Cisplatin-induced Nephrotoxicity In Patients Research Articles

Proton pump inhibitors may increase the risk of cisplatin-induced acute kidney injury in patients with nasopharyngeal carcinoma: a prospective cohort study

Cisplatin is the most commonly used platinum-based treatment for nasopharyngeal carcinoma (NPC). However, its clinical application is limited owing to its nephrotoxicity and gastrointestinal reactions. Proton pump inhibitors (PPIs) have been reported to increase nephrotoxicity risk in previous studies. We aimed to evaluate whether PPIs increase cisplatin-induced nephrotoxicity in patients with NPC. In total, 295 patients were included in this prospective cohort study: 145 in the PPIs group and 150 in the non-PPIs group. All patients underwent cisplatin-based induction chemotherapy, followed by cisplatin-based concurrent chemoradiotherapy. The PPIs group received 40 mg of intravenous esomeprazole sodium for 7 days in each chemotherapy cycle. Chi-squared test and logistic regression analyses with odds ratios and 95% confidence intervals were applied to assess the association between PPIs and the risk of acute kidney injury (AKI). AKI incidence in the PPIs group was significantly higher than that in the non-PPIs group (P = 0.005). After adjusting for various confounders including demographic features, clinical features, and renal function indices, PPIs use was significantly associated with a higher AKI risk (odds ratio: 2.775; 95% confidence interval 1.280–6.020; P = 0.010). The incidences of acute and chronic kidney diseases were similar between both groups (P > 0.05), whereas the incidence of nausea was lower in the PPIs group than in the non-PPIs group (P = 0.029). This study has shown that PPIs use may increase the risk of cisplatin-induced acute nephrotoxicity in patients with NPC.

Eliminating the need for preoperative intravenous hyperhydration: Sodium thiosulfate as nephrotoxicity prevention in HIPEC-treated patients – A retrospective analysis

BackgroundCytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is an effective treatment for peritoneal metastases. However, HIPEC with cisplatin is associated with renal toxicity. Sodium thiosulfate (ST) has been shown to prevent cisplatin-induced toxicity. MethodsA retrospective, single-center analysis of patients treated curatively for peritoneal surface malignancy, who underwent cytoreductive surgery with cisplatin-based HIPEC between 2015 and 2020. Patients were categorized into three groups based on the management of cisplatin-induced renal toxicity: preoperative hyperhydration alone (PHH), preoperative hyperhydration with ST (PHH + ST), and ST alone. Renal function and complications, in terms of Acute (AKI) and chronic kidney injury (CKI), were monitored and analyzed during 3 postoperative months. ResultsThis study included 220 consecutive patients. Mean serum creatinine levels were 95, 57 and 61 mmol/L, for PHH, PHH + ST and ST groups, respectively (p < 0.001). Glomerular Filtration Rate (GFR) were 96, 94 and 78 ml/min/1.73 m2, respectively (p < 0.001). AKI and CKI are respectively for PHH, PHH + ST and ST groups were 21 % (n = 46), 1 % (n = 2) and 0 % vs 19 % (n = 42), 0 % and 0 % (p < 0.001), for pairwise analysis did not show any difference between PHH + ST and ST alone combination, regarding nephrological outcomes. All patients were followed 3 months postoperatively. ConclusionThere is no need for preoperative hyperhydration when sodium-thiosulfate is used to prevent cisplatin-induced nephrotoxicity in patients undergoing cytoreductive surgery with HIPEC. These findings have implications for improving and simplifying the management of patients with peritoneal metastases undergoing HIPEC with cisplatin.

