klotho: a végzet vagy inkább a kezdet asszonya?
DESCRIPTION
Klotho: a végzet vagy inkább a kezdet asszonya?. Dr. Mátyus János. egyetemi docens. DEOEC Belgyógyászati Intézet, I. sz. Belgyógyászati Klinika Nephrológiai Tanszék, Debrecen. Klotho: a végzet vagy inkább a kezdet asszonya?. Mátyus János DNN XVIII. 2012.05.30. - PowerPoint PPT PresentationTRANSCRIPT
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Klotho: a vgzet vagyinkbb a kezdet asszonya?DEOEC Belgygyszati Intzet, I. sz. Belgygyszati Klinika Nephrolgiai Tanszk, DebrecenDr. Mtyus Jnosegyetemi docens
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Klotho: a vgzet vagy inkbb a kezdet asszonya?Mtyus Jnos
DNN XVIII. 2012.05.30
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VZMoe SM, et al. Kidney Int 2006;69:194553VZ Vesebetegsghez trsul svnyi anyagcsere Zavar (CKD-MBD)VZ: ROD szlesebb rtelmezse
CKD-hez trsul szisztms svnyi s csont anyagcsere zavar, melyet az albbiak kzl egy vagy tbb eltrs jellemez
Laboratoriumi: Ca, P, PTH, vagy D vitamin anyagcsereCsont: turnover, mineralizci, tmeg, linearis nvekeds, szilrdsgSzv-rrendszeri : erek s ms szvetek kalcifikcija, cardilis vltozsokcsonttrs cardiovasc. betegsghallozsSzv-rrendszerivltozsokLaboratriumieltrsekCsont betegsgek(ROD)
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Serum iPTH0255075100125150175200100+909980897079606950594049303920291019CrCl (mL/min)iPTH (pg/mL)Serum ionized Ca and P23456100+909980897079606950594049303920291019CrCl (mL/min)Ca and P (mg/dL)CaP CKD-ben a SHPT korn elkezddik s fokozatosan slyosbodikMartinez I et al. Am J Kidney Dis 1997;29:496502Foszftkt, Ca, D-vitamin kezelsben nem rszesl betegek
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Bricker: intact nephron hypothesisAm J Med 1960, NEJM 1972Alapbetegsgtl fggetlenl, ahogy a funkcinl nephronok szma cskkenmindegyikk egyre nagyobb rszt vllal a vese sszes kivlaszt funkcijbl ez a nephron adaptci biztostja a beteg tllst.Slatapolsky KI 2011
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Klasszikus teria: nephron adaptci kvetkezmnye a secunder hyperparathyreosisGFR+vltozatlan P bevitelse-P se-Ca PTH Ca-P mobilizci , P kivlaszts norm. se-Ca, norm. se-P, magas PTH
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P bevitel proporcionlis cskkentsvel a 2HP kivdhet (Slatopolsky KI 1972)
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A calcitriol gtolja a PTH gn transzkriptiojt (Silver PNAS 1985, JCI 1986)A calcitriol gtolja a mellkpajzsmirigy prolifercijt (Szab A. Kidney Int. 1989)
A 2HP oka elssorban a calcitriol hinya
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Alacsony Ca - alacsony P dita calciumtl s calcitrioltl fggetlenl mrskli a 2HP-t llatkisrletben (Lopez-Hilker Am J Physiol 1990)
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A magas phosphat kzvetlenl stimullja a mellkpajzsmirigyet(Slatopolszky JCI 1996, Almaden J Bone Mineral Res 1996, Nielsen NDT 1996)
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SHPT progresszija: parathyroid hyperplasiaNormalDiffuseEarlynodularityNodularSingle noduleContinuous functional demandGland volumeSecretorycellsTominaga Y et al. Curr Opin Nephrol Hypertens 1996;5:33641 NormalVery highPTH
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13 vvel ezeltti teria: Slatopolszky KI 1999
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A calcitriol szintje mr korai veseelgtelensgben cskken, nem a 250HD3 hiny miattLevin et al Kidney Int 2007;71:31-38. n > 1800
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Mtyus J.: A foszft anyagcsere szablyozsnak j szerepli. DNN 2000Hypophosphataemival jr onkogn osteomalacia. Orv Hetil 20001985 19 ffi csipfjdalom 1986 patol. fractura? opushypophosphataemis rachitisismtelt intzeti kivizsglsok Bp3x0,5ug calcitriol ellenre P:0,4-0,62x1 indomethacin, bicegve jr
1998 Db nephrol.1,5cm-es gingiva nvedk eltvolitsAznap P szint normalizldik1 v mlva csont BMD normlisphosphatonint termel epulis
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Izollt hypophosphataemival jr krkpekJan de BeurJAMA 2005
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FGF23FGF csald tagja, 12p13, 251 aminosavTIO-k egy rszben jelen vanADHR-ban mutci akadlyozza az enzimatikus lebontststabil molekula, tarts FGF23 hatsFGF23 mRNS kimutathat: dnten osteocytk, osteoblastok,mj, szv, pajzsmirigy, mellkpajzsmirigyFGF receptorok a szervezetben mindenttFGF23 (-/-) egerek: hyperphosphataemia +generalizlt calcinosis, osteopenia regeds, korai pusztuls
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Klotho gn: regedsgtl gnKuro-o Nature 1997Felfedezs 1997: transgenicus egrtrzs,P, Ca, calcitriol, media calcif.regeds, rvid lettartamtransgenicus Klotho overexpresszi 20-30% hosszabb lettartam1014 aminosav; extracellulris rsz: 980 cytoplasmatikus C-term. 11 aminosavExpressio: vese distalis (prox.) tubulus, mellkpajzsmirigyB-glucoronidz, sialidz aktivitsglycoproteinek cukorlnc mdosts?
