Abstract:
BACKGROUND:Current renal substitution therapy for acute or chronic renal failure with hemodialysis or hemofiltration is life sustaining, but continues to have unacceptably high morbidity and mortality rates. This therapy is not complete renal replacement therapy because it does not provide active transport nor metabolic and endocrinologic functions of the kidney, which are located predominantly in the tubular elements of the kidney. METHODS:To optimize renal substitution therapy, a bioartificial renal tubule assist device (RAD) was developed and tested in vitro for a variety of differentiated tubular functions. High-flux hollow-fiber hemofiltration cartridges with membrane surface areas of 97 cm2 or 0. 4 m2 were used as tubular scaffolds. Porcine renal proximal tubule cells were seeded into the intraluminal spaces of the hollow fibers, which were pretreated with a synthetic extracellular matrix protein. Attached cells were expanded in the cartridge as a bioreactor system to produce confluent monolayers containing up to 1.5 x 109 cells (3. 5 x 105 cells/cm2). Near confluency was achieved along the entire membrane surface, with recovery rates for perfused inulin exceeding 97 and 95% in the smaller and larger units, respectively, compared with less than 60% recovery in noncell units. RESULTS:A single-pass perfusion system was used to assess transport characteristics of the RADs. Vectorial fluid transport from intraluminal space to antiluminal space was demonstrated and was significantly increased with the addition of albumin to the antiluminal side and inhibited by the addition of ouabain, a specific inhibitor of Na+,K+-ATPase. Other transport activities were also observed in these devices and included active bicarbonate transport, which was decreased with acetazolamide, a carbonic anhydrase inhibitor, active glucose transport, which was suppressed with phlorizin, a specific inhibitor of the sodium-dependent glucose transporters, and para-aminohippurate (PAH) secretion, which was diminished with the anion transport inhibitor probenecid. A variety of differentiated metabolic functions was also demonstrated in the RAD. Intraluminal glutathione breakdown and its constituent amino acid uptake were suppressed with the irreversible inhibitor of gamma-glutamyl transpeptidase acivicin; ammonia production was present and incremented with declines in perfusion pH. Finally, endocrinological activity with conversion of 25-hydroxy(OH)-vitamin D3 to 1,25-(OH)2 vitD3 was demonstrated in the RAD. This conversion activity was up-regulated with parathyroid hormone and down-regulated with increasing inorganic phosphate levels, which are well-defined physiological regulators of this process in vivo. CONCLUSIONS:These results clearly demonstrate the successful tissue engineering of a bioartificial RAD that possesses critical differentiated transport, and improves metabolic and endocrinological functions of the kidney. This device, when placed in series with conventional hemofiltration therapy, may provide incremental renal replacement support and potentially may decrease the high morbidity and mortality rates observed in patients with renal failure.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Humes HD,MacKay SM,Funke AJ,Buffington DAdoi
10.1046/j.1523-1755.1999.00486.xsubject
Has Abstractpub_date
1999-06-01 00:00:00pages
2502-14issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)46214-3journal_volume
55pub_type
杂志文章abstract::Human renal dysplasia is frequently associated with urinary tract obstruction and the abnormal expression of mitogen-activated protein kinase (MAPK). Here, we determined the renal responses and MAPK expression in developing kidneys that were obstructed in fetal lambs. Kidneys were harvested at various times after obst...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.3
更新日期:2008-05-01 00:00:00
abstract::Viral peritonitis is an exceptionally rare occurrence in peritoneal dialysis. In fact, up to now, only one case report has been documented in the literature. In a prospective study, peritoneal dialysis effluent (PDE) was specifically cultured for the following viruses: the herpes group of viruses, including herpes sim...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1989.191
更新日期:1989-08-01 00:00:00
abstract::Chronic balance studies were performed in six adrenalectomized patients to investigate the renal and systemic acid-base consequences of mineralocorticoid deficiency in the absence of either glucocorticoid deficiency or parenchymal renal disease. Constant glucocorticoid replacement was provided with dexamethasone, 750 ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.195
更新日期:1980-12-01 00:00:00
abstract::Nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI) when used in triple combination with renin-angiotensin system inhibitors and diuretics, but previous research reported that NSAIDs in dual combinations with either renin-angiotensin system inhibitors or diu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2015.101
更新日期:2015-08-01 00:00:00
abstract::Complement factor 5a (C5a) interaction with its receptor (C5aR1) contributes to the pathogenesis of inflammatory diseases, including acute kidney injury. However, its role in chronic inflammation, particularly in pathogen-associated disorders, is largely unknown. Here we tested whether the development of chronic infla...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2016.04.023
更新日期:2016-09-01 00:00:00
abstract::Increasing evidence points to the importance of aberrant O-glycosylated immunoglobulin A1 (IgA1) in the pathogenesis of IgA nephropathy (IgAN), a disease widely considered to be a polygenic disorder. We earlier found that haplotypes in two key glycosyltransferase genes, C1GALT1 and ST6GALNAC2, were associated with sus...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.99
