Contiguous gene deletion in a Chinese family with X-linked nephrogenic diabetes insipidus: challenges in early diagnosis and implications for affected families.

Nephrogenic diabetes insipidus (NDI) is a rare disorder of the renal collecting tubules, characterized by an inability to concentrate urine due to an impaired response to arginine vasopressin (AVP), resulting in dilute urine and polyuria. Causes of NDI are heterogeneous and diagnosing congenital NDI (cNDI) in young infants is clinically challenging, as typical symptoms are often unappreciated or inconspicuous. Instead, young infants may present with non-specific signs such as vomiting, poor feeding, failure to thrive, unexplained fevers, irritability, constipation or diarrhea. We report a 37-day-old infant who presented with polyuria and severe hypernatremic dehydration that was unresponsive to vasopressin. The patient was treated with amiloride, indomethacin and hydrochlorothiazide. Genetic analysis revealed a novel contiguous deletion involving the entire AVPR2 gene and the last exon of the adjacent ARHGAP4 gene. A study of the family confirmed the carrier status in the mother. This case illustrates the importance of molecular testing in confirming the diagnosis in the index patient, as well as in identifying asymptomatic at-risk female carriers so that appropriate genetic counselling can be given for reproductive planning. All pediatric patients with suspected cNDI should undergo genetic analysis for a definitive diagnosis.

Risk factors for damage in childhood-onset systemic lupus erythematosus in Asians: a case control study.

BACKGROUND: Accumulated damage is an important prognostic factor in systemic lupus erythematous. However, the pattern of disease damage and its risk factors have not been well studied in childhood-onset systemic lupus erythematosus (cSLE) in Asia. The objectives are to evaluate the pattern of damage and to identify the risk factors for accumulated damage in an Asian group of cSLE. METHODS: A retrospective chart review was conducted on a group of 59 patients with cSLE. Patient demographics and clinical variables were first collected at diagnosis. Over the course of their disease, clinical variables considered as risk factors for damage were also collected. Damage was measured using the Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI) for each patient at their last encounter. Based on their SDI scores, patients were then dichotomized to two groups: a group with presence of disease damage (SDI ≥1) and a group with absence of disease damage (SDI score = 0). Clinical variables including age at diagnosis, gender, ethnicity, disease duration, disease manifestations, laboratory values at diagnosis, disease activity at diagnosis and last encounter, major organ involvement, number of lupus flares, major infection, and intensity of immunosuppressive medications were compared between the two groups. Growth failure and estimated glomerular filtration rate (eGFR) were also analysed as secondary outcomes. RESULTS: After a median disease duration and follow up of 7.8 years, 39 patients (66.1%) had no disease damage while 20 patients (33.9%) had acquired disease damage. Disease damage most frequently occurred in the ocular (15.3%), neuropsychiatric (11.9%) and musculoskeletal (11.9%) domains. The most frequent forms of damage were cataracts (11.9%), and avascular necrosis (unilateral and bilateral combined 10.2%). After controlling for other variables, presence of neuropsychiatric manifestations remained the only statistically significant risk factor for damage. The rate of growth failure in our group of patients was 16%. Patients who experienced growth failure were significantly younger at disease diagnosis. The median age of diagnosis was 10 for those who experienced growth failure, whereas the median age of diagnosis was 13 for those who did not experience growth failure. Despite a high rate of renal involvement in the group (79.7%), renal damage was only seen in 3.2% of the patients. 91.5% of the studied group had normal eGFR of ≥90 ml/min/1.73m2 at their last follow up. CONCLUSION: This group of patients had a low rate of damage accrual, with one of the lowest rates in renal damage when compared to other cohorts reported. The presence of neuropsychiatric manifestations was identified as the most significant risk factor for disease damage, while the most frequent forms of damage were cataracts and avascular necrosis, which were both related to prolonged steroid use. Despite the limitations of this study, it highlights the need for larger prospective studies to understand the relationship between childhood-onset SLE and its resulting damage.

Vascular calcification in a young patient with end-stage renal disease.

Vascular calcification in children with long-standing dialysis is a unique phenomenon. Hyperphosphataemia and hyperparathyroidism are the major pathogenic risk factors. We describe a young patient with end-stage renal disease diagnosed since childhood and underwent prolonged dialysis therapy. He was admitted for recurrent episodes of acute joint pain. Investigations confirmed diffuse periarticular, vascular, and intracardiac calcifications which were rarely seen in the young population. He underwent parathyroidectomy and incidentally found to have a co-existing papillary carcinoma of thyroid. After parathyroidectomy, serial X-rays showed resorption of these calcifications.

Acute kidney injury in the paediatric intensive care unit: identification by modified RIFLE criteria.

