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.
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Acknowledgements
This study was supported in part by research fund of Chang Gung Memorial Hospital (CMRPG3H0361, CMRPG3H0911, CMRPG3I0021), the Ministry of Science and Technology (MOST 106-2314-B-182A-123-MY3), and the Research Fund of Tri-Service General Hospital (TSGH-C106-110, TSGH-C108-132). We thank Professor Martin Konrad for critical review of the revised manuscript and Professor Yu-Ching Chou for the critical help of statistical analysis.
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M.-H.T. and S.-H.L. interpreted the data analyses and reviewed and revised the manuscript. J.-L.H., S.-M.H., and J.-D.T. carried out the data analysis, assisted with interpretation of the data analyses, and reviewed and revised the manuscript for important intellectual content. T.-W.W. assisted with acquisition of the data, interpreted the data analyses, and reviewed and revised the manuscript for important intellectual content. W.-L.F. and J.-J.D. conceptualized and designed the study, assisted with acquisition of data, and provided analysis and interpretation of the data. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.
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Tseng, MH., Huang, JL., Huang, SM. et al. Clinical features, genetic background, and outcome in infants with urinary tract infection and type IV renal tubular acidosis. Pediatr Res 87, 1251–1255 (2020). https://doi.org/10.1038/s41390-019-0727-7
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DOI: https://doi.org/10.1038/s41390-019-0727-7
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