Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022672 (acute tubular necrosis)
 2,175 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Bisphosphonates are valuable agents for the treatment of post-menopausal osteoporosis (PMO), hypercalcemia of malignancy, and osteolytic bone metastases. Oral bisphosphonates are used mainly to treat PMO and are not associated with significant nephrotoxicity. In contrast, nephrotoxicity is a significant potential limiting factor to the use of intravenous (IV) bisphosphonates, and the nephrotoxicity is both dose-dependent and infusion time-dependent. The two main IV bisphosphonates available to treat hypercalcemia of malignancy and osteolytic bone disease in the United States are zoledronate and pamidronate. Patterns of nephrotoxicity described with these agents include toxic acute tubular necrosis and collapsing focal segmental glomerulosclerosis, respectively. With both of these agents, severe nephrotoxicity can be largely avoided by stringent adherence to guidelines for monitoring serum creatinine prior to each treatment, temporarily withholding therapy in the setting of renal insufficiency, and adjusting doses in patients with pre-existing chronic kidney disease. In patients with PMO, zoledronate and pamidronate are associated with significantly less nephrotoxicity, which undoubtedly relates to the lower doses and longer dosing intervals employed for this indication. Ibandronate is approved in the US for treatment of PMO and in Europe for treatment of PMO and malignancy-associated bone disease. Available data suggest that ibandronate has a safe renal profile without evidence of nephrotoxicity, even in patients with abnormal baseline kidney function.
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PMID:Bisphosphonate nephrotoxicity. 1868 74

Bisphosphonates are eliminated from the human body by the kidney. Renal clearance is both by glomerular filtration and proximal tubular secretion. Bisphosphonates given rapidly in high doses in animal models have induced a variety of adverse renal effects, from glomerular sclerosis to acute tubular necrosis. Nevertheless in the doses that are registered for the management of postmenopausal osteoporosis (PMO), oral bisphosphonates have never been shown to adversely affect the kidney, even (in post-hoc analysis of clinical trial data) down to estimated glomerular filtration rates of 15 ml/min. In addition fracture risk reduction has also been observed in these populations with stage 4 chronic kidney disease (CKD) with age-related reductions in glomerular filtration rate (GFR). Intravenous zoledronic acid is safe when the infusion rate is no faster than 15 min though there have been short-term (days 9-11 post-infusion) increases in serum creatinine concentrations in a small sub-set of patients from the postmenopausal registration trials. For these reasons intravenous zoledronic acid should be avoided in patients with GFR levels <35 ml/min; and the patients should be well hydrated and have avoided the concomitant use of any agent that may impair renal function. Intravenous ibandronate has not to date been reported to induce acute changes in serum creatinine concentrations in the PMO clinical trial data, but the lack of head-to-head comparative data between ibandronate and zoledronic acid precludes knowing if one intravenous bisphosphonate is safer than the other. In patients with GFR levels <30-35 ml/min, the correct diagnosis of osteoporosis becomes more complex since other forms of renal bone disease, which require different management strategies than osteoporosis, need to be excluded before the assumption can be made that fractures and/or low bone mass are due to osteoporosis. In addition, in patients who may have pre-existing adynamic renal bone disease, there is a lack of evidence of any beneficial effect or harm by reducing bone turnover by any pharmacological agent, including bisphosphonates on bone strength or vascular calcification. Bisphosphonates are safe and effective for the management of osteoporosis when used in the right dose and in the right patient population for the right duration.
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PMID:The kidney and bisphosphonates. 2123 48

Zoledronate is a highly potent bisphosphonate widely used in the treatment of postmenopausal osteoporosis. We report the first occurrence of toxic acute tubular necrosis (ATN) following treatment with zoledronate in a patient with osteoporosis. A 63-year-old Caucasian female with rheumatoid arthritis on anti-immune agents received a single dose of zoledronic acid (reclast) for worsening osteoporosis. Twelve days later, she developed renal failure with a rise in serum creatinine from a baseline level of 1.1 mg/dL to 5.5 mg/dL. Renal biopsy showed toxic ATN. Zoledronate was discontinued and the patient had subsequent gradual improvement in renal function with final serum creatinine of 1.8 mg/dL at 1 month of follow up. Careful monitoring of serum creatinine and awareness of the potential nephrotoxicity may avert the development of acute renal failure in osteoporosis patients treated with this agent.
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PMID:Early onset acute tubular necrosis following single infusion of zoledronate. 2792 Aug 15