The role of renal biomarkers to predict the need of surgery in congenital urinary tract obstruction in infants.

INTRODUCTION: The diagnosis of renal function impairment and deterioration in congenital urinary tract obstruction (UTO) continues to be extremely challenging. The use of new renal biomarkers in this setting may favor early renal injury detection, allowing for a reliable choice of optimal therapeutic options and the prevention or minimization of definitive renal damage. OBJECTIVE: The aim of the study was to investigate a selection of promising biomarkers of renal injury with the intention of evaluating and comparing their profile with clinically based decisions for surgical intervention of infants with congenital obstructive uropathies. STUDY DESIGN: The first-year profile of renal biomarkers, serum creatinine (sCr), serum and urine cystatin C (CyC), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), transforming growth factor beta-1 (TGF-ß1), retinol-binding protein (RBP), and microalbuminuria (µALB), was analyzed in a cohort of 37 infants with congenital UTO, divided into three subgroups, 14 cases with grade III unilateral hydro(uretero)nephrosis, 13 cases with grade III bilateral hydro(uretero)nephrosis, and 10 cases with low urinary tract obstruction (LUTO), compared with 24 healthy infants matched by gestational age and birth weight. Serum and urine samples were stored at -70 °C and thereafter analyzed by quantitative enzymatic immunoassay. RESULTS: Compared with the control group (Figure), all renal biomarker values were significantly increased in patients (P ≤ 0.02). In the unilateral hydronephrosis and LUTO group, RBP (P ≤ 0.043), NGAL (P ≤ 0.043), KIM-1 (P ≤ 0.03), and TGF-ß1 (P ≤ 0.034) values dropped significantly after surgery. Neutrophil gelatinase-associated lipocalin alone and in combination with urine and serum CyC demonstrated the best performance in determining the need for surgery (area under the curve, 0.801 and 0.881, respectively). Biomarker profile analysis was suggestive of surgical intervention in 55.4% (7/13) of non-operated cases, and most of the biomarker values were above the cutoff levels within at least 3 months before the clinically based surgical decision in 58% (14/24) of all operated patients. DISCUSSION: To the best of the authors' knowledge, this is the first study to present the clinical use of selected group of serum and urinary biomarkers in the setting of UTO to distinguish between patients who would benefit from surgery intervention. The most promising results were obtained using NGAL, RBP, TGF-ß1, and KIM-1, especially in the unilateral hydro(uretero)nephrosis and LUTO subgroups when compared with the control group. CONCLUSIONS: Urine biomarkers, alone and in combination, demonstrated high potential as a non-invasive diagnostic tool for identifying infants who may benefit from earlier surgical intervention.

Children with nocturnal enuresis have posture and balance disorders.

INTRODUCTION: Integration of the neuromuscular system is required for maintaining balance and adequate voiding function. Children with enuresis have delayed maturation of the motor cortex, with changes in the sensory and motor systems. Along with various alterations, including the genetic, hormonal, behavioral, and sleep disturbances, and neuromotor and sensory deficits associated with nocturnal enuresis (NE) in children and adults, a consistent alteration in the posture of children with NE has been observed in the current practice. Because posture and the balance control system are strongly connected, this study aimed to investigate posture and balance in children and teenagers with NE. MATERIAL AND METHODS: A total of 111 children with enuresis were recruited to the enuretic group (EG) and 60 asymptomatic children made up the control group (CG). The participants were divided into two age subgroups: (A) 7-11 years old, N = 77 for EG/A, N = 38 for CG/A; and (B) 12-16 years old, N = 34 for EG/B, N = 22 for CG/B. Balance was assessed using an electronic force plate (100 Hz) to calculate the area of the center of pressure (COP) displacement. The COP is the point that results from the action of vertical forces projected onto the force plate. Sensory integration was analyzed using a 60-s trial with the subject standing under four conditions: (1) eyes open, stable surface; (2) eyes closed, stable surface; (3) eyes open, unstable surface; (4) eyes closed, unstable surface. Posture was assessed by placing reflective anatomical landmarks on the anterior superior iliac spine, the posterior superior iliac spine, the greater trochanter, and lateral malleolus. A photograph was taken while the subject stood quietly. The angles were obtained from landmark connections using software to assess the following posture variables: pelvic ante/retroversion and pelvic ante/retropulsion. RESULTS: The EG showed a greater area of COP displacement compared with the CG under all four sensory conditions and both subgroups, except for EG/B in condition 3. Regarding posture, EG showed higher pelvic anteversion angles than CG. CONCLUSIONS: Enuretic children showed forward inclination of the pelvis and had worse balance compared with control children.

