Abstract:
:To investigate the direct toxicity of human Bence Jones protein (BJP), individual nephrons of male Sprague-Dawley rats were perfused in vivo at 20 nl/min with an artificial tubule fluid (ATF) that contained no protein, a human kappa BJP (5 g/dl), or bovine serum albumin (5 g/dl), and proximal convoluted tubule function and morphology were examined. Perfusion with BJP perfusate for less than or equal to 5 minutes produced no changes (P = NS) in absorption of water, Jv, (1.09 +/- 0.20 vs. 1.50 +/- 0.25 nl/min/mm), chloride, JCl, (95 +/- 47 vs. 123 +/- 41 pEq/min/mm), and glucose, JG, (39 +/- 3 vs. 40 +/- 5 pmol/min/mm) compared to perfusions with only ATF. However, perfusion for at least 20 minutes with the same BJP perfusate produced decreased (P less than 0.025) in Jv (0.58 +/- 0.12 vs. 1.15 +/- 0.14 nl/min/mm) and JG (27 +/- 3 vs. 38 +/- 3 pmol/min/mm) compared to perfusions with ATF alone; the decrease in JCl (64 +/- 47 vs. 119 +/- 27 pEq/min/mm) did not reach statistical significance. Perfusion for 20 minutes with ATF containing albumin resulted in no changes in Jv (1.22 +/- 0.21 vs. 1.15 +/- 0.14 nl/min/mm), JCl (207 +/- 29 vs. 119 +/- 27 pEq/min/mm), and JG (31 +/- 1 vs. 38 +/- 3 pmol/min/mm), when compared to the ATF perfusions. Immunocytochemistry, immunofluorescence and immunoelectron microscopy of the BJP-perfused tubules demonstrated the kappa light-chain protein in endosomes and activated lysosomes. In addition, cellular desquamation and fragmentation, prominent cytoplasmic vacuolation, and focal loss of the microvillus border were found in the BJP-perfused tubules, but not in the albumin-perfused tubules. In conclusion, these functional and morphologic data show that a human kappa light-chain is toxic to the proximal convoluted tubule of the rat. This toxicity occurred in a time-dependent fashion when the lysosomal system was markedly activated. Direct damage of the tubule epithelium by BJP's may be involved in the development of the tubulointerstitial nephropathy associated with multiple myeloma.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Sanders PW,Herrera GA,Galla JHdoi
10.1038/ki.1987.286subject
Has Abstractpub_date
1987-12-01 00:00:00pages
851-61issue
6eissn
0085-2538issn
1523-1755pii
S0085-2538(15)34156-9journal_volume
32pub_type
杂志文章abstract:BACKGROUND:Segmental glomerular necrosis has been described in the biopsy material in a minority of patients with idiopathic IgA nephropathy in the oldest studies on this disease, but this marker of active capillaritis has received little attention in the subsequent literature, and its significance and relevance for th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2001.059002682.x
更新日期:2001-02-01 00:00:00
abstract::To investigate whether the administration of cimetidine can improve the reliability of creatinine as a marker of GFR, we compared the creatinine clearance (CCr) to the clearance of the true filtration markers 51Cr-EDTA (CEDTA) and inulin (CIn), after oral ingestion of cimetidine in 10 healthy men and 29 patients with ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.331
更新日期:1991-12-01 00:00:00
abstract::The role of calcitonin on the calcemic response to parathyroid hormone (PTH) in renal failure has not been evaluated previously. Often animal studies evaluating the calcemic response to PTH in renal failure are performed in thyroparathyroidectomized (TPTX) animals, and thus eliminate any potential physiologic effect o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1991.203
更新日期:1991-08-01 00:00:00
abstract::To determine whether Cyclosporine A (CsA) alters the intrarenal expression of the renin and type 1 angiotensin II receptor genes, male adult Sprague-Dawley rats were given 25 mg/kg/day CsA s.c. for three weeks (CsA, N = 20) and were compared to pair-fed vehicle treated rats (Con, N = 20). The intrarenal distribution o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1993.90
更新日期:1993-03-01 00:00:00
abstract::Experiments were performed using a variety of methods to assess the functional status of different nephron populations following 45 min of renal ischemia in the rat. Micropuncture techniques revealed that SNGFR and reabsorption in the surface nephrons are only modestly reduced after ischemia, whereas kidney GFR and re...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1983.122
更新日期:1983-07-01 00:00:00
abstract::Acute kidney injury (AKI) is a major complication of cardiac bypass surgery. We examined whether levels of liver fatty acid-binding protein (L-FABP) can be an early biomarker for ischemic injury by measuring this protein in the urine of 40 pediatric patients prior to and following cardiopulmonary bypass surgery. AKI w...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002721
