ABSTRACT Introduction Radical nephrectomy (RN), a recommended treatment option for patients with Renal cell carcinoma (RCC) leads to an inevitable decline in global renal function. Pathological changes in the non-tumour parenchyma of the kidney may help predict the function of the remaining kidney. Materials and Methods Aim of this prospective, observational study was to find histopathological factors in the non-tumor renal parenchyma that could predict the decline in global renal function postoperatively and its association with co-morbidities like diabetes (DM). Data of consecutive patients undergoing RN from December-2013 to January-2015 was collected. Non-tumor parenchyma of the specimen was reported by a dedicated histopathologist. eGFR was calculated using Cockcroft-Gault formula before the surgery and at last follow up of at least 12 months. Results 73 RN specimens were analyzed. Mean follow up was 12.3 months. The mean decrease in eGFR was 22% (p=.0001). Percent decrease in eGFR did not show association with any of the histopathological parameters studied. DM was significantly associated with decrease in percent eGFR (p<0.05) and increase in arteriolar hyalinosis (p=0.004), Glomerulosclerosis (p=0.03) and Interstitial fibrosis/ Tubular atrophy (p=.0001). Maximum size of the tumor showed a negative correlation with percentage change in eGFR (p=.028). Conclusion Histological parameters in the non-tumour portion of the RN specimen may not be able to predict renal function outcome over a short follow up. However, presence of DM was associated with adverse pathological changes and significant decrease in renal function postoperatively.