Cisplatin is a platinum-based antineoplastic drug that is widely prescribed alone or in combination for the treatment of patients with solid-organ tumors.1 The drug’s side effects include ototoxicity, gastrointestinal distress, serum electrolyte disturbances, hyperuricemia, neurotoxicity, nephrotoxicity, ocular toxicity, hepatotoxicity, and myelosuppression.2,3 The prevention and management of cisplatin-induced toxicities are of great benefit, because these adverse events can be irreversible.
Cisplatin-induced nephrotoxicity is a major dose-limiting adverse event associated with the drug that can occur despite preventive measures. According to Miller and colleagues, approximately 20% to 30% of patients who receive cisplatin will have acute renal injury.1 High rates of nephrotoxicity are attributed to the elevated levels of cisplatin accumulation within renal parenchymal cells, compared with the blood and other organs.1 Multiple cellular mechanisms have been attributed to the induction and exacerbation of nephrotoxicity. One mechanism includes the entry of cisplatin into the cell via the transporters organic cation transporter 2 and copper transporter 1.1,4 Once inside the cell, the cisplatin binds to chromosomal and mitochondrial DNA, forming inter- and intrastrand cross-links. This disrupts the DNA structure, which ultimately leads to the induction of caspase-dependent and independent cell apoptotic pathways.1,4,5 Extrinsic apoptotic pathways include the activation of the Fas system and the activation of tumor necrosis factor (TNF) receptors via an increase in intracellular reactive oxygen species. The induction of TNF-alpha is involved in the inflammatory process, which can exacerbate nephrotoxicity.1,4,5
Multiple definitions of nephrotoxicity are available in the literature, making study comparisons difficult. The validated criteria for classifying acute kidney injury previously used in studies include the Risk, Injury, Failure, Loss, and End-Stage Kidney Disease (RIFLE) crite ria, as well as the Acute Kidney Injury Network (AKIN) criteria. The RIFLE criteria are defined by glomerular filtration rate (GFR) and urine output, and include the 5 classifications of risk, injury, failure, loss, and end-stage kidney disease.6 The AKIN criteria are defined by serum creatinine (SCr) levels and urine output and include stages 1, 2, and 3.7
Over the past several years, evidence has suggested that the original RIFLE criteria did not identify 9% of cases detected by the AKIN criteria, and that AKIN did not detect 26.9% of acute kidney injury cases detected by RIFLE.7 Furthermore, cases missed by the AKIN criteria were generally the RIFLE injury and failure classifications, whereas the RIFLE criteria generally missed AKIN stage 1 acute kidney injury cases.7
In 2012, the Kidney Disease Improving Global Outcomes (KDIGO) guideline proposed a new set of acute kidney injury criteria, which coalesced previous RIFLE and AKIN criteria.7 The new definition includes 3 stages that are defined by SCr or GFR changes, or by urine output (Table 1).7 In addition, the National Cancer Institute (NCI) published Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 in 2009, which lists common toxicities to chemotherapy medicines, including those related to SCr.8 The NCI toxicity grading system uses SCr changes to define acute kidney injury toxicity and includes 4 grades (Table 1).8
No toxicity grading system is used universally, but the signs of renal injury from cisplatin are generally understood to begin approximately 3 to 5 days after a dose of cisplatin, which is evidenced by increases in SCr, blood urea nitrogen (BUN), and serum uric acid.1,2 Other renal manifestations of cisplatin include hypomagnesemia, hypokalemia, hypocalcemia, renal salt wasting, proteinuria, thrombotic microangiopathy, Fanconi-like syndrome, and erythropoietin deficiency.1,2,9,10
The dosage guidelines for cisplatin indicate that doses of the drug should not be repeated until the SCr is <1.5 mg/dL and/or the BUN is <25 mg/dL.2 The guidelines also state that renal toxicity can be more severe and prolonged with repeat dosing, and that cisplatin should not be given more frequently than once every 3 to 4 weeks, to allow for renal and electrolyte recovery.2,3 In addition, doses greater than 100 mg/m2 per cycle should be reevaluated by the physician.2 The current dosing guidelines do not specify how changes in SCr, BUN, and serum uric acid levels should be evaluated, nor do they address the newer definitions of acute kidney injury or preventive measures to reduce cisplatin-induced kidney injury.