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Klotho (-/-)
Rvid lettartamNvekeds retardciHypogonadismusKorai thymus involuciBr atrophiaArteriosclerosisOsteoporosisPulm. emphysemaLgyrszmeszesedsHyperphosphataemiaHyper D vitaminosisHypercalcaemiaHypoglycaemiaFGF23 (-/-)
Rvid lettartamNvekeds retardciHypogonadismusKorai thymus involuciBr atrophiaArteriosclerosisOsteoporosisPulm. emphysemaLgyrszmeszesedsHyperphosphataemiaHyper D vitaminosisHypercalcaemiaHypoglycaemiaFGF23 > 1000 xKlotho (+/+)Klotho (-/-)
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Klotho a FGF23 koreceptoraKlotho rszt vesz az FGF23 jeltovbbtsban?FGF receptorokkal komplexet kpezFGF23 a Klotho/FGFR komplexhez ktdik
Foszft megszorts a fenotpust korriglja (pedig Ca/1,25D!)Kuro-o KI 2011
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Kuro-o
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A distlis kanyarulatos tubulus Klotho-ja hogy tudja a proximlis tubulus P reabszorcijt befolysolni?ADAM10/17 protez lehastja
Extracellularis trbe szekretldik
(secretlt Klotho inj. phosphaturia)
Paracrin hatsTranscytosis(?) a prox. tubuluson
NaPi2a cukorlncait eltvoltja
NaPi2a mkdse gtldik
P reabszorpci cskken
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Hrom feedback hurok szorosan szablyozza a foszftszintet
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Calcitriol fokozza a vese Klotho expressiojtTsujikawa Molecular Endocrin 2003
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Klotho cskkens a legkorbbi jel?Kuro-o KJIM 2011
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Vizelet Klotho korn cskken!
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A Klotho koncentrcitl fgg mdon befolysolja a vascularis simaizomsejtek Pi felvtelt (Na-dep. P co-transp. t.III)
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Secretlt -Klotho serumszintje mr a korai CKD-ban cskken Shimamura Y Clin Exp Nephrol 2012.03.29.Klotho s eGFR szoros poz. kapcs.Se-Klotho mr CKD2-bensign. kisebb mint CKD1-benSzekretlt -Klotho cskkens a membrn kttt -Klotho cskkenst jelziOka: nephronszm cskkens, RAAS aktivlds?
Az -Klotho rzkeny biomarkere a korai CKD-nak!
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AngII KlothoMitani Hypertension 2002Saito FEBS Lett 2003Zou Kidney Blood Press Res 2010Joon NDT 2011
Mechanizmus?Oxydativ stressTACE (ADAM17) upregulls
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Se Klotho s se FGF23 negatv korrelcit mutat CKD betegekbenShimamura Y. Clin Exp Neprol 2012
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FGF23 s vesefunkcis rtkek(MANET Sopron 2005)A GFR s az FGF23 kapcsolataA szrum kreatinin s FGF23 kapcsolata
Diagram11
50.2
10.1
6.6
41.4
33.7
65
66.7
59.1
11.9
8.9
30.2
118.1
16
6
11.9
127.5
345.7
36.1
26.6
59.7
76.2
381.7
197.7
17.2
39
36.1
gfr
GFR
FGF23
Munka1
NvnemszlHD1idophdtartkorFGF23crgfrccrPCaCa++OCCrosslapsPTHD3
Ujvri Lszl119647/1/054150.2124740.73
Tth Gyula119837/1/05220101114480.63
Makula Iboly219747/1/053110.1371161.2748.9181414.414.5
Szab Lszln219657/1/05406.6761071140.7711.266.53.545
Pti Jzsef119607/1/054541.4731291990.7412.42131.725
Dvid Anett219827/1/052333.712369581.41304763.220
Losonczi Attila119727/1/053365103103561.62.151.187.73751.740
Varga Jzsef119467/1/055966.716342500.632.241.1930.85353.957.5
Zilahi Istvnn219617/1/054459.112062681.072.231.1428.84134.762.5
Fldi Istvnn219527/1/05531835396111.362.191.26141.6111213.447.5
Bodnr Lszln219557/1/055011.9751011150.532.351.27151051.465
Bodnr Zsuzsa219807/1/05250601211680.732.451.2516.82681.472
Tihanics Tams119847/1/05218.997121780.882.421.224812341.8102
Erlichn Jenei Mria219607/1/054530.29685580.942.411.26462122.825
