Long-term treatment of rats with FGF-2 results in focal segmental glomerulosclerosis.

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 Int

journal_title

Kidney international

authors

Kriz W,Hähnel B,Rösener S,Elger M

doi

10.1038/ki.1995.433

subject

Has Abstract

pub_date

1995-11-01 00:00:00

pages

1435-50

issue

5

eissn

0085-2538

issn

1523-1755

pii

S0085-2538(15)59205-3

journal_volume

48

pub_type

杂志文章
  • ACE inhibition limits chronic injury of kidney transplant even with treatment started when lesions are established.

    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

    authors: Noris M,Mister M,Pezzotta A,Azzollini N,Cassis P,Benigni A,Gagliardini E,Perico N,Remuzzi G

    更新日期:2003-12-01 00:00:00

  • An increasing number of calcium oxalate stone events worsens treatment outcome.

    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

    authors: Parks JH,Coe FL

    更新日期:1994-06-01 00:00:00

  • Effect of acute potassium load on reabsorption in Henle's loop in chronic renal failure in the rat.

    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

    authors: Milanes CL,Jamison RL

    更新日期:1985-06-01 00:00:00

  • Time course studies on phosphate transfer in frog urinary bladder.

    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

    authors: Parisi M,Cancela L

    更新日期:1988-01-01 00:00:00

  • The prolactin gene is expressed in the mouse kidney.

    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

    authors: Sakai Y,Hiraoka Y,Ogawa M,Takeuchi Y,Aiso S

    更新日期:1999-03-01 00:00:00

  • Dietary NaCl-restriction prevents the calciuria of KCl-deprivation and blunts the calciuria of KHCO3-deprivation in healthy adults.

    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

    authors: Lemann J Jr,Pleuss JA,Hornick L,Hoffman RG

    更新日期:1995-03-01 00:00:00

  • The renal lesions that develop in neonatal mice during angiotensin inhibition mimic obstructive nephropathy.

    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

    authors: Miyazaki Y,Tsuchida S,Fogo A,Ichikawa I

    更新日期:1999-05-01 00:00:00

  • Treatment of experimental renal osteodystrophy with pamidronate.

    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

    authors: Jokihaara J,Pörsti IH,Kööbi P,Jolma PM,Mustonen JT,Saha HH,Sievänen H,Kannus P,Iwaniec UT,Turner RT,Järvinen TL

    更新日期:2008-08-01 00:00:00

  • Association of thin glomerular basement membrane with other glomerulopathies.

    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

    authors: Cosio FG,Falkenhain ME,Sedmak DD

    更新日期:1994-08-01 00:00:00

  • MDM2 (murine double minute-2) links inflammation and tubular cell healing during acute kidney injury in mice.

    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

    authors: Mulay SR,Thomasova D,Ryu M,Anders HJ

    更新日期:2012-06-01 00:00:00

  • Ultrastructure of a specialized neck region in the rabbit nephron.

    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

    authors: Sch0nheyder HC,Maunsbach AB

    更新日期:1975-03-01 00:00:00

  • Hemoglobin is inversely related to flow-mediated dilatation in chronic kidney disease.

    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

    authors: Yilmaz MI,Sonmez A,Saglam M,Gulec M,Kilic S,Eyileten T,Caglar K,Oguz Y,Vural A,Yenicesu M,Zoccali C

    更新日期:2009-06-01 00:00:00

  • Patients double-seropositive for ANCA and anti-GBM antibodies have varied renal survival, frequency of relapse, and outcomes compared to single-seropositive patients.

    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

    authors: McAdoo SP,Tanna A,Hrušková Z,Holm L,Weiner M,Arulkumaran N,Kang A,Satrapová V,Levy J,Ohlsson S,Tesar V,Segelmark M,Pusey CD

    更新日期:2017-09-01 00:00:00

  • Nocturnal hypoxemia, night-day arterial pressure changes and left ventricular geometry in dialysis patients.

    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

    authors: Zoccali C,Benedetto FA,Tripepi G,Cambareri F,Panuccio V,Candela V,Mallamaci F,Enia G,Labate C,Tassone F

    更新日期:1998-04-01 00:00:00

  • Cell surface aminopeptidase A and N activities in human glomerular epithelial cells.

    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

    authors: Stefanovic V,Vlahovic P,Ardaillou N,Ronco P,Ardaillou R

    更新日期:1992-06-01 00:00:00

  • Modulation of growth factors by growth hormone in children with chronic renal failure. The Southwest Pediatric Nephrology Study Group.

