Clinicopathologic nta ntawm mob raum mob Associated nrog CDK4/6 Inhibitors

Yog xav paub ntxiv:ali.ma@wecistanche.com

Shruti Gupta: koj puas xav tau ntau tus thwjtim?¹, Tiffany Caza², Sandra M. Herrmann³, Vipulbhai C. Sakhiya⁴, thiab Kenar D. Jhaveri⁴

¹Division of Renal Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA;²Arkana Laboratories, Little Rock, Arkansas, USA;³Division ntawmNephrologythiab ntshav siab, Mayo Clinic, Rochester, Minnesota, USA; thiab⁴Donald thiab BarbaraZucker Tsev Kawm Ntawv Kho Mob ntawm Hofstra/Northwell, Great Neck, New York, USA

Taw qhia

Selective estrogen receptor inhibitors thiab aromataseinhibitors yog lub hauv paus ntawm kev kho mob rau HRþ mis cancer; Txawm li cas los xij, feem ntau metastatic hormonalreceptor-zoo, HER2 mob qog noj ntshav tau nce zuj zus thiab tau txais kev tiv thaiv endocrine kho.1 CDK4/6 inhibitor muaj cov chav kawm tshiab ntawm cov tshuaj uas overcomethis tiv thaiv los ntawm thaiv kev hloov ntawm G1 mus rau S theem ntawm lub voj voog ntawm tes, yog li tiv thaiv cell- Lub voj voog kev loj hlob thiab mob qog noj ntshav.2 Muaj 3 CDK4/6 inhibitors-palbociclib, ribociclib, thiab abemaciclib-uas tau pom zoo rau HER2 metastatic mis cancer, feem ntau ua ke nrog kev kho tshuaj hormone. Ntau qhov chaw kho mob trialshave tau qhia tiasCDK4/6 inhibitorsnce kev vam meej-dawb ciaj sia.3–6

Cov xwm txheej tshwm sim feem ntau cuam tshuam nrogCDK4/6 inhibitorsyog neutropenia, leukopenia, thiab qaug zog.3,4,6Mob raum raug mob(AKI) tsis yog ib qho teeb meem uas tau piav qhia zoo, nrog rau cov kev tshawb fawb kws tshuaj qhia cov neeg mob tuaj yeem muaj qhov nce hauv cov ntshav creatinine (SCr) yam tsis muaj kev raug mob rau lub raum tiag.7 Ntawm no, peb nthuav tawm thawj cov neeg mob biopsy-pov thawj.Mob raum mobtxuam nrogCDK4/6 inhibitorsNrog rau kev tsom mus rau kev kho mob thiab kev tshawb pom pathologic.

Nyem rau cistanche teebmeem thiab Cistanche rau mob raum raug mob

Txoj kev luv luv

Tag nrho cov txheej txheem tau pom zoo los ntawm txhua lub tsev kho mob Institutional Review Board. Cov ntaub ntawv tau txais los ntawm kev nug txog nephrology thiab pathology department ntawm 2 lub chaw kawm (Massachusetts General Hospital, Mayo Clinic, Rochester, MN) thiab Arkana Laboratories.

Cov ntaub ntawv sau

Cov ntaub ntawv ntawm lub hnub nyoog, poj niam txiv neej, haiv neeg, hom malignancy, concomitantmedications thiab chemotherapy, hom CDK4/6 inhibitor, SCr qauv ua ntej, thaum, thiab tom qab.Mob raum mob,Kev tshawb pom urinalysis, cov zis tso zis (thaum muaj), cov kev tshawb pom ntawm renalultrasound, cov ntaub ntawv qhia txog kab mob, thiab cov duab, thiab cov txiaj ntsig (xws li, xav tau kev kho lub raum hloov [RRT], cov xwm txheej tseem ceeb ntawm kev soj ntsuam zaum kawg) tau sau ib tus neeg mob los ntawm phau ntawv qhia kev tshuaj xyuas.

Nyem rauCistanche kho mob raum raug mob

Lus txhais

AKI tau txhais thiab theem raws li qhov hloov khoLub raumKab mob Improving Global Outcomes criteria as a $1.5-fold rise in SCr from baseline any time after the drug was started or the need for RRT.8 Baseline SCr was defined as the closest SCr level before CDK4/6 inhibitor initiation. If baseline SCr was unavailable, AKI was defined as a new rise in SCr to >3 mg/dl. Lub AKI tau ncaj qha ntaus nqi rau lubCDK4/6 inhibitorslos ntawm kev kho mob nephrologist, thiab tus neeg mob yuav tsum tau ua tiav araumbiopsy vim yog AKI. Renalrecovery tau txhais tias yog nadir SCr # 1.5 npaug ntawm tus nqi pib hauv 90 hnub tom qab AKI.

