In 2020, 309 750 cases are expected among men and 316 280 cases among women in Brazil. Most of the cases were nonmelanoma skin cancers.^1–3 Of the chemotherapeutic drugs used in the clinical treatment of cancer, cisplatin (CDDP) was one of the first platinum-derived drugs discovered and was approved by the U.S. Food and Drug Administration (FDA) in 1979.^3–6

Since its approval by the FDA, CDDP has been used as the first line of treatment for breast, lung, head and neck, and ovary and testis cancers, but its use has been limited due to neurotoxicity, ototoxicity, and nephrotoxicity.^3–5 The main excretion route of CDDP is through the kidneys, thus nephrotoxicity occurs in ~20% of outpatients and hospitalized patients.³

It is important to note that CDDP nephrotoxicity is dose-dependent and that trials have shown that low doses of CDDP cause late kidney damage differently than high doses of CDDP.^4–6 Changes in glomerular filtration were found in 20% to 40% of patients 7 to 10 days after the first dose of CDDP was administered.⁶

The main mechanisms of CDDP-induced damage in the renal tubular cell include DNA damage, changes in cell transport, loss of cell polarity/cytoskeleton, mitochondrial dysfunction, inhibition of fatty acid oxidation, oxidative stress, inflammatory response, activation of apoptotic pathways, activates p53, and apoptosis in renal tubules.^5, 6

After discovery of CDDP and identification of its side effects, second and third generation drugs derived from CDDP, such as carboplatin (CARBO) and oxaliplatin (OXA) were synthesized to reduce unwanted side effects, including nephrotoxicity.^7–11 CARBO has the same effect as CDDP on cell proliferation, but CARBO does not reduce the cell detoxification mechanisms that remove free radicals.^10, 11

OXA induces DNA damage, but to a lesser extent, and more effectively inhibits DNA replication and induces apoptosis in normal and mutant cells than CDDP and CARBO.

It is unclear whether nephrotoxicity remains a risk after switching to CARBO or OXA after a previous cycle of CDDP treatment, studies that evaluate CARBO or OXA nephrotoxicity after a CDDP treatment are needed.^10–16

The methods that can assess renal function after long-term treatment with CDDP or CDDP analogs include the serum creatinine (sCR), urea, and fractional sodium excretion.¹⁷ Although sCR is a standard serological marker, its serum levels are variable and should be evaluated with caution and several variables, including age, sex, muscle mass, and hydration must be considered.¹⁷

Therefore, this study aimed to survey the incidence of acute kidney disease in outpatient chemotherapy patients treated with CDDP, CARBO, or OXA and to analyze the clinical factors associated with renal dysfunction occurrences in the chemotherapy patients.

Among the demographic characteristics of the patients in this study, there was a slight predominance of males over females, and this is consistent with estimates of new cancer cases in Brazil.

Among the associated morbidities, we observed incidences of hypertension in 30% of cases, diabetes in 11% of cases, and CVD in 8% of cases, which is compatible with cancer risk factors, such as obesity, smoking, alcoholism, and physical inactivity observed in other study.¹²

In our study, a predominance of cases had an ECOG of 0 and 1, which are cases with higher performance of clinical conditions, early treatment initiation, and better prognosis than the late onset cases described in other studies.^19, 20

In our study, we found no significant difference in sCR levels pre- and post-infusion (Table 2 and Figure 2). In our study, there were more cases of patients treated with less nephrotoxic drugs, such as CARBO and OXA, and this may reflect careful selection of appropriate chemotherapy for patients with previous renal dysfunction and effective nephroprotection strategies by the oncology team based on previous studies.^{11–15, 21, 22}

However, when assessing renal dysfunction after chemotherapy, the presence of dyslipidemia was no longer significant. Some authors showed that AH and CVD morbidities correlated significantly with renal dysfunction that worsened after treatment with CDDP.^{11, 12, 21, 23–25}

The presence of renal dysfunction did not correlate significantly with lower survival (Figure 4); a non-significant trend of lower survival was seen in patients with eGFRs <60 mL/min than in patients with eGFRs >60 mL/min. Perhaps with a larger sample, a significant survival difference may have been observed. The adequacy of treatment could also affect survival as noted other studies.^3, 21, 23

We were also unable to verify an association between AKD and platinum-derived chemotherapeutics (Table 4), perhaps due to the method used for infusion, or due to the predominance of patients treated with CARBO and OXA, which are less or non-nephrotoxic drugs.^16, 22 However, upon analysis of survival curves of patients who presented with AKD after the start of chemotherapy we found that patients with AKD during treatment had the lowest survival (Figure 4), which is compatible with previous studies.^{11, 21, 26–30}

In this study, analysis of survival curves based on the chemotherapy agent used showed no differences (Figure 5). In the literature, the use of CDDP associated with the presence of complications due to its recognized toxicity and side effects, and the use of new platinum derivatives associated with adverse events less.^{3, 10, 16, 19, 20} This study demonstrated that, regardless of the type of chemotherapy, the presence of AKD or other morbidities may be responsible for a patient’s poorest performance and that multidisciplinary care during platinum-derived chemotherapy should be provided to these patients.