Abstract: SA-PO0161
CKD in SERPINA1 Carriers
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
- Jahanshahi, Atousa, University of California Los Angeles, Los Angeles, California, United States
- Arman, Farid, University of California Los Angeles, Los Angeles, California, United States
Background
Alpha-1 antitrypsin (AAT) deficiency due to SERPINA1 mutations (chromosome 14q32.13) leads to lung and liver disease. CKD has been reported in severe deficiency. Whether CKD reflects direct AAT nephropathy or high comorbidity is unclear. SERPINA1 resides within chromosomal region harboring multiple kidney disease-associated genes.
Methods
We analyzed 21,192 SERPINA1 carriers and stratified by CKD, ESRD, kidney biopsy, and mortality. We assessed comorbidity burden(Charlson and Elixhauser indices). Systematic review of chromosome 14 kidney disease genes was performed.
Results
Of subjects,66.1% F, 38.8% White), 1,231 (5.81%) had CKD, 51 had ESRD, 20 had kidney biopsy. Mortality was markedly elevated in CKD group (21.2% vs. 7.6% overall; 49.0% in ESRD).
CKD patients had doubling of comorbidities: HTN 72.5% vs. 40.4%, CHF 22.6% vs. 9.0%, DM 35.3% vs. 18.0%, and PVD 37.4% vs. 18.8%, consistent with cardiovascular-kidney-metabolic syndrome (CKM). Dose-response relation of liver disease and ESRD (mild 6.74%, moderate-to-severe 13.92% vs. overall 4.14%) signals possible AAT-associated renal contribution.
Systematic review identified 14 chromosome 14 kidney disease genes: podocytopathies (INF2, COQ6, OSGEP, GON7), tubular disorders (SLC7A7, VIPAS39), ciliopathies (IFT43, TTC8), immune/vascular (PLD4), neoplastic (DICER1), and structural (TMEM260). The 14q32 subregion alone contains 4 genes, SERPINA1, INF2, DICER1, and GON7, causing distinct renal phenotypes.
Conclusion
CKD affects 6% of SERPINA1 carriers. Doubling of comorbidities in CKD patients is consistent with CKM. There is a signal for potential AAT-associated renal contribution. Testing of chromosome 14 genes may be warranted in carriers with unexplained CKD given treatable conditions like COQ6 deficiency.
Chromosome 14 CKD genes
| Catagory | Gene | Location | Inheritence | Typical Onset | Kidney Phenotype | Mechanism | Evidence Strength | Key Clinical Feature |
| Protein deposition glomerulopathy | SERPINA1 | 14q32.13 | Codominant | Adult | CKD ± rare MPGN association | Z-AAT polymer deposition / inflammatory injury | Observational | Liver disease–associated renal dysfunction |
| Podocytopathy | INF2 | 14q32.13 | AD | Young Adult | FSGS | Actin cytoskeleton / podocyte injury | Established | Progressive proteinuria → ESRD |
| Podocytopathy | COQ6 | 14q24.3 | AR | Childhood | Steroid-resistant nephrotic syndrome | Mitochondrial CoQ biosynthesis defect | Established | Hearing loss; CoQ10-responsive |
| Podocytopathy | OSGEP | 14q11.2 | AR | Infancy | Galloway-Mowat syndrome type 3 | tRNA modification (KEOPS complex) | Syndromic | Microcephaly, severe nephrotic syndrome, high mortality |
| Podocytopathy | GON7 | 14q32.33 | AR | Infancy/Childhood | Galloway-Mowat syndrome type 9 | tRNA modification (KEOPS complex) | Syndromic | FSGS / diffuse mesangial sclerosis |
| Tubular disorder | SLC7A7 | 14q11.2 | AR | Childhood | Proximal tubulopathy ± nephrocalcinosis | Cationic amino acid transport defect | Established | Lysinuric protein intolerance |
| Tubular disorder | VIPAS39 | 14q24.3 | AR | Neonatal/infancy | Tubulopathy (RTA, Fanconi syndrome) | Endosomal trafficking / cell polarity | Syndromic | ARC syndrome type 2 |
| Ciliopathy | IFT43 | 14q24.3 | AR | Childhood | Nephronophthisis | IFT-A ciliary transport dysfunction | Established | Progressive ESRD |
| Ciliopathy | TTC8 | 14q31.3 | AR | Childhood/adolescent | Renal anomalies ± CKD | BBSome complex dysfunction | Syndromic | Bardet-Biedl syndrome type 8 |
| Immune-mediated | PLD4 | 14q32.33 | AR | Variable | Lupus nephritis | Immune activation / nucleic acid sensing | Emerging | Monogenic SLE type 18 |
| Microangiopathy | MTHFD1 | 14q23.3 | AR | Variable | Thrombotic microangiopathy (aHUS-like) | Folate metabolism / endothelial injury | Rare mongenic | aHUS + immune features |
| Neoplastic | DICER1 | 14q32.13 | AD | Childhood | Wilms tumor / cystic nephroma | miRNA biogenesis defect | Established | Low penetrance germline disease; somatic mosaic forms carry higher Wilms tumor risk |
| Structural anomaly | TMEM260 | 14q22.3 | AR | Neonatal | Congenital renal anomalies | O-mannosylation / organogenesis | Emerging | Multisystem congenital defects |