Mszrosn Csod Ildik219617/1/0544118.1681061261.182.25151952.123
Paluska Attila119677/1/05381805785992.232.211.18256146612.240
Deli Jnos119737/1/05321616450170.672.4226.64001.395
Deli Attila119787/1/0527612085311.112.5343941.475
Mricz Tams119807/1/052511.9118890.992.55
Demeter Jzsef119547/1/0551127.599960.782.14
Ss rpd119337/1/0572345.7407121.522.395.37
Pocsai Jnosn219307/1/057536.185791.052.2212.23162.518.3
Kerkgyrt Gyrgy119527/1/055326.6741221210.812.4
Tarnczi Jzsef119667/1/053959.7651340.522.467.9
Gyni Pter119767/1/052976.2581442700.732.34
Varga Hajnalka219557/1/0550381.7119601.482.18
Balogh Gza 2.119767/1/05290199381.222.5560.28281.572.3
Nagy Gbor119387/1/0567197.7244221.182.4319.14138.830
Nagy Lajos119817/1/052417.218544861.362.2917.55313.358.2
Balogh Gza119497/1/05563998940.812.725899585.6
Zubara Lszln219447/1/05611808264170.622.2675.876533.5
Dani Jnos119507/1/055536.1418131.252.1741.671.3
Czak Lajosn219465/19/937/1/05148591872hd02.172.2577.4
Budai Lszln2193612/28/947/1/05128691870hd01.82.1399617141
Urbn Ptern219395/12/947/1/05136661857hd02.072.4225717.730.9
Cseri Imre119591/12/977/1/05103461882hd01.591.640.8663.23.7449.5
Szegedi Csaba119642/1/837/1/0527341954hd01.991.572229.2648.7
Fodor Rza219305/10/957/1/0512475319hd01.821.860.884.4
Juhsz Elemr119613/22/977/1/05101442716hd02.391.960.94326
Lakatos Tibor119514/26/997/1/0575542757hd03.672.511.16110.2
Szab Tibor119617/28/047/1/051144572hd02.082.161.0746.8
Szatmri Zsolt1196911/14/027/1/0532362706hd02.931.650.8
Szab Sndorn2196311/1/997/1/0569422748hd01.811.940.9582.4
Madai Sndorn2193610/22/917/1/05167691915hd02.292.211.0291.2
Sipos Sndor119482/13/917/1/05175572686hd03.572.030.932.4
Fnyi Gbor119405/31/997/1/0574652637hd01.532.151.1637
Szab Imrn219536/24/937/1/05146522729hd02.82.45132.1
Zagarits Kroly1195610/2/967/1/05106491725hd01.652.121.0729.8
Lokodi Attila1197612/4/017/1/0544292754hd03.122.231.0675.2
Juhsz Sndorn219293/19/977/1/05101762801hd01.841.640.777.9
Nagy Lszl119355/12/997/1/0575702710hd01.662.411.2388.4
Takr Jzsef119454/1/937/1/05149602803hd01.832.271.2318.5
Takcs Jnos1194811/20/047/1/057572697hd02.962.050.9916.6
Gajdor Magda219361/18/057/1/05569597hd01.432.061.0520.5
Nagy Miklsn219486/11/847/1/05256572687hd02.232.381.1358.5
Nagy Istvnn219387/23/027/1/0536672690hd02.592.21.0624.1
krs Imrn219555/24/047/1/0513501022hd01.692.111.0314.6
Molnr Jnos119526/15/907/1/05183532772hd03.012.060.9672.3
Ulveczki Menyhrt119378/23/037/1/0523682238hd01.992.161.0723.5
Burai Zoltnn219338/22/017/1/0547722601hd03.561.550.7430.8
Br Mihly1193012/22/017/1/0543752735hd01.92.271.1425.8
Kovcs Balzs119527/17/007/1/0560532628hd02.272.15149.6
Mller Jen119518/31/047/1/0510542701hd03.2720.9432.8
Balogh Imre1196411/10/047/1/058412732hd02.862.061.0224.5
Barcza Lszl119483/23/007/1/0564571633hd01.72.191.0915.5
Papp Barnabs119398/27/027/1/0535661643hd02.042.11.0140.7
Rcz Andrsn219329/8/037/1/0522731307hd01.782.371.1720.7
Kllai Ferenc1194810/5/047/1/05957254hd01.871.750.9396.6
Hodosn Vince119492/3/057/1/055561116hd02.41.790.9125.7
Dinnys Istvnn219572/19/977/1/05102482682hd02.162.441.156.7
Val Jnosn219404/6/057/1/05365331hd01.322.311.16
Fur Ferencn2194011/9/017/1/0544652720hd01.362.371.3237.8
Hetei Gyrgy119622/13/937/1/05151432743hd02.382.291.188.5
Istk Gborn2193211/14/007/1/055673175hd01.482.111.1222.3
Farkas Jnosn219292/8/027/1/0541761200hd01.631.950.9325.4
Szegedi Antaln219423/30/057/1/053632543hd01.812.121.0631.7
Munka2
gfrcrPFGF23
741240.7350.2
116371.2710.1
107760.776.6
129730.7441.4
691231.4133.7
1031031.665
421630.6366.7
621201.0759.1
101750.5311.9
121970.888.9
85960.9430.2
106681.18118.1
501640.6716
851201.116
891180.9911.9
96990.78127.5
124071.52345.7
79851.0536.1
122740.8126.6
134650.5259.7
