UNIVERSA MEDICINA pISSN: 1907-3062 / eISSN: 2407-2230 Univ Med 2025. 44:345-351 DOI: https://doi. org/10. 18051/UnivMed. ORIGINAL ARTICLE Clinical significance of pre-operative prognostic nutritional index in predicting survival in patients with renal cell carcinoma Eldo Taufila Putra Utama1 and Raden Danarto2 Urology Residency Training Program. Department of Surgery. Faculty of Medicine. Public Health, and Nursing. Universitas Gadjah Mada/Dr. Sardjito Hospital. Yogyakarta. Indonesia Department of Surgery. Faculty of Medicine. Public Health, and Nursing Universitas Gadjah Mada. Yogyakarta. Indonesia * Correspondence Author: eldotaufila@gmail. Date of first submission. October 26, 2025 Date of acceptance. December 15, 2025 Date of publised. December 17, 2025 Cite this article as: Utama ETP. Danarto R. Clinical significance of pre-operative prognostic nutritional index in predicting survival in patients with renal cell carcinoma. Univ Med 44:345-351 ABSTRACT BACKGROUND Renal cell carcinoma (RCC) is a prevalent urologic malignancy with heterogeneous outcomes even after Conventional prognostic factors are insufficient to capture host-related influences on survival. The prognostic nutritional index (PNI), derived from serum albumin and lymphocyte count, reflects nutritional and immunological status and has emerged as a potential prognostic biomarker. The objective of this study was to determine preoperative PNI in predicting survival outcomes of RCC patients. METHODS This was a retrospective cohort study involving 107 RCC patients who underwent radical or partial Patients were categorized into normal and low PNI. Associations between PNI and clinicopathological features were assessed, while survival outcomes were evaluated using KaplanAeMeier analysis and Cox proportional hazards regression. RESULTS PatientsAo mean age was 53. 1 A 13. 5 years, and 58. 9% of the patients were male. Clear cell carcinoma was the most common histological type . 2%). Low PNI was significantly associated with older age . =0. metastatic disease . <0. , and advanced tumor stage . =0. KaplanAeMeier analysis demonstrated significantly poorer survival in the low-PNI group . <0. In the multivariate Cox model. PNI remained the strongest independent predictor of overall survival (HR = 0. 29, 95% CI: 0. 13Ae0. 67, p=0. , while metastasis also retained independent significance (HR = 2. 04, 95% CI: 1. 06Ae3. 93, p=0. CONCLUSION The PNI is an independent, simple, and cost-effective prognostic factor for overall survival in RCC. Incorporating PNI into preoperative risk stratification may enhance clinical decision-making. Therefore. PNI could be used as an effective prognostic indicator in RCC. Keywords: Renal cell carcinoma, prognostic nutritional index, overall survival, cancer prognosis, immunological status Copyright@Author. - https://univmed. org/ejurnal/index. php/medicina/article/view/1848 Utama ETP. Danarto R INTRODUCTION Renal cell carcinoma (RCC) is one of the In 2020, an estimated 431,288 new cases of kidney cancer (KC) were reported . In China, approximately 66,000 new RCC cases were documented annually between 2000 and 2011. Clinically, 20Ae30% of patients with localized RCC who undergo surgical recurrence or develop metastatic disease. Therefore, accurate prognostic assessment of RCC is critically important for both clinicians and patients in guiding postoperative management. Among patients undergoing nephrectomy, conventional prognostic parametersAisuch as tumor stage, nuclear grade, and tumor sizeAi remain insufficient to fully account for hostrelated factors that substantially influence oncological outcomes. Consequently, the identification of reliable host-related prognostic markers remains an unmet clinical need to improve risk stratification and inform treatment decision-making. The concentration of serum albumin is an important biomarker that reflects both the nutritional and immunological status of cancer . Decreased serum albumin levels have been associated with unfavorable prognosis in cancer patients. By combining serum albumin levels with peripheral lymphocyte counts, the prognostic nutritional index (PNI) has been proposed as a prognostic indicator. Several subsequent studies have reported associations between PNI and short-term outcomes, including postoperative infections and wound healing. ,6,. Furthermore. Takushima et al. demonstrated a significant correlation between PNI and cancer outcomes and formally introduced a formula for its calculation. Subsequent investigations from diverse