Limits...
Rhabdomyolysis-induced acute kidney injury in a cancer patient exposed to denosumab and abiraterone: a case report.

Neyra JA, Rocha NA, Bhargava R, Vaidya OU, Hendricks AR, Rodan AR - BMC Nephrol (2015)

Bottom Line: Kidney biopsy confirmed the diagnosis of rhabdomyolysis-induced AKI.Whether one of these drugs individually, or the combination, was the bona fide culprit of muscle breakdown is unknown.Nonetheless, our report is hypothesis-generating for further investigations on the effect of these drugs on muscle cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8516, USA. Javier.NeyraLozano@UTSouthwestern.edu.

ABSTRACT

Background: Denosumab and abiraterone were approved by the United States Food and Drug Administration in 2011 for the treatment of metastatic castration-resistant prostate cancer. Neither denosumab nor abiraterone is known to cause rhabdomyolysis.

Case presentation: A 76-year-old Caucasian man with metastatic prostate cancer presented with non-oliguric severe acute kidney injury (AKI) 3 weeks after receiving simultaneous therapy with denosumab and abiraterone. The patient had been on statin therapy for more than 1 year with no recent dose adjustments. His physical exam was unremarkable. Blood work on admission revealed hyperkalemia, mild metabolic acidosis, hypocalcemia, and elevated creatine kinase (CK) at 44,476 IU/L. Kidney biopsy confirmed the diagnosis of rhabdomyolysis-induced AKI. The patient responded well to intravenous isotonic fluids and discontinuation of denosumab, abiraterone, and rosuvastatin, with normalization of CK and recovery of kidney function.

Conclusion: We report the first case of biopsy-proven rhabdomyolysis-induced AKI in a cancer patient acutely exposed to denosumab and abiraterone. Whether one of these drugs individually, or the combination, was the bona fide culprit of muscle breakdown is unknown. Nonetheless, our report is hypothesis-generating for further investigations on the effect of these drugs on muscle cells.

No MeSH data available.


Related in: MedlinePlus

Kidney biopsy light microscopy. a Hematoxylin & eosin (X200) showing dark pink, filamentous tubular casts (yellow arrow); b) Jones’ silver stain (X400) showing dark pink, coarsely granular and filamentous tubular casts (yellow arrow)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4519001&req=5

Fig2: Kidney biopsy light microscopy. a Hematoxylin & eosin (X200) showing dark pink, filamentous tubular casts (yellow arrow); b) Jones’ silver stain (X400) showing dark pink, coarsely granular and filamentous tubular casts (yellow arrow)

Mentions: A 76-year-old Caucasian man with a history of type 2 diabetes, chronic kidney disease (CKD) stage 3A, essential hypertension, hypothyroidism, antiphospholipid antibody syndrome, prior cerebellar strokes, and prostate cancer (Gleason 10) with widespread metastasis to the bone presented with non-oliguric severe AKI 3 weeks after receiving simultaneous therapy with denosumab (120 mg subcutaneous injection once) and abiraterone (1 g per day orally). The patient had failed prior antineoplastic therapy with leuprolide acetate, bicalutamide, and nilutamide. On admission, his serum creatinine (SCr) was elevated at 5.7 mg/dL from a baseline of 1.2 mg/dL (Fig. 1). His active outpatient medications consisted of rosuvastatin (40 mg daily), benazepril, metoprolol tartrate, metformin, warfarin, low-dose prednisone (started concomitantly with abiraterone), and levothyroxine. The patient had been on statin therapy for more than 1 year and the dose had not been recently modified. The patient denied prior episodes of myopathies, rhabdomyolysis, or AKI. His physical exam was unremarkable. Further blood work showed hyperkalemia, mild metabolic acidosis, hypocalcemia, mild transaminemia (predominantly AST), and creatine kinase (CK) of 44,476 IU/L (Table 2). Urine studies revealed dipstick proteinuria (100 mg/dL), large dipstick blood, only a few normomorphic erythrocytes, and negative culture. All serologic work-up (ANA, PR3- and MPO-ANCA, anti-GBM antibodies, ENA panel, C3, C4, RF) and viral studies (HBV, HCV, CMV, EBV, Influenza A/B, Parainfluenza, Adenovirus, RSV) were negative or normal. Thyroid function tests were normal. Kidney sonogram and Doppler studies were negative for hydronephrosis and renal vein thrombosis, respectively. On admission, abiraterone therapy was discontinued and no further doses of denosumab were administered. Subsequently, the patient underwent kidney biopsy that was consistent with severe acute tubular injury with presence of myoglobin casts, confirming the diagnosis of rhabdomyolysis-induced AKI (Figs. 2 and 3). The patient responded well to intravenous isotonic fluids and discontinuation of denosumab, abiraterone, and rosuvastatin. CK levels normalized by day 25 of hospitalization and the SCr at the time of hospital discharge was 3.1 mg/dL (Fig. 1). After hospital discharge, the patient resumed all prior medications, including rosuvastatin, except for denosumab and abiraterone. His successive antineoplastic therapy consisted of enzalutamide. Kidney function returned to baseline 12 months after discharge and he had no recurrent episodes of rhabdomyolysis.Fig. 1


Rhabdomyolysis-induced acute kidney injury in a cancer patient exposed to denosumab and abiraterone: a case report.

