Abstract:
:Long-term treatment (8 and 13 weeks) of rats with FGF-2 led to albuminuria and to increase in serum creatinine indicating the development of chronic renal failure. Histologically, the classic picture of focal segmental glomerulosclerosis (FSGS) was found; males were more severely affected than females. Among the early changes podocyte lesions were most prominent. Surprisingly, mitotic figures in podocytes and a considerable fraction of bi(multi)nucleated podocyte profiles were found in treated animals (roughly 16% in males, 8% in females). Since an increase of cell number of podocytes was not evident, we conclude that FGF-2 stimulates podocytes to re-enter the cell cycle and to undergo mitosis (nuclear division). However, podocytes-probably due to their highly differentiated cell shape in the adult-are unable to complete cell division (cytokinesis) resulting in bi- or multinucleated cells; in others cell division may fail totally leading to podocyte degeneration. Most podocytes in FGF-2-treated rats exhibited degenerative changes including cell body attenuation, extensive pseudocyst formation, widespread foot process effacement, as well as detachments from the glomerular basement membrane (GBM). The development of FSGS in this model is very uniform. In the case of podocyte detachments from peripheral capillaries, parietal cells become attached to naked GBM-areas, establishing the nidus for development of a tuft adhesion to Bowman's capsule. Tuft adhesions grow by encroaching of parietal cells onto adjacent capillary loops, resulting eventually in a solid synechia with collapsed capillaries, that is, what represents segmental sclerosis. The distribution of adhesions on the inner surface of Bowman's capsule appeared to be random, including all locations between the vascular and urinary pole. The two main aspects of this study (inability of podocytes to replicate and development of FSGS based on progressing podocyte degeneration) may be part of a vicious cycle. FGF-2 stimulates podocytes to enter cell division thereby conveying them into a hazardous situation. If a podocyte fails and degenerates it cannot be replaced, aggravating the situation for the remaining cells and possibly increasing their predisposition to respond to mitogenic stimuli. Similar mechanisms may constitute the development of FSGS in other experimental as well as human glomerulopathies.
journal_name
Kidney Intjournal_title
Kidney internationalauthors
Kriz W,Hähnel B,Rösener S,Elger Mdoi
10.1038/ki.1995.433subject
Has Abstractpub_date
1995-11-01 00:00:00pages
1435-50issue
5eissn
0085-2538issn
1523-1755pii
S0085-2538(15)59205-3journal_volume
48pub_type
杂志文章abstract:BACKGROUND:Inhibition of the renin-angiotensin system (RAS) prevents development of chronic allograft dysfunction in experimental animals. Whether this therapeutic approach is effective even if started when signs of allograft nephropathy are already manifested has not been investigated. METHODS:To address this issue, ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.2003.00318.x
更新日期:2003-12-01 00:00:00
abstract::Current practice recommends metabolic evaluation of patients who have formed multiple renal stones, but not those with one stone or temporally remote stones. This presumes that recentness and recurrence imply greater risk of new future stones. We hypothesize that number of stones reflects how long patients are permitt...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.224
更新日期:1994-06-01 00:00:00
abstract::To determine the effect of an acute load of potassium on potassium reabsorption by the loop of Henle in chronic renal failure, the right kidney was removed and branches of the left renal artery were ligated in 17 rats. One week later and after 2 days of a potassium-free diet, rats were studied before (period 1) and af...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1985.100
更新日期:1985-06-01 00:00:00
abstract::Unidirectional 32P-phosphate and 3H-mannitol fluxes were simultaneously measured, at two minutes intervals, in frog urinary bladders. The spontaneous or externally imposed transepithelial potential (PD) and short circuit current (SCC) were also recorded in most experiments. It was observed that: (1) Phosphate transfer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1988.9
