Removal of nitrate and nitrite by hemodialysis in end-stage renal disease and by sustained low-efficiency dialysis in acute kidney injury".

BACKGROUND & PURPOSE: It is well established that end-stage renal disease (ESRD) is associated with increased cardiovascular morbidity and mortality both in the adult and pediatric population. Although the underlying molecular mechanisms are poorly understood, compromised nitric oxide (NO) bioactivity has been suggested as a contributing factor. With this in mind, we investigated the effects of hemodialysis on NO homeostasis and bioactivity in blood. METHODS & RESULTS: Plasma and dialysate samples were obtained before and after hemodialysis sessions from adults (n = 33) and pediatric patients (n = 10) with ESRD on chronic renal replacement therapy, and from critically ill adults with acute kidney injury (n = 12) at their first sustained low-efficiency dialysis session. Levels of nitrate, nitrite, cyclic guanosine monophosphate (cGMP) and amino acids relevant for NO homeostasis were analyzed. We consistently found that nitrate and cGMP levels in plasma were significantly reduced after hemodialysis, whereas post-dialysis nitrite and amino acids coupled to NO synthase activity (i.e., arginine and citrulline) were only significantly reduced in adults with ESRD. The amount of excreted nitrate and nitrite during dialysis were similar to daily endogenous levels that would be expected from endothelial NO synthase activity. CONCLUSIONS: Our results show that hemodialysis significantly reduces circulating levels of nitrate and cGMP, indicating that this medical procedure may impair NO synthesis and potentially NO signaling pathways.

Clinical value of ambulatory blood pressure in pediatric patients after renal transplantation.

Hypertension is a highly prevalent co-morbidity in pediatric kidney transplant recipients. Undertreated hypertension is associated with cardiovascular complications and negatively impacts renal graft survival. Thus, the accurate measurement of blood pressure is of the utmost importance for the correct diagnosis and subsequent management of post-renal transplant hypertension. Data derived from the general population, and to a lesser extent from the pediatric population, indicates that ambulatory blood pressure monitoring (ABPM) is superior to blood pressure measurements taken in the clinical setting for the evaluation of true mean blood pressure, identification of patients requiring antihypertensive treatment, and in the prediction of cardiovascular outcome. This Educational Review will discuss the clinical value of ABPM in the identification of individual blood pressure phenotypes, i.e., normotension, new-onset hypertension, white-coat hypertension, masked hypertension, controlled blood pressure, and undertreated/uncontrolled hypertension in pediatric kidney transplant recipients. Finally, we examine the utility of performing repeated ABPM for treatment monitoring of post-renal transplant hypertension and on surrogate markers related to relevant clinical cardiovascular outcomes. Taken together, our review highlights the clinical value of the routine use of ABPM as a tool for identifying and monitoring hypertension in pediatric kidney transplant recipients.

Influence of CYP3A5 polymorphism on tacrolimus maintenance doses and serum levels after renal transplantation: age dependency and pharmacological interaction with steroids.

TAC, MMF and MP are used in pediatric kidney tx. The cytochrome P450 (CYP)3A5 enzyme appears to play a role in TAC metabolism. The aims of this study were to investigate CYP3A5 polymorphism's effect on TAC dosing and the age dependency of TAC dosing by testing blood concentrations, and the interaction between steroids and TAC during the first year after tx. Genomic DNA was extracted and amplified with specific primers. CYP3A5 alleles were confirmed by direct sequencing of PCR products on an automated AB13100 capillary sequencer. We studied 48 renal transplant patients (age at tx 12±0.5yr, 22 boys) receiving TAC, MMF, MP. Of these, 79% were CYP3A5*3/*3 (non-expressers homozygotes) and 21% were CYP3A5*1/*3 (expressers). TAC trough levels were 7.1±0.4ng/mL in CYP3A5*3/*3 patients and 6.5±0.7ng/mL in CYP3A5*1/*3 group (p=0.03). CYP3A5*1/*3 patients had lower levels of dose-adjusted TAC (36.7±5.8ng/mL/mg/kg/day) to achieve target blood concentration and required higher daily dose per weight (0.21±0.03mg/kg/day) than CYP3A5*3/*3 patients, 72.4±8.0ng/mL/mg/kg/day and 0.13±0.01mg/kg/day (p<0.001). Prepubertal patients with different CYP3A5 polymorphisms required significant higher TAC doses and achieved lower dose-normalized concentration compared with pubertal patients. Both TAC dose and adjusted-dose correlated with daily MP dose in CYP3A5*1*3 (r: 0.4, p<0.03 and r: 0.4, p<0.03) and in CYP3A5*3*3 (r: 0.6, p<0.01 and r: 0.47, p<0.001) patients. CYP3A5 polymorphism performed before tx could contribute to a better individualization of TAC therapy. The higher TAC dose in prepubertal patients and the pharmacological interactions between MP and TAC may not be fully explained by different CYP3A5 polymorphisms.