MiR-6805-5p as a biomarker of cisplatin-induced nephrotoxicity in patients with head and neck cancer

Introduction: The standard treatment for head and neck squamous cell carcinoma (HNSCC) is cisplatin chemoradiotherapy. One of the main treatment adverse reactions is nephrotoxicity, for which there is currently no adequate specific and sensitive biomarker. Thus, this study aimed to evaluate the use of microRNAs (miRNAs) as renal biomarker candidates.Methods: This was a retrospective cohort study. Nephrotoxicity was assessed through blood samples collected before and 5 days (D5) after chemotherapy. MiRNAs were extracted from urine samples collected at baseline and D5, and RNA sequencing identified miRNAs differentially expressed between participants with and without cisplatin-induced nephrotoxicity.Results: A total of 49 participants were included (n = 49). A significant difference was seen between the two groups for traditional renal markers (serum creatinine and creatinine clearance) and for the acute kidney injury (AKI) categories. Among the six miRNAs evaluated as biomarkers, four were upregulated (hsa-miR-6729-5p, hsa-miR-1238-5p, hsa-miR-4706, and hsa-miR-4322) and two were downregulated (hsa-miR-6805-5p and hsa-miR-21-5p), but only hsa-miR-6805-5p had a significant difference (p &amp;lt; 0.0001). Its receiver operating characteristic curve revealed excellent specificity (0.920) for its expression fluctuation assessment, while its absolute expression in D5 showed greater sensitivity (0.792).Conclusion: So, the integrated use of these two parameters seems to be an interesting approach for AKI.

Correlation between magnesium pre-loading and cisplatin-induced nephrotoxicity in 5-fluorouracil/cisplatin combination therapy for esophageal cancer.

The use of cisplatin may cause nephrotoxicity in patients. Hydration solutions supplemented with magnesium could reduce cisplatin-induced nephrotoxicity. In this study, we evaluated the preventive effect of magnesium pre-loading on cisplatin-induced nephrotoxicity in patients with esophageal cancer. We retrospectively evaluated the prevalence of, and risk factors for, nephrotoxicity in 160 patients with esophageal cancer treated with the 5-fluorouracil/cisplatin regimen from 2014 to 2016 with and without magnesium supplementation. Significant differences were observed between the magnesium and non-magnesium groups in terms of frequency of estimated creatinine clearance of grade 2 or higher that was at 4% (n = 3) and 13% (n = 10) (p = 0.027), respectively. The logistic regression analysis revealed that eCcr of grade 2 or higher was significantly associated with the non-magnesium regimen (odds ratio (OR), 4.175; 95% confidence interval (CI) = 1.061-16.430; p = 0.041) and age ≥ 65 years (OR, 13.951; 95% CI = 1.723-112.974; p = 0.014). This study suggests that 20 mEq magnesium pre-loading significantly reduces the prevalence of cisplatin-induced nephrotoxicity. Furthermore, when cisplatin is administered to individuals older than 64 years, a close observation for the onset of cisplatin-induced nephrotoxicity is crucial.

MiR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity in patients with head and neck cancer

BackgroundNo biomarker is available for identifying cancer patients at risk of developing nephrotoxicity when treated with cisplatin.MethodsWe performed microRNA (miRNA) sequencing using plasma collected 5 days after cisplatin treatment (D5) from twelve patients with head and neck cancer with and without nephrotoxicity (grade ≥ 2 increased serum creatinine). The most differentially expressed miRNAs between the two groups were selected for quantification at baseline and D5 in a larger cohort of patients. The association between miRNAs and nephrotoxicity was evaluated by calculating the odds ratio (OR) from univariate logistic regression. Receiver operating characteristic curves (ROC) were used to estimate the area under the curve (AUC), sensitivity, and specificity.ResultsMiR-3168 (p = 1.98 × 10− 8), miR-4718 (p = 4.24 × 10− 5), and miR-6125 (p = 6.60 × 10− 5) were the most differentially expressed miRNAs and were further quantified in 43, 48, and 53 patients, respectively. The baseline expression of miR-3168 (p = 0.0456, OR = 1.03, 95% CI: 1.00–1.06) and miR-4718 (p = 0.0388, OR = 1.56, 95% CI: 1.03–2.46) were associated with an increased risk of nephrotoxicity, whereas miR-6125 showed a trend (p = 0.0618, OR = 1.73, 95% CI: 0.98–3.29). MiR-4718 showed the highest AUC (0.77, 95% CI: 0.61–0.93) with sensitivity of 66.76 and specificity of 79.49.ConclusionsWe have provided evidence of baseline plasmatic expression of miR-3168, miR-6125, and miR-4718 as potential predictors of cisplatin-induced nephrotoxicity.

