Abstract:
BACKGROUND:Inbred miniature swine treated for 12 days with high-dose cyclosporine A develop tolerance to histocompatibility complex (MHC) class I-mismatched renal allografts. When this protocol was modified by adding thymectomy before transplant, all animals developed acute rejection. Thereafter, by day 100, one half developed chronic rejection (progression group) and the other half recovered (recovery group). This provides an excellent experimental model to identify the mechanisms of chronic rejection as well as the early changes that may predict chronic rejection. METHODS:We assessed the cellular infiltration, immune activation, humoral immunity, and cell- and antibody-mediated graft injury in the progression and the recovery groups. In addition, we also examined circulating donor reactive cytotoxic T lymphocyte (CTL) and antidonor antibody in both groups. RESULTS:From days 8 to 18 after transplantation, the two groups were indistinguishable. Both showed acute rejection with endarteritis (type II); had IgG and IgM deposition in glomeruli and small vessels; had an infiltrate with similar numbers of T cells, proliferating (PCNA+) and activated (interleukin-2 receptor+) cells; and had a similar degree of parenchymal cell apoptosis [in situ DNA nick-end labeling (TUNEL)+]. However, by days 30 to 60, the two groups could be distinguished by several intragraft features. The recovery group became tolerant and had diminished T-cell infiltration, activation and proliferation, and no detectable antibody deposition. The number of TUNEL+-injured parenchymal cells decreased. In contrast, the progression group showed persistent cell infiltration with activation and proliferation. Significantly prominent TUNEL+ apoptotic parenchymal cells in tubules, glomeruli, peritubular capillaries and arteries were seen from day 30 to day 100. Circulating donor reactive CTL and antidonor class I IgG were detected in the progression group at higher levels than in the recovery group from days 30 to 60. CONCLUSION:In tolerance-induction protocols, unstable tolerance induction is associated with the persistent immunologic activation that mediates immunologic destruction of graft parenchymal cells and chronic rejection. Certain of the described immunopathologic findings (activation, proliferation, apoptosis, and antibody deposition) may be useful in distinguishing the type of rejection, that is, whether the allograft will progress to chronic rejection or recovery.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Shimizu A,Yamada K,Sachs DH,Colvin RBdoi
10.1046/j.1523-1755.2000.00440.xsubject
Has Abstractpub_date
2000-12-01 00:00:00pages
2546-58issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)47373-9journal_volume
58pub_type
杂志文章abstract:BACKGROUND:Mesangial immunoglobulin A (IgA) deposition is incidentally encountered in asymptomatic individuals, but its precise frequency and significance had not been clarified. The background of the latent IgA deposition is related to the epidemiology and pathogenesis of IgA nephropathy. METHODS:Zero-hour allograft ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.63.6s.2.x
更新日期:2003-06-01 00:00:00
abstract:BACKGROUND:Population-genetic studies investigating genetic polymorphisms of Mendelian inheritance should always test whether the measured genotype frequencies deviate from the expected one. For this purpose Hardy-Weinberg (HW) criteria are generally used. If genotype distribution of control population misses HW equili...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00596.x
更新日期:2004-05-01 00:00:00
abstract::In studying the metabolic effects of diet potassium (K+) variation in normal humans, we noted that varying diet K+ within its normal range influenced inorganic phosphorus (Pi) homeostasis and serum calcitriol (1,25-dihydroxyvitamin D) levels. In six men who ingested a constant whole-foods diet containing (per 70 kg bo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.120
更新日期:1990-05-01 00:00:00
abstract::The hypercalcemia of malignancy is mediated by complex and heterogeneous mechanisms. Once thought of as a simple paraneoplastic syndrome mediated by the effects of tumor production of PTH, it is now clear that multiple mechanisms are involved and that these mechanisms involve abnormalities in calcium transport in bone...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.21
更新日期:1987-01-01 00:00:00
abstract::The release of cytokines and prostaglandins (PG) by peritoneal macrophages (PM luminal diameter of) may influence the cytokine network controlling peritoneal inflammation and in the long-term the function of the peritoneum as a dialysis membrane. In the present study, an evaluation of the long-term effects of peritone...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1996.75
更新日期:1996-02-01 00:00:00
abstract::Acid (H+) retention appears to contribute to progressive decline in glomerular filtration rate (GFR) in patients with chronic kidney disease (CKD), including some patients without metabolic acidosis. Identification of patients with H+ retention but without metabolic acidosis could facilitate targeted alkali therapy; h...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2018.11.033
