Carboplatin-induced hematuria in a patient with stage I seminoma: a case report

Abstract

Background

Platinum-based antineoplastic drugs are widely used in the treatment of solid tumors. Carboplatin is a safe and efficacious adjuvant treatment for stage I seminoma following a risk-adapted treatment strategy. It consists in the administration of one or two courses for patients with one or both of rete testis involvement or tumor size more than 4 cm. Carboplatin is used with the purpose of minimizing nephrotoxicity and ototoxicity caused by cisplatin while achieving excellent results. We present a case of carboplatin-induced hematuria that led to an acute kidney injury as a rare complication.

Case presentation

A 48 year-old Caucasian man with no medical history and no history of renal disease presented with a painless testicular mass. He underwent an orchiectomy for stage I testicular seminoma and received one course of adjuvant carboplatin (area under the curve of 7); 2 days later, he developed frank hematuria associated with back pain. The physical examination revealed mild suprapubic tenderness and Goldflam’s sign was positive bilaterally. Blood tests did not reveal anemia, his platelet count was normal, and creatinine levels were in range. Due to persisting hematuria requiring continuous bladder irrigation, he was hospitalized to monitor renal function and was initially managed conservatively with intravenous analgesics and adequate hydration. The following day, he developed an acute kidney injury (serum creatinine 1.90 mg/dL, glomerular filtration rate 41 mL/min/m²). Transurethral cystoscopy showed a blood clot on the left urinary meatus, which was irrigated and removed, revealing a clear ureteral jet. With no further measures, creatinine started declining and back pain improved. His acute kidney injury resolved in the following 72 hours. Computed tomography urogram showed a left ureteral ectasia with an enhanced urothelium within the upper and middle ureter, suggesting ureteral obstruction. The patient improved completely and was discharged successfully. On further follow-up 2 months later, a computed tomography urogram showed a complete resolution of obstructive changes.

Conclusions

Hematuria and acute kidney injury are rare but clinically relevant adverse events associated with the administration of carboplatin, regardless of the administered and accumulated dose.

It is crucial to recognize this event and start adequate hydration promptly to prevent further kidney damage and the need for more aggressive measures, such as ureteral stenting or percutaneous nephrostomy.

Background

Carboplatin is a second-generation platinum-based chemotherapeutic agent that is used to treat a variety of cancers, such as head and neck cancer, lung cancer, ovarian cancer, brain cancer, and testicular cancer. Compared with cisplatin, carboplatin is better tolerated but less active [1]. Cisplatin and carboplatin have similar mechanisms of action; they are cytotoxic drugs that bind DNA and inhibit DNA replication, interfering with mitosis and resulting in cell apoptosis [2].

Carboplatin nephrotoxicity is lower as compared with cisplatin. This is because of its enhanced stability: carboplatin has carboxylate and cyclobutene moieties in the cis position, rather than chloride. Almost 60% of the administered dosage of carboplatin is excreted unchanged in the urine within 24 hours (compared with 25–40% of cisplatin). The importance of renal clearance to the metabolism and excretion of carboplatin is highlighted by its usual dosing schema, which is based on an estimated glomerular filtration rate (eGFR) along with the desired level of drug exposure, according to the area under the concentration–time curve (AUC, mg/mL × min) [1].

Hematuria is not a well-recognized complication of carboplatin therapy. However, previous reports describe hemorrhagic cystitis associated with high doses of carboplatin [3]. Although the exact mechanism is not fully elucidated, it seems to be caused by a direct toxic effect of carboplatin on the transitional epithelial cells of the renal pelvis and ureters, and the formation of obstructive clots within the renal collecting system [4]. To spread knowledge about this rare but serious complication, we report a case of carboplatin-induced hematuria and acute kidney injury (AKI) after a course of adjuvant carboplatin.

Case presentation

We present the case of a 48 year-old Caucasian man with no history of renal disease, hypertension, diabetes, or hyperuricemia. He had a history of nicotine use and occasional alcohol consumption. He underwent a radical, inguinal orchiectomy for stage I seminoma and received one course adjuvant carboplatin (AUC 7); 2 days later, he developed frank hematuria associated with back pain, with no decrease in urine output.

The physical examination revealed normal vital signs, including pulse rate of 88 beats per minute, blood pressure of 120/70 mmHg, temperature of 36.7 °C, and oxygen saturation of 98% on room air.

The abdomen was soft and nontender, with no palpable masses and mild suprapubic tenderness. Goldflam’s sign was positive bilaterally.

Blood tests taken in the emergency room did not reveal anemia, his platelet count was normal, and creatinine levels were in range. Ultrasonography indicated that the kidneys were of the correct shape, size, and localization.

Due to persisting hematuria requiring continuous bladder irrigation, he was admitted to monitor renal function and was initially managed symptomatically with intravenous analgesics and adequate hydration.

The following day, he developed an AKI during his hospitalization, showing creatinine levels of 1.90 mg/dL and eGFR 41 mL/min/m². The evolution of renal function is shown in Fig. 1.

Fig. 1.

Evolution of renal function following the development of hematuria

A transurethral cystoscopy showed a blood clot on the left urinary meatus, which was irrigated and removed, revealing a clear ureteral jet. The urine was clear at the end of the procedure with slow irrigation, and no further bleeding was observed.

