Abstract：
:Apolipoprotein L1 (APOL1) genetic variants account for much of the excess risk of chronic and end-stage kidney disease, which results in a significant global health disparity for persons of African ancestry. We estimate the lifetime risk of kidney disease in APOL1 dual-risk allele individuals to be at least 15%. Experimental evidence suggests a direct role of APOL1 in pore formation, cellular injury, and programmed cell death in renal injury. The APOL1 BH3 motif, often associated with cell death, is unlikely to play a role in APOL1-induced cytotoxicity because it is not conserved within the APOL family and is dispensable for cell death in vitro. We discuss two models for APOL1 trypanolytic activity: one involving lysosome permeabilization and another involving colloid-osmotic swelling of the cell body, as well as their relevance to human pathophysiology. Experimental evidence from human cell culture models suggests that both mechanisms may be operative. A systems biology approach whereby APOL1-associated perturbations in gene and protein expression in affected individuals are correlated with molecular pathways may be productive to elucidate APOL1 function in vivo.
journal_name
Semin Nephroljournal_title
Seminars in nephrologyauthors
Dummer PD,Limou S,Rosenberg AZ,Heymann J,Nelson G,Winkler CA,Kopp JBdoi
10.1016/j.semnephrol.2015.04.008subject
Has Abstractpub_date
2015-05-01 00:00:00pages
222-36issue
3eissn
0270-9295issn
1558-4488pii
S0270-9295(15)00068-6journal_volume
35pub_type
杂志文章,评审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：:Recombinant human erythropoietin (rHuEPO) has revolutionized the treatment of anemia of chronic renal failure. RHuEPO has been shown to increase survival, decrease hospitalizations, improve brain and cognitive function, and improve quality of life for renal patients. Much has been learned about the normal and patholog...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1053/snep.2001.20939
更新日期：2001-03-01 00:00:00
abstract：:Several studies have shown an association between the hemodialysis session length (the t of Kt or Kt/V) and favorable outcomes for patients on maintenance hemodialysis. In a single randomized controlled trial that systematically varied hemodialysis session length, shorter session length was associated with an increase...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2004.09.015
更新日期：2005-03-01 00:00:00
abstract：:Chronic kidney disease mineral and bone disorder (MBD) encompasses changes in mineral ion and vitamin D metabolism that are widespread in the setting of chronic kidney disease and end-stage renal disease. MBD components associate with cardiovascular disease in many epidemiologic studies. Through impacts on hypertensio...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2018.08.001
更新日期：2018-11-01 00:00:00
abstract：:On completion of a Nephrology fellowship, I went back to the inner city community where I was raised to begin my practice. Filled with idealism, I believed that, by returning, I could slow the devastation that hypertension was imparting on the black community, and in doing so, prevent end-stage renal disease (ESRD). I...
journal_title：Seminars in nephrology
pub_type： 杂志文章
doi：10.1053/snep.2001.23688
更新日期：2001-07-01 00:00:00
abstract：:Acute ingestion of protein and intravenous infusion of amino acids are known to stimulate increases in renal blood flow and glomerular filtration rate (GFR) in animals and humans. Although some investigators believe that these changes are mediated by a circulating hormonal factor, there is considerable evidence that i...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1995-09-01 00:00:00
abstract：:Acute renal failure (ARF) is an important clinical syndrome. Despite the frequent occurrence of ARF, nephrologists have not made major therapeutic inroads in the treatment or prevention of ARF. This article will speculate as to why it has been so difficult to gain a substantial foothold in the ongoing battle against A...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1998-09-01 00:00:00
abstract：:Remarkable advances have been made in the past decade in understanding the pathophysiology of idiopathic nephrotic syndrome. Although the initiating events leading to the onset of proteinuria still are not well defined, it has become increasingly clear that many glomerular diseases can be classified as podocytopathies...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2009.03.015
更新日期：2009-07-01 00:00:00
abstract：:The importance of hypertension as a cardiovascular risk factor increases progressively with aging, but diastolic blood pressure plateaus at age 50, which leads to a rise in pulse pressure in the elderly. Thus, isolated systolic hypertension with a widened pulse pressure is the most common type of hypertension seen in ...
journal_title：Seminars in nephrology
pub_type： 杂志文章
doi：
更新日期：2002-01-01 00:00:00
abstract：:Hotspots of chronic kidney disease of unknown etiology (CKDu) have been identified throughout the globe, of which the Mesoamerican nephropathy in Central America is the most conspicuous example. It affects mainly agricultural workers, heat exposure during extenuating shifts leading to sudden dehydration and subsequent...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2019.02.008
更新日期：2019-05-01 00:00:00
abstract：:In aggregate, the evidence reviewed here supports a very important role for PDGF expression and action at local glomerular and interstitial sites in human kidney development and disease. PDGF delivered by platelets, or produced by endogenous cells of the kidney is capable of stimulating responses including proliferati...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1993-01-01 00:00:00
abstract：:The progressive decline of glomerular filtration rate in chronic kidney disease patients is associated with a significant reduction in food intake. Approximately one third of chronic dialysis patients complain of a fair or poor appetite and this is related directly to poor patient outcomes. Appetite regulation involve...
