Abstract: TH-PO598
Noninvasive Diagnostic Strategies for Membranous Nephropathy in the NEPTUNE Study
Session Information
- Membranous Nephropathy, FSGS, and Minimal Change Disease
October 24, 2024 | Location: Exhibit Hall, Convention Center
Abstract Time: 10:00 AM - 12:00 PM
Category: Glomerular Diseases
- 1402 Glomerular Diseases: Clinical, Outcomes, and Therapeutics
Authors
- Zee, Jarcy, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
- Hogan, Jonathan, Cabaletta Bio Inc, Philadelphia, Pennsylvania, United States
- Abdullah, Ahmed, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States
- Liu, Lili, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
- Kiryluk, Krzysztof, Columbia University Vagelos College of Physicians and Surgeons, New York, New York, United States
- Beck, Laurence H., Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, United States
Background
Clinical practice guidelines recommend that a kidney biopsy is no longer required to confirm a diagnosis of membranous nephropathy (MN) in patients with nephrotic syndrome and a positive test for anti-phospholipase A2 receptor antibodies (PLA2R-Ab). However, the optimal diagnostic strategy for using the different PLA2R-Ab tests and their optimal thresholds for positivity among incident patients with proteinuria is still unknown.
Methods
We used serum samples at or before the first kidney biopsy from NEPTUNE study participants to analyze diagnostic test performance using different combinations and cut-offs of the PLA2R-Ab enzyme-linked immunosorbent assay (ELISA), PLA2R-Ab indirect immunofluorescence (IIF) test, and genetic risk score for diagnosing MN. Secondary analyses included serum samples within 6 months after biopsy but before any immunosuppression use.
Results
N=325 study participants had serum samples on or before the day of kidney biopsy and an additional N=143 had samples within 6 months after biopsy but before any immunosuppression use. N=85 had biopsy-confirmed MN. The combination of ELISA ≥2 RU/mL and positive IIF was the optimal approach, with sensitivity of 0.600, specificity of 1.000, negative predictive value of 0.925, and positive predictive value of 1.000 (Table). Using IIF to confirm only borderline ELISA titers between 2 and 20 resulted in similar sensitivity but specificity of 0.996. In our multiethnic study sample, we did not find improved diagnostic performance with the addition of genetic risk scores.
Conclusion
Given the possibility of false positives by ELISA alone, both ELISA and IIF testing should be performed to establish PLA2R-Ab seropositivity before making a non-invasive diagnosis of PLA2R-associated MN among patients with proteinuria. Further studies in multiethnic populations are needed to assess whether genetic data can augment this approach.
PLA2R-Ab ELISA and IIF diagnostic test characteristics
| Sensitivity | Specificity | Positive Predictive Value | Negative Predictive Value | |
| ELISA ≥2 | 0.636 | 0.837 | 0.443 | 0.919 |
| ELISA ≥14 | 0.564 | 0.996 | 0.969 | 0.918 |
| ELISA ≥20 | 0.527 | 0.996 | 0.967 | 0.912 |
| ELISA ≥2 and IIF+ | 0.600 | 1.000 | 1.000 | 0.925 |
| ELISA >20 or (20≥ELISA≥2 and IIF+) | 0.600 | 0.996 | 0.971 | 0.924 |
| ELISA >20 or (20≥ELISA≥14 and IIF+) | 0.564 | 0.996 | 0.969 | 0.918 |
| ELISA >20 and IIF+ | 0.527 | 1.000 | 1.000 | 0.912 |