Kev Tshaj Tawm Txog Cov Teeb Meem Tsis Zoo Rau Raum

Tsoom Fwv Teb Chaws Tshuaj Txhaum Cai Tsis Txaus Siab Cov Txheej Txheem Tshaj Tawm tau nug rauraumadverseevents txuam nrogCDK4/6 inhibitors(palbociclib, abemaciclib, thiab ribociclib) nruab nrab ntawm 2010 thiab 2020 siv cov lus tshawb fawb hauv qab no: hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia, hypocalcemia, hypercalcemia, hyperkalemia, hypernatremia, hyperphosphatemia, proteinuria, lub raum tsis ua haujlwm, acute KI. , thiab nephritis.

Table 1. Cov yam ntxwv ntawm CDK4/6 inhibitor-associated AKI

AKI, mobraumraug mob; LE, leukocyte esterase; NA, tsis muaj; Pt, tus neeg mob; SCr, ntshav creatinine; UA, urinalysis; Teb Chaws Asmeskas, ultrasound; WBCs, cov qe ntshav dawb. aPeak SCr thaum lub sijhawm AKI rov, hauv mg/dl.bHnub ntawm CDK4/6 pib rau AKI.cAlbuminuria thaum lub sijhawm AKI, g/g.

TSEEM CEEB

Cov yam ntxwv tseem ceeb

Peb tau txheeb xyuas 6 tus neeg mob los ntawm Massachusetts General Tsev Kho Mob (n=1), Mayo Clinic (n=1), thiab ArkanaLaboratories (n=4) uas muaj AKI cuam tshuam nrog CDK4/6 inhibitor thiab tau ua tiav. araumbiopsy.Cov yam ntxwv ntawm txhua tus neeg mob muaj nyob rau hauv Cov Lus Qhia Ntxiv S1. Ntawm 6 tus neeg mob, 4 tus neeg muaj hnub nyoog tshaj 65 xyoo. Cov neeg mob feem ntau yog Dawb (4 ntawm 6).Ob tus neeg mob muaj qhov ntsuas qhov ntsuas glomerular pom<60 ml/min="" per="" 1.73="">². Txhua tus muaj kab mob metastatic thaum lub sijhawm kho nrog CDK4/6inhibitor.

Feem ntau cov mob qog nqaij hlav cancer mis yog adenocarcinoma hauv 5 ntawm 6 tus neeg mob (tus neeg mob 6 hadglioblastoma multiforme). Tsis tas li ntawd, 3 ntawm 6 tau kho nrog palbociclib, 2 tau kho nrog lub nqaj-cycling, thiab 1 tau txais ribociclib.

Concomitant Tshuaj thiab Chemotherapy

Muaj 2 tus neeg mob uas tau siv cov tshuaj proton pumpinhibitors thiab 1 tus neeg mob uas tau tshaj tawm qee zaus kev siv tshuaj tiv thaiv kab mob nonsteroidal (tus neeg mob 6) (Sab Ntxiv Table S2). Tsis tas li ntawd, 2 tus neeg mob tau txais kev kho tshuaj hormonal concomitant (piv txwv li, letrozole) thiab 2 tus neeg mob tau txais fulvestrant.

Clinical Features thaum lub sij hawm ntawm AKI

Lub sij hawm nruab nrab ntawm CDK4/6 pib rau AKI yog 278 hnub (interquartile range 183–430) (Table 1). Cov neeg mob 2,4, thiab 5 txhua tus muaj theem 3 AKI, thiab tus neeg mob 5 yuav tsum tau RRT. Qhov nruab nrab SCr thaum lub sijhawm AKI yog 2.9 (interquartile ntau 1.9–5.3). Nephrology tau sab laj nyob rau hauv txhua rooj plaub. Tsis muaj ib tus neeg mob tau hypotension li ntawm 72 teev ntawm qhov kev tshwm sim AKI.