更新日期:2009-07-01 00:00:00
abstract::Hyperhomocysteinemia, an arteriosclerotic risk factor, persists in 75% of dialysis patients despite routine low dose supplementation with the B-vitamin co-factors/substrates for homocysteine (Hcy) metabolism, and normal or supernormal plasma status of these vitamins (Atherosclerosis 114:93, 1995). We conducted a place...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1038/ki.1996.19
更新日期:1996-01-01 00:00:00
abstract::We sought to study glomerular pathophysiology in a model of IgA nephropathy (IgAN). Preliminary experiments with oral immunization indicated that Lewis rats had higher IgA levels and IgA/IgG ratios than Wistar, Fischer or Sprague-Dawley rats. Six groups of Lewis rats were studied: four continuously orally immunized fo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.268
更新日期:1992-07-01 00:00:00
abstract::Protein misfolding in the endoplasmic reticulum (ER) leads to ER stress. The unfolded protein response and ER-associated degradation (ERAD) interact in a coordinated manner with the ubiquitin-proteasome system and autophagy to alleviate protein misfolding or its consequences. The intersecting actions of these processe...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2012.390
更新日期:2013-07-01 00:00:00
abstract:BACKGROUND:In addition to nitric oxide (NO) and prostacyclin (PGI2), the vascular endothelium can influence local vascular tone by a mechanism involving the hyperpolarization of vascular smooth muscle cells. This response is attributed to the release of an endothelium-derived hyperpolarizing factor (EDHF). The present ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00910.x
更新日期:2003-05-01 00:00:00
abstract::Excess fatty acids accompanied by triglyceride accumulation in parenchymal cells of multiple tissues including skeletal and cardiac myocytes, hepatocytes, and pancreatic beta cells results in chronic cellular dysfunction and injury. The process, now termed lipotoxicity, can account for many manifestations of the 'meta...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/sj.ki.5001834
更新日期:2006-11-01 00:00:00
abstract:BACKGROUND:Redox-active iron can promote oxidative stress and tissue injury by catalyzing hydroxyl radical generation and lipid peroxidation. Intravenous iron preparations are routinely administered in conjunction with erythropoietin to treat anemia in patients with chronic renal failure (CRF), a condition that is mark...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00580.x
更新日期:2004-05-01 00:00:00
abstract:BACKGROUND:Clinical studies have shown that the angiotensin-converting enzyme (ACE) inhibitors or angiotensin II (Ang II) receptor antagonists decrease proteinuria and slow the progression of nephropathy in diabetes, indicating that Ang II plays an important role in the development of nephropathy. We have previously re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00271.x
更新日期:1999-02-01 00:00:00
abstract::Hemodynamic factors may play a role in the development of acute renal failure following administration of contrast media (CM). In this study the effect of intravenous injection of contrast media and mannitol on red blood cell velocity (VRBC) and red blood cell aggregation in renal medullary vessels was studied in 58 r...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.181
更新日期:1996-05-01 00:00:00
abstract::The microcirculation is regulated by oxygen gradients and by endothelial release of nitric oxide, which can react with hemoglobin to form S-nitroso derivatives. Here we induced flow-mediated dilatation of the brachial artery in response to ischemia in 141 non-diabetic patients with stage 3-4 chronic kidney disease who...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.63
更新日期:2009-06-01 00:00:00
abstract::Epigenetic mechanisms have been the focus of intensive research. De Marinis et al. demonstrated that high glucose levels exert stimulatory effects on activation histone marks, leading to the upregulation of thioredoxin-interacting protein (TXNIP) gene expression, which is proinflammatory. They also showed that the eff...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2015.12.026
更新日期:2016-02-01 00:00:00
abstract::Initiation of dialysis is associated with increased morbidity and mortality. However, a question could be asked whether these events are caused by initiation of dialysis or whether dialysis serves as a trigger unveiling or worsening underlying preexisting cardiovascular comorbidities that could be pre-treated. ...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2015.271
更新日期:2015-11-01 00:00:00
abstract::Daily calcitriol therapy has been reported to improve linear growth in children with renal bone disease, and 1,25-dihydroxyvitamin D is a key regultor of chondrocyte proliferation and differentiation. Whereas large intermittent doses of calcitriol can lower serum parathyroid hormone (PTH) levels and reverse the skelet...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00724.x
更新日期:1998-01-01 00:00:00
abstract::The importance of the endothelial isoform of nitric oxide synthase (eNOS) has been well established. Endothelium-derived nitric oxide has been shown to be essential for vascular homeostasis and modulation of eNOS has thus become a target in prevention of cardiovascular disease. The role of the inducible form of nitric...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2002.00235.x
更新日期:2002-03-01 00:00:00
abstract::Rare autosomal dominant tubulointerstitial kidney disease is caused by mutations in the genes encoding uromodulin (UMOD), hepatocyte nuclear factor-1β (HNF1B), renin (REN), and mucin-1 (MUC1). Multiple names have been proposed for these disorders, including 'Medullary Cystic Kidney Disease (MCKD) type 2', 'Familial Ju...