geographic regions have similarly demonstrated the potential prognostic value of PNI in RCC. However, substantial heterogeneity among studiesAiincluding variation in PNI cutoff thresholds and differences in study populations, such as the inclusion of metastatic cases and patients receiving targeted therapiesAihas contributed to inconsistent findings and underscores the need for further validation. Hofbauer et al. reported that a low preoperative PNI was an independent predictor of poor longterm survival in patients with localized RCC. contrast, in a cohort of 660 patients with RCC who significant association was reported between preoperative PNI and cancer-specific survival (CSS) (HR=0. 95% CI: 0. 41Ae1. p=0. In addition, several meta-analyses have evaluated the prognostic significance of PNI in RCC. Kim et al. and Mao et al. consistently demonstrated that a reduced PNI is associated with greater tumor aggressiveness and inferior survival outcomes across multiple However, it should be noted that, when the PNI is treated as a continuous variable, its prognostic significance may diminish. In their multivariate Cox regression analysis of patients with metastatic RCC receiving targeted therapy. Kwon et al. did not observe a statistically significant association between pretreatment PNI and overall survival (HR=0. 96, 95% CI: 0. 00, p=0. or progression-free survival (HR = 94, 95% CI: 0. 03, p=0. These inconclusive results require further This study aims to determine whether pre-operative PNI constitutes an independent prognostic factor in predicting survival outcomes of RCC patients. METHODS Research design A retrospective cohort study was conducted at Dr. Sardjito General Hospital. Yogyakarta. Indonesia, from January 2018 to August 2024. Research subjects A total of 107 patients diagnosed with RCC and treated with radical or partial nephrectomy with curative intent were included. Inclusion criteria: . histopathologically confirmed RCC. availability of complete preoperative laboratory and clinical records. followAcup data Exclusion criteria: . incomplete clinical or laboratory data. prior systemic . concurrent inflammatory or autoimmune disease affecting PNI. bilateral RCC or hereditary syndromes. RCC diagnosis followed WHO classification criteria. Data collection Demographic, clinical, and pathological data were obtained from hospital medical records and pathology reports. Variables collected included age, sex, histological RCC subtype, tumor grade, and metastatic status. Preoperative laboratory Pre-operative prognostic nutritional index values, including serum albumin concentration . /dL) and lymphocyte counts . ells /mm. , were used to calculate the PNI using the standard formula: PNI = . y serum albumin . /dL]) . 005 y total lymphocyte count . ells/mmA]). Patients were followed every three months during the first postoperative year, and survival status was determined from hospital records. Overall survival (OS) was defined as the interval from surgery to death from any cause. For analytical purposes, patients were categorized into low-PNI and normal-PNI groups. Given the absence of a universally accepted cutoff value, the median PNI of the cohort was used to define these categories. Age was classified into two groups (<60 and Ou60 year. Histological RCC subtype was categorized into clear cell and nonAeclear cell. Tumor grade was assessed according to the WHO/ISUP grading system and categorized as low grade . rades 1Ae. or high grade . rades 3Ae. Metastatic status was classified as either present or absent. Statistical analysis Associations PNI clinicopathological features were examined using non-parametric tests. Survival curves were estimated using the KaplanAeMeier method and compared with the log-rank test. Multivariate Cox proportional hazards regression was performed to evaluate the independent prognostic value of PNI after adjusting for age, sex, tumor stage, metastasis, and histological subtype. Results were expressed as hazard ratios (HR. with 95% confidence intervals (CI. All analyses were performed using SPSS version 29. 0 (IBM, Armonk. NY. USA), with a two-sided p value <0. 05 considered statistically significant. Ethics approval and consent to participate This study received approval from the Ethics Committee of Gadjah Mada University prior to initiation (Validation No. approved on October 6, 2. RESULTS A total of 107 patients with renal cell carcinoma (RCC) were included in this study. The majority were younger than 60 years . %), with a mean age of 53. 1 A 13. 