Iziyobisi eziza phezulu nezizayo zingabamba unyango kwi-PKD
Isifo sesifo se-Polycystic ( PKD ) sisifo esiyimfuyo esichazwe ngobukho kunye nokukhula okuqhubekayo kwama-cysts ezintso. Ngokungafani nezinto ezibizwa ngokuba ngama- cysts alula , i-PKD ayiyona isifo esiyingozi kunye nengxowankulu enkulu yezigulane ze-PKD zisengozini yokungaphumeleli kwezintso, zifuna i-dialysis okanye i-kidney transplant.
Xa isiguli sifunda malunga nokuxilongwa kwe-PKD, umbuzo wokuqala oza kuvela kukuba ngaba uyayiphatha.
Ngaphambi kokuba sinokuqonda ukuba yintoni unyango onokusebenza ukuthoba isifo, umgca omfutshane kwi-hormone ebizwa ngokuba yi-ADH, okanye i-hormone ye-diuretic (eyaziwayo njenge-vasopressin) iyimfuneko.
Indima ye-ADH kwi-PKD
I-ADH yasize ubomi buguquke ukusuka elwandle ukuya ezweni, ngeenyanga ezidlulileyo. Ukuba kwakungengenxa ye-ADH, ezininzi izinto eziphilayo aziyi kukwazi ukumelana nempembelelo enzima yefuthe lomhlaba ofudumalayo phantsi kwelanga elivuthayo!
Ekhutshwe yinxalenye yengqondo ebizwa ngokuthi "hypothalamus," i-ADH iyi-hormone esebenza ezintsheni kwaye yenza ukuba igcine kwaye igcine amanzi. Yiloo nto eyenza umchamo ubonakale umnyama kwaye ugxininise xa ungenayo amanzi aneleyo ukusela okanye uchithe imini ngaphandle kwelanga elitshisayo. Ngako oko, unakho ukuchaphazela ukuba amanzi afuna ukukhutshwa kangakanani kwaye kufuneka ukuba "kufuneka uphinde uphinde" ukuhlangabezana neemfuno zethu (kuxhomekeka kwezinye iimeko, kubandakanywa ukuthambisa kwamanzi kunye nokushisa kwamanzi).
U-ADH ungene njani kwingxoxo kwiCKD? Izifundo zibonise ukuba i-ADH ingomnye wabakhuthazi abakhulu bokukhula kwe-cyst (isizathu sokungaphumeleli kwezintso) kwi-PKD. Ngamanye amagama, ukuba unokuthi ungaphantsi kwamazinga e-ADH, okanye uvimbele isenzo salo kuma-cysts, kunokwenzeka ukuba kuncitshiswe ukukhula kwe-cyst kunye nokuqhubela phambili kwePKD.
Izinketho zangoku zonyango
Ukuqonda indima ye-ADH kukunceda ekuqondeni ukhetho olukhoyo kunye nokuba kutheni bangasebenza, ukusuka ekunyuseni kwamanzi ukuya kwizidakamizwa zokusika.
- Ukongezwa kwamanzi okunyuka : Njengoko kulula njengoko oku kuvakalayo, amanzi okusela yindlela efanelekileyo yokugcina amanqanaba e-ADH phantsi. Amanqanaba e-ADH aya kunyuka xa uqala ukuphelelwa amanzi. Oku kuya kumisa impendulo yomelezi okwenza uphuze amanzi, okuya kukukhokelela ekunciphiseni amanqanaba e-ADH. Kule meko, le ngcamango kukugcina i-ADH ihlale iphantsi ngokukhusela i-ADH ukunyuka. Kucetyiswa ukuba oku kunganciphisa ukuqhubeka kwePKD. Eyona ndlela iphumelelayo kwaye inentsingiselo ekhoyo ngokwenene isengqinelaniyo nangona kunjalo.
- Ukulawula iingxaki: Ukungabikho kwamanye unyango okhoyo okwangoku, sinqunyelwe ukulawula iingxaki zePKD. Ezi zibandakanya uxinzelelo lwegazi oluphezulu, izifo zeengtso, amatye eentso, kunye ne-electrolytes engavamile. Uxinzelelo lwegazi oluphezulu luphathwa ngokusetyenziswa ngamachiza athile abizwa ngokuba yi- ACE inhibitors okanye i-ARB . Ukwandiswa kwamanzi kwamanzi kunokunceda ekunciphiseni umngcipheko wezinye ezimbini ezibalulekileyo ezinxulumene ne-PKD: izifo zengqondo kunye namatye entso.
Izinketho zonyango lwexesha elizayo
Ukuqonda kwethu indima ye-ADH ekwenzeni ukonakala kwe-PKD kuye kwakhokelela ekuphandeni okuthembisayo okuza kunika ukhetho olungakumbi lwezonyango ngaphandle kwongenelelo lwe-"band-aid" oluchazwe ngasentla.
Uphando lwangoku lujolise ekufumaneni iziyobisi ezinokubethisa isenzo se-ADH kwaye ngoko ke ukuthintela ama-cyst ukuba angakhudlwana (kuba ukwanda kwe-cyst ukukhula kwe-cyst ukuhluleka kwezintso kwizigulane ze-PKD).
