Abstract：
:Exposure is a critically important aspect to consider in the study and management of drug-induced kidney injury. Although blood concentrations of kidney toxicants often may provide a valid surrogate measure of kidney exposure, the kidney has several unique physiological and biochemical properties that lend themselves to accumulation or exclusion of some drugs at sites of toxicity. In such cases, an understanding of these pharmacokinetic mechanisms can be as important as understanding the underlying mechanisms of toxicity. Physiologically based pharmacokinetic models, which mathematically codify such mechanisms in a biologically plausible form, increasingly are being used for developing an understanding of pharmacokinetics across patient populations, drug-drug interactions, and pharmacokinetic-pharmacodynamic relationships. This perspective provides a review of the physiological and biochemical mechanisms as well as the physiochemical properties that theoretically could drive drug accumulation or exclusion within the kidney, along with examples in which these mechanisms have proven important in driving the manifestation of toxicity in vivo. In addition, an overview of the structure, applications, and limitations of existing kidney physiologically based pharmacokinetic models is provided. Finally, a perspective on gaps and associated challenges to such models in the field of toxicology is discussed briefly.
journal_name
Semin Nephroljournal_title
Seminars in nephrologyauthors
Li Z,Fisher C,Gardner I,Ghosh A,Litchfield J,Maurer TSdoi
10.1016/j.semnephrol.2018.12.006subject
Has Abstractpub_date
2019-03-01 00:00:00pages
176-189issue
2eissn
0270-9295issn
1558-4488pii
S0270-9295(18)30185-2journal_volume
39pub_type
杂志文章,评审abstract：:Premature menopause defined as secondary amenorrhea is common in women with kidney disease. Moreover, the aging population has resulted in increasing numbers of postmenopausal women with kidney disease. Though the pathophysiology is poorly understood, kidney transplantation and more frequent hemodialysis can restore m...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2017.05.013
更新日期：2017-07-01 00:00:00
abstract：:In recent years, it has become apparent that parietal epithelial cells (PECs) play an important role within the renal glomerulus, in particular in diseased conditions. In this review, we examine current knowledge about the role of PECs and their interactions with podocytes in development and under physiological condit...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2012.06.007
更新日期：2012-07-01 00:00:00
abstract：:The identification of natriuretic peptides as key regulators of natriuresis and vasodilatation, and the appreciation that their secretion is under the control of cardiac hemodynamic and neurohumoral factors, has caused wide interest. The natriuretic peptides are structurally similar, but genetically distinct peptides ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1053/snep.2002.35666
更新日期：2002-09-01 00:00:00
abstract：:Traditionally, renal ischemia has been regarded as central to the pathogenesis of sepsis-associated acute kidney injury (SA-AKI). Accordingly, hemodynamic management of SA-AKI has emphasized restoration of renal perfusion, whereas, experimentally, ischemia reperfusion models have been emphasized. However, in human bei...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2015.01.007
更新日期：2015-01-01 00:00:00
abstract：:Amiloride is a prototypic inhibitor of epithelial sodium channels. Rapid progress has been made in our understanding of the structure of the sodium channel and related cation-selective channels. This work, coupled with experiments examining how selected sodium channel mutations affect amiloride binding, provides criti...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1999-11-01 00:00:00
abstract：:A number of organic acids including phenols are accumulated in plasma of uremic patients because of reduced renal clearance. Some of them account for uremic problems such as reduced drug binding. Protein-bound organic acids such as hippuric acid, indoxyl sulfate, and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1996-05-01 00:00:00
abstract：:Worldwide, more than 250,000 individuals who have received a liver, heart, lung, or intestinal transplant are living longer. Twenty percent to 25% of these recipients experience perioperative acute renal failure, with 10% to 15% requiring renal replacement therapy. Chronic kidney disease (CKD) is also highly prevalent...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2007.03.010
更新日期：2007-07-01 00:00:00
