Abstract
Background/Aim: Acute kidney injury (AKI) is one of the most frequent adverse effects induced by cisplatin (CDDP). One clinical indicator of CDDP-induced AKI is urine output, which reflects water balance; however, urine collection can expose healthcare workers to anticancer drugs. An alternative monitoring approach for CDDP-induced AKI is weight-based assessment of fluid balance. Although previous studies have evaluated the relationship between body weight change and CDDP-induced AKI, few have evaluated the amount of water ingested. Therefore, we evaluated water intake, urine output, and body weight changes in patients treated with CDDP to determine the utility of weight monitoring as an indicator of fluid balance during CDDP-based chemotherapy.
Patients and Methods: We evaluated 15 patients who received CDDP-vinorelbine as postoperative adjuvant chemotherapy for non-small cell lung cancer from March to December 2019. Patients recorded their oral fluid intake, and body weight changes were evaluated on days 2-4 relative to baseline on day 1.
Results: No cases of CDDP-induced AKI occurred. Compared with day 1, urine output decreased on day 2 but recovered on day 3. Body weight fluctuations were highest (+3.6 kg) on day 3 and started decreasing on day 4. Serum creatinine and estimated glomerular filtration rate did not differ significantly pre- and post-chemotherapy. A positive correlation was observed between water balance and next-morning weight change (r=0.68).
Conclusion: Weight monitoring may reduce healthcare workers’ exposure to anticancer agents while serving as a practical indicator of fluid balance during CDDP-based chemotherapy.
Introduction
Lung cancer, which is broadly classified into small cell lung cancer and non-small cell lung cancer (NSCLC) based on its histological type, remains the leading cause of cancer-related deaths worldwide, with NSCLC accounting for approximately 80% of all lung cancer cases (1, 2). Cisplatin (CDDP)-vinorelbine (NP regimen) is a postoperative adjuvant chemotherapy regimen that improves survival in patients with pathological stage II-IIIA NSCLC after complete resection (3). However, CDDP is associated with dose-limiting nephrotoxicity, resulting in a high incidence (20-30%) of CDDP-induced acute kidney injury (AKI) (4, 5). Early detection of renal dysfunction in patients receiving chemotherapy is pivotal, as the severity of renal impairment may adversely affect life expectancy (6). Following administration of CDDP, approximately 90% binds to plasma proteins, whereas the remaining 10% exists in an unbound form (7). In addition to glomerular filtration, free CDDP is excreted into the urine via tubular secretion. The mechanism of CDDP-induced AKI is thought to involve the uptake and accumulation of free CDDP in the proximal tubular epithelial cells, leading to tubular necrosis (8, 9). Free CDDP, a key contributor to the development of AKI, is excreted from the body approximately 2 h after administration (7); therefore, rapid elimination of free CDDP is critical for preventing AKI. Adequate hydration prior to CDDP administration is widely recognized as an essential preventive measure to maintain urine output and mitigate the risk of AKI.
The initial manifestations of CDDP-induced AKI are often subtle and typically present as non-oliguric renal failure (10). Oliguric renal injury may occur in cases of severe tubular damage caused by CDDP administration and is often accompanied by uremic symptoms, including headache, nausea, vomiting, inappetence, and malaise (10). Given the lack of early subjective symptoms, it is difficult for patients to detect CDDP-induced AKI at an early stage. A common clinical indicator of CDDP-induced AKI is the measurement of urine output to assess fluid balance (11). However, because patients’ urine may contain residual anticancer agents, urine collection should be avoided to reduce the risk of occupational exposure among healthcare providers. Therefore, monitoring changes in body weight has been proposed as an alternative approach to assess fluid balance (10). Although Koshikawa et al. (11) reported an association between weight gain and the onset of CDDP-induced AKI in patients receiving CDDP, few studies have examined patient fluid intake in detail. Therefore, the aim of this study was to investigate the relationship between water balance and daily body weight change during CDDP-based chemotherapy, and to evaluate the clinical utility of body weight monitoring as an indicator of fluid status.
Patients and Methods
Study design and patients. A total of 15 patients who received the NP regimen as postoperative adjuvant chemotherapy for NSCLC between March and December 2019 were included in this study. Patient data were analyzed retrospectively using anonymized medical records. This study was conducted in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of the Niigata Cancer Center Hospital (approval no. 1331).
