MP47-16: Decline to "Severe" CKD-S is a predictive marker for all-cause and non-cancer mortality in Renal Cell Carcinoma: analysis of the International Marker Consortium for Renal Cancer (INMARC)

Mimi Nguyen*, Arman Walia, Rekha Narasimhan, Ava Saidian, John Matthew Perry, La Jolla, CA, Hajime Tanaka, Tokyo, Japan, Kevin Hakimi, Margaret Meagher, La Jolla, CA, Dattatraya Patil, Atlanta, GA, Yosuke Yasuda, Kazutaka Saito, Yasuhisa Fujii, Tokyo, Japan, Viraj Master, Atlanta, GA, Ithaar Derweesh, La Jolla, CA

Introduction: Impact of surgically induced Chronic Kidney Disease (CKD-S) on outcomes in renal cell carcinoma (RCC) is controversial. We evaluated effects of worsening CKD-S on oncologic and non-oncologic survival outcomes in RCC.

Methods: We performed a retrospective multicenter analysis of patients who underwent Partial (PN) or Radical Nephrectomy (RN). Primary outcome was all-cause mortality (ACM). Secondary outcomes were non-cancer mortality (NCM), cancer specific mortality (CSM), and de novo CKD-S Stage 4 [estimated glomerular filtration rate <30 mL/min/1.73m2). Patients were stratified by CKD stage: no CKD-S (eGFR=60), de novo “moderate” CKD-S 3a (eGFR 59-45), de novo “moderate-severe” CKD-S 3b (eGFR 44-30) and de novo “severe” CKD-S 4 (eGFR 29-15). Multivariable analysis (MVA) was utilized to identify risk factors associated with development of CKD-S Stage 4 and mortality outcomes. Kaplan-Meier analysis (KMA) was utilized to evaluate for overall survival (OS), non-cancer survival (NCS), and cancer-specific survival (CSS) with respect to CKD-S categories.

Results: We analyzed 3239 patients [no CKD-S (n=1876), de novo CKD-S 3a (n=606), de novo CKD-S 3b (n=489) and de novo CKD-S 4 (n=268)]. On MVA, de novo CKD-S 4 was independently associated with ACM (HR 2.1, p<0.001) and NCM (OR 2.8, p<0.001), but not CSM (p=0.219); de novo CKD-S 3b was independently associated with ACM (HR 1.3, p=0.033) and NCM (OR 1.5, p=0.021), but not CSM (p=0.909); de novo CKD-S 3a was not predictive for any mortality outcomes (p=0.81-0.102). RN was independently associated with de novo CKD-S 4 (HR 1.4, p=0.047). Comparing no CKD, CKD-S 3a, CKD-S 3b and CKD-S 4, KMA demonstrated worsening outcomes with progressive CKD-S stage: 5 year OS 84% vs. 78% vs. 71% vs. 60%, p<0.001; 5 year NCS 93% vs. 87% vs. 83% vs. 72%, p<0.001; 5 year CSS, 91% vs. 92% vs. 86% vs. 83%, p<0.001 (Figure).

Conclusions: Development of CKD-S Stage 3b and 4, but not Stage 3a, was associated with worsened ACM and NCM. Worsening CKD-S was not associated with increased oncological risk. While RN was predictive of “severe” CKD-S, decision to proceed with nephron preservation via PN should be individualized based on oncological risk and risk of functional decline to CKD-S 3b or 4, and not CKD-S 3.

Source of Funding: Stephen Weissman Kidney Cancer Research Fund