更新日期:2019-05-01 00:00:00
abstract::This study was done to investigate the mechanisms that underly the changes of renal renin gene expression upon hypoperfusion of one kidney. To this end the left renal arteries of male Sprague-Dawley rats were clipped with 0.2 mm silver clips and renal renin mRNA levels were assayed by RNase protection during the first...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.440
更新日期:1994-12-01 00:00:00
abstract::Atrial natriuretic peptide (ANP) is known to suppress platelet-derived growth factor (PDGF)-stimulated proliferation of rat cultured vascular smooth muscle cells. The present study examined whether ANP inhibits the PDGF receptor (PDGFR) tyrosine kinase activation, an initial event for PDGF cellular signaling. ANP redu...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.341
更新日期:1997-08-01 00:00:00
abstract::Fifty-one adults with HIV infection, including 20 chronic hemodialysis patients with superimposed HIV infection and 31 patients with HIV-associated nephropathy requiring chronic maintenance hemodialysis were followed to evaluate survival on outpatient dialysis in relation to the clinical stage of the HIV infection. Re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.172
更新日期:1988-08-01 00:00:00
abstract::Tremendous progress has been made over recent years in the understanding of the mechanisms regulating calcium, phosphorus, vitamin D, and parathyroid hormone homeostasis in the normal human body and in patients with different degrees of renal failure. In addition, some of these findings have been translated into clini...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.692
更新日期:2009-05-01 00:00:00
abstract::Angiotensinase A (aminopeptidase A; ATA) is an angiotensin II splitting exopeptidase, which is localized in endothelial and epithelial cells of the glomerular tuft. In order to investigate the influence of a reduction in renal mass on enzyme activity, ATA activity was measured in isolated rat glomeruli five and 14 wee...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1990.283
更新日期:1990-11-01 00:00:00
abstract::Diabetic kidney disease is the leading cause of kidney failure. However, studies of molecular mechanisms of early kidney damage are lacking. Here we examined for possible linkage between transcriptional regulation and quantitative structural damage in early diabetic kidney disease in Pima Indians with type 2 diabetes....
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1016/j.kint.2017.08.013
更新日期:2018-02-01 00:00:00
abstract::The clinical value of biocompatible peritoneal dialysis solutions is uncertain because of inconsistent findings in randomized controlled trials. A systematic review by Cho et al. examining 20 such trials suggests a beneficial effect on residual renal function. However, the finding is not robust and may relate to decre...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.303
更新日期:2013-11-01 00:00:00
abstract::Identifying subjects with progressive chronic kidney disease will be important both in clinical practice and in conducting clinical trials. Pruijm et al. (in this issue) demonstrate for the first time that cortical oxygenation as evaluated by blood oxygenation level-dependent magnetic resonance imaging can predict fut...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1016/j.kint.2017.11.029
更新日期:2018-04-01 00:00:00
abstract::Progressive kidney fibrosis precedes end-stage renal failure in up to a third of patients with diabetes mellitus. Elevated intra-renal transforming growth factor-beta (TGF-beta) is thought to underlie disease progression by promoting deposition of extracellular matrix and epithelial-mesenchymal transition. GW788388 is...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002717
更新日期:2008-03-01 00:00:00
abstract::A morphometric technique is used to estimate the absolute and relative surface areas of the brush border microvilli and cell walls bordering lateral intercellular spaces. In isolated, perfused proximal tubule from rabbit, the luminal and lateral surfaces are equal in area. For proximal convoluted tubules (PCT) each su...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.125
更新日期:1975-12-01 00:00:00
abstract::We examined the process of receptor-mediated endocytosis in A-9 lung fibroblast and chinese hamster ovary (CHO) cells transfected with the recently cloned vasopressin V1a receptor (51). We used a fluorescent labeled vasopressin analog (rhodamine-mercaptopropionic acid lysine vasopressin) and radiolabeled vasopressin t...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.119
更新日期:1993-04-01 00:00:00
abstract::Cisplatin is a platinum-containing antitumor agent whose usefulness is limited by nephrotoxicity. We examined the effects of cisplatin on a representative, transporting epithelium--the frog skin. Cisplatin (10(-3)M) from the mucosal surface increased the active transport of sodium by 35 to 40%, as monitored by short-c...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.2