journal_title：Seminars in nephrology
pub_type： 杂志文章
doi：10.1016/j.semnephrol.2008.10.003
更新日期：2009-01-01 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：:Recent breakthroughs in genomics have led to a critical reappraisal of factors once thought to initiate common complex forms of kidney disease. The tenet that diabetes mellitus and hypertension routinely initiate kidney disease whenever blood glucose concentrations or systemic blood pressures reach critical levels for...
journal_title：Seminars in nephrology
pub_type： 杂志文章
doi：10.1016/j.semnephrol.2010.01.002
更新日期：2010-03-01 00:00:00
abstract：:The Human Genome Project is rapidly producing insights into the molecular basis of human genetic disorders. The most immediate clinical benefit is the advent of new diagnostic methods. Molecular diagnostic tools are available for several genetic renal disorders and are in development for many more. Two general approac...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1999-07-01 00:00:00
abstract：:In chronic kidney disease the excessive production of parathyroid hormone increases the bone resorption rate and leads to histologic bone signs of secondary hyperparathyroidism. However, in other situations, the initial increase in parathyroid hormone and bone remodeling may be slowed down excessively by a multitude o...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2014.09.004
更新日期：2014-11-01 00:00:00
abstract：:Studies performed over the last 10 years have evaluated the role of nitric oxide (NO) in the control of renal hemodynamics. This article reviews the effects of administration of nitric oxide synthase (NOS) blockers on renal function in experimental animals and human volunteers. These studies show that NOS blockade inc...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1999-05-01 00:00:00
abstract：:An expanding proportion of people in the United States and worldwide are affected by kidney disease, leading to a growing concern over the public health implications. Despite the high prevalence and the considerable associated health risks of kidney disease, major gaps in our knowledge base hinder the delivery of opti...
journal_title：Seminars in nephrology
pub_type： 评论,杂志文章,评审
doi：10.1016/j.semnephrol.2009.06.002
更新日期：2009-09-01 00:00:00
abstract：:Long-term continuous ambulatory peritoneal dialysis (CAPD) often causes peritoneal fibrosis and sclerosis with a loss of function, and some CAPD patients develop sclerosing encapsulating peritonitis. Glucose-based peritoneal dialysis fluids readily produce glucose degradation products by heat sterilization, and glucos...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2004.06.027
更新日期：2004-09-01 00:00:00
abstract：:An important component of nephrology research is the discovery of novel proteins that control cellular and molecular events that contribute to normal kidney cell biology and disease. Identifying perturbation of normal cellular protein expression and interactions within signaling networks is critical for understanding ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2007.09.008
更新日期：2007-11-01 00:00:00
abstract：:There are emerging data that the skeleton is connected to systemic biological functions through the release of two osteoblast-/osteocyte-derived hormones, fibroblastic growth factor 23 (FGF23) and undercarboxylated osteocalcin (Ocn). FGF23 is important in the regulation of phosphate and vitamin D metabolism, whereas O...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2012.12.014
更新日期：2013-03-01 00:00:00
abstract：:Cardio-Renal syndrome (CRS) is a common and complex clinical condition in which multiple causative factors are involved. The time window between renal insult and development of acute kidney injury (AKI) in acute heart failure (AHF) can be varied in different patients and AKI often is diagnosed too late, only when the ...
journal_title：Seminars in nephrology
pub_type： 杂志文章
doi：10.1016/j.semnephrol.2011.11.015
更新日期：2012-01-01 00:00:00
abstract：:In humans, idiopathic hypercalciuria is associated with stone formation. To study the mechanisms that are responsible for the excess urine calcium excretion in ways that are difficult to impossible in humans, we have developed a rat model of idiopathic hypercalciuria. Hypercalciuric rats were successively inbred for m...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：1996-09-01 00:00:00
abstract：:Nephritic edema results from the primary retention of salt. Acute glomerulonephritis is the prototypical form of the disorder. The stimulus for the salt retention arises within the kidney by an unknown mechanism. As effective arterial blood volume (EABV) was normal at the start of the disease process, it becomes expan...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1053/snep.2001.21653
更新日期：2001-05-01 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：:Novel erythropoiesis stimulating protein (NESP) is a hyperglycosylated analogue of recombinant human erythropoietin (rHuEPO) that stimulates erythropoiesis by the same mechanism as the native hormone. The addition of two extra carbohydrate chains, however, gives NESP greater metabolic stability in vivo, and its termin...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：
更新日期：2000-07-01 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：:Assessment of adiposity should include measurements of both body mass index and waist circumference. The prevalence of obesity, based on a body mass index of 30 kg/m(2) or greater, has increased substantially over the past 2 decades in Western societies. Obesity remains the number one preventable risk factor for chron...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2012.12.006
更新日期：2013-01-01 00:00:00
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 ...
journal_title：Seminars in nephrology
pub_type： 杂志文章,评审
doi：10.1016/j.semnephrol.2018.12.006
更新日期：2019-03-01 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
