Nephrotoxicity Ntawm Immune Checkpoint Inhibitors: Kev Ntsuam Xyuas Tsis Zoo Los Ntawm 2013 txog 2020 Ⅱ

Kev sib tham

Kev txheeb cais yog cov cuab yeej siv tau

Table 6 qhia cov ntaub ntawv ntawm tag nrho thiab tshwj xeeb ICI suav hauv 2 * 2 lub rooj sib tham thiab suav cov txiaj ntsig los ntawm kev txheeb xyuas qhov tsis sib xws. Cov ntawv sau yuav ua siab tawv yog ROR025 siab dua 1 lossis IC025 siab dua 0. (a) Cov ntawv sau nrogcev AEsqhia rau ICIs. (b) Tus naj npawb ntawm cov ntaub ntawv nrog lwm cov AEs qhia rau ICIs. (c) Tus naj npawb ntawm cov ntaub ntawv nrog ib qhocev AEsrau lwm yam tshuaj. (d) Tus naj npawb ntawm cov ntaub ntawv qhia lwm yam AEs rau lwm yam tshuaj. ROR, qhia qhov sib txawv piv txwv; ROR025, qis kawg ntawm 95% kev ntseeg siab ntawm ROR; IC, cov ntaub ntawv tivthaiv; IC025, qis kawg ntawm 95% kev ntseeg siab ntawm IC.

Fig. 1. Tag nrho cov cim qhia qhia txog qhov sib txawv ntawm qhov sib txawv (RORs) ntawm cov tshuaj tiv thaiv kab mob tiv thaiv kab mob (ICI) hauv cov ncauj lus kom ntxaws nephrotoxic adverse events (AEs). PT, lub sij hawm nyiam; ROR025, qis kawg ntawm 95% kev ntseeg siab ntawm ROR. ROR025 ntau dua 1 tau suav tias yog lub teeb liab.

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nyob rau hauv pab teeb liab nrhiav kom tau nyob rau hauv spontaneous ceeb toom systems. Hauv kev tshawb fawb yav dhau los, ROR tau raug xaiv los ua qhov kev txheeb xyuas haiv neeg tsis tsim nyog los ua tus yam ntxwv ntawm spectrum, zaus, thiab kev kho mob ntawm ICI ntsig txog cov xwm txheej tsis zoo (Raschi li al. 2019). Txawm li cas los xij, tsis muaj ib tus neeg txoj hauv kev los txheeb xyuas cov teeb liab txaus thiab kev siv lwm txoj hauv kev yog qhov tseem ceeb (van Puijenbroek li al. 2002). Yog li ntawd, ob txoj kev, ROR thiab BCPNN, yog siv nyob rau hauv txoj kev tshawb no. Kev xaiv ntawm lub sijhawm luv luv yuav tsum tau them sai sai rau. Hauv kev tshawb fawb yav dhau los, kev tsis sib haum xeeb thiab kev tsom xam Bayesian tau siv hauv cov ntaub ntawv mining los tshuaj xyuas cov neeg xav tiasraum tsis zoo tshwm simTom qab kev tswj hwm ntawm ICIs sib txawv, raws li FAERS txij Lub Ib Hlis 2004 txog Lub Cuaj Hli 2019 (Chen li al. 2020). Txawm li cas los xij, ICI kuj tseem loj dua kev lag luam, ipilimumab, tau teev nyob rau hauv 2011. Cov ntaub ntawv rov qab ua rau cov kev ntsuam xyuas ua rau muaj qhov yuam kev. Peb txoj kev tshawb fawb yog kev tshawb fawb pharmacovigilance ntawm ICI-koom nrog neph toxicities raws li ntau dua 50 lab cov ntaub ntawv nyob rau lub sijhawm tsim nyog. Qhov no ua rau peb cov lus xaus ruaj khov dua piv nrog lwm cov kev tshawb fawb.

Fig. 2. Tag nrho cov teeb liab qhia txog cov khoom siv (ICs) ntawm cov tshuaj tiv thaiv kab mob tiv thaiv kab mob (ICI) hauv cov ncauj lus kom ntxaws nephrotoxic adverse events (AEs). PT, lub sij hawm nyiam; IC025, qis kawg ntawm 95% kev ntseeg siab ntawm IC. IC025 ntau dua 0 tau suav tias yog lub teeb liab.

