Impact of age on functional decline following radical nephrectomy: Analysis of the International Marker Consortium for Renal Cancer (INMARC).
Authors: Nguyen Mimi Vu , Chakoumakos Madison , Master Viraj A. , Saito Kazutaka , Walia Arman , Saidian Ava , Perry John M , Narasimhan Rekha S , Meagher Margaret F , Patil Dattatraya H , Javier-Desloges Juan , Fujii Yasuhisa , Derweesh Ithaar 
Published: February 2022

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Background: Radical nephrectomy (RN) is a mainstay of management of localized renal cancer larger than 4 cm in size. RN is associated with renal functional decline, however impact of age on functional decline is unclear. We investigated impact of age on post RN function, focusing on decline to moderate and severe chronic kidney disease (CKD). Methods: This was a retrospective analysis of the International Marker Consortium for Renal Cancer (INMARC) registry of patients who underwent RN. Primary outcome was development of de novo CKD stage IIIB [estimated glomerular filtration rate (eGFR)<45 mL/min/1.73m2). Secondary outcomes included de novo CKD stage III (eGFR<60) and CKD Stage IV (eGFR>30). Patients clinical characteristics were stratified by age groups (<50, 50-70 and >70 years old). Multivariable logistic regression analysis (MVA) was utilized to identify risk factors with renal functional decline to different CKD stages. Kaplan-Meier analysis (KMA) was utilized to evaluate functional outcomes with respect to the different age groups. Results: Overall, 2,436 patients were analyzed (≤50 years, n=513; 50-70 years, n=1,344; >70, n=579; median follow up 31.9 months). On MVA, increasing age was independently associated with increased risk of development of CKD Stage IIIb [compared to ≤50 years (referent), 50-70 years, OR 3.35, p<0.001 and >70 years OR 7.7, p<0.001]. In addition, increasing BMI (OR 1.029, p=0.002), coronary artery disease (OR 1.70, p=0.01), diabetes mellitus (OR 1.37, p=0.029) and African American race (OR 1.6, p=0.01) were independent risk factors for CKD stage IIIb. Increasing age was also independently associated with an increased risk of development of CKD Stage III [compared to ≤50 years (referent), 50-70 years, OR 3.4 p<0.001 and >70 years OR 9.4, p<0.001]. Increasing BMI (OR 1.032, p=0.002) and coronary artery disease (OR 1.87, p=0.015) were also risk factors for CKD stage III. Age >70 years was independently associated with increased risk of development of CKD Stage IV [OR 1.96, p=0.027]. In addition, male (OR 1.49, p= 0.036), increasing BMI (OR 1.03, p=0.003), diabetes mellitus (OR 2.69, p <0.001), and African American race (OR 2.02, p=0.002) were risk factors for CKD stage IV. Kaplan-Meier Analyses demonstrated age associated declines in 5 year freedom from CKD Stage III (≤50 years 73.9%, 50-70 years 53.7%, and >70 years 37.06%, p<0.001), CKD Stage IIIb (age ≤50 years 92.7%, 50-70 years 71.8%, and >70 years 55.5%, p<0.001) and CKD Stage IV (age ≤50 years 93.7%, 50-70 years 89.8%, and >70 years 81.2%, p< 0.001). Conclusions: Increasing age is an independent risk factor for progressive and clinically significant renal functional decline after radical nephrectomy. Prioritization for nephron sparing management should be considered whenever safe and feasible in elderly patients to reduce potential risk of sequelae of functional decline.