Abstract：
:The kidney clears numerous solutes from the plasma; however, retention of these solutes causes uremic illness when the kidneys fail. We know remarkably little about which retained solutes are toxic and this limits our ability to improve dialysis therapies. To explore this, we employed untargeted mass spectrometry to identify solutes that are efficiently cleared by the kidney. High-resolution mass spectrometry detected 1808 features in the urine and plasma ultrafiltrate of 5 individuals with normal renal function. The estimated clearance rates of 1082 peaks were greater than the creatinine clearance indicating tubular secretion. Further analysis identified 90 features representing solutes with estimated clearance rates greater than the renal plasma flow. Quantitative mass spectrometry with stable isotope dilution confirmed that efficient clearance of these solutes is made possible by the combination of binding to plasma proteins and tubular secretion. Tandem mass spectrometry established the chemical identity of 13 solutes including hippuric acid, indoxyl sulfate, and p-cresol sulfate. These 13 efficiently cleared solutes were found to accumulate in the plasma of hemodialysis patients, with free levels rising to more than 20-fold normal for all but two of them. Thus, further analysis of solutes efficiently cleared by secretion in the native kidney may provide a potential route to the identification of uremic toxins.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Sirich TL,Aronov PA,Plummer NS,Hostetter TH,Meyer TWdoi
10.1038/ki.2013.154subject
Has Abstractpub_date
2013-09-01 00:00:00pages
585-90issue
3eissn
0085-2538issn
1523-1755pii
S0085-2538(15)55992-9journal_volume
84pub_type
杂志文章abstract：BACKGROUND:Normalization of proteinuria and even regression of glomerulosclerosis seem to occur in progressive renal disease upon blockade of the renin-angiotensin system. Here we quantified the effect of a combination of an angiotensin converting enzyme (ACE) inhibitor and an angiotensin II (Ang II) receptor antagonis...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00526.x
更新日期：2002-09-01 00:00:00
abstract：UNLABELLED:Predicting renal survival in primary focal glomerulosclerosis from the time of presentation. BACKGROUND:To predict the risk of developing chronic renal failure in patients with primary focal glomerulosclerosis (FGS) using predictors available at the time of presentation, a retrospective analysis was perform...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.4491164
更新日期：1999-12-01 00:00:00
abstract：:The content of platelet activating factor (PAF) in glomeruli isolated from rats with nephrotoxic serum glomerulonephritis (NSGN) was quantified at various stages of the disease and the role of complement, platelets and neutrophils in mediating changes in glomerular PAF levels was evaluated. PAF content was assessed fo...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.40
更新日期：1990-02-01 00:00:00
abstract：BACKGROUND:It has been shown that non-congenic mice strains with lower levels of renal meprin develop less renal injury following renal ischemia and reperfusion. We have demonstrated that following ischemia-reperfusion renal injury, there is a rapid shift of meprin localization and intensity from the brush border to th...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00209.x
更新日期：2002-03-01 00:00:00
abstract：:The mechanism of the binding of IgA to the mesangium in IgA nephropathy (IgAN) is unknown. Interactions between IgA and components of the mesangial matrix may contribute. We measured by enzyme-linked immunosorbent assay the binding of serum IgA, IgG, and IgM from patients with IgAN, human immunodeficiency virus type I...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1992.298
更新日期：1992-08-01 00:00:00
abstract：:To date direct evidence for the presence of a H-K-ATPase in the medulla comes from proton and potassium transport studies performed on K-restricted animals and K dependent ATP hydrolysis and Rb uptake in both normal and K-depleted animals. The present work examines K-dependent acidification in the medulla of rabbits o...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1992.392
更新日期：1992-11-01 00:00:00
abstract：:Urinary proteomics is a promising tool for biomarker investigation, particularly in complex kidney diseases. Fabris and colleagues report that urinary laminin subunit alpha-2 is a potential diagnostic marker of medullary sponge kidney (MSK) disease by using a label-free quantitative proteomics platform and a clinicall...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1016/j.kint.2016.10.032
更新日期：2017-02-01 00:00:00
abstract：:The purpose of these studies was to quantitatively assess the role of endogenous angiotensin II activity in controlling transport in the proximal convoluted tubule (PCT) and whole nephron. We used the nonpeptide angiotensin II receptor antagonist DuP 753, which lacks the agonist and kinin/prostaglandin-inducing proper...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.228
更新日期：1990-09-01 00:00:00
abstract：:Despite the high costs of treatment of people with kidney disease and associated comorbid conditions, the amount of reliable information available to guide the care of such patients is very limited. Some treatments have been assessed in randomized trials, but most such trials have been too small to detect treatment ef...