5 years. Males were more common than females . 9% vs. 1%). Earlystage disease . T1/. accounted for 57. 9% of Regarding histopathological subtypes, clear cell carcinoma was the most prevalent . 2%), 8% consisted of nonAeclear cell variants. At diagnosis, 28. 9% of patients presented with metastatic disease, whereas 71. 1% had localized Patients were subsequently categorized into two groups based on their PNI values: a lowPNI group (<. and a normal-PNI group (Ou. (Table . KaplanAeMeier survival analysis revealed significant differences in overall survival according to PNI categories (Log Rank = 23. p<0. Patients with low PNI had a mean survival of 7. 0 months . % CI: 5. 7Ae8. Patients with normal PNI had a mean survival of 10. % CI: 9. 9Ae11. (Figure . Univariate Cox regression analysis identified PNI. T stage, and metastasis as significant predictors of survival. Low PNI was associated with increased risk of mortality (HR=0. 94, 95% CI: 0. 92Ae0. 97, p<0. Advanced T stage was significantly associated with higher mortality risk (HR=3. 04, 95% CI: 1. 60Ae5. 76, p=0. The presence of metastasis increased the risk of death 45-fold (HR=3. 454, 95% CI: 1. 85Ae6. p<0. Age, gender, and histopathology were not significant predictors . >0. (Table . the multivariate model that included PNI. T stage, and metastatic status. PNI remained an independent prognostic factor (HR=0. 29, 95% CI: 13Ae0. 67, p<0. Metastasis was also identified as a significant prognostic factor (HR= 04, 95% CI: 1. 06Ae3. 93, p=0. , whereas T stage did not retain statistical significance . =0. (Table . Table 1. Demographic and clinico-pathological characteristics of patients with RCC . Variables Age . O 60 > 60 Sex Male Female Stage (T) I-II i-IV Metastasis Yes Histopathology Clear cell Non clear cell PNI Normal (Ou . Low (< . n (%) 73 . Note : data presented as n (%) Utama ETP. Danarto R KaplanAeMeier survival analysis revealed significant differences in overall survival according to PNI categories (Log Rank = 23. p<0. Patients with low PNI had a mean survival of 7. 0 months . % CI: 5. 7Ae8. Patients with normal PNI had a mean survival of 10. 7 months . % CI: 9. 9Ae11. (Figure . Figure 2. Kaplan-Meier survival analysis (A) overall survival and (B) Hazard function in normal/Low PNI Time: time after surgery . Table 2. Univariate and multivariate Cox analyses of overall survival Univariate analysis Multivariate Analysis Variable 95% CI p value 95% CI p value Age 52Ae1. Sex 76Ae2. Stage 60Ae5. <0. 95Ae3. Metastasis 85Ae6. <0. 06Ae3. Histopathology 945Ae3. PNI 92Ae0. <0. 13Ae0. Note : PNI : prognostic nutritional index. HR : hazard ratio. : confidence interval Pre-operative prognostic nutritional index DISCUSSION Our findings demonstrated that PNI was a significant and independent predictor of overall Patients with low PNI had substantially shorter survival times compared to those with normal PNI, as confirmed by KaplanAeMeier and Cox Importantly. PNI retained its prognostic significance even after adjusting for tumor stage and metastasis, underscoring its robustness as a prognostic biomarker in RCC. This finding reinforces the clinical relevance of nutritional and immunological status in cancer progression and The PNI, which combines serum albumin concentration and peripheral lymphocyte count, reflects both nutritional reserves and systemic immune response. Hypoalbuminemia often indicates chronic inflammation and poor nutritional status, while lymphopenia reflects impaired cell-mediated immunity, both of which may contribute to tumor progression and decreased survival. Our results are consistent with a previous study, which showed that a low PNI is associated with an adverse prognosis in RCC patients across various stages of disease, including metastatic cases. Hu et al. analyzed 660 patients with RCC who underwent nephrectomy and reported that those with a low preoperative PNI were more likely to be older, have a higher pathological stage, and present with distant metastases. In the univariate analysis, tumor stage and metastatic status were significantly associated with survival, aligning with the well-established understanding that tumor burden and disease dissemination are key determinants of . However, in the multivariate model, the prognostic significance of T stage diminished, whereas metastasis remained a significant Kermani et al. in a cohort of 230 RCCpatients, also reported that advanced tumor stage and the presence of metastasis were significantly associated with poorer overall In our multivariate analysis, the