Nazi izibonelo ezimbalwa:
- I-Tolvaptan: Le yonyango eyayivunyiwe ngokusesikweni ukuba unyango lwezinga le-sodium eliphantsi kwaye lenza ngokuthintela indawo (ebizwa ngokuba yi-V2 receptor) apho i-ADH yayiqhele ngokunamathela kwiintso (cinga nge-V2 receptor njenge "keyhole" apho i-ADH idinga ukunamathela, ngelixa i-tolvaptan "yinto ephambili yokubamba inkohliso" ukuba xa okwangoku iyakuthintela ukuba kwenzeke).
Isilingo se-TEMPO esetyenziswe kakuhle siye sabonisa isicelo esinokliniki esingaba se-tolvaptan ekunciphiseni ukwehla komsebenzi wezintso kwi-PKD. Inkqubo ibonakala iyancipha ukukhula kweentso ', okukhokelela ekusebenzeni kwencinci encinci kwehla kwiminyaka emithathu. U-Tolvaptan, nangona kunjalo, akafumananga iintsikelelo ze-FDA e-US ukwenzela unyango lwe-PKD, ngenxa yenkxalabo malunga nemiphumo yalo esibindi. Sekuvunyelwe ukuba unyango lwe-PKD kwezinye iindawo zehlabathi).
- I-Octreotide: Lona nguqulelo olude lwama-synthetic of hormone okuthiwa somatostatin. Ulingo ngo-2005 lwabikwa okokuqala ukuba unyango lwenyanga ezintandathu kunye ne-somatostatin lunokuphuza ukukhula kwe-cyst. Nangona siyazi ukuba ukuhla kwenkonzo yeengso kwi-PKD kulandela ukukhula kwe-cyst, isifundo sagqiba ukuthetha ukuba ukucotha ukukhula kwe-cyst, kule ngxaki, kuya kuguqulwa kwintsholongwane ekhuselweyo yezintso.
Emva koko, ngo-2013 sabona iziphumo zeesilingo ze-ALADIN ezipapashwe kwiLancet. Olu phofu lunexesha elide lokulandelela kunezifundo zangaphambilini kwaye lubonise umthamo wezintso eziphantsi kakhulu kwizigulane eziphathwe nge-octreotide ekulandelelweni komnyaka owodwa, kodwa kungekhona kwiminyaka emithathu.
Ukunikezelwa kwedatha esikude ngoku, kubonakala ukuba i-octreotide inokuthatha inxaxheba ekunyanga kwe-PKD. Ngesizathu esithile, kubonakala sengathi i-octreotide iyancipha ukukhula kwimiqulu yengqondo ngaphezu konyaka owodwa, kodwa iziphumo ziba zizinto ezingabalulekanga kwixesha elide. Kuyacaca ukuba kukho iinkcukacha ezipheleleyo ezijongene nedatha yenkqubela yexesha elide ezifunekayo.
Nangona zombini ezo zithunywa zibonise isithembiso ngokude (ngaphezu kweminye abadlali abafana ne-MTOR inhibitors kunye nezinye iziyobisi kwizilingo zeclini), indleko yinkxalabo enkulu. Zonke ezinye izinto zilingana, i-octreotide ingaba yindlela engabizi ngaphezu kwe-tolvaptan yinto enokuthi ibe yonyango lobomi bonke. Ngo-2017, i-30-day supply (15 mg) ye-tolvaptan iipilisi ixabiso kwi-11,000 ukuya kwi-12,000 kwi-US, ngelixa i-amps ezingama-90 ze-octreotide (i-100 mcg injection) ziqhuba i $ 300 ukuya kwi-400!
> Imithombo:
> Nagao S, Kazuhiro N, Makoto K, et al. Ukunyuswa kwamanzi okuNyuka kunciphisa ukunyuka kwee-Polycystic kwiintsholongwane zeentso kwi-PK Rat. J Am Soc Nephrol. 2006 Aug; 17 (8): 2220-7. Epub 2006 Juni 28.
> Higashihara E, Nutahara K, Tanbo M, et al. Ngaba ukunyuka kwamanzi okuthintelo kukuthintela ukuqhubela kwesifo kwi-autosomal isifo sofuba se-polycystic? I-Nephrology Dialysis Transplantation. 2014 Sept; 29 (9): 1710-9.
> Torres V, Chapman A, Devuyst O, et al. I-Tolvaptan kwizigulane nge-Autosomal Dominant Polycystic Iintsholongwane zeentso. N Engl J Med 2012; 367: 2407-2418, 2012. INGXELO: 10.1056 / NEJMoa1205511
> Caroli A, Perico N, Perna A, et al. Impembelelo ye-analogue eqhubekayo ye-somatostatin kwiintso kunye nokukhula kwe-cyst kwi-autosomal isifo esiphambili se-polycystic (ALADIN) Lancet. Ngo-2013 uNgo-2; 382 (9903): 1485-95. i-doi: 10.1016 / S0140-6736 (13) 61407-5.