Min-Hua Tseng1, Jing-Long Huang2, Shih-Ming Huang3, Jeng-Daw Tsai4,5,6,7, Tai-Wei Wu8, Wen-Lang Fan9, Jhao-Jhuang Ding1,10, Shih-Hua Lin11. 1. Division of Pediatric Nephrology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. 2. Division of Pediatric Allergy, Asthma, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan. 3. Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan. 4. Division of Nephrology, Department of Pediatrics, MacKay Children's Hospital, Taipei, Taiwan. 5. Department of Medicine, MacKay Medical College, New Taipei City, Taiwan. 6. Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan. 7. Department of Pediatrics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan. 8. Fetal and Neonatal Institute, Division of Neonatology, Children's Hospital Los Angeles, Department of Pediatrics, University of Southern California Keck School of Medicine, Los Angeles, CA, USA. 9. Genomic Medicine Core Laboratory, Chang Gung Memorial Hospital, Linkou, Taiwan. 10. Department of Pediatrics. Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. 11. Division of Nephrology. Department of Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan. l521116@ndmctsgh.edu.tw.
Abstract
BACKGROUND: Type IV renal tubular acidosis (RTA) is a severe complication of urinary tract infection (UTI) in infants. A detailed clinical and molecular analysis is still lacking. METHODS: Infants with UTI who exhibited features of type IV RTA were prospectively enrolled. Clinical, laboratory, and image characteristics and sequencing of genes responsible for phenotype were determined with follow-up. RESULTS: The study cohort included 12 infants (9 males, age 1-8 months). All exhibited typical type IV RTA such as hyperkalemia with low transtubular potassium gradient, hyperchloremic metabolic acidosis with positive urine anion gap, hypovolemic hyponatremia with renal salt wasting, and high plasma renin and aldosterone levels. Seven had hyperkalemia-related arrhythmia and two of them developed life-threatening ventricular tachycardia. With prompt therapy, all clinical and biochemical abnormalities resolved within 1 week. Five had normal urinary tract anatomy, and three of them carried genetic variants on NR3C2. Three variants, c.1645T>G (S549A), c.538G>A (V180I), and c.1-2C>G, on NR3C2 were identified in four patients. During follow-up, none of them had recurrent type IV RTA, but four developed renal scaring. CONCLUSIONS: Genetic mutation on NR3C2 may contribute to the development of type IV RTA as a complication of UTI in infants without identifiable risk factors, such as urinary tract anomalies.
BACKGROUND:Type IV renal tubular acidosis (RTA) is a severe complication of urinary tract infection (UTI) in infants. A detailed clinical and molecular analysis is still lacking. METHODS:Infants with UTI who exhibited features of type IV RTA were prospectively enrolled. Clinical, laboratory, and image characteristics and sequencing of genes responsible for phenotype were determined with follow-up. RESULTS: The study cohort included 12 infants (9 males, age 1-8 months). All exhibited typical type IV RTA such as hyperkalemia with low transtubular potassium gradient, hyperchloremic metabolic acidosis with positive urine anion gap, hypovolemic hyponatremia with renal salt wasting, and high plasma renin and aldosterone levels. Seven had hyperkalemia-related arrhythmia and two of them developed life-threatening ventricular tachycardia. With prompt therapy, all clinical and biochemical abnormalities resolved within 1 week. Five had normal urinary tract anatomy, and three of them carried genetic variants on NR3C2. Three variants, c.1645T>G (S549A), c.538G>A (V180I), and c.1-2C>G, on NR3C2 were identified in four patients. During follow-up, none of them had recurrent type IV RTA, but four developed renal scaring. CONCLUSIONS: Genetic mutation on NR3C2 may contribute to the development of type IV RTA as a complication of UTI in infants without identifiable risk factors, such as urinary tract anomalies.