Ambulatory hypertension in a pediatric cohort of sickle cell disease.

Hypertension is an established risk factor for subsequent cardiovascular and renal disease in children as well as adults. Sickle cell disease (SCD) is a genetic disorder associated with chronic hemolytic anemia with the major manifestation of vaso-occlusive crises. Although this disease entity involves most organ systems causing vascular and pulmonary injury, little is known about blood pressure (BP) levels or prevalence of hypertension in children with SCD. A cross-sectional study was conducted on 56 children with SCD (54 with hemoglobin SS disease; 2 with hemoglobin Sß0 thalassemia; 29 females). Study participants underwent 24-hour ambulatory BP monitoring (ABPM). Serum creatinine and cystatin C were obtained to assess estimated glomerular filtration rate with age-based formulas. A random urine sample was obtained to estimate urine osmolality and urine albumin to creatinine ratio. Mean age range was 11.9 (±4.5) years. Seventeen participants (30%) met criteria for hypertension based on ABPM. Of the 17 participants classified with hypertension, three had office hypertension with ambulatory hypertension, and 14 had masked hypertension detected on ABPM. Another 28 participants (50%) had some abnormal ABPM parameters in the form of either prehypertension and/or lack of normal nocturnal dipping status. The prevalence of confirmed hypertension, largely manifest by masked hypertension, is high in children, as young as 6 years of age with SCD. Early identification of hypertension in SCD children can confer benefit as it is an important modifiable risk factor for progression of cardiovascular and renal disease.

Outcomes of dialysis initiated during the neonatal period for treatment of end-stage renal disease: a North American Pediatric Renal Trials and Collaborative Studies special analysis.

OBJECTIVE: We sought to determine the outcomes of initiating long-term dialysis of neonates and children aged > 1 to 24 months with end-stage renal disease. PATIENTS AND METHODS: By querying the North American Pediatric Renal Trials and Collaborative Studies database, we obtained information on 193 neonates (< or = 1 month of age) and 505 children (> 1-24 months of age) with a presumptive diagnosis of end-stage renal disease who initiated long-term dialysis. Dialysis characteristics and likelihood of hospitalization were compared using the chi2 test, and duration of hospitalization was compared using the Wilcoxon 2-sample test. Product limit methods were implemented, and the log rank test was used to compare time-to-event analyses. Multivariate analyses were performed using Cox proportional hazards models. RESULTS: Neonates with end-stage renal disease were more likely to receive peritoneal dialysis versus hemodialysis than older children with end-stage renal disease. Moreover, neonates who initiated dialysis during the first month of life were just as likely to terminate dialysis as were the older children. Rates of renal transplantation were significantly lower in the neonates compared with the older children, but neonates were more likely to recover function of the native kidney. Although neonates were more often hospitalized, their overall risk of mortality was similar to that observed in older children. CONCLUSIONS: Neonates with a presumptive diagnosis of end-stage renal disease may initiate long-term dialysis during the first month of life with outcomes comparable to those of patients who initiate dialysis later in infancy.

Persistent secondary hyperparathyroidism after renal transplantation in children.

Secondary hyperparathyroidism (HPTH) is a frequent complication of chronic kidney disease (CKD). Renal transplantation corrects the biochemical abnormalities that cause HPTH; however, HPTH persists in some patients. The factors that contribute to the persistence of HPTH after transplantation in children are poorly understood. We examined 57 children who underwent renal transplantation and determined whether baseline clinical and biochemical parameters could predict the persistence of HPTH at 1 year post-transplantation, using multivariate logistic regression. At the time of transplantation, serum parathyroid hormone (PTH) levels were >300 pg/ml in 60%, 150-300 pg/ml in 17%, and <150 pg/ml in 23% of recipients. HPTH (PTH >73 pg/ml) persisted in 78% of patients at 6 months and in 56% at 1 year after transplant. Older age at transplantation was the strongest predictor of HPTH at 1 year (OR=1.17, P<0.05). After adjustment for age, other baseline clinical or laboratory parameters were not predictive of HPTH at 1 year. The relationship between older age and persistent HPTH may be explained by longer duration of CKD. Given the potential morbidities associated with persistent HPTH, the role of interventions that would prevent or reverse persistent HPTH post-transplantation requires further investigation.

Nephrogenic syndrome of inappropriate antidiuresis.

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a common cause of hyponatremia. We describe two infants whose clinical and laboratory evaluations were consistent with the presence of SIADH, yet who had undetectable arginine vasopressin (AVP) levels. We hypothesized that they had gain-of-function mutations in the V2 vasopressin receptor (V2R). DNA sequencing of each patient's V2R gene (AVPR2) identified missense mutations in both, with resultant changes in codon 137 from arginine to cysteine or leucine. These novel mutations cause constitutive activation of the receptor and are the likely cause of the patients' SIADH-like clinical picture, which we have termed "nephrogenic syndrome of inappropriate antidiuresis."

