Revisão: transportadores de água

Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

A novel mutation in the anion exchanger 1 gene is associated with familial distal renal tubular acidosis and nephrocalcinosis

Objective. The anion exchanger gene (AE1) or band 3 encodes a chloride- bicarbonate (Cl-/ HCO3-) exchanger expressed in the erythrocyte and in the renal alpha-intercalated cells involved in urine acidification. The purpose of the present study was to screen for mutations in the AE1 gene in 2 brothers ( 10 and 15 years of age) with familial distal renal tubular acidosis (dRTA), nephrocalcinosis, and failure to thrive. Methods. AE1 mutations were screened by single-strand conformation polymorphism, cloning, and sequencing. Results. A complete form of dRTA was confirmed in the 2 affected brothers and an incomplete form in their father. All 3 were heterozygous for a novel 20-bp deletion in exon 20 of the AE1 gene. This deletion resulted in 1 mutation in codon 888 (Ala-8883 --> Leu) followed by a premature termination codon at position 889, truncating the protein by 23 amino acids. As band 3 deficiency might lead to spherocytic hemolytic anemia or ovalocytosis, erythrocyte abnormalities were also investigated, but no morphologic changes in erythrocyte membrane were found and the osmotic fragility test was normal. Conclusions. A novel mutation in the AE1 gene was identified in association with autosomal dominant dRTA. We suggest that RTA be considered a diagnostic possibility in all children with failure to thrive and nephrocalcinosis.11261361136

Ultrasound is Superior to Computed Tomography for Assessment of Medullary Nephrocalcinosis in Hypoparathyroidism

CONTEXT: Nephrocalcinosis is a complication of hypoparathyroidism and other metabolic disorders. Imaging modalities include ultrasonography (US) and computed tomography (CT). Few studies have compared these modalities, and standard clinical practice is not defined. OBJECTIVE: The objective of the study was to determine the preferred method for assessing nephrocalcinosis. DESIGN: The design of the study was a retrospective, blinded analysis. SETTING: The study was conducted at a clinical research center. PATIENTS: Twenty-two hypoparathyroid subjects and 7 controls participated in the study. INTERVENTIONS: Contemporaneous renal US and CT images were reviewed in triplicate by 4 blinded radiologists. Nephrocalcinosis was classified using a 0–3 scale with 0 meaning no nephrocalcinosis and 3 meaning severe nephrocalcinosis. MAIN OUTCOME MEASURES: Intraobserver, interobserver, and interdevice agreements were measured. RESULTS: Intraobserver agreement was high, with an overall weighted kappa of 0.83 for CT and 0.89 for US. Interobserver agreement was similar between modalities, with kappas of 0.74 for US and 0.70 for CT. Only moderate agreement was found between US and CT scores, with an intermodality kappa of 0.47 and 60% concordance. Of discordant pairs, 81% had higher US scores and only 19% had higher CT scores. Of nephrocalcinosis seen on US and not CT, 45%, 46%, and 9% were grades 1, 2, and 3, respectively. Overall, US scores were higher than CT with a cumulative odds ratio (95% confidence interval) of 5.97 (2.60, 13.75) (P < .01). In controls, 100% of US ratings were 0, and 95% of CT ratings were 0. CONCLUSIONS: US is superior to CT for assessment of mild to moderate nephrocalcinosis in patients with hypoparathyroidism. This finding, in combination with its low cost, lack of radiation, and portability, defines US as the preferred modality for assessment of nephrocalcinosis