Neyra JA, Rocha NA, Bhargava R, Vaidya OU, Hendricks AR, Rodan AR - BMC Nephrol (2015)

Kidney biopsy light microscopy. a Hematoxylin & eosin (X200) showing dark pink, filamentous tubular casts (yellow arrow); b) Jones’ silver stain (X400) showing dark pink, coarsely granular and filamentous tubular casts (yellow arrow)
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4519001&req=5

Fig2: Kidney biopsy light microscopy. a Hematoxylin & eosin (X200) showing dark pink, filamentous tubular casts (yellow arrow); b) Jones’ silver stain (X400) showing dark pink, coarsely granular and filamentous tubular casts (yellow arrow)
Mentions: A 76-year-old Caucasian man with a history of type 2 diabetes, chronic kidney disease (CKD) stage 3A, essential hypertension, hypothyroidism, antiphospholipid antibody syndrome, prior cerebellar strokes, and prostate cancer (Gleason 10) with widespread metastasis to the bone presented with non-oliguric severe AKI 3 weeks after receiving simultaneous therapy with denosumab (120 mg subcutaneous injection once) and abiraterone (1 g per day orally). The patient had failed prior antineoplastic therapy with leuprolide acetate, bicalutamide, and nilutamide. On admission, his serum creatinine (SCr) was elevated at 5.7 mg/dL from a baseline of 1.2 mg/dL (Fig. 1). His active outpatient medications consisted of rosuvastatin (40 mg daily), benazepril, metoprolol tartrate, metformin, warfarin, low-dose prednisone (started concomitantly with abiraterone), and levothyroxine. The patient had been on statin therapy for more than 1 year and the dose had not been recently modified. The patient denied prior episodes of myopathies, rhabdomyolysis, or AKI. His physical exam was unremarkable. Further blood work showed hyperkalemia, mild metabolic acidosis, hypocalcemia, mild transaminemia (predominantly AST), and creatine kinase (CK) of 44,476 IU/L (Table 2). Urine studies revealed dipstick proteinuria (100 mg/dL), large dipstick blood, only a few normomorphic erythrocytes, and negative culture. All serologic work-up (ANA, PR3- and MPO-ANCA, anti-GBM antibodies, ENA panel, C3, C4, RF) and viral studies (HBV, HCV, CMV, EBV, Influenza A/B, Parainfluenza, Adenovirus, RSV) were negative or normal. Thyroid function tests were normal. Kidney sonogram and Doppler studies were negative for hydronephrosis and renal vein thrombosis, respectively. On admission, abiraterone therapy was discontinued and no further doses of denosumab were administered. Subsequently, the patient underwent kidney biopsy that was consistent with severe acute tubular injury with presence of myoglobin casts, confirming the diagnosis of rhabdomyolysis-induced AKI (Figs. 2 and 3). The patient responded well to intravenous isotonic fluids and discontinuation of denosumab, abiraterone, and rosuvastatin. CK levels normalized by day 25 of hospitalization and the SCr at the time of hospital discharge was 3.1 mg/dL (Fig. 1). After hospital discharge, the patient resumed all prior medications, including rosuvastatin, except for denosumab and abiraterone. His successive antineoplastic therapy consisted of enzalutamide. Kidney function returned to baseline 12 months after discharge and he had no recurrent episodes of rhabdomyolysis.Fig. 1

Bottom Line: Kidney biopsy confirmed the diagnosis of rhabdomyolysis-induced AKI.Whether one of these drugs individually, or the combination, was the bona fide culprit of muscle breakdown is unknown.Nonetheless, our report is hypothesis-generating for further investigations on the effect of these drugs on muscle cells.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX, 75390-8516, USA. Javier.NeyraLozano@UTSouthwestern.edu.

ABSTRACT

Background: Denosumab and abiraterone were approved by the United States Food and Drug Administration in 2011 for the treatment of metastatic castration-resistant prostate cancer. Neither denosumab nor abiraterone is known to cause rhabdomyolysis.

Case presentation: A 76-year-old Caucasian man with metastatic prostate cancer presented with non-oliguric severe acute kidney injury (AKI) 3 weeks after receiving simultaneous therapy with denosumab and abiraterone. The patient had been on statin therapy for more than 1 year with no recent dose adjustments. His physical exam was unremarkable. Blood work on admission revealed hyperkalemia, mild metabolic acidosis, hypocalcemia, and elevated creatine kinase (CK) at 44,476 IU/L. Kidney biopsy confirmed the diagnosis of rhabdomyolysis-induced AKI. The patient responded well to intravenous isotonic fluids and discontinuation of denosumab, abiraterone, and rosuvastatin, with normalization of CK and recovery of kidney function.

Conclusion: We report the first case of biopsy-proven rhabdomyolysis-induced AKI in a cancer patient acutely exposed to denosumab and abiraterone. Whether one of these drugs individually, or the combination, was the bona fide culprit of muscle breakdown is unknown. Nonetheless, our report is hypothesis-generating for further investigations on the effect of these drugs on muscle cells.

No MeSH data available.


Related in: MedlinePlus