Lower Blood Pressure-Induced Renal Hypoperfusion Promotes Cisplatin-Induced Nephrotoxicity

Abstract

Background and Aims: Cisplatin-induced nephrotoxicity primarily occurs in the proximal tubules, and tubular injuries reduce glomerular filtration rates. Lower blood pressure causes renal hypoperfusion, which promotes ischemic acute kidney injury (AKI). Our study examined the relationship between lower blood pressure-induced renal hypoperfusion and cisplatin-induced nephrotoxicity. Methods: The relationship between cisplatin use and hypoalbuminemia is not clear. This study consisted of Japanese patients who received cisplatin as the first-line chemotherapy at Fujita Health University Hospital from April 2006 to December 2012. Hypoalbuminemia was defined as serum albumin levels ≤3.5 mg/dl. Results: Patients who experienced lower blood pressure during chemotherapy were included in the lower blood pressure group (n = 229), and those who did not were included in the normal blood pressure group (n = 743). Total cisplatin dose in the normal blood pressure and lower blood pressure groups was 58.9 ± 23.8 and 55.0 ± 20.4 mg/m², respectively. The rate of severe nephrotoxicity was higher and overall survival was shorter in the lower blood pressure group than in the normal blood pressure group. In a multivariable analysis, lower blood pressure significantly correlated with hypoalbuminemia. Conclusions: To prevent ischemic AKI, nutrition and cachexia controlling are important parts of cancer treatment.

Causal relationship between hypoalbuminemia and acute kidney injury

“…Mizuno et al[55] demonstrated significantly lower serum albumin in patients receiving cisplatin as first-line chemotherapy who had low ( n = 229) vs normal ( n = 743) blood pressure (mean 3.73 g/dL vs 3.87 g/dL; P = 0.001), suggesting that hypoalbuminemia associates with low blood pressure, leading to renal hypoperfusion and thereby promoting ischemic AKI. Hypoalbuminemia was similarly associated with AKI in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome undergoing induction chemotherapy ( n = 537; 187 with AKI)[56].…”

Risk Factors Associated with Cisplatin-Induced Nephrotoxicity in Patients with Advanced Lung Cancer

“…In this study, we suggested that low Alb value is a risk factor of renal dysfunction, and several previous reports support these results. 12,26) Although sensitivity was definitely not high (56.8%) when using Alb values, a high Alb value is less likely to be a risk of renal dysfunction. Thus, close monitoring of changes in Alb value during CDDP treatment may prevent the development of CIN in these patients.…”

“…Previous studies have reported 12,26) on the relationship of CIN and Alb value. It has been suggested 12,37) that hypoalbuminemia reduces platinum excretion due to its effect on peritubular oncotic pressure and on the half-life of the CDDP, because the protein binding rate of the CDDP decreases and free CDDP increases, resulting in greater exposure to free CDDP.…”

“…Second, several previous studies reported that intravenous supplementation with Mg (magnesium) can prevent CIN. 26,38,39) Because our treatment protocol did not include Mg administration, we cannot state its efficacy in patients with these risk factors. Third, we defined the patients with a history of the cardiac disease such as angina and myocardial infarction as patients with cardiac disease in this study.…”

Prediction model of acute kidney injury induced by cisplatin in older adults using a machine learning algorithm

“…Although cisplatin is a “traditional anti-cancer agent,” it is used in combination chemotherapy with immune checkpoint inhibitors [ 25 , 26 ]. Since Cis-AKI is a risk factor for mortality [ 3 , 27 ] and therapeutic interventions for Cis-AKI are limited, preventing AKI improves the treatment outcome of cisplatin-based chemotherapy. The preventive approaches include hydration and magnesium administration; however, these approaches do not entirely prevent Cis-AKI.…”