Infant nephrolithiasis and nephrocalcinosis: Natural history and predictors of surgical intervention.

INTRODUCTION: Renal stone disease diagnosed in the first year of life is relatively uncommon. While risk factors such as low birth weight, furosemide exposure, and metabolic disorders are well established, there exists little information regarding resolution rates and need for surgical intervention. Our study objective was to evaluate urolithiasis and renal calcification resolution rates, time to resolution, and need for surgical intervention in children diagnosed in their first year of life. MATERIAL AND METHODS: REB approved retrospective chart review of children younger than 12 months of age (corrected for prematurity) diagnosed with nephrolithiasis and/or nephrocalcinosis in a tertiary pediatric hospital between April 2000 and August 2015 with a minimum 1-year follow-up period. Exact logistic regression was performed to assess the relationship between size of the largest stone (on either side) and the need for surgical intervention. Kaplan-Meier curves were constructed to examine time to stone resolution among those not requiring surgical intervention. RESULTS: 62 patients (61% male) were diagnosed with stones or nephrocalcinosis by ultrasound at a median age of 2.9 months. Of these, 37% had been admitted to the NICU because of prematurity, low birth weight or comorbidities. A total of 45 patients were found to have stones (Table); 35 of these had a stone at initial ultrasound and 10 initially diagnosed as nephrocalcinosis were later confirmed to have a stone. 67% of all stones were asymptomatic on presentation. Metabolic anomalies were present in 56% (35/62), and 16% (10/62) required medical treatment. Seven patients ultimately required surgical intervention. Stone size was found to predict the eventual need for surgical intervention (OR 3.52, 95% CI 1.47-12.78) for each 0.1 mm increase in diameter). Among patients not requiring surgical intervention (n = 38), the estimated median time to spontaneous resolution of urolithiasis was 1.1 years (95% CI 0.89-1.53, range 2 months-6 years) and 1.2 years for nephrocalcinosis (95% CI 0.59-2.13). CONCLUSIONS: Spontaneous resolution was a common outcome for newborns and infants diagnosed with urolithiasis in the first year of life, but high variability in time-to-resolution was observed. Only a small proportion who had confirmed stones on ultrasound required surgical intervention (15%), and large stone size was a predictive factor for surgery.

Defects in expression of genes related to synaptic vesicle trafficking in frontal cortex of Alzheimer's disease.

Loss of synapses correlates with cognitive decline in Alzheimer's disease (AD). However, molecular mechanisms underlying the synaptic dysfunction and loss are not well understood. In this study, microarray analysis of brain tissues from five AD cases revealed a reduced expression of a group of related genes, all of which are involved in synaptic vesicle (SV) trafficking. By contrast, several synaptic genes with functions other than vesicle trafficking remained unchanged. Quantitative RT-PCR confirmed and expanded the microarray findings. Furthermore, immunoblotting showed that the protein level of at least one of these gene products, dynamin I, correlated with its reduced transcript. Immunhistochemical analysis exhibited an altered distribution of dynamin I immunolabeling in AD neurons. Microarray analysis of transgenic mice with mutated amyloid precursor protein showed that although the transcript levels for some of the SV trafficking-related genes are also decreased, the change in dynamin did not replicate the AD pattern. The results suggest a link among SV vesicle-trafficking pathways, synaptic malfunction, and AD pathogenesis.