Abstract:
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 69.2 years received bisphosphonate therapy for multiple myeloma (five patients) or Paget's disease (one patient). In all patients, zoledronate was administered at a dose of 4 mg intravenously monthly, infused over at least 15 minutes, and the duration of therapy was mean 4.7 months (range, 3 to 9 months). RESULTS:All patients developed renal failure with a rise in serum creatinine from a mean baseline level of 1.4 mg/dL to 3.4 mg/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, 2.3 mg/dL at 1 to 4 months 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.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Markowitz GS,Fine PL,Stack JI,Kunis CL,Radhakrishnan J,Palecki W,Park J,Nasr SH,Hoh S,Siegel DS,D'Agati VDdoi
10.1046/j.1523-1755.2003.00071.xsubject
Has Abstractpub_date
2003-07-01 00:00:00pages
281-9issue
1eissn
0085-2538issn
1523-1755pii
S0085-2538(15)49317-2journal_volume
64pub_type
杂志文章abstract::The addition of spironolactone or hydrochlorothiazide enhances the antialbuminuric effect of renin-angiotensin blockers. However, comparative studies on the effect of different diuretics are lacking. We conducted a prospective randomized crossover study to compare the effects of spironolactone (25 mg/day), hydrochloro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.249
更新日期:2015-12-01 00:00:00
abstract::Acute kidney injury (AKI) is a major complication of cardiac bypass surgery. We examined whether levels of liver fatty acid-binding protein (L-FABP) can be an early biomarker for ischemic injury by measuring this protein in the urine of 40 pediatric patients prior to and following cardiopulmonary bypass surgery. AKI w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002721
更新日期:2008-02-01 00:00:00
abstract::Glutamine accumulation in rat kidney was investigated by giving large loads of gluta, mate and aspartate and measuring glutamine changes in seven completely defined portions of the nephron and in small patches from the thin limb area and from the papilla. Both glutamate and aspartate (which is partly coverted to gluta...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1978.145
更新日期:1978-11-01 00:00:00
abstract::The kidney is a likely source for some urinary epinephrine (E) since adrenalectomized animals and humans continue to excrete urinary E and the human kidney contains E synthesizing enzymes. We studied subjects during an intravenous infusion of 3H-E to determine the fraction of urinary E derived from the kidney. Eight n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.40
更新日期:1997-01-01 00:00:00
abstract::The incidence of acute kidney injury (AKI) is high in elderly people, and is difficult to prevent and treat. One of its major causes is renal ischemia-reperfusion injury (IRI). A young systemic environment may prevent the senescence of old organs. However, it is unknown whether a young milieu may reduce renal IRI in t...
journal_title:Kidney international
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doi:10.1016/j.kint.2018.03.019
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abstract::Atypical hemolytic uremic syndrome (aHUS) is a form of thrombotic microangiopathy (TMA) caused by dysregulated complement activation. Clinically, aHUS is effectively treated by an anti-C5 monoclonal antibody (mAb) but whether the disease is mediated by the C5a receptor (C5aR) or C5b-9 pathway, or both, is unknown. Her...
journal_title:Kidney international
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doi:10.1016/j.kint.2019.01.009
更新日期:2019-07-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.10.021
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abstract::The thick ascending limb of Henle's loop ( TAL ) develops a specific and consistent structural lesion during perfusion of the isolated rat kidney that progresses from mitochondrial swelling at 15 min to complete cellular disruption at 90 min. Because it seemed possible that damage localized to this metabolically activ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1984.9
更新日期:1984-01-01 00:00:00
abstract::The International Pediatric Peritonitis Registry (IPPR) was created to assess and evaluate the validity of the pediatric peritonitis treatment guidelines issued by the International Society for Peritoneal Dialysis. The study by Schaefer et al., one of the first to emerge from the IPPR, describes regional variability i...