The purpose of this study was to evaluate the predisposing factors to cisplatin-induced nephrotoxicity and the possible implementation of preventive measures.
This retrospective chart review was conducted between January 2012 and January 2015 at the Hennepin County Medical Center Cancer Center in Minneapolis, MN, in patients with cancer who met certain inclusion criteria. Inclusion criteria included age ≥18 years and patients who had received ≥1 doses of cisplatin in the outpatient or the inpatient setting. Patients were excluded from the study if they were under age 18 years, had not been administered a dose of cisplatin during the specified time frame, or if they opted out of research studies, as evidenced by the annual information disclosure form. Institutional Review Board forms were submitted and were approved at the Minneapolis Medical Research Foundation and the University of Minnesota.
The data were collected and tabulated for each patient, including the patient’s age, sex, smoking status, mean cisplatin dose administered, actual mean frequency of cisplatin administration, total number of doses in the course of treatment, body surface area and weight at time of dose, relevant medical history, relevant medications, and relevant laboratory values.
In addition to a cancer diagnosis, the relevant medical conditions included a diagnosis of congestive heart failure; hepatorenal syndrome; preexisting incidence and status of renal insufficiency, acute renal failure, acute renal injury (within 1 month of the first cisplatin dose and up to the day before the first cisplatin dose was given to a patient), and/or chronic kidney disease; diabetes; recent hypovolemia, recent surgery (not including port placement), or recent sepsis (recent for hypovolemia, surgery, and sepsis was defined as within 2 weeks of the first cisplatin dose administration and up to the last dose given); and cardiovascular conditions, including hypertension, dyslipidemia, history of myocardial infarction, history of ischemic or hemorrhagic stroke, history of thrombosis, arrhythmia, heart valve problems, congenital heart defects, and coronary heart diseases.
The relevant medications included any combination of chemotherapy; agents used for nephrotoxic preventive measures, including furosemide or hydration regimens; and medications associated with acute kidney injury, such as nonsteroidal anti-inflammatory drugs (NSAIDs), vancomycin, aminoglycosides, angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), and others, as listed by Choudhury and Ahmed.11
The relevant laboratory values include BUN; SCr; serum albumin; GFR, as calculated by the Jelliffe equation; serum potassium; and serum magnesium levels. All levels were collected at baseline, and the day of or day before the first dose of cisplatin. The Jelliffe equation is used, because it is the standard of practice at this site and does not require ideal body weight calculation. Peak levels of BUN and SCr, and trough levels of serum albumin, serum magnesium, serum potassium, and GFR were collected during the course of the cisplatin treatment and up to 4 weeks after the last dose of cisplatin. The time (in days) for the return to baseline of SCr, GFR, serum potassium, and serum magnesium was recorded. If the values did not return to baseline within 4 weeks, the new baseline laboratory values were recorded for the continuation of treatment.
Nephrotoxicity was evaluated using the KDIGO 2012 Acute Kidney Injury criteria and the NCI CTCAE.7,8 The demographic and clinical characteristics were evaluated per patient and were grouped into 2 cohorts. The first cohort includes patients in which renal changes were observed (ie, SCr increase of >15% from baseline), and the second cohort includes patients in which no renal changes were observed (ie, SCr increase of <15% from baseline).
The statistical analysis that was performed included a 2-sample t-test and a 2-population proportion z-test using Microsoft Excel (2016). A P value of <.05 was considered to be significant.
Of the 109 patients identified as having received cisplatin within the 3-year time frame, a total of 58 patients met the inclusion criteria. In all, 51 patients were excluded from the study; 10 patients did not receive cisplatin during the specified time frame, and 41 patients opted out of research. Of the 58 patients included in the study, 69% were male, 31% were female, and the mean age was 59.5 years (Table 2).