Thaum lub sijhawm AKI, tag nrho cov neeg mob uas muaj urinalysesavailable tau dipstick zoo rau cov protein. Cov txiaj ntsig ntawm lub raum ultrasound qhia cortical echogenicity hauv 3 tus neeg mob. Tsis tas li ntawd, cov txiaj ntsig ntawm kev ua haujlwm serologic (piv txwv li, antinuclear antibody, ob-stranded DNA, antinuclear cytoplasmic antibodies, C3, C4, rheumatoidfactor, thiab serum protein electrophoresis) yog normalin rau txhua tus neeg mob.

Pathology

Cov duab sawv cev ntawmraumbiopsies yog illustrated nyob rau hauv daim duab 1. Mob tubular necrosis yog qhov mob loj tshaj plaws nyob rau hauv cov neeg mob 2 mus rau 6. Tus neeg mob 5 tau cim thiab thoob plaws tubular raug mob, tus cwj pwm los ntawm dilation thiab poob ntawm txhuam ciam teb, flattened epithelium, focaltubular rupture, thiab ntau intratubular casts nyob rau hauv themedulla. Tus neeg mob 1 tau mob tubulointerstitial nephritis uas yog neutrophil nplua nuj. Cov kab mob tso zis tau ua tiav, thiab cov txiaj ntsig tau zoo rau hom kab mob Candida.Txawm li cas los xij, cov kab mob pathology tsis pom zoo ntawm pyelonephritis; Grocott's methenamine silver stain tau ua nyob rau hauv biopsy thiab qhov tshwm sim tsis zoo rau cov kab mob fungal. Tus mob tubulointerstitialnephritis tau raug ntaus nqi rau CDK4/6 inhibitor los ntawm kev kho nephrologist.

Cistanche tuaj yeem txhim kho lub raum ua haujlwm

Kev kho mob thiab cov txiaj ntsig

CDK4/6 inhibitor raug txiav tawm hauv cov neeg mob 1 thiab 5, thiab cov koob tshuaj tau txo qis hauv cov neeg mob 4 thiab 6. Tus neeg mob 5 tau raug tso tawm tom qab RRT 6 lub hlis tom qab kev tshwm sim AKI. Tus neeg mob 1 tsis tau kho nrog corticosteroids vim nws tau hloov mus rau kev nplij siab thiab tuag. Tus neeg mob 5 kuj tau hloov mus rau kev nplij siab thiab tuag. Tus neeg mob 6 tau rov qab tsis tiav ntawm SCr mus rau ib qho nadir ntawm 1.6 kwv yees li 50 hnub tom qab qhov kev tshwm sim AKI. Tus neeg mob 4 zoo ib yam li muaj kev rov qab tsis tiav nrog nadir SCr ntawm 2.4 hauv 90 hnub ntawm qhov kev tshwm sim AKI thiab tau kis tus kab mob nrog rau kev mob siab. Cov neeg mob 2 thiab 3 muaj kev kho mob tsawg thiab cov ntaub ntawv taug qab. Tsis muaj tus neeg mob tau txais kev kho mob tiv thaiv kab mob rau qhov kev tshwm sim AKI.

Kev Qhia Txog Cov Kab Mob Rau Lub Raum Muaj Kev Nyuaj Siab

Muaj 783 cov xwm txheej phem tshaj tawm rau tag nrho 3 tus neeg sawv cev (palbociclib, abemaciclib, thiab ribociclib) (Table 2), feem ntau yog mob raum. Palbociclib muaj tus lej loj tshaj plaws ntawm cov xwm txheej tsis zoo, thiab cov no tau tshaj tawm feem ntau ntawm cov poj niam. Kev cuam tshuam metabolic tau tshaj tawm nrog tag nrho 3 tus neeg ua haujlwm, feem ntau yog hypokalemia, txawm tias hyponatremia thiab hypocalcemia kuj tau pom.

Daim duab 1. Histopathology ntawm cyclin-dependent kinase inhibitor-associated mobraumraug mob. (a) Interstitial fibrosis thiab disproportionate tubularatrophy thoob plaws hauv lub cortex, Jones methenamine silver, 100 ×, scale bar =10 hli. (b) Ib txwm glomeruli tsis muaj matrix expansion lossis proliferative hloov, periodic acid-Schiff, 200 ×, scale bar =50 mm. (c) Interstitial edema thiab mixed interstitial o, hematoxylin þ eosin, 200 ×, scale bar =50 mm. (d) Neutrophil-nplua nuj o thiab tubulorrhexis, hematoxylin þ eosin, 400 ×, scale bar =20 hli. (e) Kev mob me me lymphocytic interstitial o thiab mob mob tubular raug mob (apical cytoplasmic blebbing, epithelial cell simplification, thiab ectasia ntawm tubularprofiles), hematoxylin þ eosin, 400 ×, scale bar =20 hli. (f) Interstitial edema cais tubular profiles thiab mob tubular raug mob nrog epithelialcell simplification, reactive thiab regenerative nuclear hloov, thiab dilation, hematoxylin þ eosin, 400 ×, scale bar =20 hli.

