Multidisciplinary management of people with spina bifida across the lifespan.

The average worldwide prevalence of neural tube defects (NTDs) is 1.0 per 1000 births. Its development is multifactorial due to genetic and non-genetic factors. Spina bifida (SB) is one of main representatives of NTD. The spinal cord lesion level is the main determinant of the level of paralysis, numbness, and difficulties with bladder/bowel functions. Myelomeningocele prenatal repair reduces hydrocephalus and hindbrain herniation and improves motor function. The severity of hydrocephalus is associated with poorer neurodevelopmental outcomes whether operated on prenatally or after birth. People with SB tend to have a lower IQ and cognitive difficulties. Early diagnosis, proactivity, and lifelong multidisciplinary follow-up are key protective issues. Invasive urological interventions should be considered in selected patients after failure of conservative treatment. Transition to adult care should be well planned as it is challenging. Health literacy is directly associated with success at transition. Sexuality and fertility should be addressed before/during puberty. Overall, the rates of fecal and urinary continence and skin breakdown increase with age, whereas the ability to ambulate declines with age. Bowel and urinary incontinence are independent predictors of lower health-related quality of life (HRQoL) in adults with SB. Bowel incontinence has negative impact on HRQoL regardless of frequency or amount. Long-term caregiver support should be offered at diagnosis. Survival at a mean of 50 years is poor, at 32%, due to central nervous system deaths, cancer, urological disease, and sepsis. Challenges to implementation of recommended practices exist, especially in low and middle-income countries.

Obesity Facts and Their Influence on Renal Function Across the Life Span.

Obesity is a chronic disease, with a rapidly increasing prevalence worldwide. Body mass index (BMI) provides the most useful population-level measure of overweight and obesity. For adults, overweight is defined as a BMI (Kg/m2) ≥ 25, and obesity as a BMI ≥ 30, for non-Asians and ≥ 27.5 for Asians. Abdominal obesity can be defined as a waist circumference equal to or higher than 102 cm for men and ≥88 cm for women. The definition of children and adolescents BMI changes with age and sex. Obesity may be exogenous or endogenous obesity, the latter is multifactorial and predominantly manifested during childhood. Presently, overweight and obesity are linked to more deaths worldwide than underweight. The total kidney glomerular filtration rate (GFR) is determined by the sum of nephrons and the GFR within each nephron or single nephron GFR. In clinical practice, GFR is more frequently calculated by GFR estimating equations based upon the plasma levels of creatinine, cystatin C, or both. The measured value of plasma creatinine is strongly influenced by non-GFR factors, by its tubular and gastrointestinal secretion, and by the problems associated with the lack of standardization of creatinine's laboratory assay discrediting it as an ideal GFR biomarker. Unlike creatinine, cystatin C plasma levels are mainly determined by GFR. Obesity may affect the kidney, via development of systemic arterial hypertension and/or diabetes mellitus, or directly, by ectopic accumulation of adipose tissue in the kidney. As obesity is a clinical condition associated with altered body composition, creatinine may not be the ideal biomarker for GFR measurement in obese individuals.

Study of the association between generic and disease-specific quality of life and behavior problems in pediatric patients with chronic kidney disease stage 3 or higher and the quality of life and mental health of their primary caregivers.

BACKGROUND: Chronic kidney disease (CKD) can affect quality of life and mental health of patients and their primary caregivers (PCs) in different disease stages. METHODS: This prospective, cross-sectional, descriptive, comparative, and analytical study of patients with stage 3-5 CKD, aged 8-18 years, assesses the association between patients' general and disease-specific health-related quality of life (HRQOL) and behavioral problems and their PCs' QoL and mental health status. PedsQL 4.0, PedsQL ESRD, CBCL, and YSR questionnaires were used to evaluate 80 patients while their PCs were assessed by SF-36 and MINI questionnaires. The study participants were divided into three groups: G1: stage 3-4 CKD, G2: peritoneal dialysis and hemodialysis, and G3: kidney transplantation. RESULTS: Lower indexes in PedsQL 4.0 and PedsQL ESRD were demonstrated in G2 patients. No deviant internalizing and/or externalizing conducts were shown by the CBCL questionnaire while the YSR questionnaire demonstrated significant differences in all domains with higher scores in G2 patients without reaching clinical range for individual syndromes. G3 PCs presented the lowest SF-36 scores and the highest occurrence of psychiatric diagnoses, according to MINI, when compared to other PCs. Parallelism was found between scores of PedsQL 4.0 and PedsQL ESRD with tendency to higher scores in the PC's view compared to the patient's view. CONCLUSIONS: CKD affects HRQOL of patients and their PCs, as well as patients' behavior problems and their PCs' mental health. PCs' perceptions of patients' QOL and behavioral problems may be related to their mental health status and QOL self-perceptions.