OBJECTIVE: To evaluate the prevalence and outcome of acute kidney injury in paediatric intensive care units using the modified RIFLE score (pRIFLE). DESIGN: Historical cohort study. SETTING: A paediatric intensive care unit in a regional Hong Kong hospital. PATIENTS; All paediatric patients aged 1 month to 18 years admitted to a local paediatric intensive care unit in the years 2005 to 2007. MAIN OUTCOME MEASURES; For every paediatric intensive care unit admission, acute kidney injury was classified according to the pRIFLE criteria ("R" for risk, "I" for injury, "F" for failure, "L" for loss, and "E" for end-stage). Prevalence and outcome of acute kidney injury were therefore categorised according to the pRIFLE staging. RESULTS: A total of 140 such patient admissions constituted the study population. The point prevalence of acute kidney injury in these patients on admission was 46% (n=59), whilst 56% (n=78) endured acute kidney injury at some time during their paediatric intensive care unit stay. Worsening of pRIFLE grading during their intensive care unit admission was observed in 20% of the patients who had no acute kidney injury on admission, in 30% of those who had an initial "R" grade, and in 40% of those who had an initial "I" grade of acute kidney injury. Overall mortality in this cohort was 12%, which was significantly higher among patients with acute kidney injury. Having acute kidney injury of grade "F" on admission to the paediatric intensive care unit was an independent predictor of mortality (hazard ratio=5.94; 95% confidence interval, 1.06-33.36; P=0.043). CONCLUSION: Among critically ill paediatric patients, the pRIFLE score serves as a suitable classification of acute kidney injury when stratified according to clinical severity. It also provides prognostic information on mortality and renal outcomes.

Children on continuous renal replacement therapy: prognostic factors.

OBJECTIVES: To identify prognostic factors in children receiving continuous renal replacement therapy. DESIGN: Historical cohort study. SETTING: Neonatal and paediatric intensive care unit of a Hong Kong hospital. PATIENTS: Neonatal or paediatric patients who received continuous renal replacement therapy from January 1998 to December 2008. RESULTS: In all, 37 patients who received 39 episodes of continuous renal replacement therapy were identified. The male-to-female ratio was 1.5:1. Among the 39 episodes, 15 (39%) were performed on neonates with a mean birth weight of 2.6 (standard deviation, 0.7; range, 0.9-3.7) kg, and 24 (62%) were performed on paediatric patients with a mean age of 7.9 years (standard deviation, 6.4 years; range, 6 months to 18 years). The overall mortality was 41%; in the neonatal and paediatric groups it was 60% and 29%, respectively. There was no significant difference in the mean and maximal ultrafiltration rate in survivors and non-survivors. Multivariate analysis identified the PRISM III score and fluid overload as independent predictors of mortality. Kaplan-Meier survival analysis showed that patients with pre-continuous renal replacement therapy fluid overload of 5.5% or more was associated with reduced survival in the intensive care unit as compared to those having less severe fluid overload (P=0.011). In neonatal patients, there was a higher proportion with multi-organ failure and severe fluid overload. CONCLUSION: High PRISM III scores and the degree of pre-continuous renal replacement therapy fluid overload were independent predictors of mortality.

Pneumatosis intestinalis in a child with nephrotic syndrome and norovirus gastroenteritis.

We report a child with idiopathic nephrotic syndrome whose condition was complicated by extensive pneumatosis intestinalis during a nephrotic relapse. The concomitant use of steroid and immunosuppressive agents and a preceding norovirus gastroenteritis infection were identified as risk factors.

Effects of concomitant therapy with diltiazem on the lipid responses to simvastatin in Chinese subjects.

Diltiazem increases systemic exposure to simvastatin via inhibition of CYP3A. This study assessed the impact of this interaction on the lipid-lowering effects of simvastatin. Chinese patients with hypercholesterolemia were randomized to receive simvastatin 20 mg daily alone or together with diltiazem 60 mg 3 times daily for 4 weeks with a washout period of 4 weeks in an open-label, crossover study. Blood pressure, fasting serum lipid profile, and safety tests were determined at baseline and after each treatment period. Trough serum diltiazem was measured at the end of the 4-week combination treatment. In the 30 patients who completed the study, simvastatin treatment significantly reduced low-density lipoprotein cholesterol by mean (± standard error) 41.0% ± 2.2% (P < .001), and the combination with diltiazem showed an additional reduction of 1.66% (95% confidence interval: -4.63 to 7.96, P > .05). The additional change in low-density lipoprotein cholesterol with diltiazem showed a nonsignificant positive correlation with the trough serum diltiazem concentration (R(2) = 0.142, P = .058). Co-administration of diltiazem 60 mg 3 times daily with simvastatin 20 mg daily tended to increase the changes in lipid parameters in these Chinese subjects, but the effects did not reach significance.