journal_title：Kidney international
pub_type：
doi：10.1016/j.kint.2017.04.019
更新日期：2017-08-01 00:00:00
abstract：:A novel variant of the LLC-PK1 cell line was used to examine directly the mechanism whereby PGF2 alpha and TPA inhibit renal ammoniagenesis. The variant cells, which exhibit a growth pattern and morphology similar to the parent cell line, were isolated by a self selection process utilizing long-term cultures of parent...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1994.368
更新日期：1994-10-01 00:00:00
abstract：:Angiotensin II (Ang II) is a major contributor to the progression of renal fibrosis. Wang and colleagues provide evidence that signaling through the prolyl-4-hydroxylase domain (PHD)-hypoxia-inducible factor-1 (HIF-1) pathway mediates profibrotic effects of Ang II in rat renal medullary interstitial cells under normox...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2010.434
更新日期：2011-02-01 00:00:00
abstract：:Experimental studies have demonstrated the cardinal role played by the mononuclear phagocyte system in the removal of antigen-antibody complexes. To assess the functional capacity of phagocytes in patients with renal disease, 33 normal subjects, 10 patients with mesangial proliferative glomerulonephritis, 8 patients w...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1983.105
更新日期：1983-06-01 00:00:00
abstract：:Segerer et al. report the expression and localization of macrophage and dendritic-cell markers in human renal biopsies and indicate that both cell types express CD68, findings that resonate with murine studies. The functional and phenotypic distinction between macrophages and dendritic cells is discussed. ...
journal_title：Kidney international
pub_type： 评论,杂志文章,评审
doi：10.1038/ki.2008.189
更新日期：2008-07-01 00:00:00
abstract：:Studies were undertaken to examine the mechanism whereby changes in intraluminal flow rates after reabsorption in the isolated perfused proximal tubule of the rabbit. All protocols employed the technique of in vitro perfusion of isolated segments of the proximal convoluted tubule. Stepwise elimination of d-glucose and...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1977.3
更新日期：1977-01-01 00:00:00
abstract：:The hormonal responsiveness profile of the cortical collecting duct varies from one species to another. To identify the hormones and agonists that modulate the functions of this tubule segment in the human species, we generated a cell line (HCD) immortalized by SV40 virus. The tubular origin of this cell line was asse...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1995.186
更新日期：1995-05-01 00:00:00
abstract：:Inflammation is a protective response to remove dangerous stimuli from the body. The multiprotein complex called the inflammasome regulates inflammation through the cleavage of proinflammatory cytokines into mature forms. Shahzad et al. unravel the importance of the Nlrp3 inflammasome, especially activated in glomerul...