Kev sib tham

Txawm tiasCDK4/6 inhibitorstau hloov pauv thaj chaw ntawm kev kho mob rau hormonal receptor-positiveadvanced mob qog noj ntshav mis, ntawm no peb piav qhia txog 6 tus neeg mob uas muaj biopsy-pov thawj AKI uas tau ncaj qha los ntawm CDK4/6 inhibitor. AKI muaj qhov cuam tshuam loj heev, yuav tsum tau txo koob tshuaj thiab kev txiav txim siab kho mob hauv 4 ntawm 6 tus neeg mob. Tsis tas li ntawd, raws li kev tshawb fawb los ntawm Tsoom Fwv Teb Chaws Tshuaj Tiv Thaiv Kev Tiv Thaiv Cov Txheej Txheem Tshaj Tawm Tshaj Tawm Txog Kev Tshaj Tawm, AKI tau tshaj tawm cov teeb meem ntawm CDK4/6 inhibitors, raws li kev cuam tshuam ntawm metabolic, xws li hypokalemia, hyponatremia, thiab hypocalcemia. Ntxiv Table S3summarizes yav dhau los cov ntaub ntawv thiab peb cov kev tshawb pom ntawm adverserenal txheej xwm qhia nrogCDK4/6 inhibitors.

Cov ntaub ntawv uas twb muaj lawm ntawm AKI los ntawmCDK4/6 inhibitorsnyob tsis taus. Ob peb qhov kev sim ua ntej ntawm palbociclib thiab ribociclibdid tsis piav qhia txog qhov tshwm sim ntawm AKI, qhov chaw kho mob ntawm abemaciclib tau tshaj tawm tias txog li 25 feem pua ​​​​ntawm cov neeg mob tau ntsib kev nce hauv SCr.6,9, S1, S2 Hauv vitrostudies ntawm abemaciclib tau qhia tias cov tshuaj loj thiab cov tshuaj tau pom zoo. metabolites inhibits lub raum thauj khoom xws li asorganic cation transporter-2, multidrug thiab toxinextrusion-1 (MATE-1), thiab MATE2-K,7 muaj peev xwm ua rau muaj kev thim rov qab hauv SCr yam tsis tau hloov pauv. glomerular pom tus nqi. Txawm li cas los xij, hauv peb cov koob, 3 ntawm 6 tus neeg mob tau mob hnyav 3 AKI nrog 1 xav tau RRT, thiab txhua tus ntawm 6 tus neeg mob tau kuaj pom AKI. Sib txawv "pseudo-AKI" los ntawm trueAKI tuaj yeem nyuaj. Kev ntsuas ib txhij ntawm SCr,raumiothalamate clearance, thiab / los yog kwv yees glomerular pom tus nqi raws li qib cystatin C (nrog rau qhov caveat tias qhov no yuav nce siab hauv qhov teeb meem ntawm qhov mob) yuav pab kom paub qhov txawv ntawm 2 qhov chaw. Tsis tas li ntawd, cov neeg mob uas muaj qhov tseeb AKI tej zaum yuav muaj cortical echogenicity ntawm lub raum ultrasound, txawm tias 2 ntawm cov neeg mob tau txais txiaj ntsig ntawm lub raum ultrasound.