Nephrotoxicity raws li kev sib deev

Qhov tseem ceeb, piv nrog cov txiv neej cov neeg mob, nephrotoxic AEs tau tshaj tawm ntau dua li cov lus qhia ntawm cov poj niam cov neeg mob (63.66% vs. 29.96%). Qhov tshwm sim qhia tau hais tias cov txiv neej yog cov neeg muaj kev pheej hmoo siab rau nephrotoxic AEs tom qab kho nrog ICI tshuaj. Kev tshawb fawb yav dhau los kuj tau lees paub qhov no (Chen li al. 2020). Yog vim li cas rau qhov sib txawv ntawm qhov tshwm sim ntawm nephrotoxicity ntawm cov txiv neej thiab poj niam tej zaum yuav muaj feem xyuam rau qib ntawm cov tshuaj hormones poj niam txiv neej. Cov txiv neej cov tshuaj hormones ua rau muaj kev cuam tshuam loj heev nyob rau hauv cov nqe lus ntawm kev ua kom oxidative kev nyuaj siab, ua rau lub cev renin-angiotensin, thiab ua rau fibrosis nyob rau hauv lub raum puas, tab sis poj niam cov tshuaj hormones ua rau cov nyhuv renoprotective (Valdivielso li al. 2019). Yog li, kev siv tshuaj kho mob ICI yuav tsum tsom mus rau qhov tshwm sim ntawm nephrotoxicity hauv cov txiv neej cov neeg mob.

Lub koom haum ntawm tag nrho nephrotoxicity nyob rau hauv tag nrho ICI siv Lub raum yog ib qho tseem ceeb hauv lub cev rau cov zis ntau lawm, kev tswj ntawm electrolytes thiab dej, thiab homeostasis ntawm as-ham thiab metabolites nyob rau hauv lub cev (Liu li al. 2019). Cov tshuaj yog ib qho ua rau mob raum (Markowitz thiab Perazella 2005; Perazella 2005, 2009, 2012; Uchino li al. 2007; Izzedine et al. 2009; Moffett and Goldstein 2011; Hoste et al. 2011). Drug-induced nephrotoxicity muaj ntau dua hauv cov neeg mob hauv tsev kho mob, tshwj xeeb tshaj yog cov neeg mob hauv tsev kho mob hnyav (Mehta li al. 2004; Uchino li al. 2007; Moffett thiab Goldstein 2011; Hoste et al. 2015), thiab cuam tshuam los ntawm qhov muaj peev xwm ntawm nephrotoxic hauv lub cev. cov tshuaj, cov yam ntxwv hauv qab ntawm tus neeg mob uas txhim kho txoj kev pheej hmoo rau lub raum raug mob, thiab cov metabolism thiab tso tawm ntawm cov neeg ua txhaum cai los ntawm lub raum (Perazella 2003, 2005, 2009; Markowitz thiab Perazella 2005). Pawg tswj hwm yuav nthuav qhia ntau dua qhov feem ntawmraum toxicity.Tsis tas li ntawd, cov ntaub ntawv ICI tuaj yeem qhia ntau dhau ntawm lwm yam kabmob hauv nruab nrog cev, uas yuav ua rau tsis muaj kev cuam tshuam tseem ceeb ntawm lub cev.cev AEsthiab ICIs.

Nephrotoxicity thiab atezolizumab

Covlub raummuaj li ntawmglomeruli thiab tubules. Tsis muaj kev xav ntawm toxicity ntawm txhua feem yog pom tseeb nyob rau hauv pawg atezolizumab (Table 7), uas tej zaum yuav raug ntaus nqi rau cov txheej txheem ntawm cov tshuaj no. Atezolizumab yog ib tug engineered humanized monoclonal IgG1 antibody uas khi xaiv rau PD-L1 thiab tiv thaiv nws cov kev cuam tshuam nrog PD-1 thiab B7.1 thaum sib cuam tshuam ntawm PD-L2 thiab PD-1. Rau qee qhov kev kawm, atezolizumab yuav muaj kev noj qab haus huv ntau dua ntawm PD-L1 receptors uas tau tawg mus rau hauv lub raum, uas yuav tsum tau lees paub los ntawm kev tshawb fawb ntau dua.