Home blood pressure monitoring in paediatric chronic hypertension.

Blood pressure (BP) measurement is the basis for the diagnosis and management of arterial hypertension. The aim of this study was to compare BP measurements performed in the office and at home (home blood pressure monitoring, HBPM) in children and adolescents with chronic arterial hypertension. HBPM was performed by the patient or by his/her legal guardian. During a 14-day period, three BP measurements were performed in the morning or in the afternoon (daytime measurement) and in the evening (night-time measurement), with 1-min intervals between measurements, totalling six measurements per day. HBPM was defined for systolic blood pressure (SBP) and diastolic blood pressure (DBP) values. HBPM was evaluated in 40 patients (26 boys), mean age of 12.1 years (4-18 years). SBP and DBP records were analysed. The mean differences between average HBP and doctor's office BP were 0.6+/-14 and 4+/-13 mm Hg for SBP and DBP, respectively. Average systolic HBPM (daytime and night-time) did not differ from average office BP, and diastolic HBPM (daytime and night-time) was statistically lower than office BP. The comparison of individual BP measurements along the study period (13 days) by s.d. of differences shows a significant decline only for DBP values from day 5, on which difference tends to disappear towards the end of the study. Mean daytime and night-time SBP and DBP values remained stable throughout the study period, confirming HBPM as an acceptable methodology for BP evaluation in hypertensive children and adolescents.

Percutaneous ultrasound-guided renal biopsy in children - safety, efficacy, indications and renal pathology findings: 14-year Brazilian university hospital experience.

INTRODUCTION: Pediatric percutaneous renal biopsy (Bx) is a routine procedure in pediatric nephrology to obtain renal tissues for histological study. We evaluated the safety, efficacy, indications and renal findings of this procedure at a tertiary care pediatric university hospital and compared our findings with the literature. METHODS: Retrospective study based on medical records from January 1993 to June 2006. RESULTS: In the study period, 305 Bx were performed in 262 patients, 127 (48.5%) male, aged 9.8 A+/- 4.2 years. A 16-gauge needle was utilized in 56/305 Bx, an 18-gauge needle in 252/305 Bx (82.6%). 56.1% Bx were performed under sedation plus local anesthesia, 43.9% under general anesthesia. The number of punctures per Bx was 3.1 A+/- 1.3. Minor complications occurred in 8.6% procedures. The 16-gauge needle caused a higher frequency of renal hematomas (p = 0.05). The number of glomeruli per puncture was >or= 5 in 96.7% and >or= 7 in 92%. Glomeruli number per puncture and frequency of complications were not different according to the type of anesthesia used. A renal pathology diagnosis was achieved in 93.1% Bx. The main indications of Bx were nephrotic syndrome (NS), lupus nephritis (LN) and hematuria (HE). The diagnosis of minimal change disease (MCD) (61.3%), class V (35.6%) and IgA nephropathy (26.3%) predominated in NS, LN and HE patients, respectively. CONCLUSION: Pediatric real-time ultrasound-guided percutaneous renal biopsy was safe and effective. The main clinical indications for Bx were NS and LN, the predominant renal pathology diagnoses were MCD and class V LN.

Neonatal arterial hypertension in nephro-urological malformations in a tertiary care hospital.