Cisplatin was used for the treatment of head and neck cancer in 26% of the patients, non–small-cell lung cancer (22%), small-cell lung cancer (19%), gastroesophageal cancer (10%), bladder cancer (9%), anal cancer (3%), cholangiocarcinoma (3%), neuroendocrine tumor (3%), squamous renal cancer (2%), and testicular cancer (2%; Table 2).
The 45 patients who had an SCr increase of ≥15% from baseline were grouped together as patients who had a renal function decline (Table 3). The 13 patients who did not have an SCr change of >15% were considered the nonaffected group. No statistical difference was noted between these 2 groups with regard to age, sex, smoking status, frequency of recent acute kidney injury, chronic kidney disease, congestive heart failure, diabetes, recent surgery or sepsis, and cardiovascular diseases. In patients who had a change in creatinine, hypovolemia (within the first 2 weeks of cisplatin dosing) occurred in 29% of the patients with a renal function decline compared with only 8% of patients without a creatinine change.
The mean dose given was the same between the 2 groups (65 mg/m2 vs 61 mg/m2; P = .63), with a mean frequency of 21 (±8 standard deviation [SD]) days and 19 (±10 SD) days (P = .62; Table 3). Weight and body surface area were also similar between the groups. The baseline SCr was slightly lower, at 0.77 mg/dL for the patients with a renal function decline and 0.88 mg/dL for the group with no renal function change (P = .08). Patients who were hospitalized and received treatment in the inpatient setting were more likely to have a renal function change than patients who received treatment in the outpatient setting (40% vs 23%; P = .26; Table 3). The mean SCr peak level during cisplatin treatment was 1.74 mg/dL and 0.92 mg/dL (P = .002), and the mean change in SCr from baseline was 0.97 mg/dL and 0.05 mg/dL (P = .0003), or 2.22 and 1.04 times the baseline SCr (P = .00009) for the patients with renal function decrease and patients with no renal function change, respectively.
The mean number of days to reach peak SCr was 10 (±9 SD) days, and 36% of patients that had a SCr peak did not return to SCr baseline levels within 4 weeks. It took 16.5 (±22 SD) days for those patients with renal dysfunction to return to baseline SCr levels (Table 3). The baseline GFR was 113.8 mL/min and 101.1 mL/min (P = .15), and the lowest mean GFR during treatment was 67.1 mL/min and 96 mL/min (P = .001) for the patients with renal function decrease versus patients with no renal function change, respectively. The baseline BUN was 13.6 mEq/dL and 12.6 mEq/dL (P = .55), and peak BUN was 30.5 mEq/dL and 20.2 mEq/dL (P = .001) for the patients with renal function decrease and patients with no renal function change, respectively.
The baseline serum magnesium level was 1.6 mEq/dL, and the baseline potassium was 3.9 mEq/dL for both groups (Table 3). The mean trough magnesium level was 1.3 mEq/dL for both groups (P = .88), and the mean trough potassium levels were 3.1 mEq/dL and 3.5 mEq/dL (P = .002), respectively. Of all the patients, 31% and 38% of patients did not return to baseline magnesium levels in the renal function change group and the no renal function change group, respectively. In addition, 18% and 8%, respectively, (P = .38) did not return to baseline potassium levels in the renal function change group and the no renal function change group.
The mean number of concurrent nephrotoxic agents was 2.5 for the renal function change group and 2.6 for the no renal function change group (Table 3). In the renal function change group, 82% received concurrent chemotherapy, 18% received NSAIDs daily, 36% received nephrotoxic antimicrobial and/or antiretroviral drugs, 53% received a proton pump inhibitor daily, 13% received an ACE inhibitor or ARB daily, 29% received another antihypertensive agent daily, and 27% received at least 1 other nephrotoxic agent daily.
Of the patients with no renal change, 77% received concurrent chemotherapy, 31% received NSAIDs daily, 38% received nephrotoxic antimicrobial and/or antiretroviral drugs, 38% received a proton pump inhibitor daily, 31% received an ACE inhibitor or ARB daily, 46% received another antihypertensive agent daily, and 31% received at least 1 other nephrotoxic agent daily (Table 3).