Intervention. Patients received CDDP at a dose of 80 mg/m2 and vinorelbine at a dose of 25 mg/m2 as postoperative adjuvant chemotherapy. To prevent the risk of CDDP-induced AKI, patients received intravenous fluids totaling 2,050 ml on day 1, followed by 1,050 ml on days 2 and 3. Patients were instructed to maintain an oral intake of at least 1,000 ml (Table I) and received 300 ml of 20% D-mannitol solution as an osmotic diuretic, as well as fosaprepitant as an antiemetic, on day 1. On day 4, only minimal intravenous fluid (50 ml) was administered for line maintenance. The collected data included age, sex, body weight, body mass index, serum creatinine level, estimated glomerular filtration rate (eGFR), CDDP dosage, concomitant use of non-steroidal anti-inflammatory drugs, history of hypertension, diabetes, chronic renal failure, heart failure, urine output, oral fluid intake, and number of chemotherapy cycles. All data were extracted retrospectively from the patients’ medical records. Oral fluid intake was recorded by the patients themselves. Body weight change was defined as the change from baseline body weight measured on day 1 prior to CDDP administration. Serum creatinine levels and eGFR were measured on days 0 (prior to CDDP administration) and 15. To assess whether water balance was reflected in next-morning body weight change, water balance (intravenous fluid volume + oral fluid intake − urine output) was plotted on the horizontal axis, and body weight change relative to day 1 was plotted on the vertical axis. The correlation between water balance and next-morning body weight change was subsequently examined.
Electrolyte composition and total infusion volume of intravenous fluids.
Statistical analysis. Statistical analyses were performed using EZR software version 1.68 (Saitama Medical Center, Jichi Medical University, Saitama, Japan) (12). The paired t-test was used to compare serum creatinine levels and eGFR values before (day 0) and after chemotherapy (day 15). Pearson’s product-moment correlation coefficient was used to assess the correlation between water balance and next-morning body weight change. A p-value of <0.05 was considered statistically significant.
Results
Patient characteristics are summarized in Table II. No cases of CDDP-induced AKI were observed among the patients, and no patient required supplemental fluids beyond the study protocol. Two patients experienced grade 2 adverse events during the first cycle (one with nausea and one with malaise). In both cases, treatment was discontinued after the second course at the patients’ request. The total fluid intake [(median (min-max)], defined as the sum of intravenous fluids and oral fluid intake, was 4,075 ml (3,210-5,350 ml) on day 1, 2,800 ml (1,250-5,850 ml) on day 2, and 2,350 ml (1,350-6,900 ml) on day 3 (Figure 1). Urine volume [median (min-max)] was 4,064 ml (2,262-6,011 ml) on day 1, 2,515 ml (1,175-4,377 ml) on day 2, and 3,609 ml (1,838-5,115 ml) on day 3 (Figure 2A). Compared with day 1, urine volume on day 2 decreased to approximately 60% of the day 1 value but recovered to a level comparable to that on day 1 by day 3. The median (min-max) change in body weight from day 1 was +0.7 kg (−1.1 to +1.2 kg) on day 2, +1.0 kg (−0.8 to +3.6 kg) on day 3, and −0.25 kg (−2.0 to +2.4 kg) on day 4 (Figure 2B). Body weight change from day 1 showed a maximum increase of +3.6 kg on day 3 and subsequently began to decrease on day 4. Urine volume and body weight showed temporal changes across days (Figure 2A and B). Serum creatinine levels did not differ significantly before and after chemotherapy (0.83 mg/dl vs. 0.81 mg/dl, respectively; p=0.124). Similarly, eGFR values were not significantly different before and after chemotherapy (64.7 ml/min/1.73 m2 vs. 69.6 ml/min/1.73 m2, respectively; p=0.312). A positive correlation (r=0.68, Pearson’s correlation coefficient) was observed between water balance (intravenous fluid volume + oral fluid intake − urine output) and next-morning body weight change (Figure 3).
Patient characteristics.
Total fluid intake. Intravenous fluid replacement was administered on days 1-3 (day 1, 2,050 ml; days 2 and 3, 1,050 ml). Total fluid intake, defined as the sum of oral fluid intake and intravenous fluids, is 4,075 ml [median (min-max), 3,210-5,350 ml] on day 1, 2,800 ml (1,250-5,850 ml) on day 2, and 2,350 ml (1,350-6,900 ml) on day 3.
Urine volume (A) and body weight change (B). These parameters show opposite temporal trends, suggesting transient water retention followed by subsequent fluid clearance. Urine volume [median (min-max)] is 4,064 ml (2,262-6,011 ml) on day 1, 2,515 ml (1,175-4,377 ml) on day 2, and 3,609 ml (1,838-5,115 ml) on day 3. The change in body weight [median (min-max]) from day 1 is +0.7 kg (−1.1 to +1.2 kg) on day 2, +1.0 kg (−0.8 to +3.6 kg) on day 3, and −0.25 kg (−2.0 to +2.4 kg) on day 4.
Water balance and body weight change. Change in body weight from day 1 is plotted on the vertical axis, and water balance (intravenous fluid volume + oral fluid intake − urine output) is plotted on the horizontal axis. A positive correlation is observed between water balance and next-morning body weight change (r=0.68).