An increase in the survival of neonates with antenatal diagnosis of malformations was achieved by the recent technical advances in neonatal intensive care units. The aim of this article is to describe the experience with neonatal arterial hypertension, in newborns with nephro-urological malformations, in a tertiary care referral Nursery, in a period of 4 years. Newborn medical records from the Nursery Annex to the Maternity of Hospital das Clinicas, School of Medicine, University of Sao Paulo, with the diagnosis of nephro-urological malformations and systemic arterial hypertension (SAH) at hospital discharge, in a period from January 1999 to January 2003, were retrospectively analysed. Among 10.278 live newborns in the studied period, 15 (0.15%) newborns were compatible with our inclusion criteria. Of these 15 newborns, 12 (80%) were male and three were premature (20%). In relation to aetiology, 13 (87%) showed urological malformations, 1 (6%) chronic renal insufficiency secondary to kidney dysplasia and one (6%) autosomal recessive polycystic kidney disease. SAH control was achieved with monotherapy in eight patients (53%), five patients (33%) needed an association of two drugs (calcium-channel blocker and angiotensin converting enzyme (ACE) inhibitor), one child used three types of antihypertensive drugs (calcium-channel blocker, ACE inhibitor and hydrochlorothiazide) for pressoric control and one child's blood pressure (BP) was controlled exclusively by peritoneal dialysis. The incidence of nephro-urological malformations in our service during the studied period was 0.89%. SAH incidence among these newborns was 19%. Our data reinforce previous studies pointing to the necessity to consider children with nephro-urological malformations as a risk group for SAH, who should have the BP evaluated since the neonatal period.

Comparison between casual blood pressure and ambulatory blood pressure monitoring parameters in healthy and hypertensive adolescents.

Casual blood pressure measurements were compared with mean ambulatory blood pressure values during wakefulness and sleep in 45 normotensive and 30 hypertensive adolescents of both sexes aged 10-18 years. Two sets of auscultatory casual blood pressure were obtained, one in a pediatric office setting (office blood pressure), performed by the physician, and one in the ambulatory blood pressure monitoring (ABPM) unit, performed by a trained nurse, prior to the initiation of ABPM (pre-ABPM blood pressure). In normotensive and hypertensive subjects of both sexes, the mean office systolic blood pressure (SBP) was lower than the mean pre-ABPM SBP, and the mean office diastolic blood pressure (DBP) was lower than the mean pre-ABPM DBP. In normotensive participants, the mean pre-ABPM SBP/DBP was lower than the mean ABPM SBP/DBP while awake, the mean ABPM SBP/DBP during sleep being lower than the mean ABPM SBP/DBP values while awake and the mean pre-ABPM SBP/DBP. No statistical difference was demonstrated between the mean office SBP and the mean ABPM SBP during sleep, the mean ABPM DBP during sleep being lower than the mean office DBP. The hypertensive adolescents presented a blood pressure profile similar to that of the normotensive group, albeit shifted upwards, with no significant difference between the mean pre-ABPM SBP and the mean ABPM SBP while awake but a higher mean pre-ABPM DBP than mean ABPM DBP while awake. This study suggests that, by evaluating the casual blood pressure in different environment/observer situations, the power of casual blood pressure to predict inadequate blood pressure control, manifested as abnormal ABPM parameters, can be enhanced. Our data indicate ABPM to be the method of choice for the early diagnosis and adequate follow-up of adolescent hypertension.

White coat hypertension in adolescents.

BACKGROUND: Although white coat hypertension (WCH) seems to occur in 20% or more of the adult hypertensive population, this clinical condition has rarely been described in adolescents. DESIGN: Routine use of ambulatory blood pressure monitoring (ABPM) procedure as part of the investigation of arterial hypertension in adolescents. METHODS: Office blood pressure was checked after 5 minutes of rest in the seated position by the auscultation method and ABPM was performed with oscillometrical equipment (SpaceLabs 90207, Redmond, Washington, USA). RESULTS: In the present study 6 adolescents (5 females, 3 white), suspected to suffer from arterial hypertension as judged by office blood pressure measurements, mean age 15.1 years (12.2 - 17.7), mean height 164.5 cm, mean weight 77.2 kg, mean body mass index 28.8 kg/m2 (25 - 35.2), were diagnosed with WCH using ambulatory blood pressure monitoring (ABPM). CONCLUSION: White coat hypertension should also be considered in the evaluation of arterial hypertension in adolescents.