Identification of urinary candidate biomarkers of cisplatin-induced nephrotoxicity in patients with carcinoma

Nephrotoxicity limits the use of cisplatin (CP) in cancer therapy; however, current clinical measures of renal health do not reflect low degrees of kidney injury. Therefore, discovering new biomarkers for CP-induced acute kidney injury (AKI) is essential for monitoring kidney health during therapy. To identify novel candidate biomarkers in urine for reduced renal function due to CP therapy, we conducted a pilot study on cancer patients eligible for CP treatment. Urine from 30 patients was collected before (baseline) and after 3d of intravenous CP infusion. Urine samples were subjected to Isobaric Tag for Relative Absolute Quantitation (iTRAQ) analysis. Biological roles and pathways for the proteins with altered urine concentrations were identified using bioinformatic tools ITRAQ analysis detected 1411 proteins, 12 of which showed significantly altered levels. Growth differentiation factor-15 (GDF15), leucine-rich alpha-2-glycoprotein 1 (LRG1), and secreted phosphoprotein 1 (SPP1/ osteopontin, OPN) were identified as potential candidate markers by proteomic analysis and were validated by ELISA in another 30 patients and in a CP-induced AKI mouse model. Therefore, GDF15, LRG1, and SPP1 may be applied as novel candidate urinary markers of kidney injury after cisplatin treatment. These findings may facilitate the development of new methods to monitor kidney function, particularly in CP-based chemotherapy. SignificanceCisplatin is pivotal for cancer treatment; however, nephrotoxicity limits its use. Clinical measures for renal health are not reflective of early signs of acute kidney injury. Thus, new indicators of the state of renal health following cisplatin treatment will have to be discovered. This study reports the use of proteomics to mine for candidate markers of kidney injury in the urine of patients undergoing treatment with cisplatin. Results were experimentally validated using patient urine and a mouse model of cisplatin-induced acute kidney injury. The novel candidate biomarkers reported in this study may be used for the non-invasive monitoring of renal health and in mitigating the side-effects of cisplatin during the course of cancer treatment.

Evaluation of the Protective Effect of Cystone Against Cisplatin-induced Nephrotoxicity in Patients with Cancer: A Pilot Study.

Introduction:Cisplatin is a widely used anti-cancer drug that is commonly administered for the treatment of various cancers. However, nephrotoxicity is the most important side effect of this drug which limits its use. This study aimed to investigate the protective effect of Cystone against nephrotoxicity induced by Cisplatin in patients with cancer.Methods:This pilot clinical trial study was conducted on 43 cancer patients treated with Cisplatin (75 mg/m2 for a period of six months). The subjects were divided into treatment group (receiving Cystone, two per 8 hours; n = 21) and control group (n = 22). The two groups were compared with each other in terms of demographic and laboratory variables.Results:In the intervention group receiving Cystone, serum creatinine-based GFR level (P = 0.453) and 24-hour urine creatinine-based GFR level (P = 0.397) did not change significantly during the studied period, but in the control group, serum creatinine-based GFR level (P = 0.013) and 24-hour urine creatinine-based GFR level (P = 0.016) significantly changed. Serum creatinine-based GFR level increased by 2.3 units in the intervention group and 10.5 units in the control group (P = 0.005) in the six months of the study. At the end of the sixth month, 24-hour urine creatinine-based GFR level increased by 2.2 units in the intervention group and 0.8 unit in the control group (P = 0.008).Conclusions:The use of Cystone resulted in more stable kidney function indices in the intervention group, as compared with the control group. Therefore, Cystone seems to have a protective effect against nephrotoxicity induced by Cisplatin in cancer patients.

