Abstract: FR-PO0136
PBX1 Variant-Associated Congenital Anomalies of the Kidney and Urinary Tract with Secondary FSGS Presenting in Adulthood: A Case Report
Session Information
- Hereditary Glomerular and Tubulointerstitial Kidney Diseases
October 23, 2026 | Location: Exhibit Hall A, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Genetic Diseases of the Kidneys
- 1202 Genetic Diseases of the Kidneys: Non-Cystic (Complex and Non-Cystic Monogenic)
Authors
- Ghimire, Sandip, Geisinger Medical Center, Danville, Pennsylvania, United States
- Sanghi, Pooja, Geisinger Medical Center, Danville, Pennsylvania, United States
Introduction
Pathogenic PBX1 variants cause congenital anomalies of the kidney and urinary tract (CAKUT), often as CAKUTHED syndrome (CAKUT ± hearing loss, abnormal ears, developmental delay). Loss of one functional copy of PBX1 results in fewer nephrons and abnormal kidney structure leading to secondary FSGS from adaptive hyperfiltration. We present a case with PBX1-associated CAKUT, secondary FSGS, and intestinal nonrotation identified during transplant evaluation.
Case Description
A 39-year-old female was referred for transplant evaluation with CKD stage 4 and subnephrotic proteinuria (UPCR 2067 mg/g; creatinine 3.4, eGFR 17).Family history of kidney disease was absent. CT showed bilateral small kidneys with dysmorphic right kidney in ectopic position in the right lower abdomen and developmental midgut nonrotation. Renal biopsy in 2015 showed FSGS, perihilar variant, with mild-moderate interstitial fibrosis and tubular atrophy (creatinine 1.7, eGFR 38, 24-hour urine protein 2080 mg at that time). Genetic testing in 2025 revealed a pathogenic heterozygous PBX1 variant (c.550C>T (p.Arg1848)) establishing PBX1-associated CAKUT with secondary FSGS. Medical history included gout on allopurinol and one episode of nephrolithiasis.
Discussion
PBX1 is a transcription factor essential for nephrogenesis. The perihilar FSGS variant and subnephrotic proteinuria are consistent with adaptive hyperfiltration from reduced nephron mass rather than primary podocytopathy. Intestinal nonrotation is a notable extrarenal finding previously described in Pbx1-knockout mice. The secondary FSGS from CAKUT has low post-transplant recurrence risk unlike primary FSGS (30–50% recurrence), avoiding unnecessary immunosuppression. While most PBX1 mutations are de novo, genetic screening of potential living donors remains essential given variable expressivity and reported somatic mosaicism.
This case highlights PBX1 mutation as a rare monogenic cause of CAKUT with secondary FSGS in adulthood. Genetic testing in adults with unexplained CKD and CAKUT directly impacts transplant planning by predicting low recurrence risk and guiding living donor evaluation.