With no further measures, creatinine started trending down and loin pain improved. Our patient received 1500 mL per day of normal saline for 3 days, and 1000 mL of normal saline per day once renal function started to improve. His AKI resolved in the following 72 hours.

CT urogram (Figs. 2 and 3) showed a left ureteral ectasia with an enhanced urothelium within the upper and middle ureter, suggesting the possibility of ureteral obstruction.

Fig. 2.

Ureteral ectasia and enhancement in upper (A, red arrow) and middle (B, red arrow) portion of left ureter

Fig. 3.

A Irregular wall thickening and urothelial enhancement in the left ureter (red arrow). B Reconstruction in coronal orientation longitudinal to the long axis of the left kidney. Hydroureteronephrosis. C Resolution of wall thickening and urothelial enhancement (red arrow). D Complete resolution of hydroureteronephrosis

The patient improved completely and was discharged successfully.

On further follow-up 2 months later, a CT urogram (Fig. 3) showed a complete resolution of obstructive changes.

Discussion and conclusions

The present case illustrates carboplatin-induced hematuria in a patient with a stage I testicular seminoma, an infrequent but potentially serious complication that can occur during the administration of carboplatin.

Seminoma accounts for more than half of testicular germ cell tumors (GCTs). About 80% of seminomas present with clinical stage I disease, with an estimated relapse rate of 13–20% without adjuvant treatment. The high curability at relapse has led to ongoing debate about whether optimal postoperative management is adjuvant treatment or surveillance. Risk‐based management is proposed by some studies and guidelines, reserving one course of adjuvant carboplatin for patients with one or both of RTI or tumor size more than 4 cm [5]. Our patient presented both risk factors, so adjuvant carboplatin was indicated. In this scenario, due to the high curability and survival rate these tumors present, it is essential to manage and avoid the toxicity this treatment can cause.

There are few cases described of carboplatin-induced hematuria. Table 1 describes the reported cases, indicating doses, malignancy, and treatment administered [4, 6–11]. Although considered a dose-dependent adverse event (per administration and cumulative) [4, 6], our case represents a carboplatin-induced hematuria that led to an AKI with only one course of carboplatin. On the basis of the Calvert formula, our patient received a total dose of 1000 mg (555.56 mg/m² or AUC 7) of carboplatin. He did not receive any pre-chemotherapy intravenous hydration, as it is not part of standard protocol. Unlike in prior reports, he had not received cisplatin or carboplatin previously and there was no concurrent use of other nephrotoxic chemotherapy such as cyclophosphamide. Consequently, although not very common, this adverse effect can appear regardless of both the administered and the cumulative dose. Previous evidence suggests that carboplatin may exhibit toxicity to the transitional epithelium in the renalpelvis and ureters causing gross hematuria and blood clots, resulting in ureteral obstruction and hydronephrosis [7, 10].

Table 1.

Literature review of carboplatin-induced hematuria reports

	Drug and dosage	Cancer	Symptoms	Management
Ettinger et al., 1993	Carboplatin 336 mg/m2 for 5 days (1680 mg/m2) (previously received cyclophosphamide)	Pediatric patients with AML	Gross hematuria	Conservatively
Agraharkar et al., 1998	1100 mg carboplatin (753 mg/m2) 250 mg paclitaxel (175 mg/m2)	Ovarian carcinoma	Gross hematuria obstructive AKI	Conservatively
Krishnan S.G., 2007	792 mg carboplatin 292 mg paclitaxel (175 mg/m2)	Ovarian carcinoma	Gross hematuria bilateral hydronephrosis	Ureteral stenting
Taj et al., 2011	Carboplatin, docetaxel, and trastuzumab	Breast carcinoma	Gross hematuria	Conservatively
Sato M., 2020	Carboplatin (560 mg/m2), after eight doses	Pediatric low grade glioma	Gross hematuria bilateral hydronephrosis	Conservatively
Pastorello J., 2022	Carboplatin, docetaxel, trastuzumab, and pertuzumab	Breast carcinoma	Gross hematuria obstructive AKI	Conservatively
Nallathambi et al., 2024	700 mg carboplatin 250 mg paclitaxel	Breast carcinoma	Gross hematuria, loin pain, bilateral hydronephrosis	Ureteral stenting

It is essential to identify this adverse event by monitoring patients for signs of this complication and to be prepared to initiate treatment with no delay to prevent further kidney damage and the need for more aggressive measures, such as ureteral stenting or percutaneous nephrostomy. In our case, although initially the renal function was in range, the prompt introduction of adequate hydration may have mitigated the apparition of further renal complications and improved patient outcomes.

It may be prudent to timely hydrate patients receiving carboplatin, similar to when using cisplatin, to avoid this toxicity, especially if they have been treated with nephrotoxic drugs before.

Author contributions

All authors have all contributed as authors to this manuscript in terms of planning, conception and design, writing, and editing the final manuscript.

Funding

The presentation of this case report did not receive any specific grant from funding agencies.

Availability of data and materials

The data that support the conclusions of this article are included within the article.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.