144580.7376.2
601191.48381.7
222441.18197.7
441851.3617.2
94980.8139
134181.2536.1
Munka2
gfr
GFR
FGF23
Munka3
Diagram13
50.2
10.1
6.6
41.4
33.7
65
66.7
59.1
11.9
8.9
30.2
118.1
16
6
11.9
127.5
345.7
36.1
26.6
59.7
76.2
381.7
197.7
17.2
39
36.1
cr
Kreatinin
FGF23
Munka1
NvnemszlHD1idophdtartkorFGF23crgfrccrPCaCa++OCCrosslapsPTHD3
Ujvri Lszl119647/1/054150.2124740.73
Tth Gyula119837/1/05220101114480.63
Makula Iboly219747/1/053110.1371161.2748.9181414.414.5
Szab Lszln219657/1/05406.6761071140.7711.266.53.545
Pti Jzsef119607/1/054541.4731291990.7412.42131.725
Dvid Anett219827/1/052333.712369581.41304763.220
Losonczi Attila119727/1/053365103103561.62.151.187.73751.740
Varga Jzsef119467/1/055966.716342500.632.241.1930.85353.957.5
Zilahi Istvnn219617/1/054459.112062681.072.231.1428.84134.762.5
Fldi Istvnn219527/1/05531835396111.362.191.26141.6111213.447.5
Bodnr Lszln219557/1/055011.9751011150.532.351.27151051.465
Bodnr Zsuzsa219807/1/05250601211680.732.451.2516.82681.472
Tihanics Tams119847/1/05218.997121780.882.421.224812341.8102
Erlichn Jenei Mria219607/1/054530.29685580.942.411.26462122.825
Mszrosn Csod Ildik219617/1/0544118.1681061261.182.25151952.123
Paluska Attila119677/1/05381805785992.232.211.18256146612.240
Deli Jnos119737/1/05321616450170.672.4226.64001.395
Deli Attila119787/1/0527612085311.112.5343941.475
Mricz Tams119807/1/052511.9118890.992.55
Demeter Jzsef119547/1/0551127.599960.782.14
Ss rpd119337/1/0572345.7407121.522.395.37
Pocsai Jnosn219307/1/057536.185791.052.2212.23162.518.3
Kerkgyrt Gyrgy119527/1/055326.6741221210.812.4
Tarnczi Jzsef119667/1/053959.7651340.522.467.9
Gyni Pter119767/1/052976.2581442700.732.34
Varga Hajnalka219557/1/0550381.7119601.482.18
Balogh Gza 2.119767/1/05290199381.222.5560.28281.572.3
Nagy Gbor119387/1/0567197.7244221.182.4319.14138.830
Nagy Lajos119817/1/052417.218544861.362.2917.55313.358.2
Balogh Gza119497/1/05563998940.812.725899585.6
Zubara Lszln219447/1/05611808264170.622.2675.876533.5
Dani Jnos119507/1/055536.1418131.252.1741.671.3
Czak Lajosn219465/19/937/1/05148591872hd02.172.2577.4
Budai Lszln2193612/28/947/1/05128691870hd01.82.1399617141
Urbn Ptern219395/12/947/1/05136661857hd02.072.4225717.730.9
Cseri Imre119591/12/977/1/05103461882hd01.591.640.8663.23.7449.5
Szegedi Csaba119642/1/837/1/0527341954hd01.991.572229.2648.7
Fodor Rza219305/10/957/1/0512475319hd01.821.860.884.4
Juhsz Elemr119613/22/977/1/05101442716hd02.391.960.94326
Lakatos Tibor119514/26/997/1/0575542757hd03.672.511.16110.2
Szab Tibor119617/28/047/1/051144572hd02.082.161.0746.8
Szatmri Zsolt1196911/14/027/1/0532362706hd02.931.650.8
Szab Sndorn2196311/1/997/1/0569422748hd01.811.940.9582.4
Madai Sndorn2193610/22/917/1/05167691915hd02.292.211.0291.2
Sipos Sndor119482/13/917/1/05175572686hd03.572.030.932.4
Fnyi Gbor119405/31/997/1/0574652637hd01.532.151.1637
Szab Imrn219536/24/937/1/05146522729hd02.82.45132.1
Zagarits Kroly1195610/2/967/1/05106491725hd01.652.121.0729.8
Lokodi Attila1197612/4/017/1/0544292754hd03.122.231.0675.2
Juhsz Sndorn219293/19/977/1/05101762801hd01.841.640.777.9
Nagy Lszl119355/12/997/1/0575702710hd01.662.411.2388.4
Takr Jzsef119454/1/937/1/05149602803hd01.832.271.2318.5
Takcs Jnos1194811/20/047/1/057572697hd02.962.050.9916.6
Gajdor Magda219361/18/057/1/05569597hd01.432.061.0520.5
Nagy Miklsn219486/11/847/1/05256572687hd02.232.381.1358.5
Nagy Istvnn219387/23/027/1/0536672690hd02.592.21.0624.1
krs Imrn219555/24/047/1/0513501022hd01.692.111.0314.6
Molnr Jnos119526/15/907/1/05183532772hd03.012.060.9672.3
Ulveczki Menyhrt119378/23/037/1/0523682238hd01.992.161.0723.5
Burai Zoltnn219338/22/017/1/0547722601hd03.561.550.7430.8
Br Mihly1193012/22/017/1/0543752735hd01.92.271.1425.8