    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

    authors: Powell DR,Liu F,Baker BK,Hintz RL,Lee PD,Durham SK,Brewer ED,Frane JW,Watkins SL,Hogg RJ

    更新日期:1997-06-01 00:00:00

  • Calcium channel blockers protect transplant patients from cyclosporine-induced daily renal hypoperfusion.

    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

    authors: Ruggenenti P,Perico N,Mosconi L,Gaspari F,Benigni A,Amuchastegui CS,Bruzzi I,Remuzzi G

    更新日期:1993-03-01 00:00:00

  • In vivo unaltered muscle protein synthesis in experimental chronic metabolic acidosis.

    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

    authors: Maniar S,Laouari D,Dechaux M,Motel V,Yvert JP,Mathian B,Kleinknecht C

    更新日期:1994-12-01 00:00:00

  • Enteral nutrition in patients with acute renal failure.

    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

    authors: Fiaccadori E,Maggiore U,Giacosa R,Rotelli C,Picetti E,Sagripanti S,Melfa L,Meschi T,Borghi L,Cabassi A

    更新日期:2004-03-01 00:00:00

  • The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility.

    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

    authors: Working Group of the International IgA Nephropathy Network and the Renal Pathology Society.,Roberts IS,Cook HT,Troyanov S,Alpers CE,Amore A,Barratt J,Berthoux F,Bonsib S,Bruijn JA,Cattran DC,Coppo R,D'Agati V,D'Amico G,Emanci

    更新日期:2009-09-01 00:00:00

  • Prevalence and risk factors for microalbuminuria in a referred cohort of type II diabetic patients: a global perspective.

    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

    authors: Parving HH,Lewis JB,Ravid M,Remuzzi G,Hunsicker LG,DEMAND investigators.

    更新日期:2006-06-01 00:00:00

  • Renal CD14 expression correlates with the progression of cystic kidney disease.

    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

    authors: Zhou J,Ouyang X,Cui X,Schoeb TR,Smythies LE,Johnson MR,Guay-Woodford LM,Chapman AB,Mrug M

    更新日期:2010-09-01 00:00:00

  • Angiopoietin-1 therapy enhances fibrosis and inflammation following folic acid-induced acute renal injury.

    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

    authors: Long DA,Price KL,Ioffe E,Gannon CM,Gnudi L,White KE,Yancopoulos GD,Rudge JS,Woolf AS

    更新日期:2008-08-01 00:00:00

  • Innate immune receptors and autophagy: implications for autoimmune kidney injury.

    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

    authors: Anders HJ,Schlondorff DO

    更新日期:2010-07-01 00:00:00

  • Furosemide-induced vasodilation: importance of the state of hydration and filtration.

    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

    authors: Gerber JG,Nies AS

    更新日期:1980-10-01 00:00:00

  • Pre-existing renal disease promotes sepsis-induced acute kidney injury and worsens outcome.

    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

    authors: Doi K,Leelahavanichkul A,Hu X,Sidransky KL,Zhou H,Qin Y,Eisner C,Schnermann J,Yuen PS,Star RA

    更新日期:2008-10-01 00:00:00

  • Evolutionary aspects of renal function.

    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

    authors: Natochin YV

    更新日期:1996-06-01 00:00:00

  • Effect of dietary protein restriction on nutritional status in the Modification of Diet in Renal Disease Study.

    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

    authors: Kopple JD,Levey AS,Greene T,Chumlea WC,Gassman JJ,Hollinger DL,Maroni BJ,Merrill D,Scherch LK,Schulman G,Wang SR,Zimmer GS

    更新日期:1997-09-01 00:00:00

  • Mesangial cell signaling cascades in response to mechanical strain and glucose.

    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

    authors: Ingram AJ,Ly H,Thai K,Kang MJ,Scholey JW

    更新日期:1999-11-01 00:00:00

  • Nlrp3-inflammasome activation in non-myeloid-derived cells aggravates diabetic nephropathy.

    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

    authors: Shahzad K,Bock F,Dong W,Wang H,Kopf S,Kohli S,Al-Dabet MM,Ranjan S,Wolter J,Wacker C,Biemann R,Stoyanov S,Reymann K,Söderkvist P,Groß O,Schwenger V,Pahernik S,Nawroth PP,Gröne HJ,Madhusudhan T,Isermann B

    更新日期:2015-01-01 00:00:00