Nephrotoxicity Evaluation on Cisplatin Combined with 5-HT3 Receptor Antagonists: A Retrospective Study

Objective 5-HT3 receptor antagonist (ondansetron) has been reported to have nephrotoxic effect when combined with cisplatin in mice; however, little evidence exists in explaining its nephrotoxic effects on patients. The aim of this present study was to investigate whether 5-HT3 receptor antagonist could enhance or aggravate the incidence of cisplatin-induced nephrotoxicity in patients. Methods We retrospectively reviewed 600 tumor patients which were treated with cisplatin (⩾60 mg/m2) as a first-time chemotherapy and combined with 5-HT3 receptor antagonist (i.e., ondansetron, tropisetron, or ramosetron, each kind of 5-HT3 receptor antagonist contains 200 cases) between January 2010 and December 2015. Cisplatin dosing, the baseline creatinine clearance, and other independent risk factors such as patient's age, sex, PS score, and weight associated with nephrotoxicity were evaluated in a multivariable model. Results The incidence of Grade ⩾ 2 serum creatinine elevation in cisplatin + ondansetron group was significantly higher than cisplatin + tropisetron group (P = 0.04), but no significant difference was found between cisplatin + ondansetron group and cisplatin + ramosetron group (P = 0.3). It was also found that cisplatin dosage and tumor type were independent risk factors in the development of nephrotoxicity. Conclusion Higher cisplatin dosage and regular use of ondansetron combined with cisplatin are more likely to increase the incidence of nephrotoxicity; tropisetron showed the relatively mild effect on kidney function, suggesting that tropisetron is a preferable alternative in the process of cisplatin chemotherapy.

Renal protective effect of a hydration supplemented with magnesium in patients receiving cisplatin for head and neck cancer

BackgroundOur study analyzes the effect of magnesium supplementation on nephrotoxicity in patients receiving cisplatin for head and neck cancer.MethodsWe retrospectively reviewed the medical records of patients with head and neck cancer who received two doses of cisplatin (80 mg/m2) and 5-fluorouracil (800 mg/m2) 3 weeks apart from August 2008 to October 2012. The regimen prior to 2011 (crystalloid-only) involved the administration of 1000 mL of lactated Ringer’s solution on the day prior to cisplatin infusion and 2000 mL of continuous infusion of saline on the day of cisplatin infusion. The regimen after 2011 (magnesium-supplemented) did not involve hydration on the day before cisplatin administration but used 1000 mL of 0.9% saline with magnesium sulfate (20 mEq) administered for 3 hours before cisplatin infusion.ResultsSixty-five patients were treated with the crystalloid-only regimen and 56 patients with the magnesium-supplemented regimen. The mean creatinine clearance in the magnesium-supplemented group decreased by 4.9 mL/kg/min, whereas that in the crystalloid-only group decreased by 15.0 mL/kg/min after two courses. In multivariate analysis, only magnesium-supplemented hydration was an independent predictive factor for preventing cisplatin-induced nephrotoxicity (odds ratio = 0.157, 95% confidence interval 0.030–0.670, P = 0.0124).ConclusionWe demonstrated that an intravenous hydration regimen supplemented with magnesium prevented cisplatin-induced nephrotoxicity in patients with head and neck cancer.

Influence of magnesium and parathyroid hormone on cisplatin-induced nephrotoxicity in esophageal squamous cell carcinoma.

Magnesium (Mg) supplementation has previously been demonstrated to confer protective effects against nephrotoxicity induced by cisplatin. Parathyroid hormone (PTH) regulates Mg homeostasis. The aim of present study was to determine the protective effects of Mg supplementation against cisplatin-induced nephrotoxicity and its association with PTH levels in patients with esophageal squamous cell carcinoma (ESCC). A total of 55 patients with primary ESCC who received chemotherapy with high-dose cisplatin were examined. Mg was administered intravenously, and serum concentrations of PTH, parathyroid hormone-related protein (PTH-rP), creatinine and Mg were prospectively measured. Of the 55 patients, 37 received Mg supplementation. Post-chemotherapeutic creatinine concentrations were significantly increased in patients without Mg supplementation (P=0.01), with grade 1 and 2 increases of 22.2 and 5.6%, respectively, whereas these increases were suppressed by Mg supplementation (change in creatinine, P=0.21), with grade 1 and 2 increases of 8.1 and 0%, respectively. In addition, PTH and PTH-rP concentrations were high in 8 (14.5%) and 6 (10.9%) of all 55 patients, respectively. Alterations in creatinine concentrations (post-/pre-chemotherapy) due to chemotherapy were higher in patients with high levels of PTH regardless of Mg supplementation (P<0.01). Pre-therapeutic creatinine concentrations did not correlate with the alterations in creatinine concentrations due to chemotherapy. Intravenous Mg supplementation therefore conferred protective effects against cisplatin-induced nephrotoxicity in patients with ESCC. Furthermore, increases in PTH or PTH-rP may have influenced the extent of nephrotoxicity.