The patients with a renal function change received 2.1 L of crystalloid hydration with each cisplatin dose, and 87% received a bolus dose of furosemide (Table 3). The patients who did not have a renal function change received 1.9 L of crystalloid hydration (P = .53) and 85% received a bolus dose of furosemide before each cisplatin dose (P = .85; Table 3). In addition, continuous crystalloid hydration (over a 24-hour period) was given to some patients in addition to the standard 1L to 2 L of pre- and posthydration. In addition, 14 patients—including 12 (27%) of the 18 patients who had renal toxicity and 2 (15%) of the 13 patients without renal changes (P = .4)—received continuous crystalloid hydration within the hospital.
Of the 45 patients who had a renal function change, 24 (53%) had grade 1 nephrotoxicity; 15 (33%) had grade 2; 3 (6.7%) had grade 3; and 3 (6.7%) had grade 4 nephrotoxicity according to the NCI CTCAE criteria (Table 3).8 Overall, 21 (47%) patients in this group had a grade ≥2 nephrotoxic incident, per the NCI criteria,8 and 28 (62%) patients were deemed to have experienced an incidence of acute kidney injury per KDIGO 2012 guidelines.7 A diagnosis of any-cause acute kidney injury during cisplatin administration was made in 12 (27%) of the 45 patients.
Only a few studies have evaluated the demographic factors that may affect the risk for cisplatin-induced nephrotoxicity, and, of those factors, some have shown an increased propensity for nephrotoxicity in female patients, older patients, and patients who smoke.12-14 In our study, the renal decline group and the nonaffected group had comparable ages (60 years vs 55 years, respectively), smoking histories (71% vs 77%, respectively), and had a similar male-to-female ratio (Table 3).
However, de Jongh and colleagues found that male patients had a 15% faster clearance of cisplatin than female patients.12 Furthermore, a 2003 study showed that females had twice the risk for cisplatin-induced nephrotoxicity than their male counterparts.13 In addition, it was reported that smokers had an increased risk for nephrotoxicity while receiving cisplatin versus nonsmokers, which is thought to be attributed to oxidative stress that increases nephrotoxic platinum metabolites.13,15 With regard to age, a study found that patients aged >62 years had a 41% risk for nephrotoxicity compared with 26% in patients aged <48 years.13,16 Furthermore, a multivariate logistic regression analysis identified 4 significant risk factors for cisplatin-induced nephrotoxicity, including age ≥65 years.17 Thus, although this study showed no association between cisplatin-induced nephrotoxicity and the stated demographic factors, it may still be reasonable to take these factors into consideration when starting and monitoring cisplatin-induced nephrotoxicity.
Certain medical conditions are known to increase the propensity for cisplatin-induced nephrotoxicity, including preexisting renal insufficiency, history of acute renal failure, acute renal injury, and/or chronic kidney disease. Additional conditions are those that are known to increase susceptibility to acute kidney injury, including hypovolemia, surgery, congestive heart failure, hepatorenal syndrome, and sepsis.1,7,18
In our study, patients who had a decline in renal function were more likely to have had a hypovolemic episode 2 weeks before the administration of cisplatin or throughout the encounter (P = .12; Table 3). We also found a higher frequency of patients who had an acute kidney injury episode within 1 month of receiving the first cisplatin dose, those who were previously diagnosed with chronic kidney injury, or had chronic heart failure in the renal change group (8.8%) compared with the nonaffected group (0%). Because of the limited number of individuals with congestive heart failure, chronic kidney disease, recent acute kidney injury, and diabetes in our study population, a correlation between these conditions and renal function changes could not be adequately evaluated.
