Impact of Body Mass Index on renal function impairment in patients treated for Renal Cell Carcinoma at high risk of recurrence: key implications for systemic therapy eligibility

Purpose: Adjuvant or salvage systemic therapy after nephrectomy for intermediate and high-risk clear cell Renal Cell Carcinoma (ccRCC) improve overall survival. However, severe renal impairment represents a relative contraindication to systemic therapy administration. This study aimed to analyze the impact of overweight and obesity at the time of nephrectomy in determining subsequent renal function impairment and limited accessibility to systemic therapy. Methods: Within a prospectively maintained database, we identified 795 non-metastatic ccRCC patients at intermediate of high risk of recurrence. BMI was calculated as weight/height (kg/m²), and chronic kidney disease (CKD)-upstage was defined as estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m². Multivariable Cox regression models (MCRs) assessed the association between BMI and the risk of CKD-upstage. Cumulative incidence curves illustrated the risk of disease relapse across different risk groups. Results: Overall, 504 (63%) were classified as intermediate and 291 (37%) as high-risk of recurrence. The median BMI was 26 kg/m² (IQR: 24–28), with 407 (51%) patients being overweight and 89 (11%) classified as obese. The 5-year risk of disease recurrence was 20% for intermediate and 70% for high-risk patients (p<0.001). After accounting for patient, surgical, and tumor characteristics, the adjusted risk of CKD-upstage increased from 24%-35% to 42% to 61% in normal vs. overweight vs. obese patients. BMI resulted an independent predictor of CKD-upstage (hazard ratio [HR] 1.08, p=0.04). Specifically, overweight [Hazard ratio (HR): 2.11] and obese (HR: 3.26) patients were at higher risk of CKD-upstage (all p<0.05). Conclusion: BMI represents a relevant risk factor for significantly severe renal function decline after surgery. Overweighted and obese patients with ccRCC at intermediate and high-risk of recurrence should be evaluated within a multidisciplinary and nutritional assessment which could limit the access to subsequent adjuvant or salvage systemic therapies when needed.