Ambulatory blood pressure monitoring of chronically dialyzed pediatric patients.

BACKGROUND: Background Ambulatory blood pressure monitoring (ABPM) has been shown to be more representative of blood pressure levels in adult patients than are casual measurements of blood pressure. OBJECTIVE: To evaluate, by means of ABPM, the behavior of blood pressure in children with chronic renal failure submitted to continuous ambulatory peritoneal dialysis and compare the results with casual blood pressure monitoring measurements. DESIGN: Evaluation of blood pressures in chronically dialyzed pediatric patients by ABPM. METHODS: Ten pediatric patients, treated by continuous ambulatory peritoneal dialysis were evaluated by ABPM using the oscillometric SpaceLabs 90207 monitor, every 10 min during the day and every 15 min during the night, for 24h. RESULTS: Six of 10 patients were found normotensive by office measurement of blood pressure; four of 10 patients were found hypertensive by casual measurements of blood pressure. With ABPM we obtained a mean success rate of 92.5%, confirmed hypertension in all the patients classified hypertensive in terms of office readings and reclassified six of six patients from normotensive to hypertensive. The mean systolic and diastolic physiologic falls in blood pressure at night were respectively by 10 and 15%. At the time of the ABPM study end-organ damage was present in two patients judged to be normotensive in terms of office blood pressures. CONCLUSION: Casual recordings of blood pressure are not representative of average blood pressure in dialyzed pediatric patients. ABPM seems to be a useful diagnostic aid for assessing treatment of hypertension in children with end-stage renal disease.

Population studies of ambulatory blood pressure monitoring in Brazilian children.

BACKGROUND: The determination of hypertension in a given population depends on the knowledge of population norms for blood pressure. This is true for both casual blood pressure (CBP) measurements and the newest and most promising technology of ambulatory blood pressure monitoring (ABPM). OBJECTIVE: To design an ambitious multinational co-operative study to determine normal blood pressure data in Brazilian children. METHODS: The study was designed to determine normative data for CBP, using the Task Force technical recommendations for age-, sex- and height-percentile-specific blood pressure values. The proposed procedure is as follows. ABPM will be studied in a random subgroup of individuals, to develop similar normative data. These data will be correlated to CBP measurements and to echocardiographic findings as a measure of end-organ damage. All patients who are diagnosed by CBP measurement to be hypertensive will also be studied by ABPM, and studies of target-organ damage will be performed. Family and medical histories will be evaluated by questionnaire and first-degree relatives will be evaluated for CBP measurement. Hypertensive patients will form a cohort for long-term follow-up. These data will be the foundation for studies of hypertension in Brazilian children.

Primary hyperparathyroidism in children: patient report and review of the literature.

Although primary hyperparathyroidism has rarely been described in pediatric patients, prompt diagnosis can avoid severe CNS and metabolic consequences. The aim of this paper is to report a 6 year-old girl whose first symptoms began at eight days of age with cyanosis, hypotonia, and upward gaze deviation. At 4 months, she was admitted due to neurologic disorders and recurrent infection, but the definite diagnosis was made only six years later. Her serum calcium levels are among the highest ever reported in the medical literature, reaching 25.5 mg/dl (6.36 mmol/l). Hypercalcemia, very high levels of parathormone (1550 ng/l--normal range 10-65) and bone deformities posed no problem to diagnosis when she first came to our attention. Nephrocalcinosis and impaired renal function were detected and this child had to be treated with diuretics (furosemide) and hydration that were able to lower her serum calcium levels. Imaging studies including 99mTc-sestamibi scan were not diagnostic. At surgery, the four parathyroid glands were mildly enlarged, with primary hyperplasia. The four glands were removed, cryopreserved, and 14 fragments (1 mm each) were autotransplanted to the braquioradial muscle of the left forearm. After a first phase of hypocalcemia (hungry-bone syndrome), treated with calcium and calcitriol, the calcium levels stabilized. The question is whether she will experience some degree of recovery from her neurological problems, since her severely high calcium levels have been maintained for such a long time.