Pharmacogenomic Prediction of Cisplatin-Induced Nephrotoxicity in Patients Treated for Childhood Cancer

Pharmacogenomic Prediction of Cisplatin-Induced Nephrotoxicity in Patients Treated for Childhood Cancer

Multivariate analysis of risk factors for cisplatin-induced nephrotoxicity in gynecological cancer.

Risk factors for cisplatin-induced nephrotoxicity (CIN) vary by population. This study aimed to assess risk factors for CIN in patients with gynecological cancer. Patients who underwent cisplatin-based chemotherapy for gynecological cancer between January 2009 and December 2015 at Aichi Medical University School of Medicine were included in this study. CIN was defined according to the 'risk, injury, failure, loss, and end-stage kidney disease' (RIFLE) criteria and classified as either risk (Class R) or injury (Class I). Analyses were performed using univariate and multivariate logistic regression models. Among 112 patients enrolled, 30 had CIN. Multivariate analysis revealed that hydration with magnesium (odds ratio [OR], 0.223), history of cisplatin use (OR, 4.420), and hypoalbuminemia (OR, 4.170) were risk factors for Class R, and that frequency of cisplatin administration (OR, 5.620) and hydration with magnesium (OR, 0.216) were risk factors for Class I. This study confirmed that hydration without magnesium, history of cisplatin use, frequency of cisplatin administration, and hypoalbuminemia are significant risk factors for CIN.

Effect of Honey and Royal Jelly against Cisplatin-Induced Nephrotoxicity in Patients with Cancer

ABSTRACTObjectives: Cisplatin constitutes one of the most potent antineoplastic drugs; however, nephrotoxicity limited its eligibility for optimal clinical use. This study was designed to evaluate the role of honey and royal jelly with antioxidant properties in the protection of cisplatin-induced acute kidney injury in patients with cancer.Methods: Patients with cancer assigned for cisplatin chemotherapy were randomly divided into bee honey and royal jelly groups pretreated before the initiation and during cisplatin chemotherapeutic regimen and control group on cisplatin only. Serum creatinine and urea levels were measured before and after the chemotherapeutic cycle and over 2 cycles.Results: Patients on crude bee honey and royal jelly capsules showed lower serum levels of renal injury products (creatinine and urea) compared to those in the control group. The changes in kidney parameters were significantly (p < 0.05) lower when compared within the bee honey group before and after cisplatin treatment. Royal jelly was found to be effective; however, the difference in creatinine and urea levels before and after chemotherapy was not statistically significant.Conclusions: The use of bee honey and royal jelly as natural compounds is effective in reducing cisplatin nephrotoxicity and may offer a promising chance for clinically meaningful prevention. This study has potentially important implications for the treatment of cisplatin kidney side effects and is considered to be the first to investigate this effect of honey and royal jelly in human subjects. However, due to its small sample size, we recommend further investigation using a larger sample size.

Ameliorative effect of lycopene effect on cisplatin-induced nephropathy in patient.