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.

A study on strategies for improving growth and body composition after renal transplantation.

Allograft function and metabolic effects of four treatment regimens, namely, methylprednisone (MP) standard dose (MP-STD), deflazacort (DFZ), MP-late steroid withdrawal (MP-LSW), and MP-very low dose (MP-VLD), were evaluated in prepubertal patients. MP was decreased by month 4 post-transplantation to 0.2 mg/kg/day in MP-STD and DFZ patients and to <0.1 mg/kg/day in MP-LSW and MP-VLD patients. Starting in month 16 post-transplant, MP was switched to DFZ in the DFZ group and totally withdrawn in the MP-LSW group. Creatinine clearance diminished in the MP-STD and MP-LSW groups from 77 +/- 6 to 63 +/- 6 ml/min/1.73 m(2)and from 103 +/- 5 to 78 +/- 3 ml/min/1.73 m(2), respectively (p < 0.01 and p < 0.001, respectively). Height increased >0.5 SDS only in the MP-LSW and MP-VLD groups. The body mass index and fat body mass for height-age increased only in the MP-STD patients (p < 0.05 and p < 0.01, respectively). Fat body mass decreased in the DFZ group (p < 0.05), total cholesterol and LDL-cholesterol increased in the MP-STD group, while LDL-cholesterol and total cholesterol/HDL-cholesterol ratio decreased in the DFZ group (p < 0.01). Lumbar spine bone mineral density (BMD) for height-age showed an increase in the MP-LSW and MP-VLD groups (p < 0.01). Our data suggest that MP-LSW and MP-VLD strategies improve linear growth, BMD, the peripheral distribution of fat, and preservation of the bone-muscle unit and maintain the normal lipid profile. The MP-LSW patients had a concerning rate of acute rejections and graft function deterioration in prepubertal patients.

Conversion from mycophenolate mofetil to delayed formulation in pediatric renal transplantation: higher mycophenolic acid predose level but no changes in the immune biomarkers.

EC-MPS was designed to improve MPA-related GII because of MMF, by delaying the release of MPA until reaching the small intestine. At present, its immunosuppressive activity in pediatric renal transplant recipients with GII has not been clarified. We studied eight renal transplant recipients before and after three months of the conversion from MMF to equimolar doses of EC-MPS. After three months of treatment with EC-MPA, GII decreased between 100% and 12.5%. The predose levels of MPA were about 60% higher on EC-MPS (6.9 +/- 1.1 microg/mL) compared with MMF administration (4.2 +/- 0.9 microg/mL). Hemoglobin decreased significantly post-conversion (12.0 +/- 0.4 to 11.0 +/- 0.5 g/dL). Serum creatinine, creatinine clearance, and urinary protein excretion did not change. Also, proliferative response and cytotoxic antibodies showed no significant change. The release of interleukin-10 was strikingly augmented with MMF or EC-MPS therapy; meanwhile, gamma-interferon and TNF were low under both treatments. Our data indicate that conversion from MMF to EC-MPS leads to an improvement in GII without altering key elements of immunosuppression.

[Chronic renal failure, dialysis and transplant: multicentric study: 1996-2003]. / Enfermedad renal crónica, diálisis y trasplante: Estudio multicéntrico: 1996-2003.