更新日期:1988-01-01 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::Previous studies have demonstrated that dietary potassium deprivation in healthy human subjects eating diets otherwise containing normal quantities of NaCl is accompanied by an increase in urinary calcium excretion. This increase in urinary Ca excretion occurs in association with reductions in urinary Na and Cl excret...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1995.134
更新日期:1995-03-01 00:00:00
abstract:BACKGROUND:Inhibition of angiotensin action, pharmacologically or genetically, during the neonatal period leads to renal anomalies involving hypoplastic papilla and dilated calyx. Recently, we documented that angiotensinogen (Agt -/-) or angiotensin type 1 receptor nullizygotes (Agtr1 -/-) do not develop renal pelvis n...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00420.x
更新日期:1999-05-01 00:00:00
abstract::We evaluated the effects of the bisphosphonate pamidronate on bone histomorphometry, structure and strength in male rats with uninephrectomy or with chronic renal disease induced by 5/6 nephrectomy. In rats with chronic renal disease the plasma urea, phosphate and parathyroid hormone levels were significantly increase...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.180
更新日期:2008-08-01 00:00:00
abstract::In the present study we assessed the prevalence of thin glomerular basement membrane (TGBM) in a large group of native kidney biopsies done for evaluation of renal disease. TGBM was present in 54 of 1078 biopsies (5%). In 12 of 54 biopsies (24%), TGBM was the only abnormality present. In the remaining biopsies TGBM wa...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.296
更新日期:1994-08-01 00:00:00
abstract::Murine double minute (MDM)-2, an E3 ubiquitin ligase, promotes cancer cell survival and growth, by degrading the cell cycle regulator p53. Antagonism of MDM2 by the small-molecule cis-imidazoline nutlin analogs is under current study for cancer therapy. To test whether MDM2 also promotes regenerative cell growth, we d...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2011.482
更新日期:2012-06-01 00:00:00
abstract::The transition between the glomerulus and the proximal tubule was studied by light and electron microscopy in perfusion-fixed rabbit kidneys. In most nephrons a transitional segment of tubule occurred between the Bowman's capsule and the proximal tubule proper. This initial part of the tubule was lined by flattened ce...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1975.22
更新日期:1975-03-01 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::Co-presentation with both ANCA and anti-GBM antibodies is thought to be relatively rare. Current studies of such 'double-positive' cases report small numbers and variable outcomes. To study this further we retrospectively analyzed clinical features and long-term outcomes of a large cohort of 568 contemporary patients ...
journal_title:Kidney international
pub_type: 杂志文章,多中心研究
doi:10.1016/j.kint.2017.03.014
更新日期:2017-09-01 00:00:00
abstract::It is well established that nocturnal hypoxemia in sleep apnea causes an inversion of the circadian arterial pressure rhythm and triggers nocturnal hypertension. Since sleep apnea is very frequent in dialysis patients, we hypothesized that nocturnal hypoxemia may be a factor that contributes to alter the 24-hour arter...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.1998.00853.x
更新日期:1998-04-01 00:00:00
abstract::Cell surface aminopeptidases N (APN) and A (APA) have been characterized on cultured human glomerular epithelial cells and a SV40-transformed cell line derived from them. APN had a wide substrate specificity whereas APA only attacked peptides with an acidic N terminal amino acid. Both enzymes also differed by their se...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1992.227
更新日期:1992-06-01 00:00:00
abstract::Anthropometric measurements and circulating growth factors were studied serially in 44 prepubertal children with growth failure and chronic renal failure (GFR = 10 to 40 ml/min/1.73 m2) who were randomized to receive either recombinant human growth hormone (rhGH; N = 30) or no treatment (N = 14). RhGH was given as Nut...
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.1997.268
更新日期:1997-06-01 00:00:00
abstract::Renal toxicity, possibly due to vasoconstriction and vascular injury, is the most relevant side-effect of chronic cyclosporine (CsA) therapy given to prevent graft rejection. In kidney transplant recipients each oral dose of CsA is invariably followed by a transient reduction in renal plasma flow (RPF) and glomerular ...