Discussion
CDDP-induced AKI is generally a reversible form of renal dysfunction, typically presenting as non-oliguric renal failure. However, Koshikawa et al. (11) reported a transient decrease in urine output after CDDP administration even in patients without AKI, likely due to a temporary decline in renal function leading to water retention. A similar finding was observed in the present study, in which urine output transiently decreased on day 2. These observations suggest that even non-oliguric renal dysfunction may be accompanied by a temporary reduction in urine output. In our study, urine output began to recover on day 3, whereas body weight peaked on day 3 and subsequently decreased on day 4. This temporal pattern indicates that changes in urine volume and body weight after CDDP administration may occur in opposite directions, reflecting transient water retention followed by subsequent fluid clearance.
Monitoring urine output is commonly performed for the early detection of serious CDDP-induced AKI (11). Serious CDDP-induced AKI is most often characterized by a ≥50% increase in serum creatinine from baseline occurring 3-4 days after CDDP administration (13, 14). CDDP-induced AKI is exacerbated in a dose-dependent manner, and severe CDDP-induced AKI accompanied by extensive tubular necrosis can result in irreversible renal failure (10, 15). Therefore, when CDDP-induced AKI with marked tubular damage develops, oliguric renal dysfunction is expected to occur within 3-4 days after CDDP administration. In this study, a positive correlation was observed between water balance and next-morning weight change under the hydration conditions used. This finding suggests that reduced urine output may contribute to subsequent body weight gain, reflecting changes in fluid balance. Taken together, a decrease in body weight after day 4 may reflect recovery from transient fluid retention under the hydration conditions used in this study. In contrast, Maeda et al. (16) reported a case of CDDP-induced AKI in which body weight decreased on day 4 compared with day 3. However, their patient received a 5-fluorouracil plus CDDP regimen and an intravenous fluid load that differed substantially from that used in our study (2,500 ml on day 1 and 2,000 ml on days 2-5). Despite this fluid load, a consistent trend of weight gain was observed. In addition, Maeda et al. reported the presence of edema in the patient. These findings suggest that fluid retention is an important factor to consider when monitoring patients receiving CDDP-based chemotherapy. While measurements of urine output are important for the early detection of CDDP-induced AKI, monitoring edema and body weight is also crucial.
CDDP is a known carcinogen and reproductive toxicant (17), and healthcare workers may be exposed to it through patients’ body fluids, such as urine (17, 18). Therefore, monitoring patients’ body weight represents a practical approach to reducing occupational exposure to CDDP.
The short-hydration method, which reduces the duration of hydration required for CDDP administration, has recently gained attention in Japan (19, 20). Therefore, the use of CDDP in outpatient chemotherapy settings is expected to increase. Renal dysfunction is commonly assessed using biomarkers such as serum creatinine, urinary neutrophil gelatinase-associated lipocalin, cystatin C, and the urinary albumin-to-creatinine ratio (13, 21). Biomarkers of renal dysfunction can be readily measured in the inpatient setting. Conversely, frequent measurement of renal dysfunction biomarkers or urine output is challenging in outpatient chemotherapy settings, whereas body weight can be monitored easily. Our findings suggest that body weight may serve as a practical indicator of fluid balance and is applicable to patients undergoing outpatient chemotherapy.
Study limitations. First, this was a retrospective study with a small sample size conducted at a single center using a single chemotherapy regimen. Second, because no patients in this study developed CDDP-induced AKI, the trends in urine output and body weight in patients with CDDP-induced AKI could not be evaluated in this study.
Conclusion
Severe CDDP-induced AKI can be life-threatening, and patients often exhibit few subjective symptoms in its early stages. In addition, few studies have investigated water balance and body weight changes in patients at risk of CDDP-induced AKI. Therefore, our findings provide additional insight into water intake, body weight fluctuations, and urinary volume trends after CDDP administration. Among patients with NSCLC receiving the NP regimen as postoperative adjuvant chemotherapy, body weight monitoring may serve as a valuable indicator of fluid balance while also reducing occupational exposure to anticancer agents among healthcare workers.
Acknowledgements
The Authors would like to thank Editage (www.editage.jp) for English language editing.
Footnotes
Authors’ Contributions
N. Odaira, M. Yoshino and J. Kanda conceived the study and drafted the manuscript. N. Odaira, M. Yoshino, K. Yamashita, Y. Tanaka, C. Higuchi, A. Gocho, M. Ueda, A. Kato, C. Tagawa, N. Sasaki, R. Katsuyama, and K. Aoyagi collected the data and performed the analysis. All Authors read and approved the final manuscript.
Conflicts of Interest
The Authors declare that they have no conflicts of interest in relation to this study.
Funding
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Artificial Intelligence (AI) Disclosure
No artificial intelligence (AI) tools, including large language models or machine learning software, were used in the preparation, analysis, or presentation of this manuscript.
- Received January 5, 2026.
- Revision received February 3, 2026.
- Accepted February 4, 2026.
- Copyright © 2026 The Author(s). Published by the International Institute of Anticancer Research.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
References
Jump to section
Related Articles
Cited By...
- No citing articles found.