Kovcs Balzs119527/17/007/1/0560532628hd02.272.15149.6
Mller Jen119518/31/047/1/0510542701hd03.2720.9432.8
Balogh Imre1196411/10/047/1/058412732hd02.862.061.0224.5
Barcza Lszl119483/23/007/1/0564571633hd01.72.191.0915.5
Papp Barnabs119398/27/027/1/0535661643hd02.042.11.0140.7
Rcz Andrsn219329/8/037/1/0522731307hd01.782.371.1720.7
Kllai Ferenc1194810/5/047/1/05957254hd01.871.750.9396.6
Hodosn Vince119492/3/057/1/055561116hd02.41.790.9125.7
Dinnys Istvnn219572/19/977/1/05102482682hd02.162.441.156.7
Val Jnosn219404/6/057/1/05365331hd01.322.311.16
Fur Ferencn2194011/9/017/1/0544652720hd01.362.371.3237.8
Hetei Gyrgy119622/13/937/1/05151432743hd02.382.291.188.5
Istk Gborn2193211/14/007/1/055673175hd01.482.111.1222.3
Farkas Jnosn219292/8/027/1/0541761200hd01.631.950.9325.4
Szegedi Antaln219423/30/057/1/053632543hd01.812.121.0631.7
Munka2
gfrcrPFGF23
741240.7350.2
116371.2710.1
107760.776.6
129730.7441.4
691231.4133.7
1031031.665
421630.6366.7
621201.0759.1
101750.5311.9
121970.888.9
85960.9430.2
106681.18118.1
501640.6716
851201.116
891180.9911.9
96990.78127.5
124071.52345.7
79851.0536.1
122740.8126.6
134650.5259.7
144580.7376.2
601191.48381.7
222441.18197.7
441851.3617.2
94980.8139
134181.2536.1
Munka2
gfr
GFR
FGF23
Munka3
cr
Kreatinin
FGF23
-
Eredmnyek Dializlt betegekA norml vesefunkci mellett mrt rtknl szzszor magasabb FGF23 szintek
Diagram17
1872
1870
1857
1882
954
319
2716
2757
572
2706
2748
1915
2686
2637
2729
1725
2754
2801
2710
2803
2697
597
2687
2690
1022
2772
2238
2601
2735
2628
2701
2732
1633
1643
1307
254
1116
2682
331
2720
2743
175
1200
2543
FGF23
Pi
FGF23
Foszft s FGF23
Munka1
NvnemszlHD1idophdtartkorFGF23crgfrccrPCaCa++OCCrosslapsPTHD3
Ujvri Lszl119647/1/054150.2124740.73
Tth Gyula119837/1/05220101114480.63
Makula Iboly219747/1/053110.1371161.2748.9181414.414.5
Szab Lszln219657/1/05406.6761071140.7711.266.53.545
Pti Jzsef119607/1/054541.4731291990.7412.42131.725
Dvid Anett219827/1/052333.712369581.41304763.220
Losonczi Attila119727/1/053365103103561.62.151.187.73751.740
Varga Jzsef119467/1/055966.716342500.632.241.1930.85353.957.5
Zilahi Istvnn219617/1/054459.112062681.072.231.1428.84134.762.5
Fldi Istvnn219527/1/05531835396111.362.191.26141.6111213.447.5
Bodnr Lszln219557/1/055011.9751011150.532.351.27151051.465
Bodnr Zsuzsa219807/1/05250601211680.732.451.2516.82681.472
Tihanics Tams119847/1/05218.997121780.882.421.224812341.8102
Erlichn Jenei Mria219607/1/054530.29685580.942.411.26462122.825
Mszrosn Csod Ildik219617/1/0544118.1681061261.182.25151952.123
Paluska Attila119677/1/05381805785992.232.211.18256146612.240
Deli Jnos119737/1/05321616450170.672.4226.64001.395
Deli Attila119787/1/0527612085311.112.5343941.475
Mricz Tams119807/1/052511.9118890.992.55
Demeter Jzsef119547/1/0551127.599960.782.14
Ss rpd119337/1/0572345.7407121.522.395.37
Pocsai Jnosn219307/1/057536.185791.052.2212.23162.518.3
Kerkgyrt Gyrgy119527/1/055326.6741221210.812.4
Tarnczi Jzsef119667/1/053959.7651340.522.467.9
Gyni Pter119767/1/052976.2581442700.732.34
Varga Hajnalka219557/1/0550381.7119601.482.18
Balogh Gza 2.119767/1/05290199381.222.5560.28281.572.3
Nagy Gbor119387/1/0567197.7244221.182.4319.14138.830
Nagy Lajos119817/1/052417.218544861.362.2917.55313.358.2
Balogh Gza119497/1/05563998940.812.725899585.6
Zubara Lszln219447/1/05611808264170.622.2675.876533.5
Dani Jnos119507/1/055536.1418131.252.1741.671.3
Czak Lajosn219465/19/937/1/05148591872hd02.172.2577.4
Budai Lszln2193612/28/947/1/05128691870hd01.82.1399617141
Urbn Ptern219395/12/947/1/05136661857hd02.072.4225717.730.9
Cseri Imre119591/12/977/1/05103461882hd01.591.640.8663.23.7449.5
Szegedi Csaba119642/1/837/1/0527341954hd01.991.572229.2648.7
