Medullary Injury in the Human Renal Biopsy: Assessment of Epithelial Mass
Alton B Farris, Diane Lawson, Cynthia Cohen, Seymour Rosen. Emory University, Atlanta, GA; Harvard University/Beth Israel Deaconess Medical Center, Boston, MA
Background: Renal tubulointerstitial injury assessment is often restricted to the cortex. The outer medulla has two major zones: outer stripe (OS) and inner stripe (IS). OS cellular mass is mostly formed by proximal tubules and is limited. IS consists of an epithelial cell mass (EPCM) mostly formed by thick ascending limbs and collecting ducts. Delineation of this zone depends on recognizing corticomedullary junction connective tissue/vascular components, adjacent OS, and vasa recta. With increasing injury, EPCM diminishes with thick ascending limb atrophy/loss (TA); the collecting ducts are relatively preserved. To characterize injury in these regions, we conducted a morphometric study.
Design: Consecutive native renal biopsies (n=22) were examined; the sole inclusion criteria was the availability of medulla (primarily outer medulla). Trichrome, PAS, and cytokeratin (CK) immunostained (AE1/AE3) slides were digitally scanned. For the entire cortex and entire medulla, EPCM was quantitated using a positive pixel count algorithm tuned to detect CK brown and trichrome red. Furthermore, pathologist visual assessment was recorded for %TA and % composed of EPCM.
Results: Cortical and medullary EPCM declined together, with linear regression showing direct relationships between cortical and medullary EPCM by trichrome (r=0.69 between cortex and medulla, p<0.0001) and CK (r=0.68, p=0.0007). The EPCM (mean±standard deviation [SD]) of the cortex and medulla, respectively, were 60±14% and 46±12% on trichrome;49±9% and 47±10% on CK, and 48 ± 28% and 24 ± 18% on pathologist assessment. The OS and IS width was 1.7±0.7 and 4.1±2.5 mm (mean±SD), respectively. Weak but statistically significant correlations were found between increasing IS width and cortical %TA (r=0.43,p=0.046). Conversely, both IS and OS width were inversely correlated with trichrome EPCM (r=-0.44,p=0.040 for OS width versus entire medullary EPCM and r=-0.48,p=0.023 for IS width versus entire medullary EPCM).
Conclusions: This study demonstrates relationships between diminishing cortical and medullary EPCM. Furthermore, expansion of OS and IS are both associated with reduced medullary epithelial cell mass. Thus, as epithelial cell elements are lost, reactive/fibrotic responses causes zonal expansion. Analyzing and quantitating medullary injury may provide a unique perspective to examine human chronic kidney disease.
Category: Kidney (does not include tumors)
Monday, March 4, 2013 1:00 PM
Poster Session II # 258, Monday Afternoon