journal_title:Kidney international
pub_type: 评论,杂志文章
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更新日期:2007-12-01 00:00:00
abstract::Diabetes is a major cause of chronic kidney disease, and oral antidiabetic drugs are the mainstay of therapy for most patients with Type 2 diabetes. Here we evaluated their role on renal outcomes by using a national Veterans Administration database to assemble a retrospective cohort of 93,577 diabetic patients who fil...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.444
更新日期:2012-04-01 00:00:00
abstract::The recent identification of RPGRIP1L as a Joubert syndrome gene brings the total of known genes to five. Three of these are also associated with the lethal Meckel syndrome, and two with Senior-Løken syndrome; both of these disorders share Joubert syndrome phenotypes, illustrating the genetic complexity of this. ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002577
更新日期:2007-12-01 00:00:00
abstract::An expression profile is a list based on a large scale sequencing of 1000 cDNA clones, showing the expressed genes and the abundance of their transcripts in a given cell or tissue (Okubo K et al: Nature Genet 2:173, 1992). We constructed an expression profile of mouse renal proximal tubules (PT) carefully isolated by ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00808.x
更新日期:1998-03-01 00:00:00
abstract::Fourteen Center hemodialysis (CHD) patients, 13 continuous ambulatory peritoneal dialysis (CAPD) patients, and 10 normals matched by group for age and sex were compared using a battery of evoked (EP) and event-related (ERP) brain potential measures to determine the effects on central nervous system (CNS) functioning o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.279
更新日期:1986-12-01 00:00:00
abstract::Congenital nephrotic syndrome is clinically and genetically heterogeneous. The majority of cases can be attributed to mutations in the genes NPHS1, NPHS2, and WT1. By homozygosity mapping in a consanguineous family with isolated congenital nephrotic syndrome, we identified a potential candidate region on chromosome 3p...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5001679
更新日期:2006-09-01 00:00:00
abstract::Coronary artery stenosis induces renal inflammation and kidney injury in pigs even in the absence of myocardial infarction or clinically significant heart failure. This effect is aggravated by experimentally induced renovascular hypertension. Interestingly, oxidative stress originating from the ischemic myocardium was...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2014.431
更新日期:2015-04-01 00:00:00
abstract::It is well known that uremia causes an increase in the serum anion gap (AG); however, whether changes in the AG occur earlier in the course of chronic kidney disease is not known. Here we investigated whether different measures of the AG, as a marker of kidney function, are associated with mortality. To do this, we an...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.196
更新日期:2012-09-01 00:00:00
abstract::Autosomal dominant polycystic kidney disease (ADPKD) is associated with a urine-concentrating defect attributed to renal cystic changes. As PKD genes are expressed in the brain, altered central release of arginine vasopressin could also play a role. In order to help determine this we measured central and nephrogenic c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2012.225
更新日期:2012-11-01 00:00:00
abstract:BACKGROUND:It is not known to what extent intravascular phenotypic alterations in adhesion molecule expression induced by hemodialysis influence the recruitment of monocytes and their ability to up-regulate CD11b at the local site of inflammation in the interstitium. Using a skin suction chamber technique, we addressed...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00060.x
更新日期:2000-05-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000335
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abstract::Freeze-fracture and thin-section electron microscopy and morphometry were used to characterize further the response of the rat medullary collecting duct to potassium depletion. In freeze-fracture replicas, principal cells and intercalated cells were identified based on the assumption that intercalated cells possess a ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.6
更新日期:1980-01-01 00:00:00
abstract::Insulin-like growth factor I (IGF-1) is a peptide growth factor that is synthesized in cultured mesangial cells and induces hyperplasia. We tested whether incubation with IGF-1 at concentrations of 7 nM, 70 nM, and 350 nM stimulates mesangial cell extracellular matrix mRNA and protein levels, and whether it influences...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.265
更新日期:1995-07-01 00:00:00
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pub_type: 杂志文章,评审
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更新日期:2007-04-01 00:00:00
abstract::Levels of components of the classical and alternative complement pathways and the activity of the C3 nephritic factor (C3NeF) were measured in serum specimens from patients with type I (subendothelial deposits) and type II (intramembranous dense deposits) membranoproliferative glomerulonephritis (MPGN) and the results...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1976.6
更新日期:1976-01-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00846.x
更新日期:2004-09-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.210
更新日期:2015-11-01 00:00:00
abstract:BACKGROUND:Systematic studies on safety and efficacy of enteral nutrition in patients with acute renal failure (ARF) are lacking. METHODS:We studied enteral nutrition-related complications and adequacy of nutrient administration during 2525 days of artificial nutrition in 247 consecutive patients fed exclusively by th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00459.x
更新日期:2004-03-01 00:00:00
abstract::On a typical Western diet, the body is faced with the generation of a metabolically derived acid load that must be excreted to maintain systemic acid-base balance. The kidney is responsible for this task and matches daily acid excretion with daily acid production. Multiple nephron segments are involved in the process,...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5002543
更新日期:2007-12-01 00:00:00
abstract::In organ transplantation, ischemia/reperfusion (I/R) results in damage that may affect cell viability and lead to organ failure. I/R injury involves a complex cascade of events, including loss of energy, derangement of the ionic hemostasis, production of reactive oxygen species, and cell death. In this context, mitoch...
journal_title:Kidney international
pub_type: 杂志文章,评审
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更新日期:2004-08-01 00:00:00
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journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00521.x
更新日期:2004-04-01 00:00:00
abstract::Acute kidney injury (AKI) activates pathways of cell death and cell proliferation. Although seemingly discrete and unrelated mechanisms, these pathways can now be shown to be connected and even to be controlled by similar pathways. The dependence of the severity of renal-cell injury on cell cycle pathways can be used ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.224
更新日期:2009-09-01 00:00:00