prognostic contribution of tumor stage was no longer observable after metastatic status and PNI were incorporated into the model, suggesting substantial overlap among these variables. Importantly. PNI exhibited the strongest independent association with overall survival, as reflected by a markedly protective hazard ratio, indicating that systemic host-related factors captured by this index exert significant influence on patient outcomes. The persistent statistical significance of PNI reinforces its robustness as a prognostic biomarker and highlights its capacity to provide prognostic information that extends beyond conventional anatomic parameters. Other including age, sex, and histopathological subtype, were not significantly associated with survival in this cohort. This is in line with some earlier reports that histological subtype, particularly in clear cell carcinoma, though common, may not independently predict prognosis when adjusted for other factors. The predominance of clear cell RCC in our sample may have further limited the ability to detect differences between histological Our results are supported by several metaanalyses that have demonstrated the prognostic value of PNI in RCC and other malignancies. Mao et al. reported that low PNI was associated with poorer overall survival (HR=2. 10, 95% CI: 1. 67Ae . and progression-free survival (HR=1. 95% CI: 1. 67Ae2. in RCC patients. Beyond RCC, the prognostic role of PNI has also been validated across multiple cancer types. Liao et . reported that lower PNI correlated with unfavorable prognostic factors and poor prognosis in patients with esophageal cancer, based on a meta-analysis of 3,118 patients. Various types of cancers were shown to be associated with low PNI, such as in the studies of Li et al. and Shao et al. for colorectal and lung cancer. In addition. Li et al. showed that a low PNI was associated with shorter OS in patients with pancreatic cancer. Another metaanalysis demonstrated that a low PNI could predict short- and long-term survival outcomes in patients with nasopharyngeal carcinoma. These results reaffirm PNI as a robust and clinically meaningful prognostic biomarker, and further establish its role as an independent predictor of survival in patients with RCC. This study has several limitations. First, its retrospective single-center design may limit the generalizability of the findings. Second, the relatively small number of patients with nonAeclear cell histology restricted further analysis of subtype-specific outcomes. Third. PNI was assessed only at baseline, and dynamic changes over the disease course were not evaluated. Future prospective multicenter studies with larger sample Utama ETP. Danarto R sizes and serial monitoring of PNI are warranted to validate these findings. The PNI is simple, inexpensive, and readily available from routine laboratory tests, making it feasible for integration into preoperative risk Patients with low PNI may benefit from closer surveillance, prehabilitation, or nutritionalAcimmune optimization prior to surgery. CONCLUSIONS Pre-operative PNI demonstrates a significant and independent prognostic factor for overall survival in patients with renal cell carcinoma. Patients with low PNI exhibited markedly worse survival outcomes, and PNI remained an independent predictor even after adjusting for tumor stage and metastasis. Given its simplicity, accessibility, and cost-effectiveness. PNI may serve as a valuable adjunct to conventional prognostic tools in clinical practice. Future multicenter prospective studies are warranted to validate these findings and to evaluate whether nutritional and immunological interventions can improve outcomes in patients with poor PNI. Acknowledgement The authors express their sincere gratitude to the urological surgical team at RSUP Dr. Sardjito. Indonesia, for their invaluable expertise and significant contributions to the surgical management of all patients involved in this study. Conflict of Interest All authors declare that there are no conflicts of interest Declaration the Use of AI in Scientific Writing This study utilized artificial intelligence (AI) tools and methodologies, including the AI-based language model ChatGPT, for language refinement . mproving grammar, structure, and readability of the manuscrip. All AI-assisted processes were thoroughly reviewed by the authors to ensure the integrity and reliability of the The final decisions, interpretations, and conclusions presented in this article were made solely by the authors. REFERENCES