更新日期:2008-02-01 00:00:00
abstract::Low density lipoprotein (LDL) deposition and local oxidation play a key role in the pathogenesis of atherosclerosis and may likewise contribute to glomerular injury. These studies were designed to determine whether cultured human mesangial cells oxidize homologous LDL and to compare the effects of unmodified and oxidi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.214
更新日期:1994-06-01 00:00:00
abstract:BACKGROUND:Prolonged antihypertensive therapy might be less effective in reversing the left ventricular hypertrophy (LVH) in uremics bearing the deleted (DD) allele of the angiotensin converting enzyme (ACE) gene than in patients with the inserted (II) allele or in those heterozygous (ID) for the gene. METHODS:Thirtee...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1998.00027.x
更新日期:1998-08-01 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::X-linked Alport syndrome (AS) associated with diffuse esophageal leiomyomatosis (DL) has been reported to be due to deletions removing the 5' ends of both the COL4A5 and COL4A6 genes, encoding the alpha 5 and alpha 6 chains of type IV collagen, respectively, whereas a variety of mutations in COL4A5 has been identified...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.489
更新日期:1995-12-01 00:00:00
abstract::Amylin (islet amyloid peptide) plays a critical role in islet amyloidosis and in the development of beta-cell dysfunction in patients with diabetes; however, the involvement of amylin in renal amyloidosis has not been studied. For this reason, we surveyed 149 patients with biopsy-proven diabetic nephropathy (DN). The ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5002305
更新日期:2007-07-01 00:00:00
abstract:BACKGROUND:Human immunodeficiency virus-associated nephropathy (HIVAN) has become the third leading cause of end-stage renal disease (ESRD) in African Americans, and is expected to grow exponentially. Highly active antiretroviral therapy (HAART) has significantly prolonged the survival of patients with HIV infection. D...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2005.00245.x
更新日期:2005-04-01 00:00:00
abstract:BACKGROUND:Proteoglycans are integral components of the mesangial matrix and glomerular permeability barrier. Recent studies have shown that changes in glomerular proteoglycan expression may play a major role in the pathogenesis of renal disease. Steroid hormones are used as first-choice therapy for the treatment of gl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2002.00524.x
更新日期:2002-09-01 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::Suramin is a polysulfonated naphthylurea originally designed as a treatment for trypanosomiasis; but that has also been used to treat rodent models of fulminant hepatic failure and focal brain ischemia. In this study, we determined the effects of suramin on renal ischemia/reperfusion-induced acute kidney injury in mic...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.506
更新日期:2009-02-01 00:00:00
abstract:BACKGROUND:The fibrinolytic system plays an important role in degrading fibrin-rich thrombi and in vascular and tissue remodeling. Elevated levels of plasminogen activator inhibitor-1 (PAI-1) can reduce the efficiency of the endogenous fibrinolytic system. Angiotensin (Ang) has been shown to regulate PAI-1 expression v...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2000.00160.x
更新日期:2000-07-01 00:00:00
abstract::Effect of varying concentrations (0 to 800 microM) of three different light chains on sodium-dependent L-(14C)alanine and D-(14C)glucose uptake by rat renal brush border membrane vesicles were studied. One kappa and two lambda type light chains (lambda-1 and lambda-2) were isolated from urines of patients with multipl...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1986.237
更新日期:1986-11-01 00:00:00
abstract::Effect of insulin-like growth factor-1 (IGF) on the synthesis of glomerular proteoglycans (PGs) in an ex vivo recirculating organ perfusion system was investigated. Kidneys were perfused with a medium (approximately 80 ml) containing [35S]-sulfate (250 microCi/ml) and IGF (62.5 to 625 ng/ml). After radiolabeling, a sm...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.188
更新日期:1992-05-01 00:00:00
abstract::Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine fro...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000273