journal_title:Kidney international
pub_type: 临床试验,杂志文章
doi:10.1038/ki.1993.101
更新日期:1993-03-01 00:00:00
abstract::Chronic metabolic acidosis (CMA) is a major cause of growth defect, implying disturbances of protein metabolism. Previously, in vivo studies performed in the fasting state showed enhanced whole body protein turnover, whereas in vitro studies showed unchanged muscle protein synthesis. The present study is the first to ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1994.472
更新日期:1994-12-01 00:00:00
abstract:BACKGROUND:Systematic studies on safety and efficacy of enteral nutrition in patients with acute renal failure (ARF) are lacking. METHODS:We studied enteral nutrition-related complications and adequacy of nutrient administration during 2525 days of artificial nutrition in 247 consecutive patients fed exclusively by th...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1111/j.1523-1755.2004.00459.x
更新日期:2004-03-01 00:00:00
abstract::Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glo...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2009.168
更新日期:2009-09-01 00:00:00
abstract::We described the characteristics in a referred cohort of type II diabetic patients in the Developing Education on Microalbuminuria for Awareness of renal and cardiovascular risk in Diabetes study evaluating the global prevalence and determinants of microalbuminuria (MA). A cross-sectional study evaluating 32,208 type ...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/sj.ki.5000377
更新日期:2006-06-01 00:00:00
abstract::Monocyte and macrophage markers are among the most highly overexpressed genes in cpk mouse kidneys with severely progressive renal cystic disease. We show here that one of these markers, CD14, is abnormally transcribed, activated and shed in cystic kidneys. However, these abnormalities were not associated with an incr...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2010.175
更新日期:2010-09-01 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::Inflammation is the immune system's response to infectious or noninfectious sources of danger. Danger recognition is facilitated by various innate immune receptor families including the Toll-like receptors (TLRs), which detect danger signals in extracellular and intracellular compartments. It is an evolving concept th...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.2010.111
更新日期:2010-07-01 00:00:00
abstract::The circumstances under which furosemide increases renal blood flow was examined in mongrel dogs as it may relate to a tubuloglomerular feedback mechanism. Two maneuvers, desoxycorticosterone (DOCA) plus salt treatment and inhibition of tubular fluid flow, were used in the dogs to evaluate the renal vascular effects o...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.1980.158
更新日期:1980-10-01 00:00:00
abstract::While it is known that risk of death from sepsis is higher in patients with pre-existing chronic kidney disease its mechanism is unknown. To study this we established a two-stage mouse model where renal disease was first induced by folic acid injection followed by sub-lethal cecal ligation and puncture to induce sepsi...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2008.346
更新日期:2008-10-01 00:00:00
abstract::In his hypothesis of the evolution of renal functions Homer Smith proposed that the formation of glomerular nephron and body armor had been adequate for the appearance of primitive vertebrates in fresh water and that the adaptation of homoiotherms to terrestrial life was accompanied by the appearance of the loop of He...
journal_title:Kidney international
pub_type: 杂志文章,评审
doi:10.1038/ki.1996.220
更新日期:1996-06-01 00:00:00
abstract::The safety of dietary protein and phosphorous restriction was evaluated in the Modification of Diet in Renal Disease (MDRD) Study. In Study A, 585 patients with a glomerular filtration rate (GFR) of 25 to 55 ml/min/1.73 m2 were randomly assigned to a usual-protein diet (1.3 g/kg/day) or a low-protein diet (0.58 g/kg/d...
journal_title:Kidney international
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1038/ki.1997.395
更新日期:1997-09-01 00:00:00
abstract:BACKGROUND:Elevated glucose levels and glomerular hypertension (Pgc) are considered to contribute to the elaboration of matrix protein by mesangial cells (MCs) in diabetic glomeruli. MCs grown in 30 mM of glucose produce excessive matrix protein, as do MCs exposed to cyclic strain, and the combination of the two exacer...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1046/j.1523-1755.1999.00743.x
更新日期:1999-11-01 00:00:00
abstract::Diabetic nephropathy is a growing health concern with characteristic sterile inflammation. As the underlying mechanisms of this inflammation remain poorly defined, specific therapies targeting sterile inflammation in diabetic nephropathy are lacking. Intriguingly, an association of diabetic nephropathy with inflammaso...
journal_title:Kidney international
pub_type: 杂志文章
doi:10.1038/ki.2014.271
更新日期:2015-01-01 00:00:00