Muaj pov thawj nephrotoxicity thiab ICIs

Cov txiaj ntsig qhia tau tiasmob raum raug mob,IgAnephropathy, thiab nephritis qhia qhov sib txawv tseem ceeb nrog ib feem ntawm ICIs, thiab qee qhov ntawm cov cim no muaj zog dua lwm tus (Daim duab 2). Qhov no tej zaum yuav muaj feem xyuam nrog cov txheej txheem ntawm ICIs. CTLA-4 yog ib feem ntawm B7: CD28 immunoglobulin tsev neeg pom nyob rau ntawm T-cells thiab xa cov teeb liab inhibitory mus rau T-cell. PD-1 tau nthuav tawm ntawm T-cells thiab khi rau nws cov ligands PD-L1 thiab PD-L2 uas tau nthuav tawm hauv cov qog nqaij hlav cancer thiab lwm lub cev tiv thaiv kab mob. Cov tshuaj tiv thaiv kab mob tiv thaiv PD-1, xws li nivolumab, pembrolizumab, thiab palivizumab, lossis PD-L1, xws li MEDI4736 thiab MPDL3280A ua kom cov qog nqaij hlav T-cell los tiv thaiv kev cuam tshuam ntawm PD1 thiab PD-L1 los tiv thaiv T. -cell inactivation (Curran li al. 2010). Mob raum raug mob, IgA nephropathy, thiab nephritis yog cov kab mob nyuaj nrog ntau yam subtypes, thiab muaj ntau yam ua rau tus kab mob (Cortazar li al. 2016; Mamlouk et al. 2019). Kev tshawb fawb yav dhau los tsis muaj peev xwm piav qhia txog cov txheej txheem pathological. Tab sis dab tsi yog qhov tseeb yog tias kev hloov pauv hauv lub cev tiv thaiv kab mob yuav cuam tshuam rau lwm cov ntaub so ntswg, uas yog raws li cov yam ntxwv ntawm tib neeg lub cev.

autoimmune nephritis thiab ICIs

Cov txiaj ntsig tau pom tias autoimmune nephritis thiab ntau yam tshuaj muaj feem cuam tshuam, suav nrog atezolizumab (ROR025=20.97, IC025=1.11), cemiplimab (ROR025=375.35, IC{{ 6}}.83), ipilimumab (ROR025=72.67, IC025=3.77), durvalumab (ROR025=18.27, IC025=0.72), nivolumab (ROR025=29.03, IC025=3.46) thiab pembrolizumab (ROR025=38.15, IC025=3.21). Nws tsis tau hais nyob rau hauv cov kev tshawb fawb yav dhau los. Tus kab mob autoimmune nephritis yog ib yam kab mob uas tshwm sim los ntawm kev puas tsuaj autoimmune. Cov tshuaj tau hais los saum toj no ntawm ICIs muaj feem cuam tshuam rau autoimmune nephritis. Yog li ntawd, cov neeg ua haujlwm kho mob yuav tsum tau saib xyuas lub cev ntawm cov neeg mob xws li kev siv tshuaj kho mob.

Xaus

Txoj kev tshawb no tau soj ntsuam tag nrho cov koom haum ntawm ICIs thiab muaj peev xwm nephrotoxicities los ntawm kev xyaum tiag tiag. Zuag qhia tag nrho, tsis muaj kev koom tes tseem ceeb ntawm ICIs thiab raum AEs, thaum muaj qhov sib txawv tseem ceeb ntawm AEs ntsig txog nephrotoxicity thiab atezolizumab tag nrho. Thiab cov chav kawm tshwj xeeb nephrotoxicities tau kuaj pom hauv ntau lub tswv yim ICI immunotherapy. Cov txiaj ntsig ib nrab tau ua raws li cov ntaub ntawv yav dhau los. Cov txiaj ntsig tau pom tias mob raum raug mob, IgA nephropathy, thiab nephritis qhia qhov sib txawv tseem ceeb nrog ICIs ib nrab. Nyob rau tib lub sij hawm, discoveries kuj tshwm sim. Autoimmune nephritis thiab ntau yam tshuaj muaj feem xyuam nrog, suav nrog atezolizumab, ceiplimab, ipilimumab, nivolumab, thiab pembrolizumab. Nyob rau hauv kev kho mob ntawm ICIs, yuav tsum tau saib xyuas rau cov neeg mob, tshwj xeeb tshaj yog cov txiv neej cov neeg mob thiab cov neeg laus cov neeg mob, muaj mob raum mob, nephritis, autoimmune nephritis, thiab lwm yam.nephrotoxicAEs. Related AEs ntawmnephrotoxicityraug ceeb toom los ntawm cov kws kho mob.

Kev lees paub

Txoj kev tshawb no yog nyiaj txiag los ntawm National Natural Science Foundation ntawm Tuam Tshoj (81303315) thiab Natural Science Foundation ntawm Liaoning Province (20180550342).

Cov ntaub ntawv

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