Non-REM Sleep Instability in Children With Primary Monosymptomatic Sleep Enuresis.

STUDY OBJECTIVES: Sleep enuresis is one of the most common sleep disturbances in childhood. Parental perception of deeper sleep in children with sleep enuresis is not confirmed by objective studies. However, evidence of disturbed sleep has been demonstrated by questionnaire, actigraphy, and polysomnographic studies, but no neurophysiological correlation with low arousability has been found. The goal of this study was to analyze the sleep microstructure of children with sleep enuresis using cyclic alternating pattern (CAP) analysis. METHODS: Forty-nine children were recruited, 27 with enuresis (19 males and 8 females, mean age 9.78 years, 2.52 standard deviation) and 22 normal control patients (11 males and 11 females, mean age 10.7 years, 3.43 standard deviation); all subjects underwent clinical evaluation followed by a full-night polysomnographic recording. Psychiatric, neurological, respiratory, and renal diseases were excluded. RESULTS: No differences in sex, age, and apnea-hypopnea index were noted in the patients with enuresis and the control patients. Sleep stage architecture in children with sleep enuresis showed a decrease in percentage of stage N3 sleep. CAP analysis showed an increase in CAP rate in stage N3 sleep and in phase A1 index during stage N3 sleep in the sleep enuresis group, but also a significant reduction of A2% and A3% and of phases A2 and A3 indexes, supporting the concept of decreased arousability in patients with sleep enuresis. The decrease of phase A2 and A3 indexes in our patients might reflect the impaired arousal threshold of children with sleep enuresis. Sleep fragmentation might result in a compensatory increase of slow wave activity (indicated by the increase of CAP rate in stage N3 sleep) and may explain the higher arousal threshold (indicated by a decrease of phase A2 and A3 indexes) linked to an increased sleep pressure. CONCLUSIONS: The findings of this study indicate the presence of a significant disruption of sleep microstructure (CAP) in children with sleep enuresis, supporting the hypothesis of a higher arousal threshold.

Monosymptomatic nocturnal enuresis in pediatric patients: multidisciplinary assessment and effects of therapeutic intervention.

BACKGROUND: Few studies manage patients with isolated monosymptomatic enuresis (MNE) with multidisciplinary evaluation and pre- and long-term post-intervention monitoring. METHODS: This was a prospective study of MNE patients, aged 6-16 years, diagnosed by multidisciplinary assessment. Of the 140 initial applicants (58.6%) with MNE, 82 were included in the study and randomized for therapeutic intervention in three treatment groups, namely: alarm, desmopressin and alarm + desmopressin. Therapeutic response was evaluated 12 months after treatment withdrawal. RESULTS: Of the 82 patients [mean age 9.5 (SD ± 2.6) years, n = 62 males (75.6%)], 91.1% had a family history of nocturnal enuresis (NE) in first-/second-degree relatives, 81.7% had constipation and 40.7% had mild-to-moderate apnea. Prior to randomization, management of constipation and urotherapy led to remission in seven of the 82 patients; 75 patients were randomized to intervention. There were 14/75 (18.7%) dropouts during the intervention, especially in the alarm group (p = 0.00). Initial complete/partial response was achieved in 56.6% of the alarm group, 70% of the desmopressin group and 64% in the combined group (p = 0.26). Continued success occurred in 70% of the alarm group, 84.2% of the desmopressin group and 100% of the combined group (p = 0.21). Recurrence occurred in 3/20 (15%) patients in the alarm group and 1/19 (5.2 %) patients of the desmopressin group. Post-intervention Child Behavior Checklist (CBCL) and PedsQL 4.0 scores showed significant improvement. CONCLUSIONS: The three therapeutic modalities were effective in managing MNE with low relapse rates; the alarm group showed the highest dropout rate. Therapeutic success was associated with improvement of behavioral problems and quality of life scores.

