Medullary Injury in the Human Renal Biopsy: Fibrosis Assessment
Alton B Farris, Diane Lawson, Cynthia Cohen, Seymour Rosen. Emory University, Atlanta, GA; Harvard University/Beth Israel Deaconess Medical Center, Boston, MA
Background: The assessment of renal tubulointerstitial injury is important for both native and transplant kidneys; however, past studies have primarily focused on the renal cortex. To study medullary fibrotic injury, interstitial fibrosis (IF) and tubular basement membrane (BM) mass were quantitated in both the renal cortex and medulla.
Design: The sole inclusion criteria was that medullary tissue be available for evaluation. For 22 consecutive native renal biopsies, a whole slide slide scanner was used to obtain whole slide images (WSIs). IF was quantitated on trichrome stains and collagen III immunohistochemistry using a positive pixel count algorithm applied to the WSIs. The algorithm was also used to quantitate the % composed of BM material on a PAS stain. IF was also measured by subtracting the PAS BM% from the trichrome (Trichrome%–PAS%, referred to as T–P) in order to account for BM material also detected on trichrome staining. Pathologist visual assessment of %IF was also provided.
Results: Trichrome and T-P IF% showed a wide range, from 20-59% and 2.4-44% for all tissue, respectively. Image analysis of trichrome and T-P WSIs correlated for all anatomic compartments (r=0.74–0.99, P all <0.0001). Visual measures also showed a wide range, from 15-90% for all tissue. Visual measures showed significant correlation with all of the trichrome and T-P measures except for 2 comparisons: the all tissue visual versus the all tissue T-P method and cortex visual versus the medulla T-P method. Collagen III showed a range of 9.5-47% for all tissue. Collagen III deposition correlated between compartments (r=0.74, P=0.0001 for all tissue vs. cortex, r=0.89, P<0.0001 for all tissue vs. medulla, and r=0.71, P=0.0003 for cortex vs. medulla). However, collagen III did not show a significant relationship with any of the other measures of IF.
Conclusions: Trichrome and T-P image analysis correlated between the cortex, medulla, and entire tissue; and visual assessment of these compartments also correlated with these measures. In this study, collagen III deposition correlated between compartments but did not show correlation with other IF measures, possibly suggesting that additional components are important in extracellular matrix composition. Overall, medullary measurements may show utility in larger studies prospectively correlating medullary IF with renal function in both human and animal models; and medullary measurements could prove useful in drug studies, clinical trials, and evaluation of biopsies containing only medulla.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 253, Monday Afternoon