journal_title：Kidney international
pub_type： 评论,杂志文章
doi：10.1038/ki.2014.322
更新日期：2015-01-01 00:00:00
abstract：BACKGROUND:Altered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease. METHODS:This study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1111/j.1523-1755.2005.00185.x
更新日期：2005-03-01 00:00:00
abstract：:Severe sepsis is often accompanied by acute kidney injury (AKI) and albuminuria. Here we studied whether the AKI and albuminuria associated with lipopolysaccharide (LPS) treatment in mice reflects impairment of the glomerular endothelium with its associated endothelial surface layer. LPS treatment decreased the abunda...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2013.286
更新日期：2014-01-01 00:00:00
abstract：:Glucocorticoid induced leucine zipper protein (GILZ) is an aldosterone-regulated protein that controls sodium transport in cultured kidney epithelial cells. Mice lacking GILZ have been reported previously to have electrolyte abnormalities. However, the mechanistic basis has not been explored. Here we provide evidence ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2016.10.038
更新日期：2017-05-01 00:00:00
abstract：:Nephronophthisis is an autosomal recessive kidney disease with high genetic heterogeneity. Understanding the functions of the individual genes contributing to this disease is critical for delineating the pathomechanisms of this disorder. Here, we investigated kidney function of a novel gene associated with nephronopht...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1016/j.kint.2019.04.014
更新日期：2019-08-01 00:00:00
abstract：:For reasons that are not well understood, Aboriginal people with end-stage renal disease (ESRD) have lower rates of kidney transplantation. We hypothesized that distance between residence location and the closest transplant center was greater in Aboriginal dialysis patients and would partially explain the lower rate o...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/sj.ki.5001607
更新日期：2006-09-01 00:00:00
abstract：:Quartan malarial infection causes an immune complex nephritis in some individuals, which, once established, is sustained by mechanisms not yet fully explained, but which probably involve autoimmune processes. The presenting clinical and biochemical findings of the quartan malarial nephrotic syndrome are similar to tho...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1979.103
更新日期：1979-07-01 00:00:00
abstract：:Fibroblasts in parenchymal organs potentially contribute extracellular matrix to local fibrogenic processes. This contribution, in some circumstances, may be initiated by cytokines disseminated from inflammatory lesions. Different populations of fibroblasts, however, might respond distinctively to this cytokine bath d...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1992.3
更新日期：1992-01-01 00:00:00
abstract：BACKGROUND:Low dietary phosphorus (P) prevents parathyroid gland (PTG) hyperplasia and the development of secondary hyperparathyroidism (SH) in uremic rats. The present study explores the effects of P restriction on parathyroid hormone (PTH) synthesis and secretion and PT cell growth in rats with established SH and PTG...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00265.x
更新日期：2002-04-01 00:00:00
abstract：BACKGROUND:Nitric oxide inactivation by superoxide impairs endothelium-dependent vasodilation and plays a role in various forms of hypertension. Almost no data exist regarding hypertension secondary to chronic renal failure. Previous studies have shown that endothelium-related relaxations, secondary to decreased nitric...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2002.00166.x
更新日期：2002-02-01 00:00:00
abstract：:Intrarenal angiotensin II is increased in kidney diseases independently of plasma angiotensin II and is thought to promote progressive deterioration of renal architecture. Here we investigated the mechanism of enhanced renal angiotensin II generation in kidney glomerular diseases. For this, kidney- or liver-specific a...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.2013.453
更新日期：2014-05-01 00:00:00
abstract：:Mineralocorticoid hormones stimulate Na+ absorption and K+ secretion by the cortical collecting tubule. There is good evidence that this stimulation involves increasing luminal membrane Na+ permeability and the turnover rate (or number) of the Na+-K+ pumps. These experiments were designed to examine whether mineraloco...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1985.177
更新日期：1985-10-01 00:00:00
abstract：:The role of immunoglobulin (Ig) Fc-macrophage cell surface receptor affinity (macrophage Fc-affinity) in determining the mediation systems responsible for immune glomerular injury has been studied. Glomerular injury was initiated in rabbits by the passive administration of immunoglobulin preparations directed against ...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1989.228
更新日期：1989-10-01 00:00:00
abstract：:We studied the adaptation to early (72 hr) and late (20 days) K loading (400 mmol/day, 4 equal meals every 6 hour) in six healthy humans. Throughout the study, each single K meal was followed by an acute transient rise in plasma K, aldosterone and kaliuresis. "K balance" (urinary K excretion approximately 80% of intak...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1038/ki.1990.295
更新日期：1990-11-01 00:00:00
abstract：BACKGROUND:Mast cells are growth factor-rich, bone marrow-derived cells that infiltrate injured tissue where they have been implicated in the pathogenesis of progressive fibrosis. METHODS:Mast cell infiltration and the expression of related chemoattractants was examined following 5/6 nephrectomy, a model of progressiv...
journal_title：Kidney international
pub_type： 杂志文章
doi：10.1046/j.1523-1755.2003.00183.x
更新日期：2003-09-01 00:00:00