abstract：:As kidney function declines, chronic kidney disease (CKD) becomes an increasingly systemic disorder. Most patients with CKD eventually develop subclinical or clinical abnormalities in bone and mineral metabolism. Recent observational and basic scientific studies have led to a new emphasis on the changes in phosphorus ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2009.01.002
更新日期：2009-03-01 00:00:00
abstract：:A number of antineoplastic chemotherapeutic drugs may produce fluid and electrolyte disturbances or nephrotoxic reactions extending across the clinical spectrum, from subclinical renal dysfunction to progressive chronic renal insufficiency to severe acute failure. Although some of the drugs that are highly nephrotoxic...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1997-01-01 00:00:00
abstract：:Acid-base balance is critical for normal life. Acute and chronic disturbances impact cellular energy metabolism, endocrine signaling, ion channel activity, neuronal activity, and cardiovascular functions such as cardiac contractility and vascular blood flow. Maintenance and adaptation of acid-base homeostasis are most...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2019.04.004
更新日期：2019-07-01 00:00:00
abstract：:By analogy to the findings with other transport disorders such as Bartter's or Liddle's syndrome, it might be expected that the various forms of renal tubular acidosis (RTA) could result from defects in H-ATPase or H-K-ATPase. However, the available data do not yet support such a simple explanation. With regard to dis...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1998-01-01 00:00:00
abstract：:Substantial progress has been made in the application of computer-driven methods to provide erythropoietic dosing information for patients with anemia resulting from chronic kidney disease. Initial solutions were simply computerized versions of traditional paper-based anemia management protocols. True personalization ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2018.05.010
更新日期：2018-07-01 00:00:00
abstract：:Toxic nephropathies cause acute and chronic renal failure, primarily as a result of injury to renal tubular epithelium. There is a well-known capacity in the renal nephron for the synchronous occurrence of both apoptosis and necrosis in toxic nephropathies. This has engendered interest in the differing or complementar...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/s0270-9295(03)00085-8
更新日期：2003-09-01 00:00:00
abstract：:Hypertension is growing in prevalence and most of this growth represents isolated systolic hypertension in the elderly. Attempts at prevention are critical but likely are ineffectual. Therefore, the delivery and acceptance of current medical regimens must be improved. ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2005.02.002
更新日期：2005-07-01 00:00:00
abstract：:Kidney disease has been shown to be highly prevalent in cancer patients in the IRMA studies (Renal Insufficiency and Anticancer Medications). Furthermore, anticancer drugs used in those patients, among which half have abnormal renal function, necessitate dosage adjustment in case of reduced renal function and/or is po...
journal_title：Seminars in nephrology
pub_type： 杂志文章
doi：10.1016/j.semnephrol.2010.09.003
更新日期：2010-11-01 00:00:00
abstract：:The apical membrane epithelial Na(+) channel subunit (ENaC) in series with the basolateral Na(+)/K(+)-adenosine triphosphatase mediates collecting duct Na(+) reabsorption. Aldosterone induces αENaC gene transcription, which appears to be rate limiting for ENaC activity in this segment. Although this response has long ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2013.05.010
更新日期：2013-07-01 00:00:00
abstract：:Antineutrophil cytoplasmic autoantibodies (ANCA) are the likely cause for necrotizing small-vessel vasculitis and crescentic glomerulonephritis. Unlike other forms of crescentic glomerulonephritis induced by immune complexes or anti-glomerular basement membrane antibodies that have conspicuous vessel wall immunoglobul...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2013.08.006
更新日期：2013-11-01 00:00:00
abstract：:Mineralocorticoid hypertension is hypertension associated with the presence of hypokalemia, metabolic alkalosis, and suppression of plasma renin. Mineralocorticoid hypertension represents only 10% of patients with essential hypertension. However, its recognition is important because it is a potentially reversible caus...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2006.10.004
更新日期：2006-11-01 00:00:00
abstract：:Autophagy is a ubiquitous intracellular catabolic process that contributes to homeostatic maintenance and regulates the balance between health and disease. Emerging evidence from both the immunology and renal literature suggests that important relationships exist between the immune system and renal autophagy that may ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2013.11.008