Renal toxicity can be more severe and prolonged with repeat dosing, as evidenced in a study by Hartmann and colleagues, which showed that patients who received 2 cycles of a single 50-mg/m2 dose of cisplatin had a 24% decrease in GFR after the second cycle.19 In our study, however, patients in both groups received similar doses of cisplatin at a similar frequency (Table 3). In addition, the patients’ body surface area and weight were not significantly different between the groups; thus, the actual amount (in milligrams) of cisplatin received was also similar. Furthermore, patients who had a renal function decline were more likely to have their highest SCr peak at approximately the first 1 to 3 doses (mean doses, 1.9 ± 1.4 SD).
These findings are important, because the dosing amounts and regimens for cisplatin, including higher dose, cumulative dose, rate of administration, and increased frequency, have continuously been associated with an increased risk for nephrotoxicity.1,3,17,18,20,21 A significant amount of evidence supports the theory that a higher dose of cisplatin causes nephrotoxicity in a cumulative, dose-dependent manner; thus, caution should be taken when starting patients on high doses of cisplatin.
Electrolyte levels, including serum potassium and serum magnesium, are affected by the administration of cisplatin.2,22 These levels may deplete and then normalize within 3 to 4 weeks of receiving a single dose of cisplatin.23 Studies have shown that hypoalbuminemia and hypomagnesemia are risk factors for increased susceptibility to cisplatin-induced nephrotoxicity.1,17,18 In our study, albumin levels were similar between the groups before cisplatin treatment and decreased to a similar level between groups throughout treatment.
We found no association between albumin levels and renal function decline, and the decrease in albumin may likely be attributed to poor eating habits in this patient population. The baseline magnesium and potassium levels were comparable between the 2 groups as well (Table 3). In addition, the patients’ magnesium levels decreased to approximately the same level between the 2 groups after cisplatin dosing, with an average trough of 1.3 mEq/dL (from 1.6 mEq/dL). Serum potassium levels also declined after cisplatin dosing, but the decrease was significantly greater in patients who had renal function changes.
This larger decrease in serum potassium levels in patients with renal function changes may be attributed to the greater depletion of electrolytes that occurs in patients with acute kidney injury. Ultimately, potassium, albumin, and magnesium baseline levels, which are reflective of baseline renal functioning, are not associated with an increased risk for cisplatin-induced nephrotoxicity; however, these laboratory findings decline, as expected, in patients who start cisplatin therapy.2,22
The coadministration of cisplatin with several types of medications can increase the risk for nephrotoxicity. For example, when coadministered with cisplatin, NSAIDs are associated with an approximate 36% increase in nephrotoxicity.18 NSAIDs affect water and electrolyte excretion, as well as the modulation of renal vascular tone, which ultimately reduces the rate of renal perfusion and increases the risk for cisplatin-induced nephrotoxicity.18,24
Intrinsic renal injury via tubular toxicity, similar to the mechanism of cisplatin-induced renal injury, can occur with radiocontrast media, carbamazepine, quinolones, fosfamide, zoledronic acid, mannitol, dextran, adefovir, tacrolimus, nedaplatin, methoxyflurane, amphotericin B, cephaloridine, streptozocin, mithramycin, foscarnet, pentamidine, intravenous gammaglobulin, cidofovir, and hydroxyethyl starch.11 Antibiotics, such as aminoglycosides, have also been associated with an increased incidence of nephrotoxicity when coadministered with cisplatin.25
Some medications that are frequently associated with acute kidney injury through an alternative mechanism of action include penicillin, cephalosporin, sulfonamides, proton pump inhibitors, diuretics (eg, thiazides and furosemide), warfarin, heparin, barbiturates, and diazepam.7,10 In addition, cisplatin is frequently administered with other chemotherapeutic agents, such as docetaxel, cytarabine, gemcitabine, pemetrexed, paclitaxel, or cyclophosphamide.2,26 Many of these chemotherapeutic agents are nephrotoxic alone and can become an additive in combination with cisplatin.27 A retrospective analysis of patients with gynecologic cancers who received paclitaxel plus cisplatin had a 72% incidence of nephrotoxicity with combination therapy versus a 20% incidence when dosed with cisplatin alone.27
In our study, the use of combination chemotherapy agents, NSAIDs, nephrotoxic antimicrobials and retrovirals, and other nephrotoxic medications were analyzed per the course of cisplatin use. No statistical difference was found between the groups regarding the rate of concomitant chemotherapy agent use, NSAID use, nephrotoxic antimicrobials or antiretrovirals use, and proton pump inhibitor use (Table 3). However, patients who begin receiving cisplatin at our institution are counseled to stop taking NSAIDs on the day of the cisplatin dose and for 5 days after. Thus, although some patients might have had an NSAID listed on their home medication list, it is likely that some or all of them were not actually taking them. Furthermore, the number of nephrotoxic agents used by each patient was approximately the same between the 2 groups (mean of 3.7 vs 4.1 for the renal change and nonaffected groups, respectively).