Impact of a multidisciplinary evaluation in pediatric patients with nocturnal monosymptomatic enuresis.

BACKGROUND: Enuresis (NE) is a clinical condition of multifactorial etiology that leads to difficulties in child/adolescent social interaction. METHODS: This was a prospective study on the impact of multidisciplinary assessment of 6- to 17-year-old patients with monosymptomatic nocturnal enuresis (MNE), including a structured history, clinical/neurological examination, bladder and bowel diaries, sleep diary and questionnaires, psychological evaluation [Child Behavior Checklist (CBCL) and PedsQL 4.0 questionnaires], urinary sonography, blood and urine laboratory tests, polysonography (PSG), and balance evaluation. RESULTS: A total of 140 enuretic participants were evaluated, of whom 27 were diagnosed with NE complicated by urinary disorder, four with hypercalciuria, three with nephropathy and one with attention-deficit hyperactivity disorder. Among the 87 participants who underwent PSG, six were diagnosed with severe apnea. Of the 82 MNE patients who underwent full assessment, 62 were male (75.6 %), and the mean age was 9.5 (±2.6) years. A family history of NE was diagnosed in 91.1 % of first- and second-degree relatives, constipation in 89.3 % and mild/moderate apnea in 40.7 %. Balance control alteration was identified by physical therapy evaluation of MNE patients. Participants' quality of life evaluation scores were significantly lower than those of their parents. CONCLUSION: Enuresis is a multifactorial disorder that requires a structured diagnostic approach.

Sleep disturbances associated with sleep enuresis: A questionnaire study.

PURPOSE: Sleep enuresis (SE) is the second most common sleep complaint in childhood. It has been associated with bladder hyperactivity, excessive urine production and deeper sleep. Several sleep disorders have been described in association with SE like parasomnias and sleep apnea. The aim of this study was to analyze the presence of sleep disturbances in children with SE through the use of Sleep Disturbance Scale for Children (SDSC) compared to normal children matched for age and sex. METHODS: A questionnaire evaluation was performed in 76 enuretic and 112 normal children through the Sleep Disturbance Scale for Children (SDSC) validated for Portuguese language. The Scale is grouped into six subscales: Disorders in Initiating and Maintaining Sleep (DIMS), Sleep Breathing Disorders (SBD), Disorders of Arousal (DA), Sleep-Wake Transition Disorders (SWTD), Disorders Of Excessive Somnolence (DOES), and Nocturnal Hyperhidrosis (SHY). Children with renal and neurological problems were excluded from both groups. RESULTS: Enuretics scored higher in several of the subscales (SBD, DOA, SWTD) and also in the total scale scores while scored low in the DIMS subscale. No differences were found for the DOES and SHY subscales. CONCLUSIONS: Enuretic children showed a high comorbidity with other sleep disturbances like sleep disordered breathing and parasomnias. The novel finding of this study is that we found a decreased incidence of DIMS that is consistent with the parental perception of a more deep sleep and a high arousal threshold in SE.

Health-related quality of life of children and adolescents with CKD stages 4-5 and their caregivers.

BACKGROUND: Renal replacement therapies may affect the quality of life of patients and their primary caregivers (PC). METHODS: This study describes the perception of health-related quality of life (HRQoL) of children/adolescents with CKD stages 4-5, as well as of their PC (n = 64), in comparison to healthy peers and their PC (n = 129), respectively, based on the Peds QL™ 4.0 and Short Form-36 (SF-36) questionnaires and selected biomarkers. RESULTS: Patients reported a deleterious impact on physical capacity and on social and school activities. A negative influence on emotional aspects was reported by older patients, but not by their PC. Hemodialysis, followed by peritoneal dialysis, had a more negative impact on patients' physical functioning domain. PC HRQol proxy reports differed from those of their children, especially in older patients. PC of both groups presented similar SF-36 scores. An association was demonstrated between the magnitude of treatment target inadequacies, lower specific dominion scores in the patients/PC proxy reports and PC SF-36 general health scores. CONCLUSION: The HRQoL of patients with CKD stages 4-5 is negatively affected to different degrees depending on age and treatment modality. The results suggest an association between worsening HRQoL parameters and inadequate control of recognized therapeutic CKD treatment targets.