Growth and metabolic consequences of bladder augmentation in children with myelomeningocele and bladder exstrophy.

OBJECTIVE: Bladder augmentation using intestinal segments is reported to cause decreased linear growth in bladder exstrophy and myelomeningocele patients. We studied changes in calcium metabolism, height, bone chemistry, and bone density in exstrophy and myelomeningocele patients after bladder augmentation. METHODS: Thirty-three patients were prospectively admitted to the Pediatric Clinical Research Center at the University of California San Francisco for 24 hours. Blood and urine were analyzed for electrolytes, and serum was obtained for markers of calcium metabolism. Dual radiograph bone densitometry of the forearm was performed. Myelomeningocele patients were compared with nonaugmented myelomeningocele patients matched by age, gender, level of defect, and ambulatory status. Exstrophy augmented patients were compared with nonaugmented exstrophy patients. The bone densities in both groups were compared with normal children. Laboratory values and percentile heights were statistically analyzed using the Student t test; bone densitometry was analyzed using the Tukey test. RESULTS: Twenty-two patients with myelomeningocele and 11 with bladder exstrophy were studied. Mean follow-up was 3.7 years postaugmentation (range: 1-13 years). The results indicate a significant difference in serum bicarbonate and chloride levels between myelomeningocele patients who underwent ileal augmentation and those who did not. Although this may be indicative of chronic metabolic acidosis, there was no affect on growth or bone density when compared with controls. There were no other significant differences in laboratory values, or percentile heights, nor were any differences noted in patients who underwent gastrocystoplasty. In the exstrophy group, there were no observable differences in percentile height or laboratory values between the augmented and nonaugmented group. There were no significant differences in bone density between these 2 groups when matched for age and gender. No significant difference was seen in bone density when these groups were compared with normal children. CONCLUSION: Bladder augmentation is safe and does not impact negatively on the linear growth or bone densities of patients with myelomeningocele or bladder exstrophy.

Glucocorticoids prolong Ca(2+) transients in hippocampal-derived H19-7 neurons by repressing the plasma membrane Ca(2+)-ATPase-1.

Calcium ions (Ca(2+)) play an important role in mediating an array of structural and functional responses in cells. In hippocampal neurons, elevated glucocorticoid (GC) levels, as seen during stress, perturb calcium homeostasis and result in altered neuronal excitability and viability. Ligand- and voltage-gated calcium channels have been the presumed targets of hormonal regulation; however, circumstantial evidence has suggested the possibility that calcium extrusion might be an important target of GC regulation. Here we demonstrate that GC-induced repression of the plasma membrane Ca(2+)-ATPase-1 (PMCA1) is an essential determinant of intracellular Ca(2+) levels ([Ca(2+)](i)) in cultured hippocampal H19-7 cells. In particular, GC treatment caused a prolongation of agonist-evoked elevation of [Ca(2+)](i) that was prevented by the expression of exogenous PMCA1. Furthermore, selective inhibition of PMCA1 using the RNA interference technique caused prolongation of Ca(2+) transients in the absence of GC treatment. Taken together, these observations suggest that GC-mediated repression of PMCA1 is both necessary and sufficient to increase agonist-evoked Ca(2+) transients by down-regulating Ca(2+) extrusion mechanisms in the absence of effects on calcium channels. Prolonged exposure to GCs, resulting in concomitant accumulation of [Ca(2+)](i), is likely to compromise neuronal function and viability.

Increased incidence in post-transplant diabetes mellitus in children: a case-control analysis.

There is limited information regarding the incidence and features of post-transplant diabetes mellitus (PTDM) in pediatric renal transplant recipients. We noted a recent increased frequency of PTDM and reviewed charts of children who underwent renal transplantation from 1 September 1986 to 31 August 1999 to characterize the risk factors and natural history of PTDM. Sixteen children were identified with PTDM, and were each matched with two transplanted controls who did not develop PTDM. Clinical presentation varied from asymptomatic hyperglycemia to hyperosmolar dehydration or diabetic ketoacidosis. The mean time from transplantation to PTDM presentation was 1.2 years (range 1 day to 6.2 years). Significant risk factors for PTDM included: first degree family history of type 2 DM [odds ratio (OR) 23.9]; second degree family history of type 2 DM (OR 5.8); tacrolimus use (OR 9.1 versus cyclosporin); and hyperglycemia in the 2 weeks immediately after transplantation (OR 4.7). Seven of eight children with persistent PTDM continue to receive insulin. Patients with persistent PTDM had later onset disease (mean 1.9 years) compared to those with transient PTDM (0.3 years), suggesting different pathophysiologic processes. We suggest that all children undergoing renal transplantation be screened routinely for PTDM after transplantation, and that such patients may benefit from the avoidance of tacrolimus, as it may cause permanent beta-cell injury.