Abstract: FR-PO929
Association of Podocyte Injury with Kidney Histopathologic Lesions and Disease Progression
Session Information
- Glomerular Diseases: Potpourri
October 25, 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
- Wittig, Marius, Universitat Hamburg Medizinische Fakultat, Hamburg, Hamburg, Germany
- Verma, Ashish, Boston Medical Center, Boston, Massachusetts, United States
- Bellavia, Andrea, Harvard Medical School, Boston, Massachusetts, United States
- Rosan, Sophia H., Boston Medical Center, Boston, Massachusetts, United States
- Claudel, Sophie E., Boston Medical Center, Boston, Massachusetts, United States
- Surapaneni, Aditya L., NYU Langone Health, New York, New York, United States
- Palsson, Ragnar, Massachusetts General Hospital, Boston, Massachusetts, United States
- Srivastava, Anand, University of Illinois Chicago, Chicago, Illinois, United States
- Stillman, Isaac Ely, Icahn School of Medicine at Mount Sinai, New York, New York, United States
- Grams, Morgan, NYU Langone Health, New York, New York, United States
- Rhee, Eugene P., Massachusetts General Hospital, Boston, Massachusetts, United States
- Huber, Tobias B., Universitat Hamburg Medizinische Fakultat, Hamburg, Hamburg, Germany
- Henderson, Joel M., Boston Medical Center, Boston, Massachusetts, United States
- Waikar, Sushrut S., Boston Medical Center, Boston, Massachusetts, United States
- Schmidt, Insa Marie, Boston Medical Center, Boston, Massachusetts, United States
Background
Foot process effacement (FPE), a marker of podocyte injury observable via electron microscopy (EM), is critically involved in the pathophysiology of proteinuria and kidney disease progression in glomerular diseases. The association of FPE with histopathologic lesions and adverse clinical outcomes across a range of kidney diseases has not yet been explored.
Methods
We developed a semi-quantitative scoring system to assess FPE severity using EM reports from 813 participants in the Boston Kidney Biopsy Cohort (BKBC), a prospective cohort of individuals with biopsy-confirmed kidney disease and pathologist-adjudicated assessment of histopathology. Logistic regression models assessed the relationship between FPE severity and histopathologic lesions. Accelerated failure time models examined the relationship between FPE and progression to kidney failure. Lastly, we employed mediation analyses to decompose the effect of FPE severity on kidney failure, exploring the role of proteinuria as a mediator in this pathway.
Results
Mean eGFR was 58.4 ±35.6 ml/min/1.73m2 and median proteinuria (IQR) was 1.6 [0.4–4.0] g/g creatinine. Six % had no FPE, 50% had mild FPE, 15% had moderate FPE, and 29% had severe FPE. After multivariable adjustment, more severe mesangial expansion (OR 1.91, 95% CI 1.26 to 2.88, p=0.002) and more severe interstitial fibrosis/tubular atrophy (OR 1.60, 95% CI 1.09 to 2.33, p=0.015) were significantly associated with more severe FPE (Figure 1a). In the fully adjusted model, moderate or severe FPE was associated with a 2-fold higher hazard of progression to kidney failure compared to none or mild FPE (HR=2.01 (95% CI 1.41, 2.87), (Figure 1b). Mediation analysis showed that FPE affected kidney failure survival times through both direct effects (-0.37) and indirect effects via proteinuria (-0.42), both p<0.01 (Figure 1c).
Conclusion
FPE is linked to glomerular and tubulointerstitial patterns of injury and may serve as a prognostic tool for assessing the risk of disease progression across a range of kidney diseases. Further research on the mechanistic links between FPE severity and adverse kidney outcomes is needed to evaluate targeting podocyte integrity in therapeutic strategies.