更新日期:2006-04-01 00:00:00
abstract::Plasma newly-synthesized cholesteryl ester transfer (NCET) rate and concentrations of lipids, lipoproteins and apolipoproteins A1 and B were measured in chronic renal failure patients (dialysis independent and dialysis dependent), patients with a functioning renal transplant and in healthy control subjects with compar...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1994.378
更新日期:1994-10-01 00:00:00
abstract::The loss of interstitial capillaries is a feature of several experimental models of renal disease and this contributes to secondary kidney injury. Angiopoietin-1 is a secreted growth factor which binds to Tie-2 present on endothelia to enhance cell survival thereby stabilizing capillary architecture in-vitro. Previous...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.179
更新日期:2008-08-01 00:00:00
abstract::Incretin-based drugs, i.e., glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors, are widely used for the treatment of type 2 diabetes. In addition to the primary role of incretins in stimulating insulin secretion from pancreatic β-cells, they have extra pancreatic functions ...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2014.236
更新日期:2014-10-01 00:00:00
abstract:BACKGROUND:We have previously reported that the serum concentration of 2-(alpha-mannopyranosyl)-L-tryptophan (MPT), tryptophan glycoconjugate, is a more accurate measure of renal function than that of serum creatinine concentration. The aim of the present study was to compare the diagnostic value of serum concentration...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00521.x
更新日期:2004-04-01 00:00:00
abstract::A new study by Xu et al. presents compelling evidence for an important role of the glomerular endothelium in acute kidney injury. They show that lipopolysaccharide reduces the endothelial surface layer, resulting in mild albuminuria, reduced glomerular filtration rate, and fewer endothelial fenestrae. Tumor necrosis f...
journal_title:Kidney international
pub_type: 评论,杂志文章
doi:10.1038/ki.2013.317
更新日期:2014-01-01 00:00:00
abstract::Using in situ hybridization and immunocytochemistry we describe the renal localization of the PDGF alpha-receptor. PDGF alpha-receptor mRNA was uniformly present in human metanephric kidney in interstitial cells and vascular arcades that course through the blastema. PDGF alpha-receptor mRNA was present in some mesangi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.157
更新日期:1997-04-01 00:00:00
abstract::Circulating immune complexes (CIC), measured by the solid-phase Clq method, were found to be in abnormal concentration in about half of 39 patients with membranoproliferative glomerulonephritis (MPGN). In contrast, they were present, usually in higher concentration, in nearly all patients with active lupus nephritis. ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1981.203
更新日期:1981-12-01 00:00:00
abstract:BACKGROUND:Atherogenic lipoproteins cause injury to the vascular wall in the early phase of atherogenesis. We assessed the effects of native (nLDL) and oxidized (oxLDL) low-density lipoprotein (LDL) and lipoprotein (a) [Lp(a)] on O2- formation and cell death in cultured human umbilical vein endothelial cells (HUVECs) a...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00351.x
更新日期:1999-04-01 00:00:00
abstract::Low nephron number has been related to low birth weight and hypertension. In the southeastern United States, the estimated prevalence of chronic kidney disease due to hypertension is five times greater for African Americans than white subjects. This study investigates the relationships between total glomerular number ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000041
更新日期:2006-02-01 00:00:00
abstract::The renal growth hormone--insulin-like growth factor-I system in acute ischemic renal failure. Recovery from acute tubular necrosis (ATN) is accelerated by IGF-I therapy. Furthermore, the local renal growth hormone-IGF-I system may participate in the natural repair. We examined the IGF-I system in rat kidneys subjecte...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1995.230
更新日期:1995-06-01 00:00:00
abstract::Proliferation of tubular epithelial cells underlies the development of cystic lesions and the subsequent impairment of renal function after renal mass reduction. The effect of HMG CoA reductase inhibitors (HRI) on cell proliferation was investigated in rat renal proximal tubular epithelial cells in primary culture. Tr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1997.423
更新日期:1997-10-01 00:00:00