Elevated Pre-operative C-reactive Protein Is Associated with Renal Functional Decline and Non-Cancer Mortality in Surgically Treated Renal Cell Carcinoma: Analysis from the INternational Marker Consortium for Renal Cancer [INMARC]

Objective: To investigate association of pre-treatment C-Reactive Protein (CRP) and non-cancer mortality (NCM) in a cohort of patients undergoing surgery for localized renal cell carcinoma (RCC).

Methods: Retrospective multicenter analysis of patients surgically treated for clinical stages 1-2 RCC from 2006-17, excluding all cases of cancer-specific mortality. Descriptive analyses were obtained between normal pre-treatment CRP (≤0.5mg/dL) and elevated CRP (>0.5mg/dL) groups. Primary outcome was NCM. Secondary outcomes included progression to de novo Chronic Kidney Disease (CKD) Stages 3-4 (eGFR<60, <45, and <30 ml/min/1.7m2 ). Multivariable analyses (MVA) were performed to assess for risk factors associated with functional decline and NCM, and Kaplan-Meier analysis (KMA) was use to obtain survival estimates for outcomes.

Results: 1,987 patients who underwent radical (RN) or partial nephrectomy (PN) were analyzed (normal-CRP n=963; elevated-CRP n=1,024). Groups were similar in age (59 vs. 60 years, p=0.079). Elevated-CRP was more frequent in males (36.8% vs. 27.8%, p<0.001), African-Americans (22.6% vs. 2.9%, p<0.001), and greater median BMI (30 kg/m2 vs. 25 kg/m2, p<0.001), and larger median tumor size (4.5 cm vs. 3.3 cm, p<0.001). On MVA, elevated-CRP was independently associated with development of de novo eGFR<60 (HR 1.32, p=0.015), eGFR<45 (HR 1.41, p=0.023) and eGFR<30 (OR 2.23, p<0.001). MVA for factors associated with NCM demonstrated increasing age (HR 1.06, p<0.001), pre-operative elevated CRP (HR 2.18, p<0.001) and eGFR <45 (HR 1.16; p=0.021) as independent risk factors. KMA revealed significantly higher 5-year NCM for elevated-CRP vs. normal-CRP (98%, vs. 80%, p<0.001).

Conclusions: Pre-treatment elevated CRP was independently associated with both progressive renal functional decline and NCM in patients undergoing surgery for Stage 1- 2 RCC. Patients with elevated CRP and Stage 1 and 2 RCC may be considered as having indication for nephron-sparing strategies which may be prioritized if oncologically appropriate.

Keywords: C-Reactive Protein; Carcinoma; Chronic Kidney Disease; Non-Cancer Mortality; Partial Nephrectomy; Radical Nephrectomy; Renal Cell.