MP47-15: Impact of Diabetes Mellitus on Functional Decline and Non-Cancer Mortality in Renal Cell Carcinoma: Analysis of the International Marker Consortium (INMARC)

Ava Saidian*, Arman Walia, Rekha Narashimhan, John 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: Diabetes Mellitus (DM) is a risk factor for development of renal cell carcinoma (RCC) and chronic kidney disease (CKD). Impact of DM on patients with surgical nephron loss is not well understood. We sought to evaluate risk of DM with respect to functional decline and Non-Cancer Mortality (NCM) after surgery for RCC.

Methods: We performed a multicenter retrospective analysis. The cohort was divided into two subgroups (patients with DM vs. non-DM) for analysis. Primary outcome was de novo CKD Stage 3b [estimated glomerular filtration rate <45 mL/min/1.73m2 (eGFR <45)]. Secondary outcomes included de novo CKD Stage 3(eGFR <60) and de novo CKD Stage 4(eGFR <30) and NCM. Multivariable analysis (MVA) was utilized to examine risk factors for development of de novo CKD and NCM. Kaplan Meier Analysis (KMA) was used to compare radical(RN) and partial nephrectomy  (PN) in DM and non-DM patients for freedom from de novo CKD and non-cancer survival (NCS).

Results: 4810 patients were analyzed (1119 DM/3691 non-DM; median follow up 32.7 months). MVA demonstrated DM to a risk factor for de novo CKD 3 (HR 1.2, p=0.046), CKD 3b (HR 1.6, p<0.001), CKD 4 (HR 1.9, p<0.001), and NCM (HR 1.3, p=0.022). RN was also independently associated with development of CKD 3 (HR 1.8 p<0.001), 3b (HR 1.4 p=0.002), and NCM (HR 1.4, p=0.003).  Compared to partial nephrectomy without DM (referent), patients with DM who underwent RN had significantly higher risk of NCM (HR 1.8, p<0.001), CKD 3 (HR 2.8 p<0.001), CKD 3b (HR 2.9, p<0.001), and CKD 4 (HR 2.7 p<0.001). KMA comparing RN vs. PN for freedom from de novo CKD and NCS in DM and non-DM revealed improved survivals in PN patients in all categories. NCS: Non-DM, 5 year NCS: PN 81% vs. RN 69.8% (p=0.004); DM, PN 92.2% vs. 78.9%, p<0.001). CKD 3: Non-DM, 5 year freedom from de novo CKD 3, PN 84% vs. RN 59.6% (p < 0.001); DM, 5 year freedom from de novo CKD 3, PN 73% vs. RN 54% (p < 0.001). CKD 3b: Non-DM 5 year freedom from de novo CKD 3b, PN 91% vs. RN 76.6% (p < 0.001); DM, 5 year freedom from de novo CKD 3b, PN 77.4% vs. RN 64.3% (p=0.006).  CKD 4: 5 year freedom from de novo CKD 4, Non-DM, PN 96% vs. RN 92.6% (p=0.008); DM, 5 year freedom from de novo CKD 4, PN 92.8% vs. RN 79% (p < 0.001).

Conclusions: Presence of DM was independently associated with functional decline to severe CKD threshold and with increased risk of NCM. Patients with DM who undergo RN are at higher risk of further functional decline. Presence of DM may be considered a strong indication for nephron preserving management when feasible and safe.

Source of Funding: Stephen Weissman Kidney Cancer Research Fund