Abstract: FR-PO626
Proximal Tubule Histopathologic Variability in Renal Tubular Dysgenesis: A Case Report
Session Information
- Trainee Case Reports - IV
October 26, 2018 | Location: Exhibit Hall, San Diego Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Trainee Case Reports
- 1600 Pediatric Nephrology
Authors
- Lee, Seon, University of Florida- College of Medicine, Gainesville, Florida, United States
- Gupta, Nirupama, University of Florida- College of Medicine, Gainesville, Florida, United States
- Clapp, William L., University of Florida- College of Medicine, Gainesville, Florida, United States
- Shoemaker, Lawrence R., University of Florida- College of Medicine, Gainesville, Florida, United States
Introduction
Renal tubular dysgenesis (RTD) is a rare autosomal recessive disorder that presents with antenatal oligohydramnios and anuric renal failure, despite normal renal sonography. Mutations of 4 genes that code for integral proteins of the renin-angiotensin system (RAS) are responsible for RTD. The function of these proteins is necessary for proper fetal renal tubular development. The pathologic hallmarks of RTD include a paucity of proximal tubules (PT) with aberrant developmental features, detectable by light microscopy and immunohistochemistry (IHC).
Case Description
A 32-week gestational age neonate delivered by urgent C-section for prolonged rupture of membranes and oligohydramnios had anuric renal failure since birth and severe hypotension refractory to vasopressors. Imaging revealed a normal renal sonogram and a large anterior skull ossification defect. Blood tests revealed markedly low renin activity, but normal cortisol, aldosterone, and angiotensin converting enzyme levels. Review of renal biopsy performed on DOL 20 revealed a paucity of PT. In contrast to prior reports, several developmentally mature PT were detected that stained positive with IHC targeted for PT-specific markers CD10 and CD15. Genetic confirmation was sought on DOL 23. The patient had a homozygous nonsense mutation in the REN gene, c.127C>T, which results in termination of coding of transcripts at the level of the pro-peptide of renin. This pathogenic mutation, which prevents any renin production, was previously identified and described in another patient with RTD.
Discussion
This case brings to question whether there exists a meager degree of biological redundancy in the fetal RAS that may obscure correlation of genotype and phenotype. For example in this case, might there be alternate enzymes (other than renin) capable of activating RAS? Recognition of the mild histopathologic variability in these rare cases supports early genetic testing for RTD in neonates with unexplained anuria. Furthermore, the finding of relatively mature PT in this case, associated with a mutation that prevents any renin production, suggests a greater complexity of the biology of the fetal RAS than currently appreciated.