OBJECTIVE: The multicentric study of chronic renal failure, dialysis and transplant started in 1996 by the Nephrology Committee of the Argentine Pediatrics Society with the aim of knowing the development characteristics of children with this pathology. POPULATION, MATERIAL AND METHODS: The study included children and adolescents on conservative treatment, dialysis or transplant who have registered any of the three modalities before being 19 year-old, since january 1996 to december 2003. The statistical analysis was made with the statistical software SAS; in order to calculate the survival curve, the method employed was Kaplan-Meier and the standardized height and weight z-scores were calculated. RESULTS: In this report, there is data related to 710 patients with chronic renal failure, under conservative treatment 34.2%, dialysis 57.6% and transplant 29.5%. The end-stage renal disease incidence was of 6.5/million inhabitants. The main etiologies were obstructive uropathy 18.3%, reflux nephropathy 15.1%, hemolytic uremic syndrome 14.4%, aplasia/dysplasia/hypoplasia 13.8%, and focal segmental glomerulosclerosis 8.9%. From the patients on dialysis treatment, 62.3% were under hemodialysis, and only 37.7% on peritoneal dialysis. Live-donor sources accounted for 46.2 % of the transplants, with a 1-year patient's survival of 98.7% and a 1-year graft survival of 96.4 %, similar with both donors. CONCLUSION: The results obtained, even though they do not correspond to the total population affected and the monitoring is still insufficient, allowed us to have a profile of the chronic renal failure in our country.

Improved long-term graft function in kidney transplant recipients with donor antigen-specific hyporeactivity.

We investigated the development of donor antigen-specific hyporeactivity by using donor cells as stimulator cells in the MLC and comparing the pre- and post-transplant responses of peripheral blood mononuclear cells. Twenty-two haploidentical pediatric living-relative donor recipients treated with daclizumab, methylprednisone, mofetil mycophenolate and calcineurin inhibitors were tested for study. Of these, 50% of the recipients developed in vitro donor antigen-specific hyporeactivity. The recipients who did so have higher creatinine clearance levels at 12, 24 and 36 months post-transplant (104, 92 and 81 mL/min/1.73 m(2), respectively) than those who remained responsive to donor antigens (77, 74 and 70 mL/min/1.73 m(2)) (p < 0.05). Acute rejection episodes were not observed; however, no recipients with donor-specific hyporeactivity have been diagnosed with CAN, unlike three recipients who remained responsive to donor antigens (0% vs. 27.3%, p = 0.06). Differences in accumulative doses of methylprednisone and mofetil mycophenolate were observed between hyporeactivity- and response-patients to donor antigens at the three years end-point (1.9 +/- 0.8 g/m(2) vs. 4.2 +/- 0.5 g/m(2), and 277 +/- 89 g/m(2) vs. 672 +/- 16.0 g/m(2); p < 0.01 and <0.02, respectively). We conclude that the development of donor antigen-specific hyporeactivity correlate with improved graft function and may permit lower immunosuppression.

Effects of deflazacort vs. methylprednisone: a randomized study in kidney transplant patients.

Metabolic effects of deflazacort vs. methylprednisone were studied in prepubertal patients after kidney transplantation. Thirty-one patients participated: 15 received deflazacort and 16 remained on methylprednisone. The study started at a mean of 2.1 years after transplantation, when patients were randomized to either continue with methylprednisone or switch to deflazacort. Height velocity increased more in the deflazacort than in the methylprednisone group only during the first 2 years: 5.4 +/- 0.5 vs. 3.5 +/- 0.3 cm/year, and 4.2 +/- 0.8 vs. 2.2 +/- 0.4 cm/year p=0.007, [by two-way analysis of variance (ANOVA)]. After 2 and 3 years, the number of patients who were overweight increased in the methylprednisone group and decreased in the deflazacort group; p<0.01. Lean body mass increased more in the deflazacort than in the methylprednisone group (p=0.003). Fat body mass increased only in the methylprednisone group (p<0.01). Total cholesterol and low-density-lipoprotein (LDL) cholesterol increased in the methylprednisone group (p<0.05 and p<0.01, respectively). Total and LDL cholesterol were reduced (p<0.01 and p<0.001, respectively), whereas high-density-lipoprotein (HDL) cholesterol increased (p<0.001) during deflazacort therapy. Lumbar spine bone mineral density (BMD) decreased in both groups, but total skeleton BMD decreased only in the methylprednisone group (p<0.001). Finally, normal glucose/insulin ratio, defined as > 7, was associated (p<0.05) with the deflazacort group. Our data suggest that deflazacort therapy might improve linear growth and lean body mass and prevent excessive bone loss and fat accumulation. It also leads to an improvement in lipoprotein profile without reduction in insulin sensitivity.