Hipertensão arterial na criança e no adolescente / Arterial hypertension in children and adolescent

A prevalência estimada de hipertensão arterial (HA) em crianças e adolescentes varia de 1% a 10% nos vários estudos disponíveis. A medida de pressão arterial (PA) na criança exige cuidados especiais em relação ao ambiente, técnica e equipamento utilizados. Estudos com medida única de PA tendem a gerar dados superestimados de prevalência de HA nessa população. neste artigo, são abordados aspectos epidemiológicos, diagnósticos e terapêuticos atuais da HA na criança e no adolescente. Foram incluídos aspectos das medidas por monitorização ambulatorial de pressão arterial e medida residencial de pressão arterial, por se tratarem de técnicas gradativamente mais utilizadas na população infantil.

The estimated prevalence of pediatric arterial hypertension (AH) ranges from 1% to 10% in various available studies. The measurement of blood pressure (BP) in children requires special care in relation to environmental, technical and equipment issues. Studies with single BP measurements tend to generate overestimated prevelence data on pediatric hypertension. This article examines epidemiological aspects, diagnosis and current therapeutics of hypertension in children and adolescents. Aspects on the use of ambulatory BP monitoring and home BP monitoring were included, as they are gradually being introduced in pediatric practice.

The long-term use of enalapril and hydrochlorothiazide in two novel mutations patients with Dent's disease type 1.

Dent's disease type 1 is an X-linked tubular disease caused by mutations in the renal chloride channel CLCN-5, and it is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal failure. Several cases have been described in which the only presenting symptoms were asymptomatic proteinuria, and focal segmental or global glomerulosclerosis. The renal failure in these patients may be caused by hypercalciuria and persistent proteinuria. Therefore, angiotensin converse enzyme inhibitor and thiazides could be useful. Our aim is to report the effects of these drugs in two novel mutations patients with Dent's disease type 1. In this report, no significant correlations between dosage of hydrochlorothiazide and calciuria and no significant correlations between proteinuria and dosage of enalapril were detected. This is important since these are polyuric patients and these drugs could be dangerous to their renal function.

Comparative role of PET and Kt/V determination in pediatric chronic peritoneal dialysis.

INTRODUCTION: Nutritional state and growth are considered as prognostic markers of chronic peritoneal dialysis (PD) adequacy in pediatric patients. The euvolemia, blood pressure control, and metabolic and electrolytic equilibrium are parameters to be achieved by PD treatment. OBJECTIVE: To describe the chronic PD prescription parameters of a cohort of pediatric patients and to compare the obtained hemodynamic, antrophometric and adequacy results with those suggested by the literature. METHODS: Retrospective analysis based on clinical records evaluation of 30 pediatric patients undergoing PD for more than 6 months from January 1998 to May 2005. RESULTS: In the present study, 17/30 (56.7%) were boys. Chronic kidney disease was secondary to uropathy in 66.7% of the cases. The infusion volume was > 1,000 ml/m2 in 9 patients. The peritoneal membrane was characterized as high (27.8%), high-average (33.3%), low-average (22.2%) and low transporter (16.7%). The weekly urea Kt/V was > 2.1 in all the evaluated patients. Blood pressure parameters above the 95th percentile despite the use of antihypertensive medication were observed in 5/30 patients, four of whom with CKD secondary to glomerulopathy. The initial and final Body Mass Index and weight for height ratio were preserved in 83.3% (25/30) patients. CONCLUSION: Elevated indexes of small solutes removal are easily attained in pediatric PD patients and do not imply optimal clinical management do not imply optimal climanagement.