Fodor Rza219305/10/957/1/0512475319hd01.821.860.884.4
Juhsz Elemr119613/22/977/1/05101442716hd02.391.960.94326
Lakatos Tibor119514/26/997/1/0575542757hd03.672.511.16110.2
Szab Tibor119617/28/047/1/051144572hd02.082.161.0746.8
Szatmri Zsolt1196911/14/027/1/0532362706hd02.931.650.8
Szab Sndorn2196311/1/997/1/0569422748hd01.811.940.9582.4
Madai Sndorn2193610/22/917/1/05167691915hd02.292.211.0291.2
Sipos Sndor119482/13/917/1/05175572686hd03.572.030.932.4
Fnyi Gbor119405/31/997/1/0574652637hd01.532.151.1637
Szab Imrn219536/24/937/1/05146522729hd02.82.45132.1
Zagarits Kroly1195610/2/967/1/05106491725hd01.652.121.0729.8
Lokodi Attila1197612/4/017/1/0544292754hd03.122.231.0675.2
Juhsz Sndorn219293/19/977/1/05101762801hd01.841.640.777.9
Nagy Lszl119355/12/997/1/0575702710hd01.662.411.2388.4
Takr Jzsef119454/1/937/1/05149602803hd01.832.271.2318.5
Takcs Jnos1194811/20/047/1/057572697hd02.962.050.9916.6
Gajdor Magda219361/18/057/1/05569597hd01.432.061.0520.5
Nagy Miklsn219486/11/847/1/05256572687hd02.232.381.1358.5
Nagy Istvnn219387/23/027/1/0536672690hd02.592.21.0624.1
krs Imrn219555/24/047/1/0513501022hd01.692.111.0314.6
Molnr Jnos119526/15/907/1/05183532772hd03.012.060.9672.3
Ulveczki Menyhrt119378/23/037/1/0523682238hd01.992.161.0723.5
Burai Zoltnn219338/22/017/1/0547722601hd03.561.550.7430.8
Br Mihly1193012/22/017/1/0543752735hd01.92.271.1425.8
Kovcs Balzs119527/17/007/1/0560532628hd02.272.15149.6
Mller Jen119518/31/047/1/0510542701hd03.2720.9432.8
Balogh Imre1196411/10/047/1/058412732hd02.862.061.0224.5
Barcza Lszl119483/23/007/1/0564571633hd01.72.191.0915.5
Papp Barnabs119398/27/027/1/0535661643hd02.042.11.0140.7
Rcz Andrsn219329/8/037/1/0522731307hd01.782.371.1720.7
Kllai Ferenc1194810/5/047/1/05957254hd01.871.750.9396.6
Hodosn Vince119492/3/057/1/055561116hd02.41.790.9125.7
Dinnys Istvnn219572/19/977/1/05102482682hd02.162.441.156.7
Val Jnosn219404/6/057/1/05365331hd01.322.311.16
Fur Ferencn2194011/9/017/1/0544652720hd01.362.371.3237.8
Hetei Gyrgy119622/13/937/1/05151432743hd02.382.291.188.5
Istk Gborn2193211/14/007/1/055673175hd01.482.111.1222.3
Farkas Jnosn219292/8/027/1/0541761200hd01.631.950.9325.4
Szegedi Antaln219423/30/057/1/053632543hd01.812.121.0631.7
Munka2
gfrcrPFGF23
741240.7350.2
116371.2710.1
107760.776.6
129730.7441.4
691231.4133.7
1031031.665
421630.6366.7
621201.0759.1
101750.5311.9
121970.888.9
85960.9430.2
106681.18118.1
501640.6716
851201.116
891180.9911.9
96990.78127.5
124071.52345.7
79851.0536.1
122740.8126.6
134650.5259.7
144580.7376.2
601191.48381.7
222441.18197.7
441851.3617.2
94980.8139
134181.2536.1
113961.361835
97852.231805
172642.261808
Munka2
gfr
GFR
FGF23
Munka3
cr
Kreatinin
FGF23
FGF23PiCa++
18722.17
18701.8
18572.07
18821.590.86
9541.99
3191.820.88
27162.390.94
27573.671.16
5722.081.07
27062.93
27481.810.95
19152.291.02
26863.570.9
26371.531.16
27292.8
17251.651.07
27543.121.06
28011.840.77
27101.661.23
28031.831.23
26972.960.99
5971.431.05
26872.231.13
26902.591.06
10221.691.03
27723.010.96
22381.991.07
26013.560.74
27351.91.14
26282.271
27013.270.94
27322.861.02
16331.71.09
16432.041.01
13071.781.17
2541.870.93
11162.40.91
26822.161.15
3311.321.16
27201.361.32
27432.381.1
1751.481.12
12001.630.93
25431.811.06
FGF23
Pi
FGF23
Foszft s FGF23
Diagram20
1882
319
2716
2757
572
2748
1915
2686
2637
1725
2754
2801
2710
2803
2697
597
2687
2690
1022
2772
2238
2601
2735
2628
2701
2732
1633
1643
1307
254
1116
2682
331
2720
2743
175
1200
2543
Ca x Pi
FGF23
Ca x Pi s FGF23
Munka1
NvnemszlHD1idophdtartkorFGF23crgfrccrPCaCa++OCCrosslapsPTHD3
Ujvri Lszl119647/1/054150.2124740.73
Tth Gyula119837/1/05220101114480.63
Makula Iboly219747/1/053110.1371161.2748.9181414.414.5
Szab Lszln219657/1/05406.6761071140.7711.266.53.545