更新日期：2014-01-01 00:00:00
abstract：:Pancreas transplantation is being performed with increasing frequency and increasing technical success. The availability of new immunosuppressant agents has been associated with a reduction in the previously high rates of allograft rejection in recipients of simultaneous pancreas-kidney transplants. These lower reject...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：2000-03-01 00:00:00
abstract：:Immune-mediated nephritis is a common complication of systemic lupus erythematosus (SLE). It is now clear that multiple and independent mechanisms contribute to disease onset and pathogenesis, which may explain the remarkable phenotypic and histopathological heterogeneity observed in human SLE. Identification and char...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1999-03-01 00:00:00
abstract：:The prevalence of chronic or end-stage kidney disease in pediatric girls is lower than in boys, however, girls have unique morbidities that can have great effect on their quality of life. For female adolescents, creatinine excretion peaks at approximately 14 years of age and is significantly less than males, owing to ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2017.05.003
更新日期：2017-07-01 00:00:00
abstract：:Blood pressure increases with age in all US population groups that have been studies, but does so faster in African Americans. Evidence from extensive microscopic renal vascular studies at autopsy supports the view that blood pressure increases with age because of progressive fibroplasia of renal interlobular arteries...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1996-03-01 00:00:00
abstract：:This article summarizes physiological and molecular studies of the colonic H+,K+-ATPase and active potassium (K) absorption in the rat distal colon. Active K absorption is energized by an apical membrane H+,K+-ATPase that is a member of the gene family of P-type ATPases. Physiological experiments of active K absorptio...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1999-09-01 00:00:00
abstract：:Given the prohibitive costs of end-stage renal disease (ESRD) care for certain countries and the increasing incidence of ESRD worldwide, alternative methods of funding dialysis care are increasingly necessary. We describe the paradigm of the National Kidney Foundation of Singapore (NKF-S), the provider of subsidized d...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1053/snep.2001.23776
更新日期：2001-07-01 00:00:00
abstract：:The intravascular volume consists of 40% to 45% red cells. Their production is controlled predominantly by erythropoietin (EPO), a hormone that is secreted particularly when tissue hypoxia is present. Because of this high percentage of the total intravascular volume the question comes to mind that, in addition to hypo...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2005.05.007
更新日期：2005-11-01 00:00:00
abstract：:Care of patients with type 1 diabetes (T1D) has changed during the past 30 years. Tools to control hyperglycemia have improved and it was shown that improvement in glycemic control diminished the risk of late diabetic complications, including nephropathy. Moreover, in patients with impaired renal function, aggressive ...
journal_title：Seminars in nephrology
pub_type： 杂志文章
doi：10.1016/j.semnephrol.2012.07.002
更新日期：2012-09-01 00:00:00
abstract：:Kidney function declines with age in association with the development of age-associated glomerulosclerosis. The well-established structural and functional changes with age are reviewed briefly. The modification of aging pathology by calorie restriction is discussed. The role of the podocyte as a critical cell in the a...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2009.07.012
更新日期：2009-11-01 00:00:00
abstract：:The antiphospholipid syndrome (APS) is a systemic autoimmune disorder characterized by a combination of arterial and/or venous thrombosis, pregnancy morbidity, and the persistent presence of circulating antiphospholipid antibodies (aPL). APS has been described as primary APS when it occurs in the absence of any featur...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2015.08.009
更新日期：2015-09-01 00:00:00
abstract：:Renal involvement is common in leptospirosis. Clinical manifestations vary from urinary sediment changes to acute renal failure. Renal failure is observed in 44% to 67% of patients. Hypokalemia frequently occurs. Severe hypotension is an important warning sign for the later development of renal and pulmonary complicat...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1053/snep.2003.50004
更新日期：2003-01-01 00:00:00