Uso a longo prazo de enalapril e hidroclorotiazida em dois pacientes com novas mutações com doença de Dent tipo 1 / The long-term use of enalapril and hydrochlorothiazide in two novel mutations patients with Dent's disease type 1

A doença de Dent é uma tubulopatia ligada ao X causada por mutações no gene que codifica o canal de cloro CLCN-5 e é caracterizada por proteinúria de baixo peso molecular, hipercalciúria, nefrocalcinose e insuficiência renal. Vários casos têm sido descritos, nos quais o único sintoma na apresentação foi proteinúria assintomática e glomerulosclerose global ou segmentar. A insuficiência renal nesses pacientes pode ser causada pela hipercalciúria e proteinúria persistente. Portanto, o inibidor da enzima de conversão da angiotensina e os tiazídicos poderiam ser úteis. O objetivo desta pesquisa é relatar os efeitos destas drogas em dois pacientes com doença de Dent tipo 1 com mutações novas. Neste relato não foram observadas correlações significativas entre dose de hidroclorotiazida e calciúria e entre enalapril e proteinúria. Este achado é importante, pois, sendo pacientes poliúricos, o uso destas drogas poderia prejudicar a função renal.

Dent's disease type 1 is an X-linked tubular disease caused by mutations in the renal chloride channel CLCN-5, and it is characterized by low molecular weight proteinuria, hypercalciuria, nephrocalcinosis, and renal failure. Several cases have been described in which the only presenting symptoms were asymptomatic proteinuria, and focal segmental or global glomerulosclerosis. The renal failure in these patients may be caused by hypercalciuria and persistent proteinuria. Therefore, angiotensin converse enzyme inhibitor and thiazides could be useful. Our aim is to report the effects of these drugs in two novel mutations patients with Dent's disease type 1. In this report, no significant correlations between dosage of hydrochlorothiazide and calciuria and no significant correlations between proteinuria and dosage of enalapril were detected. This is important since these are polyuric patients and these drugs could be dangerous to their renal function.

Home and ambulatory blood pressure to identify white coat and masked hypertension in the pediatric patient.

OBJECTIVE: To evaluate the effect of the environment and the observer on the measurement of blood pressure (BP) as well as to compare home BP (HBP) and ambulatory BP (ABP) measurements in the diagnosis of white coat hypertension (WCH) and masked hypertension (MH) in children and adolescents with hypertension (HT). METHODS: BP of 40 patients with HT (75% of which had secondary HT and were on antihypertensive medication), mean age 12.1 years was evaluated through casual measurements at the clinic and at the HT unit, HBP for 14 days with the OMRON HEM 705 CP monitor (Omron, Tokyo, Japan) and ABP performed with SPACELABS 90207 (Spacelabs, Redmond, WA), for 24 h. RESULTS: HT was diagnosed at the doctor's office by ABP and HBP in 30/40, 27/40, and 31/40 patients, respectively. Based on office BP and ABP, 60% of patients were normotensive, 17.5% HT, 7.5% had WCH, and 15% had MH, whereas based on office BP and HBP 65, 12.5, 10, and 12.5% of patients were classified according to these diagnoses, respectively. There was considerable diagnostic agreement of HT by ABP and HBP (McNemar test, P < 0.01) (κ = 0.56). CONCLUSION: In hypertensive children and adolescents, HBP and ABP present comparable results. HBP appears to be a useful diagnostic test for the detection of MH and WCH in pediatric patients.

Quality of life of pediatric patients with lower urinary tract dysfunction and their caregivers.

The interest in quality of life (QoL) studies has increased as they are useful instruments to evaluate and compare medical care delivery and the impact of health interventions. The perception of QoL differs among individuals. Its characterization is especially difficult in the pediatric age group as each developmental stage presents specific demands. The prevalence of congenital lower urinary dysfunction is high and their management changes the daily routine of the patients and their families. In a cross-sectional study, we evaluated the QoL of 28 children and adolescents with urinary malformations and their caregivers using the Autoquestionnaire Qualité de Vie Enfant Imagé (AUQUEI) and Short-Form 36 (SF-36), respectively, and compared the results with 38 healthy control age-paired children/caregivers. Four questions were added to patients' questionnaire to evaluate issues related to their urological management. Our results show lower AUQUEI total scoring in the patients' group (p<0.0213, Fisher's exact test), who also present problems in dealing with social aspects, such as being at classroom, manifest negative feelings in relation to diurnal urinary losses but seem to be well adapted to intermittent urethral catheterization. A tendency for worse QoL scores in the patients' group caregivers was detected in the SF-36 pain and physical limitation domains.