ABPM vs office blood pressure to define blood pressure control in treated hypertensive paediatric renal transplant recipients.

While 24-h ambulatory blood pressure monitoring (ABPM) is an established tool for monitoring antihypertensive therapy in adults, data in children are scarce. We retrospectively analysed whether office blood pressure (BP) is reliable for the diagnosis of BP control in 26 treated hypertensive paediatric renal transplants. Controlled office BP was defined as the mean of three replicate systolic and diastolic BP recordings less than or equal to the 95th age-, sex- and height-matched percentile on the three-outpatient visits closest to ABPM. Controlled ABPM was defined as systolic and diastolic daytime BP < or =95th distribution adjusted height- and sex-related percentile of the adapted ABPM reference. Eight recipients (30%) with controlled office BP were in fact categorized as having non-controlled BP by ABPM criteria. Overall, when office BP and ABPM were compared using the Bland and Altman method, the 95% limits of agreement between office and daytime values ranged from -12.6 to 34.1 mmHg for systolic and -23.9 to 31.7 mmHg for diastolic BP, and the mean difference was 10.7 and 3.9 mmHg respectively. Office readings miss a substantial number of recipients who are hypertensive by ABPM criteria. Undertreatment of hypertension could be avoided if ABPM is applied as an adjunct to office readings.

Potential cardiovascular risk factors in paediatric renal transplant recipients.

Cyclosporin (CsA) therapy is associated with side effects such as hypertension, hyperlipidemia and nephrotoxicity. Tacrolimus (Tac) has been shown to be more favourable in this respect. We retrospectively analysed office blood pressure (BP), serum total cholesterol (TC) and fasting glucose levels, and estimated graft function profiles in paediatric (n =56) and young adult (n =14) renal transplant recipients whose maintenance immunosuppressive regimen was based upon CsA (n =38) or Tac (n =32) given with mycophenolate mofetil and corticosteroids. The analysis was performed at four different time-points: at 1, 6, 12, and 24 months post-transplant, respectively. Baseline characteristics were comparable between treatment groups. Differences for both systolic and diastolic BP, and graft function between treatment groups became significant from month 1 and throughout the 2-year period. Values (mean +/- SD) for CsA-treated and Tac-treated recipients at 2 years were 118.8+/-11.1 / 74.6+/-7.4 mmHg vs 109.3+/-11.2 / 67.2+/-7.8 mmHg for systolic and diastolic BP, respectively, p <0.005/0.005; and 72.0+/-18.5 ml/min vs 84.0+/-22.4 ml/min per 1.73 m(2) for graft function, respectively, p <0.01. Office hypertension, defined as the use of antihypertensive medication at month 24, was significantly associated with CsA-therapy (chi(2), p <0.01). TC levels became significantly lower at months 6, 12, and 24 in the Tac group compared with the CsA group. Hypercholesterolemia, defined as TC>or=200 mg/dl, was significantly associated with CsA-based immunosuppressive regimen at months 6, 12, and 24 post-transplant (chi(2), p <0.05, p <0.001, and p <0.01, respectively). Although Tac therapy was associated with higher glucose levels, no recipient developed post-transplant diabetes mellitus. The number of recipients who experienced acute rejections was comparable in both groups. In conclusion, Tac-based immunosuppressive therapy was found to be associated with more favourable potential risk-factor profiles for cardiovascular disease and better graft function at 2 years post-transplant compared with CsA-therapy.

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

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.

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

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 (Delta) were different between groups (-6.0 +/- 5.1 mL/min/1.73 m(2) in the MMF group vs. -22.2 +/- 7.6 mL/min/1.73 m(2) 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. Delta 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). This study shows that long-term MMF therapy has resulted in a decrease in acute rejection and was associated with a protection against renal function deterioration. The use of MMF enables a reduction in the dose of steroids and leads to a linear growth improvement of children after renal transplantation.