[Hematuria in children: retrospective study of 128 pediatric patients] / Hematúria na criança: estudo retrospectivo de 128 casos.

OBJECTIVE: To evaluate the diagnostic frequency of the various diseases associated with the development of hematuria in children, in a pediatric nephrology unit pertaining to a university hospital. METHODS: The clinical records of 128 children (70 male, 50 female) who presented intermittent/persistent macroscopic hematuria or persistent microscopic hematuria as the chief clinical complaint/finding, in the period of 1978-1995, were retrospectively analyzed. This evaluation was performed with special attention to the patientacute;s clinical history, physical examination, personal and family morbid history information. Patients whose investigation was not complete were not considered for analysis. The mean age on presentation was 8.2 years (5 months - 16 years) and the mean period of observation was 3.2 years (1 month-15 years). RESULTS: Macroscopic hematuria occurred in 104 patients and persistent microscopic hematuria was present in 24 patients. Urinary metabolic disturbances and urinary lithiasis, alone or in association, were diagnosed in the majority of the patients (65.5%). Hypercalciuria was the urinary metabolic disturbance (90.1%) mostly detected, either alone (73.2%) or in association with hyperuricosuria (16.9%). A positive family history of lithiasis was reported in 32.1% of the patients in which the diagnosis of lithiasis/urinary metabolic disturbance was confirmed. Glomerulopathies were diagnosed in 25% of the patients, with the predominance of post-infectious acute glomerulonephritis (11 patients, 34%). In 6 children, the etiology of hematuria was not elucidated, despite extensive investigation, including renal biopsy.CONCLUSION: The authors present an algorithm for the diagnosis of hematuria in children and suggest that in cases of isolated hematuria, presenting without clinical clues to the possible etiology, laboratory investigation should be started with the evaluation of urinary metabolic disturbances / lithiasis.

[Ambulatory blood pressure monitoring in normal adolescents]. / Monitorização ambulatorial da pressão arterial em adolescentes normais.

PURPOSE: To evaluate technical aspects of ambulatory blood pressure monitoring (ABPM) in normal adolescents. METHODS: Forty five normal adolescents (27 female), 10-18 years old. RESULTS: ABPM recordings showed a mean of 90% successful readings; 30% of the patients complained of sleep disruption related to the functioning of the ABPM monitor; the mean systolic, diastolic and heart rate fall during sleep was 13%, 23% and 24% respectively; the mean systolic and diastolic blood pressure load, while awake, was in male adolescents 25.4 +/- 27.7% and 11.8 +/- 14.6%, and in female adolescents, 17.5 +/- 18.7% and 11.8 +/- 11.4%, respectively; the mean systolic and diastolic blood pressure load, while asleep, was in male adolescents 15.4 +/- 22.9% and 2.8 +/- 4.9% and, in female adolescents, 10.5 +/- 18.2% and 1.8 +/- 2.7%, respectively; the mean diastolic values of the first two hours of recording were higher than the ones obtained during the rest of the hours of recording while awake; different mean systolic, diastolic and heart rate values were found during the afternoon and nocturnal sleep periods. CONCLUSION: ABPM was well accepted by the adolescent population, with good technical results.

