Unveiling the silent burden: high prevalence of occult nephropathies in radical nephrectomy specimens

Background: Chronic kidney disease (CKD) and renal cell carcinoma share a bidirectional relationship, with radical nephrectomy posing a significant risk for postoperative renal decline. This study identifies radical nephrectomy as a critical opportunity to evaluate the non-neoplastic renal parenchyma. Methods: We conducted a prospective observational study on 30 adult patients diagnosed with renal or urothelial cancer who underwent radical nephrectomy. Samples of non-neoplastic renal parenchyma were collected during surgery and analyzed using optical microscopy and immunofluorescence. Renal function was assessed pre- and postoperatively using the CKD-EPI formula. Results: The cohort comprised 30 patients (63.3% male) with a median age of 65.5 years (min 29–max 83). Following radical nephrectomy, 50% of patients with preserved preoperative renal function experienced a decline to estimated glomerular filtration rate < 60 ml/min/1.73 m². Histopathological evaluation of the non-neoplastic parenchyma revealed chronic tubulointerstitial damage in 41% (n = 12) and arteriosclerotic vascular damage in 38% (n = 11) of cases. Notably, occult nephropathies were identified in 24% (n = 7) of the cohort, comprising diabetic glomerulosclerosis (n = 2), membranous nephropathy (n = 2), fibrillary glomerulonephritis (n = 1), IgA nephropathy (n = 1), and minimal change disease (n = 1). Two cases (IgA nephropathy and minimal change disease) demonstrated spontaneous remission postsurgery, consistent with a paraneoplastic etiology. Conclusions: The non-neoplastic renal parenchyma in renal cell carcinoma patients frequently exhibits occult pathological changes, predominantly tubulointerstitial damage likely driven by the tumor microenvironment. The study highlights a higher-than-expected prevalence of undiagnosed nephropathies (24%), including paraneoplastic cases. Routine histological evaluation during radical nephrectomy is essential for optimizing patient management, avoiding unnecessary subsequent biopsies, and guiding therapeutic decisions in the oncological setting.