Toxic acute tubular necrosis following treatment with zoledronate (Zometa)
| Autor: | David S. Siegel, Paul L. Fine, Samih H. Nasr, Jin Park, Shirley Hoh, Cheryl L. Kunis, Jai Radhakrishnan, Jay I. Stack, Winicjusz Palecki, Vivette D. D'Agati, Glen S. Markowitz |
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| Rok vydání: | 2003 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Biopsy Urology Renal function Apoptosis Kidney acute renal failure Zoledronic Acid toxic acute tubular necrosis Nephrotoxicity Cohort Studies chemistry.chemical_compound Focal segmental glomerulosclerosis Internal medicine Medicine Humans Renal Insufficiency zoledronate (Zometa) Acute tubular necrosis Aged Aged 80 and over Creatinine medicine.diagnostic_test Diphosphonates business.industry nephrotoxicity Imidazoles Kidney Tubular Necrosis Acute Middle Aged medicine.disease Endocrinology medicine.anatomical_structure chemistry Nephrology Female Renal biopsy Sodium-Potassium-Exchanging ATPase business Kidney disease |
| Zdroj: | Kidney international. 64(1) |
| ISSN: | 0085-2538 |
| Popis: | Toxic acute tubular necrosis following treatment with zoledronate (Zometa). Background Renal failure and toxic acute tubular necrosis (ATN) may be seen following exposure to a variety of therapeutic agents. Zoledronate (Zometa) is a new, highly potent bisphosphonate used in the treatment of hypercalcemia of malignancy. We report the first clinical-pathologic study of nephrotoxicity associated with this agent. Methods A cohort of six patients (four males and two females) with a mean age of 69.2years received bisphosphonate therapy for multiple myeloma (five patients) or Paget's disease (one patient). In all patients, zoledronate was administered at a dose of 4mg intravenously monthly, infused over at least 15 minutes, and the duration of therapy was mean 4.7months (range, 3 to 9months). Results All patients developed renal failure with a rise in serum creatinine from a mean baseline level of 1.4mg/dL to 3.4mg/dL. Renal biopsy revealed toxic ATN, characterized by tubular cell degeneration, loss of brush border, and apoptosis. Immunohistochemical staining revealed a marked increase in cell cycle-engaged cells (Ki-67 positive) and derangement in tubular Na + ,K + -ATPase expression. Importantly, although all patients had been treated with pamidronate prior to zoledronate, no biopsy exhibited the characteristic pattern of collapsing focal segmental glomerulosclerosis observed in pamidronate nephrotoxicity. Following renal biopsy, treatment with zoledronate was discontinued and all six patients had a subsequent improvement in renal function (mean final serum creatinine, 2.3mg/dL at 1 to 4months of follow-up). Conclusion The close temporal relationship between zoledronate administration and the onset of renal failure and the partial recovery of renal function following drug withdrawal strongly implicate this important and widely used agent in the development of toxic ATN. |
| Databáze: | OpenAIRE |
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