Abstract: SA-PO0157
CKD Resulting from Biallelic AIRE Variants
Session Information
- Tubular, Metabolic, and Systemic Noncystic Genetic Kidney Diseases
October 24, 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
- Bleyer, Heidi A., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
- Underwood, Gavin, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
- Webb, Jon C., University of Kentucky, Lexington, Kentucky, United States
- Bleyer, Anthony J., Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States
Introduction
Biallelic mutations in the autoimmune regulator (AIRE) gene lead to impaired thymic self-recognition and cause a rare condition known as autoimmune polyendocrinopathy-candidasis-ectodermal dystrophy (APECED). Patients often develop autoimmune hypoparathyroidism, adrenal insufficiency, pancreatic failure, and kidney failure.
Case Description
The patient presented at age 4 with decreased energy due to primary adrenal failure. He developed hypoparathyroidism at age 6 and type 1 diabetes at age 12. At age 35 the patient underwent genetic testing as part of in vitro fertilization and was found to have biallelic p.L323SfsX51 AIRE mutations. For hypoparathyroidism, the patient received calcitriol, 1 mcg orally each day was prescribed calcium carbonate, 1000 mg, 4-6 orally daily but would self-dose up to 20 calcium carbonate tablets daily for numbness and tingling. The patient developed progressive CKD and presented at age 40 with an eGFR of 28 ml/min. Urinalysis was unremarkable, and the the urine albumin/creatinine ratio was 92 mg/g (normal <30 mg/g). Serum calcium levels ranged from 7.4-10.6 mg/dl. The iPTH level was < 6.3 pg/ml. A 24 hour urine collection revealed 108 mg/d of calcium (normal 50-150 mg/d). A preliminary diagnosis of CKD due to APECED was made. Kidney biopsy was performed to rule out autoimmune interstitial nephritis but revealed acute tubular injury characterized by tubular dilatation and sloughing of tubular epithelial cells and frequent intratubular calcium phosphate crystals. The patient was started on palopegteriparatide (Yorvipath (®)), 15 mcg subcutaneously daily with discontinuation of calcitriol and calcium. The eGFR subsequently increased and stabilized at 48 ml/min.
Discussion
APECED is a rare autoimmune condition caused by biallelic mutations in AIRE, which encodes a thymic protein that is important in self-recognition. Patients develop autoimmune polyglandular failure and can also develop CKD due to autoimmune tubulointerstitial nephritis, diabetic nephropathy, or calcium phosphate deposition due to hypoparathyroidism. Due to the rarity of the condition, the genetic cause is often not identified. Given multiple potential etiologies of CKD, kidney biopsy is often necessary. In this case, the patient's kidney failure was due to calcium phosphate deposition and responded to treatment with palopegteriparatide. CKD in APECED is treatable and a diagnosis of the underlying cause of CKD should be pursued.