Background: Nephrotoxicity is one of the most important limitations of cisplatin-based chemotherapies which associated with many complications and high mortality rate. Objectives: To investigate the effect of lycopene on cisplatin-induced nephrotoxicity in patients with cancer. Patients and Methods: In this double-blind, randomized clinical trial, 120 patients were randomly assigned to two groups, case (treated with lycopene + standard regimen of kidney injury prevention) and control (treated with only the standard regimen of kidney injury prevention). Lycopene was orally taken from 24 hours before to 72 hours after cisplatin administration. Blood urea nitrogen (BUN), serum creatinine (Cr), and glomerular filtration rate (GFR) were measured and recorded. The data were analyzed using SPSS. Results: Changes in Cr were not significantly different between the two groups (P = 0.131). However, a significant decreasing trend was seen in GFR during the study, which was more marked in the control group (P = 0.004). BUN significantly decreased during the study (P = 0.002), and a significant decrease of BUN on the day three in both groups was seen (P = 0.001). However, BUN increased in the case group on the day 21 of treatment. The corresponding increase was less marked in the control group. Conclusions: Lycopene can be considered a useful adjuvant therapy to decrease the complications due to cisplatin-induced nephrotoxicity in patients with cancer.

SY-1-1 - Urinary biomarkers of acute kidney injury in anti-cancer drug treatment

Clinically acute kidney injury (AKI) is characterized by a rapid reduction in kidney function resulting in a failure to maintain fluid, electrolyte and acid-base homeostasis. The traditionally used markers to detect and monitor the progression of AKI, including serum creatinine, creatinine clearance and blood urea nitrogen levels, are insensitive and nonspecific. Until now, urinary biomarkers to detect AKI were reported such as kidney injury molecule (KIM) 1, neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein (MCP)-1. However, whether these urinary biomarkers can detect drug-induced AKI accurately in the clinical settings remains unclear. Therefore, in the present study, we examined whether the recently discovered urinary biomarkers for AKI can detect cisplatin-induced nephrotoxicity in patients with lung cancer. Among several potential biomarkers, we measured KIM-1, MCP-1, NGAL, N-acetyl-β-D-glucosaminidase, and β 2-microglobulin concentrations in urine samples from 11 patients with lung cancer. These samples were collected the day before cisplatin administration and on days 3, 7, and 14 after the administration. Receiver operating characteristics curve analyses revealed that KIM-1 and MCP-1, but not NGAL, could detect AKI with high accuracy (area under the curve [AUC] = 0.858, 0.850, and 0.608, respectively). The value of AUC was increased in the combination of KIM-1 and MCP-1 compared to either alone. These results suggest that some urinary biomarkers specific for each anticancer drug can help find drug-induced AKI prior to the next administration.

Influence of Renal ABC and SLC Transporter Polymorphisms on Cisplatin-induced Nephrotoxicity in Patients with Esophageal Cancer

Background: The individual and collective contributions of genetic polymorphisms in drug transporter genes in human renal proximal tubules to cisplatin-induced nephrotoxicity are still unclear. Methods: In this study, we investigated the effects of polymorphisms in SLC22A2 (808G>T), SLC31A1 (rs10981694A>C, rs12686377G>T, rs7851395A>G), SLC47A1 (rs2289669G>A), ABCB1 (1236C>A, 2677G>T/A, 3435C>T), ABCC2 (-24C>T), and ABCG2 (421C>A) on cisplatin-induced nephrotoxicity in 131 patients with esophageal cancer receiving 5-fluorouracil and cisplatin (FP) chemotherapy. The change rate of the estimated glomerular filtration rate (eGFR) was calculated according to the following formula: eGFR before FP chemotherapy-lowest eGFR during first cycle after FP chemotherapy)/eGFR before FP chemotherapy. Results: In univariate analysis, there was a significant correlation between patient age and the change rate of the eGFR by cisplatin (P = 0.021). However, there were no significant differences in the change rate of the eGFR by cisplatin between SLC22A2, SLC47A1, SLC31A1, ABCB1, ABCC2, and ABCG2 polymorphisms. Multivariate analysis revealed that only age was an independent variable predicting a higher risk of cisplatin-induced acute renal dysfunction. Conclusion: In FP chemotherapy for esophageal cancer patients, cisplatin-induced nephrotoxicity was not affected by polymorphisms in the uptake transporters OCT2 and Ctr1 or efflux transporters MATE1, P-glycoprotein, MRP2, and BCRP. Since degradation of renal function due to aging reduces cisplatin clearance, the cisplatin dosage should be carefully chosen in elderly patients.