journal_title:Kidney international
pub_type: 共识发展会议,杂志文章,实务指引
doi:10.1038/ki.2015.28
更新日期:2015-10-01 00:00:00
abstract:BACKGROUND:Various gene transfer vectors as well as delivery systems have been developed; however, many problems remain to be solved. We already achieved a technique to introduce genes into glomerular mesangial cells by hemagglutinating virus of Japan (HVJ) liposome-mediated gene transfer via renal artery. The main lim...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.0590041390.x
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND:Torsemide has predictable absorption compared to furosemide. Thereby, torsemide results in more constant exposure to active drug. Our hypothesis was that this pharmacokinetic difference between these commonly used loop diuretics may translate into disparate antihypertensive responses in patients with chronic...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1523-1755.2003.00124.x
更新日期:2003-08-01 00:00:00
abstract::There is an urgent need for therapeutic agents that target humoral alloimmunity in solid organ transplantation. This includes sensitized patients with preformed donor-specific human leukocyte antigen antibodies and patients who develop de novo donor-specific antibodies, both of which are associated with acute and chro...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2018.10.028
更新日期:2019-04-01 00:00:00
abstract::Accumulation of extracellular matrix within the mesangium is an important event in the development of glomerular disease. In this report we have used indirect immunofluorescence to positively identify a number of constituents of the mesangial matrix synthesized by rat mesangial cells (RMC) in vitro including laminin, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.412
更新日期:1995-10-01 00:00:00
abstract::Major temporal changes in the case mix of patients accepted for renal replacement therapy impede analysis of long-term mortality trends in end-stage renal disease patients. A record linkage study of 2 large electronic hospital inpatient data sets with national mortality data used standardization by age, sex, and comor...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2018.01.002
更新日期:2018-05-01 00:00:00
abstract::IgA nephropathy is the most common primary glomerulonephritis worldwide. Its frequent coexistence with inflammatory, infectious, or malignant processes raises the possibility of a pathologic rather than coincidental association. Major strides have been made to elucidate the underlying pathophysiologic events that culm...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1016/j.kint.2018.02.030
更新日期:2018-10-01 00:00:00
abstract::During online hemodiafiltration, patients are directly infused with sterile substitution solutions to maintain fluid balance. Adequate water treatment and a well-organized quality control process are essential to provide non-pyrogenic fluids with consistent optimal quality. We sought to assess water quality, the water...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.245
更新日期:2009-09-01 00:00:00
abstract::The OSCAR study was a multicenter, prospective randomized open-label blinded end-point study of 1164 Japanese elderly hypertensive patients comparing the efficacy of angiotensin II receptor blocker (ARB) uptitration to an ARB plus calcium channel blocker (CCB) combination. In this prospective study, we performed presp...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1038/ki.2012.326
更新日期:2013-01-01 00:00:00
abstract::In normal subjects, beta-adrenergic stimulation lowers the serum potassium, whereas alpha-stimulation raises it. Epinephrine, a mixed alpha and beta agonist, acutely lowers the blood potassium in normal subjects, but not in patients with end-stage renal disease. This study was designed to determine whether the resista...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.321
更新日期:1991-12-01 00:00:00
abstract::Water and small solute fluxes through cell membranes are ensured in many tissues by selective pores that belong to the major intrinsic protein family (MIP). This family includes the water channels or aquaporins (AQP) and the neutral solute facilitators such as the glycerol facilitator (GlpF). We have compared the char...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1046/j.1523-1755.2001.060002422.x
更新日期:2001-08-01 00:00:00