According to the study by Miller and colleagues, approximately 20% to 30% of patients who receive cisplatin will have acute renal injury, even with prophylactic measures.1 This study showed the rate of acute kidney injury to be slightly higher, with incidences noted in 36.2% of the total patients per the NCI guidelines and 48.3% of the total patients per the KDIGO guidelines (Table 3). In addition, the total number of risk factors per patient were similar between the groups (6 for the renal change group and 5.7 for the nonaffected group; P = .57).
Currently used methods to decrease the likelihood of acute kidney injury during cisplatin treatment include the administration of furosemide and crystalloid hydration. We found no significant difference in the mean amount of pre- and posthydration during cisplatin administration between the 2 groups. However, we observed that the patients with renal function changes did receive an increased volume of hydration when pre- and posthydration and continuous crystalloid hydration were taken into consideration (Table 3).
Hospitalized patients receive higher volumes of measurable hydration, and in our study, hospitalized patients had renal dysfunction at a higher rate. This could be attributed to patient selection, because historically a disproportionate share of medically complex and higher acuity patients have received chemotherapy in the inpatient setting versus the clinic. Although the recommended amount of fluid was administered (1-2 L) before, during, and after cisplatin therapy to all patients in our study, approximately 77.6% of them still had a significant change in renal function from baseline.
A main limitation of this study is the small sample size, which limits the generalizability of the findings and introduces uncertainty regarding the statistical power.
In addition, because of the retrospective nature of the study, a causative association could not be established between the identified clinical factors and the renal function changes that occurred during the administration of cisplatin.
Furthermore, a retrospective study does not allow for the prevention of selection bias. It is likely that some higher-risk patients were not offered cisplatin chemotherapy or they might have been offered low-dose cisplatin as a result of performance status or other comorbidities.
Further research should establish a stronger correlation between the identified clinical factors that affect the risk for cisplatin-induced nephrotoxicity in a larger sample size.
Our findings indicate that patients who are receiving cisplatin are at a high risk for nephrotoxicity, and the incidence rate may be higher than previously reported. Furthermore, acute kidney injury occurs even when renal protective measures are being introduced. Therefore, it is reasonable to take into consideration other patient risk factors that have been previously identified in the literature.
Author Disclosure Statement
Dr Nusseibeh, Dr Weber, Dr Won, and Dr Reidt have no conflicts of interest to report.
- Miller RP, Tadagavadi RK, Ramesh G, Reeves WB. Mechanisms of cisplatin nephrotoxicity. Toxins (Basel). 2010;2:2490-2518.
- Platinol (cisplatin) for injection, USP [package insert]. Princeton, NJ: Bristol-Myers Squibb; September 2010.
- Arany I, Safirstein RL. Cisplatin nephrotoxicity. Semin Nephrol. 2003;23:460-464.
- Basu A, Krishnamurthy S. Cellular responses to cisplatin-induced DNA damage. J Nucleic Acids. 2010;2010:201367.
- Taguchi T, Razzaque MS. Cisplatin-associated nephrotoxicity and pathological events. Contrib Nephrol. 2005;148:107-121.
- Bellomo R, Ronco C, Kellum JA, et al; for the Acute Dialysis Quality Initiative Workgroup. Acute renal failure - definition, outcome measures, animal models, fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care. 2004;8:R204-R212.