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

Cisplatin (CDDP) combination chemotherapy is widely administered to patients with advanced lung cancer. The dose depends on multiple factors, including whether the tumor is non-small-cell lung cancer (NSCLC) or small-cell lung cancer (SCLC). Although efficacy is limited by cisplatin-induced nephrotoxicity (CIN), little is known about the risk factors for this complication. The aim of this study was to identify the risk factors for CIN in patients with advanced lung cancer, both NSCLC and SCLC. We retrospectively reviewed clinical data for 148 patients who underwent initial chemotherapy including CDDP ≥50 mg/m2 per patient per day for the first course at Kyushu Medical Center between October 2010 and September 2013. All data were collected from the electronic medical record system. Nephrotoxicity was defined as an increase in serum creatinine concentration of at least grade 2 during the first course of CDDP chemotherapy, as described by the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. CIN was observed in nine patients. Univariate analysis revealed that cardiac disease and lower baseline serum albumin (Alb) values conferred a higher risk of nephrotoxicity (p<0.05). The cut-off value of Alb was 3.8 g/dL, calculated by receiver operating characteristics (ROC) curves. Multivariable logistic regression analysis revealed that cardiac disease (odds ratio=11.7; p=0.002) and hypoalbuminemia (odds ratio=6.99 p=0.025 significantly correlated with nephrotoxicity. In conclusion, cardiac disease and low baseline Alb values are possible risk factors for CIN.

Contribution of Organic Cation Transporter 2 (OCT2) to Cisplatin-Induced Nephrotoxicity

Cisplatin is one of the most widely used anticancer agents for the treatment of solid tumors. The clinical use of cisplatin is associated with dose-limiting nephrotoxicity, which occurs in one-third of patients despite intensive prophylactic measures. Organic cation transporter 2 (OCT2) has been implicated in the cellular uptake of cisplatin, but its role in cisplatin-induced nephrotoxicity remains unknown. In mice, deletion of Oct1 and Oct2 resulted in significantly impaired urinary excretion of cisplatin without an apparent influence on plasma levels. Furthermore, the Oct1/Oct2-deficient mice were protected from severe cisplatin-induced renal tubular damage. Subsequently, we found that a nonsynonymous single-nucleotide polymorphism (SNP) in the OCT2 gene SLC22A2 (rs316019) was associated with reduced cisplatin-induced nephrotoxicity in patients. Collectively, these results indicate the critical importance of OCT2 in the renal handling and related renal toxicity of cisplatin and provide a rationale for the development of new targeted approaches to mitigate this debilitating side effect.

Effect of concurrent medications on cisplatin-induced nephrotoxicity in patients with head and neck cancer

The goal of this study was to identify clinical characteristics and concurrent medications associated with an increased or decreased incidence of cisplatin-induced nephrotoxicity. The medical records for 62 subjects with head and neck cancer who received cisplatin 100 mg/m2 (day 1) plus fluorouracil 1000 mg/m2 (days 1-5) with or without radiation therapy were reviewed from three medical centers. The demographics, concurrent medication therapy, co-existing illnesses and clinical laboratory values were extracted from the medical records. Nephrotoxicity was defined as a minimum rise in serum creatinine of 0.5 mg/dl or above. The concurrent use of hydrochlorothiazide or multivitamins was associated with a higher incidence of nephrotoxicity after cycle 1. Use of albuterol, atenolol or hydrochlorothiazide was also associated with a higher incidence of nephrotoxicity after cycle 1 or 2. In contrast, subjects prescribed dexamethasone or ondansetron were less likely to experience nephrotoxicity. None of these medications affected treatment response. Race/ethnicity was independently correlated with the incidence of nephrotoxicity; African-American subjects were more likely to develop nephrotoxicity independent of the influence of these concurrent medications. Medications may modulate cisplatin-induced nephrotoxicity by altering the metabolic activation of cisplatin to a nephrotoxin. Genetic differences in the drug-metabolizing enzymes may contribute to the correlation with race. The results from this retrospective study provide data to support a larger prospective study to further investigate the associations between these concurrent medications and cisplatin-induced nephrotoxicity.