更新日期:1981-01-01 00:00:00
abstract:BACKGROUND:Guidelines for treating anemia in dialysis patients accept, as high-end range of serum ferritin useful to optimize erythropoietin therapy, values high as 500 to 900 microg/L, on the hypothesis that ferritin might be not representative of iron overload. METHODS:A superconducting quantum interference device (...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00480.x
更新日期:2004-03-01 00:00:00
abstract:BACKGROUND:The parathyroid (PT) hyperplasia induced by renal failure can be further enhanced by high dietary phosphate (P) or completely abolished by P restriction. To identify potential mechanisms mediating these opposing effects of dietary P on PT growth, this study first focused on p21(WAF1) (p21) because high P red...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059003855.x
更新日期:2001-03-01 00:00:00
abstract:BACKGROUND:Prolactin (PRL), originally identified as an anterior pituitary hormone exhibiting lactogenic activity, is now recognized as a versatile hormone expressed in a wide variety of tissues. METHODS:In this study, the expression of PRL in the mouse kidney was investigated by solution-phase and in situ reverse tra...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.055003833.x
更新日期:1999-03-01 00:00:00
abstract::In contrast to other nonsteroidal anti-inflammatory drugs (NSAIDs), sulindac has been reported to inhibit systemic prostaglandins (PGs) while not affecting renal PGs. We studied 11 normal volunteers who received placebo, ibuprofen, naproxen, or sulindac in a randomized, double-blind fashion. After control periods asse...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1985.11
更新日期:1985-01-01 00:00:00
abstract:BACKGROUND:Rho proteins are small guanine 5'-triphosphate (GTP)-binding proteins felt to be important regulators of several aspects of cell function, including the organization of the actin cytoskeleton. The effects of Rho proteins on the regulation of renal tubular epithelial cell function are not known. METHODS:Sele...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2000.00372.x
更新日期:2000-11-01 00:00:00
abstract::Acute phosphate nephropathy (APhN) is a clinical pathological entity characterized by acute and subsequent chronic renal failure following exposure to oral sodium phosphate (OSP) bowel purgatives. Renal biopsy findings include acute and chronic tubular injury with prominent tubular and interstitial calcium phosphate d...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2009.308
更新日期:2009-11-01 00:00:00
abstract:BACKGROUND:Tumor necrosis factor (TNF) receptor family members, such as Fas and TNF receptor 1 (TNFR1), are thought to induce apoptosis in a variety of cells and organs. Although a number of potential scenarios have been postulated for the involvement of these receptors in the pathogenesis of acute renal failure (ARF),...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00709.x
更新日期:2003-01-01 00:00:00
abstract::In uremic patients resistance to the action of insulin has been documented, but it is not known at what stage of renal disease it appears. We therefore examined 29 patients with IgA glomerulonephritis (IgAGN) and 21 patients with adult polycystic kidney disease (ADPKD) in different stages of renal failure, and in addi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00898.x
更新日期:1998-05-01 00:00:00
abstract::One reason for the inadequacy of current renoprotective therapy and the persistent poor renal prognosis in diabetic nephropathy is the large interindividual variation in response to treatment. Genetic as well as non-genetic factors are known to influence treatment efficacy. This Commentary summarizes the impact of the...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/sj.ki.5000283
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:Macrophages have been regarded as "blackguards" in the generation of glomerular injury. However, it is still unclear what kind of cellular machinery is responsible for their pathogenic actions. To explore this issue, this investigation aims at developing a novel strategy using adoptive transfer of "loss-of-f...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00893.x
更新日期:2000-02-01 00:00:00
abstract::Fourteen subjects with persistent azotemia and normal glomerular filtration rate were studied by renal clearances and hormonal determinations to establish the nephron site of altered urea transport and the mechanism(s) responsible for their azotemia. During constant alimentary protein, urea nitrogen appearance was nor...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1987.266
更新日期:1987-11-01 00:00:00
abstract::About 75% of urinary stones contain oxalate. As Oxalobacter formigenes is a Gram-negative anaerobic bacterium that degrades oxalate in the intestinal tract, we assessed the role of O. formigenes in oxalate metabolism by evaluating its intestinal absorption, plasma concentration, and urinary excretion. Of 37 calcium ox...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2013.104
更新日期:2013-06-01 00:00:00