Platinum-Based Chemotherapies-Induced Nephrotoxicity: A Retrospective Analysis of Frequency, Clinical Characteristics, and Outcomes

Technical Summary: Platinum-Based Chemotherapies-Induced Nephrotoxicity

Problem Statement
Platinum-based agents (cisplatin, carboplatin, and oxaliplatin) are fundamental to the systemic treatment of solid tumors but are associated with significant nephrotoxicity. While cisplatin is known for high nephrotoxic potential, carboplatin and oxaliplatin also carry renal risks. Acute kidney injury (AKI) in this context often leads to treatment delays, dose reductions, or discontinuation, potentially compromising tumor control and patient survival. Despite international evidence, there is a scarcity of data regarding the frequency, clinical characteristics, and outcomes of platinum-induced nephrotoxicity specifically within Latin American populations, where patient demographics, comorbidities, and care protocols may differ from established global cohorts.

Methodology
The study employed a retrospective, analytical cohort design conducted over a five-year period at a third-level referral hospital in Mexico (Hospital General de México "Dr. Eduardo Liceaga").

• Population: 114 adults (≥18 years) with solid tumors who received at least one cycle of platinum-based chemotherapy.
• Inclusion/Exclusion: Patients required baseline and follow-up serum creatinine and electrolyte measurements. Exclusion criteria included pre-existing chronic kidney disease (eGFR <60 mL/min/1.73 m²), prior renal replacement therapy, or AKI before the first platinum cycle.
• Definitions: AKI was defined and classified according to the KDIGO criteria (increase in serum creatinine ≥0.3 mg/dL in 48 hours, ≥1.5 times baseline in 7 days, or urine output <0.5 mL/kg/h for 6 hours).
• Data Collection: Variables included demographics, comorbidities, baseline renal function, electrolyte imbalances, tumor type, specific platinum agent, cumulative dose, and outcomes (renal recovery, need for renal replacement therapy [RRT], regimen modifications, and mortality).
• Statistical Analysis: Quantitative variables were compared using Student's t-test or Mann-Whitney U test; qualitative variables used chi-square or Fisher's exact test. A p-value <0.05 was considered statistically significant.

Key Results

• Incidence: AKI occurred in 36 patients (31.6%). Electrolyte imbalances were documented in 35.1% of the cohort.
• Patient Demographics: The mean age was 46.6 ± 15.5 years, with 64.9% female. Testicular cancer was the most frequent neoplasm (29.8%). Baseline renal function was generally preserved (median eGFR 109.6 mL/min/1.73 m²).
• Renal Outcomes:
  • Patients with AKI showed significant increases in serum creatinine (median 1.10 mg/dL vs. 0.80 mg/dL in non-AKI) and decreases in eGFR (median 74.4 vs. 105.9 mL/min/1.73 m²).
  • Magnesium levels were significantly lower in the AKI group (median 1.7 mg/dL vs. 1.9 mg/dL).
  • Renal replacement therapy was required in 7.9% of the total cohort (25.0% of those with AKI).
  • 7.0% of the total cohort developed chronic kidney disease (16.7% of those with AKI).
• Oncological Outcomes:
  • Treatment discontinuation occurred in 7.0% of the total population (22.2% of those with AKI).
  • Dose modification was necessary in 11.4% of the total population (27.8% of those with AKI).
  • Overall mortality was low at 1.8%, with no statistically significant difference between AKI and non-AKI groups.
• Predictors: No independent baseline predictors of AKI were identified in the univariate analysis, likely due to the homogeneous nature of the cohort (preserved baseline renal function, low comorbidity burden) and limited statistical power.

Key Contributions and Claims

• First Regional Data: The authors claim this is the first study published in Mexico and the second in Latin America to address the frequency and outcomes of platinum-induced nephrotoxicity in solid tumors.
• Risk in Low-Risk Populations: The study demonstrates that platinum exposure remains a determinant of nephrotoxicity even in patients traditionally considered low-risk (young age, preserved baseline renal function, low comorbidity burden).
• Beyond Creatinine: The findings highlight that platinum nephrotoxicity manifests not only as AKI but also as electrolyte disturbances (particularly hypomagnesemia) and persistent renal dysfunction. The authors argue that the clinical burden extends beyond transient creatinine increases to include chronic kidney disease and treatment interruptions.
• Impact on Treatment Intensity: A primary contribution is the documentation of how AKI directly influences oncological management, leading to significant rates of dose modification and treatment discontinuation, which may affect tumor control and prognosis.
• Proactive Approach: The paper supports a proactive onconephrological approach, advocating for structured monitoring of renal function and electrolytes, aggressive correction of magnesium deficiency, and early nephrologist intervention.

Significance and Limitations
The study emphasizes that the clinical consequences of platinum nephrotoxicity are substantial, affecting both renal health and the continuity of cancer therapy. The authors note that while mortality was low in this specific cohort (likely due to the young population and curative-intent treatments), the burden of treatment interruption and long-term renal sequelae is critical.

The paper acknowledges limitations, including its retrospective, single-center design, modest sample size which limited the power to identify risk factors, reliance on serum creatinine (which may underestimate subclinical tubular injury), and a relatively short follow-up period. The authors conclude that future prospective, multicenter studies with larger sample sizes and longer follow-up are necessary to validate risk prediction models and optimize renal-protective strategies in Latin American populations.