- Kidney Disease Improving Global Outcomes. Kidney Disease Improving Global Outcomes (KDIGO) Section 2: AKI Definition. Kidney Int Suppl (2011). 2012;2:19-36.
- National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 4.0. May 28, 2009. www.eortc.be/services/doc/ctc/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf. Accessed October 1, 2015.
- Lauwerys R, Bernard A. Preclinical detection of nephrotoxicity: description of the tests and appraisal of their health significance. Toxicol Lett. 1989;46:13-29.
- Perazella MA, Moeckel GW. Nephrotoxicity from chemotherapeutic agents: clinical manifestations, pathobiology, and prevention/therapy. Semin Nephrol. 2010;30:570-581. Erratum in: Semin Nephrol. 2011;31:317.
- Choudhury D, Ahmed Z. Drug-associated renal dysfunction and injury. Nat Clin Pract Nephrol. 2006;2:80-91.
- de Jongh FE, Verweij J, Loos WJ, et al. Body-surface area–based dosing does not increase accuracy of predicting cisplatin exposure. J Clin Oncol. 2001;19:3733-3739.
- de Jongh FE, van Veen RN, Veltman SJ, et al. Weekly high-dose cisplatin is a feasible treatment option: analysis on prognostic factors for toxicity in 400 patients. Br J Cancer. 2003;88:1199-1206.
- Sendur MA, Aksoy S, Yaman S, et al. Administration of contrast media just before cisplatin-based chemotherapy increases cisplatin-induced nephrotoxicity. J BUON. 2013;18:274-280.
- Maytin M, Leopold J, Loscalzo J. Oxidant stress in the vasculature. Curr Atheroscler Rep. 1999;1:156-164.
- Schetz M, Dasta J, Goldstein S, Golper T. Drug-induced acute kidney injury. Curr Opin Crit Care. 2005;11:555-565.
- Kobayashi R, Suzuki A, Matsuura K, et al. Risk analysis for cisplatin-induced nephrotoxicity during first cycle of chemotherapy. Int J Clin Exp Med. 2016;9:3635-3641.
- Kidera Y, Kawakami H, Sakiyama T, et al. Risk factors for cisplatin-induced nephrotoxicity and potential of magnesium supplementation for renal protection. PLoS One. 2014;9:e101902.
- Hartmann JT, Kollmannsberger C, Kanz L, Bokemeyer C. Platinum organ toxicity and possible prevention in patients with testicular cancer. Int J Cancer. 1999;83:866-869.
- Caglar K, Kinalp C, Arpaci F, et al. Cumulative prior dose of cisplatin as a cause of the nephrotoxicity of high-dose chemotherapy followed by autologous stem-cell transplantation. Nephrol Dial Transplant. 2002;17:1931-1935.
- Madias NE, Harrington JT. Platinum nephrotoxicity. Am J Med. 1978;65:307-314.
- Finkel M, Goldstein A, Steinberg Y, et al. Cisplatinum nephrotoxicity in oncology therapeutics: retrospective review of patients treated between 2005 and 2012. Pediatr Nephrol. 2014;29:2421-2424.
- Cisplatin injection. Rx only [prescribing information]. WG Critical Care, LLC: Paramus, NJ; February 2015.
- Ries F, Klastersky J. Nephrotoxicity induced by cancer chemotherapy with special emphasis on cisplatin toxicity. Am J Kidney Dis. 1986;8:368-379.
- Launay-Vacher V, Rey J-B, Isnard-Bagnis C, et al; for the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol. 2008;61:903-909.
- Micromedex Solutions. DrugDex Evaluations. Cisplatin. Updated periodically. www.micromedexsolutions.com. Accessed October 1, 2015. (Requires subscription to access.)
- Merouani A, Davidson SA, Schrier RW. Increased nephrotoxicity of combination taxol and cisplatin chemotherapy in gynecologic cancers as compared to cisplatin alone. Am J Nephrol. 1997;17:53-58.