Pti Jzsef119607/1/054541.4731291990.7412.42131.725
Dvid Anett219827/1/052333.712369581.41304763.220
Losonczi Attila119727/1/053365103103561.62.151.187.73751.740
Varga Jzsef119467/1/055966.716342500.632.241.1930.85353.957.5
Zilahi Istvnn219617/1/054459.112062681.072.231.1428.84134.762.5
Fldi Istvnn219527/1/05531835396111.362.191.26141.6111213.447.5
Bodnr Lszln219557/1/055011.9751011150.532.351.27151051.465
Bodnr Zsuzsa219807/1/05250601211680.732.451.2516.82681.472
Tihanics Tams119847/1/05218.997121780.882.421.224812341.8102
Erlichn Jenei Mria219607/1/054530.29685580.942.411.26462122.825
Mszrosn Csod Ildik219617/1/0544118.1681061261.182.25151952.123
Paluska Attila119677/1/05381805785992.232.211.18256146612.240
Deli Jnos119737/1/05321616450170.672.4226.64001.395
Deli Attila119787/1/0527612085311.112.5343941.475
Mricz Tams119807/1/052511.9118890.992.55
Demeter Jzsef119547/1/0551127.599960.782.14
Ss rpd119337/1/0572345.7407121.522.395.37
Pocsai Jnosn219307/1/057536.185791.052.2212.23162.518.3
Kerkgyrt Gyrgy119527/1/055326.6741221210.812.4
Tarnczi Jzsef119667/1/053959.7651340.522.467.9
Gyni Pter119767/1/052976.2581442700.732.34
Varga Hajnalka219557/1/0550381.7119601.482.18
Balogh Gza 2.119767/1/05290199381.222.5560.28281.572.3
Nagy Gbor119387/1/0567197.7244221.182.4319.14138.830
Nagy Lajos119817/1/052417.218544861.362.2917.55313.358.2
Balogh Gza119497/1/05563998940.812.725899585.6
Zubara Lszln219447/1/05611808264170.622.2675.876533.5
Dani Jnos119507/1/055536.1418131.252.1741.671.3
Czak Lajosn219465/19/937/1/05148591872hd02.172.2577.4
Budai Lszln2193612/28/947/1/05128691870hd01.82.1399617141
Urbn Ptern219395/12/947/1/05136661857hd02.072.4225717.730.9
Cseri Imre119591/12/977/1/05103461882hd01.591.640.8663.23.7449.5
Szegedi Csaba119642/1/837/1/0527341954hd01.991.572229.2648.7
Fodor Rza219305/10/957/1/0512475319hd01.821.860.884.4
Juhsz Elemr119613/22/977/1/05101442716hd02.391.960.94326
Lakatos Tibor119514/26/997/1/0575542757hd03.672.511.16110.2
Szab Tibor119617/28/047/1/051144572hd02.082.161.0746.8
Szatmri Zsolt1196911/14/027/1/0532362706hd02.931.650.8
Szab Sndorn2196311/1/997/1/0569422748hd01.811.940.9582.4
Madai Sndorn2193610/22/917/1/05167691915hd02.292.211.0291.2
Sipos Sndor119482/13/917/1/05175572686hd03.572.030.932.4
Fnyi Gbor119405/31/997/1/0574652637hd01.532.151.1637
Szab Imrn219536/24/937/1/05146522729hd02.82.45132.1
Zagarits Kroly1195610/2/967/1/05106491725hd01.652.121.0729.8
Lokodi Attila1197612/4/017/1/0544292754hd03.122.231.0675.2
Juhsz Sndorn219293/19/977/1/05101762801hd01.841.640.777.9
Nagy Lszl119355/12/997/1/0575702710hd01.662.411.2388.4
Takr Jzsef119454/1/937/1/05149602803hd01.832.271.2318.5
Takcs Jnos1194811/20/047/1/057572697hd02.962.050.9916.6
Gajdor Magda219361/18/057/1/05569597hd01.432.061.0520.5
Nagy Miklsn219486/11/847/1/05256572687hd02.232.381.1358.5
Nagy Istvnn219387/23/027/1/0536672690hd02.592.21.0624.1
krs Imrn219555/24/047/1/0513501022hd01.692.111.0314.6
Molnr Jnos119526/15/907/1/05183532772hd03.012.060.9672.3
Ulveczki Menyhrt119378/23/037/1/0523682238hd01.992.161.0723.5
Burai Zoltnn219338/22/017/1/0547722601hd03.561.550.7430.8
Br Mihly1193012/22/017/1/0543752735hd01.92.271.1425.8
Kovcs Balzs119527/17/007/1/0560532628hd02.272.15149.6
Mller Jen119518/31/047/1/0510542701hd03.2720.9432.8
Balogh Imre1196411/10/047/1/058412732hd02.862.061.0224.5
Barcza Lszl119483/23/007/1/0564571633hd01.72.191.0915.5
Papp Barnabs119398/27/027/1/0535661643hd02.042.11.0140.7
Rcz Andrsn219329/8/037/1/0522731307hd01.782.371.1720.7
Kllai Ferenc1194810/5/047/1/05957254hd01.871.750.9396.6
Hodosn Vince119492/3/057/1/055561116hd02.41.790.9125.7
Dinnys Istvnn219572/19/977/1/05102482682hd02.162.441.156.7
