Kidney Week

Abstract: TH-PO648

Modeling Chronic Damage in Lupus Nephritis Kidneys Noninvasively

Session Information

• Lupus Nephritis: Clinical, Outcomes, and Therapeutics
  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

• Rojas-Rivera, Jorge Enrique, The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Jorge Enrique Rojas-Rivera, MD, MSc

• Shapiro, John P., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

John P. Shapiro, MS

• Mejia-Vilet, Juan M., Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de Mexico, Ciudad de México, Mexico

Juan M. Mejia-Vilet, MD, MS, PhD

• Navarro Sanchez, Valeria, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de Mexico, Ciudad de México, Mexico

Valeria Navarro Sanchez, MD

• Rovin, Brad H., The Ohio State University Wexner Medical Center, Columbus, Ohio, United States

Brad H. Rovin, MD, FASN

Background

Chronic kidney damage in lupus nephritis (LN) occurs during cycles of inflammation, and healing after treatment. Urine epidermal growth factor (uEGF) correlates well with the histologic chronicity index (CI) and reflects functional tubular mass. We tested models combining uEGF with clinical variables and other putative urine biomarkers to determine whether various levels of chronic damage could be distinguished non-invasively.

Methods

Urine collected at the time of kidney biopsy for LN (n=119) was assessed by ELISAs specific for EGF, complement activation products (C5a, C5b-9, factor Ba) and macrophage-derived CD163, a biomarker of histologic activity in LN. Clinical laboratory tests for serum creatinine (SCr), proteinuria, and complement components C3 and C4 were done. Predictive models to distinguish between no (CI=0) and increasing levels of chronic damage were built by combining urine and clinical markers and were tested using the area under (AUC) the receiver operating characteristic (ROC) curve.

Results

The best models to differentiate between no chronic damage and increasingly higher levels of chronic damage are shown in the Table. The model to predict a CI of 2 or more has the best performance (Figure below Table), but the ability to identify most patients (>80%) with a CI of 4 or greater is still very good (AUC = 0.877, sensitivity = 82%, specificity = 80%). uEGF, serum C3, and uC5b-9 are common to all models.

Conclusion

At LN flare the CI of the kidney can be estimated noninvasively by urine and serum markers. These biomarkers include measures of chronic damage and disease activity consistent with active lesions healing with scarring. Identifying patients with a CI≥4 is important as this level of damage is associated with poor long-term kidney outcome and should prompt treatment with immunosuppressives and nephro-protective therapies. Interestingly, these equations suggest that intra-renal and systemic complement activation may contribute to chronic kidney damage in LN.

Funding

• Other NIH Support