SAT-338 Histological markers of chronic damage in radical nephrectomy specimens and kidney function at twelve postoperative months

Abstract

Despite trends towards nephron-sparing surgery, radical nephrectomy remains the most common management approach for kidney cancer in Australia. Compared with nephron-sparing approaches, radical nephrectomy is associated with lower postoperative glomerular filtration rate (GFR), and presumably greater risk of subsequent chronic kidney disease (CKD). This study evaluated whether evidence of chronic damage in the nephrectomised kidney was associated with GFR at 12 postoperative months. The study included 137 patients with kidney tumours. Patients were managed with radical nephrectomy at the Princess Alexandra Hospital, Brisbane, Australia. They were recruited prospectively and provided written informed consent for inclusion. Following nephrectomy, a section of cortical tissue distal to the tumour was excised, formalin-fixed and paraffin-embedded. Histological sections were stained with haematoxylin and eosin and evaluated by experienced pathologists. Degree of damage to glomeruli, vasculature, tubules and interstitium was characterised, based on previously published criteria. GFR (mL/min/1.73m2) at 12 postoperative months was compared between groups descriptively, and by performing ANCOVA, conditioning on age and sex. The degree of arteriosclerosis (AS) and glomerulosclerosis (GS) was linearly associated with postoperative GFR (p=0.04 and 0.01, respectively). Median [interquartile range] GFR for patients with <20% GS was 53 [45-65], compared with 29 [20-45] for patients with >50% GS. Similarly, average GFR of patients without AS was 58 [46-66] compared with 40 [29-59] in patients with AS causing >50% stenosis. A biphasic relationship between the degree of tubular atrophy and interstitial fibrosis (IF) and postoperative GFR was apparent. For example, patients with 6-25%, 26-50%, and >50% IF had an average GFR of 44 [34-60], 59 [41-74], and 37 [30-59]. A similar pattern was observed for the relationship between tubular atrophy and postoperative GFR, but with less marked differences. A higher degree of chronic damage was associated with lower pre-to-postoperative change in GFR across all groups. Degree of chronic damage was associated with GFR 12 months after radical nephrectomy. This relationship was linear for GS and AS; however, the U-shaped relationship observed between GFR and degree of IF and tubular atrophy was not expected. Biologically plausible explanations for this include that patients with more extensive tubular and interstitial damage are more prone to maladaptive hyperfiltration secondary to surgical nephron reduction. It could also be postulated that these counterintuitive results are the consequence of small numbers, especially because there were substantially fewer patients with signs of advanced chronic damage. The complex relationship between histopathological markers of damage and GFR warrants further study.