Val Jnosn219404/6/057/1/05365331hd01.322.311.16
Fur Ferencn2194011/9/017/1/0544652720hd01.362.371.3237.8
Hetei Gyrgy119622/13/937/1/05151432743hd02.382.291.188.5
Istk Gborn2193211/14/007/1/055673175hd01.482.111.1222.3
Farkas Jnosn219292/8/027/1/0541761200hd01.631.950.9325.4
Szegedi Antaln219423/30/057/1/053632543hd01.812.121.0631.7
Munka2
gfrcrPFGF23
741240.7350.2Magas FGF23 nlklMagas FGF23mal
116371.2710.1
107760.776.6
129730.7441.4
691231.4133.7
1031031.665
421630.6366.7
621201.0759.1
101750.5311.9
121970.888.9
85960.9430.2
106681.18118.1
501640.6716
851201.116
891180.9911.9
96990.78127.5
124071.52345.7
79851.0536.1
122740.8126.6
134650.5259.7
144580.7376.2
601191.48381.7
222441.18197.7
441851.3617.2
94980.8139
134181.2536.1
113961.361835
97852.231805
172642.261808
Munka2
gfr
GFR
FGF23
Munka3
cr
Kreatinin
FGF23
GFR
FGF23
Kreatinin
FGF23
FGF23PiCa++CaxPi
18821.590.861.37
3191.820.881.6
27162.390.942.25
27573.671.164.26
5722.081.072.23
27481.810.951.72
19152.291.022.34
26863.570.93.21
26371.531.161.78
17251.651.071.77
27543.121.063.31
28011.840.771.42
27101.661.232.04
28031.831.232.25
26972.960.992.93
5971.431.051.5
26872.231.132.52
26902.591.062.75
10221.691.031.74
27723.010.962.89
22381.991.072.13
26013.560.742.63
27351.91.142.17
26282.2712.27
27013.270.943.07
27322.861.022.92
16331.71.091.85
16432.041.012.06
13071.781.172.08
2541.870.931.74
11162.40.912.18
26822.161.152.48
3311.321.161.53
27201.361.321.8
27432.381.12.62
1751.481.121.66
12001.630.931.52
25431.811.061.92
FGF23
Pi
FGF23
Foszft s FGF23
Ca x Pi
FGF23
Ca x Pi s FGF23
-
FGF23-PTH interakci vesebetegsgbenKomaba KI 2010FGF23 nem cskkenti a PTH szekrcit hyperplasis mpm-ben
-
Magas FGF23 hozzjrul a mortalitshoz?Wolf /MucsiJASN 2011
-
J Clin Invest2011. nov.
-
A hallozs relatv rizikja a serum phosphat szinttel prhuzamosan n
Block GA: JASN 2004(n=40.538, korriglt rr)
-
Kuro-o KJIM 2011
-
Kotho hsges asszony, aki vgigkisri, tovbb fonja letnket, elvesztse esetn gyorsan megregsznk s meghalunk!
-
Az intakt nephron hypotzis ma is igaz!TeendA circulus viciosus jval hamarabb indul, mint a hyperPA phosphat megszortst korn kell kezdeni (ahogy a se Klotho cskkenni kezd?)Ennek hatsra megmaradt nephronok P tlterhelse FGF23 , 1,25DKlotho expresszio (vese, mpm)FGF23 rzkenysgadott P eltvol. szks. FGF23 mennyisg
***Parathyroid hyperplasia develops in tandem with the progressive decline in renal function. The constantly increasing functional demand on parathyroid glands (mainly as a result of hypocalcaemia) drives cell proliferation. Initially, the parathyroid glands respond by increasing the proportion of secretory (chief) cells within the gland and then by increasing the total number of cells, resulting in diffuse hyperplasia of the gland.1In diffuse hyperplasia, cell growth is polyclonal, but is accompanied by down-regulation of the CaR and VDR.1As CKD progresses to stage 5 (end-stage renal disease [ESRD]), parathyroid hyperplasia evolves even further; monoclonal abnormalities lead to nodular hyperplasia of the glands.2,3 These grossly enlarged parathyroid glands are associated with significantly reduced expression of CaRs and VDRs.4,5Parathyroid glands with nodular hyperplasia therefore become less responsive to serum calcium levels6,7 and resistant to the medical treatment of SHPT.6,81. Tominaga Y et al. Semin Surg Oncol 1997;13:78862. Tominaga Y et al. World J Surg 1996;20:744503. Tominaga Y et al. Clin Nephrol 1995;44 (Suppl 1):S4274. Gogusev J et al. Kidney Int 1997;51:328365. Wang X et al. Chin Med J (Engl) 2001;114:41046. Rodriguez M et al. Kidney Int 2002;80:S155607. Almaden Y et al. J Am Soc Nephrol 1998;9:1845528. Rodriguez M et al. Kidney Int 1999;56:30617