Tratamiento quirúrgico de neuritis hansenianas / Surgical treatment of hansenian neuritis

Los autores analizan los problemas del tratamiento quirúrgico de las neuritis hansenianas. Se establecen los criterios que deben ser utilizados. Ubican la cirugía en el contexto terapéutico. Presentan ejemplos de su casuística. Se sugiere uniformar los criterios a fin de tornar comparativos los resultados

Tratamiento quirúrgico de neuritis hansenianas / Surgical treatment of hansenian neuritis

Los autores analizan los problemas del tratamiento quirúrgico de las neuritis hansenianas. Se establecen los criterios que deben ser utilizados. Ubican la cirugía en el contexto terapéutico. Presentan ejemplos de su casuística. Se sugiere uniformar los criterios a fin de tornar comparativos los resultados

Recombinant human growth hormone (rhGH) treatment of children undergoing peritoneal dialysis.

The authors studied the effect of recombinant growth hormone (rhGH) treatment on 5 growth retarded children, age 2 2/12 to 17 8/12 years, who had end-stage renal disease (ESRD) and were undergoing continuous cycling peritoneal dialysis (CCPD). Patients received 0.125 mg/kg of subcutaneous rhGH 3 times weekly. Accelerated height velocity compared to the previous year of CCPD was noted in 2 patients and improvement in the standard deviation score (SDS) as a parameter of improved growth velocity was noted in a third patient. This was associated with an increase in weight and improvement in the midarm muscle circumference (MAMC) suggesting an anabolic effect of rhGH treatment. Bone age advancement was consistent with the period of observation; no advancement greater than that expected for the increase in chronological age was observed. No significant side effects were attributable to rhGH therapy. These preliminary results indicate some growth retarded children without growth hormone deficiency with ESRD undergoing CCPD may respond to exogenous rhGH therapy with an acceleration in growth velocity: However, the failure to achieve uniform acceleration of height velocity indicates the need for controlled studies before rhGH can be recommended for all growth retarded children with ESRD undergoing peritoneal dialysis.

Accelerated growth after recombinant human growth hormone treatment of children with chronic renal failure.

We studied the effect of recombinant human growth hormone treatment on five boys, aged 4.6 +/- 1.8 years, who had chronic renal failure secondary to congenital renal diseases (mean creatinine clearance (+/- SD): 18.3 +/- 6.3 ml/min/1.73 m2 (0.32 +/- 0.11 ml/sec/1.73 m2]. Patients received 0.125 mg/kg of growth hormone three times per week for 1 year. Before beginning treatment, the children had a mean annual growth velocity of 4.9 +/- 1.4 cm/yr (range 3.0 to 6.3 cm/yr), with a mean standard deviation score for a height of -2.98 +/- 0.73 (range -2.16 to -3.59). At the end of therapy, the mean growth velocity had increased to 8.9 +/- 1.2 cm/yr (range 7.5 to 10.7 cm/yr), and the mean height standard deviation score improved to -2.36 +/- 0.83 (range -1.15 to -3.18). Bone age advancement was consistent with the period of growth. Routine laboratory determinations, including results of glucose tolerance testing, did not vary significantly from pretreatment levels. These preliminary data indicate that growth-retarded children with chronic renal failure can respond to exogenous growth hormone therapy with a marked acceleration in growth velocity.

Accelerated growth following treatment of children with chronic renal failure with recombinant human growth hormone (somatrem): a preliminary report.

Five male children with chronic renal failure (CRF) and growth retardation were treated with recombinant human GH (somatrem) three times weekly for 6 months. The patients ranged in age from 35 to 91 months and had a mean SD score for height of -3.03 +/- 1.0 at initiation of therapy. Their mean pretreatment height velocity was 4.94 +/- 1.40 cm/year for the year prior to somatrem treatment. Following 6 months of treatment all children had a significant increase in annual height velocity, with the mean annual value for the group being 10.08 +/- 1.97 cm/year (p less than 0.01). Glucose tolerance was monitored and was not significantly affected nor were there any other complications of note. These data indicate that somatrem can produce short-term accelerated height velocity in the child with growth retardation associated with CRF. The long-term benefits of therapy in this group of children is under investigation.