Report of a Brazilian multicenter study on nephropathic cystinosis.

INTRODUCTION: The Brazilian Multicenter Nephropathic Study Group, founded in 1999, is currently composed of 16 pediatric nephrology units, which are coordinated by the Pediatric Nephrology Unit of Instituto da Criança--HCFMUSP. This Study Group intends to better know our patients, their special characteristics and facilitates the treatment. OBJECTIVE: To present an update on the demographics of the ongoing study participants with interest on renal function status, response to therapy, and extra-renal complications. METHODS: Patient recruitment to the study is based on informed consent and has been supported by the Brazilian Society of Nephrology, by the creation of an electronic homepage and by the participation in medical meetings and publications in medical periodicals. Our study protocol involves the initial and follow-up questionnaire, the measurement of intraleukocyte cystine content, initiation and follow-up therapy with cysteamine, and clinical patient follow-up based on a protocol of subsidiary exams. RESULTS: We identified 102 patients (42 females) with nephropathic cystinosis in Brazil since 1999. Forty-six children are followed at the Instituto da Criança/SP, 15 at the Hospital Pequeno Príncipe/PR, 12 at the UNICAMP/SP, 10 at the Unidade de Transplante Renal - HCFMUSP/SP and 3 at the Santa Casa/SP; the remaining patients are followed at the Instituto da Criança and at their respective doctors' offices in different nephrology services in Brazil. Of these patients, 23/102 (22.5%) have normal renal function, 19/102 (18.6%) are in chronic renal failure with conservative treatment, 26/102 are on dialysis (18 on peritoneal dialysis and 8 on hemodialysis), and 34/102 received a renal transplant. The extra-renal involvement diagnosed was: hypothyroidism in 63 patients, diabetes mellitus in 8 patients, muscular involvement in 7 patients, a compromised central nervous system in 5 patients, hepatic complications in 5 patients, and deglutition dysfunction in 2 patients. During this period, 10/102 patients died. Cysteamine has been used by 81/102 patients (20 children started the therapy under 2 years of age). Growth parameters were improved by cysteamine, mainly in the youngest patients. We used recombinant growth hormone in 15 patients with persistent low growth velocity and stature z score under 2.5%. We could also observe a delay in appearance of extra-renal complications in patients receiving cysteamine. CONCLUSION: Our study demonstrates the importance of a multi-center study for recruitment, diagnosis and management of rare diseases. This study promotes access to the adequate treatment with profound impact on the quality of life.

Nephrogenic diabetes insipidus (NDI): clinical, laboratory and genetic characterization of five Brazilian patients.

INTRODUCTION: Nephrogenic diabetes insipidus is characterized by a lack of response in the distal nephron to the antidiuretic hormone arginine vasopressin. Manifestations include polyuria, polydipsia, hyposthenuria, recurrent episodes of dehydration and fever and growth failure. Most cases are caused by mutations in the AVPR2 gene. The mutant receptors are trapped intracellularly. METHOD: We studied five boys using clinical, laboratory and molecular data. The mean age at diagnosis was 14.6 months (range 6 to 24) and 12.2 years (7.8 to 19) after the follow-up period. The mean period of follow-up was 132.2 +/- 50.9 months. RESULTS: The geometric means of the z-scores of weight and stature were -4.5 and -3.6, respectively, at diagnosis. At the last medical appointment, the z-scores of weight and stature were -0.3 and -0.9, respectively. Three patients were diagnosed with ureterohydronephrosis and exhibited increased post-void urine volume. Mutations in the AVPR2 gene were found in all patients, and the carrier status was confirmed in four of five cases. Two unrelated children presented identical mutations (S167L) in arginine vasopressin R2. Two of the patients had a mutation that has already been described in other Brazilian families (R337X), and one patient showed a de novo mutation (Y128D) in arginine vasopressin R2, since his mother's molecular analysis was normal. The recurrence risk for this family was significantly reduced. CONCLUSION: This study reports the clinical and laboratory characterization of Nephrogenic diabetes insipidus and reiterates the importance of the genetic basis that underlies the disease diagnosis and genetic counseling.