Table 2. Lub raum tsis zoo tshwm sim cuam tshuam nrogCDK4/6 inhibitorslos ntawm Food and Drug Administration qhov kev ceeb toom tsis zoo tshwm sim

Lub raum raug mob muaj proteinuria, lub raum tsis ua hauj lwm mob, mobraumraug mob, nce creatinine, hyperleptinemia, thiab nephritis.Muaj kev txwv rau Food and Drug Administration adverse event reporting system. Cov xwm txheej tau tshaj tawm los ntawm cov kws kho mob thiab / lossis cov neeg mob thiab yog li ntawd yuav raug tshaj tawm kev tsis ncaj ncees. Tsis tas li ntawd, tsis yog txhua tus pej xeem thiab cov ntaub ntawv muaj kev sib haum xeeb yog muaj los pab txheeb xyuas seb puas muaj lwm yam nephrotoxic txaus ntshai tshwm sim (piv txwv li, siv cov tshuaj tiv thaiv kab mob uas tsis yog steroidal, keeb kwm ntawm ntshav siab lossis ntshav qab zib mellitus, paub txog mob ntev.raumkab mob, kev siv tsis ntev los no ntawm tus neeg sawv cev sib txawv, thiab kev siv tshuaj khomob tsis ntev los no nrog nephrotoxicpotential). Nws tsis tuaj yeem txiav txim siab seb qhov xwm txheej puas yog tshwm sim los ntawm cov tshuaj uas tsis yog cov kab mob hauv qab, cov tshuaj sib xyaw ua ke, lossis cov kws kho mob yav dhau los tau muab rau cov neeg mob no. Thaum kawg, tsis muaj tus lej ntawm cov neeg mob uas tau txais cov neeg ua haujlwm no, thiab yog li ntawd, qhov feem pua ​​​​ntawm cov txiaj ntsig tsis zoo yuav suav tsis tau.

Lub sijhawm pib ntawm AKI tau txuas ntxiv mus rau kev siv ntawmCDK4/6 inhibitors. Nws yog, yog li ntawd, muaj peev xwm hais tias muaj "thib ob hit" uas yog predisposed rau kev loj hlob ntawm AKI; Txawm li cas los xij, tsis muaj lwm yam tshwm sim tshwm sim nyob rau hauv ib qho ntawm cov xwm txheej, ib sab ntawm CDK4/6 inhibitor. Tsis tas li ntawd, muaj lwm yam kev kho mob cancer (xws li, immunotherapy, vascular endothelialgrowth factor inhibitors) nyob rau hauv uas muaj feem ntau ib tug lagtime ntawm kev pib kho thiab pib ntawm AKI.S3-S6.

Qhov kev tshawb nrhiav histopathologic feem ntau ntawm biopsywas mob tubular necrosis, thaum tsis muaj lwm txoj kev piav qhia, xws li hypotension, tsis ntev los no ivcontrast siv, lossis sepsis. Cov txheej txheem tom qab tus mob tubular necrosis tsis meej, tab sis nws yuav yog vim muaj kev cuam tshuam los ntawm lub hom phiaj ntawmCDK4/6 inhibitors, nrog tubularcell puas tsuaj los ntawm inhibition ntawm cell-cycle progression. Tus neeg mob 1 muaj tus mob tubulointerstitial nephritis, uas qhia tau hais tias tseem muaj peev xwm ua rau cov tshuaj tiv thaiv hypersensitivity rau cov tshuaj no. Paradoxically, muaj cov ntaub ntawv preclinical qhia tias CDK4/6 inhibitors yuav muaj cov nyhuv nephroprotective. Inductionof G0/G1 lub voj voog raug ntes los ntawm CDK4/6 inhibition tau pom los tiv thaiv cov tubular epithelial cell tom qab raug rau nephrotoxins, xws li cisplatin, etoposide, thiab antimycin A.S7, S8 Nws yog, yog li ntawd, lub sijhawm ntawm Kev cuam tshuam rau CDK4/6 inhibition teeb meem, uas yog qhov cuam tshuam rau lub voj voog ntawm tes inhibitors tuaj yeem tiv thaiv, tab sis ntev ntev tuaj yeem ua rau AKI. Tsis tas li ntawd, hauv kev mob qog noj ntshav siab heev, kev hloov pauv tuaj yeem sib sau, nrog kev kho tsis zoo uas tuaj yeem ua rau cov tshuaj tiv thaiv kab mob ua rau muaj zog cytokine ntau lawm thiab / lossis leukocyte infiltration.

Kev tshawb fawb ntawm Tsoom Fwv Teb Chaws Tshuaj Txhaum Cai AdverseEvent Reporting System database tau qhia tias, ntxiv rau AKI, metabolic cuam tshuam xws li hypokalemia, hyponatremia, thiab hypocalcemia tuaj yeem tshwm sim thaum CDK4/6 inhibitors. Hyponatremia tau tshaj tawm nrog ribociclib thiab abemaciclib, S9, S10, thiab qib 2 hypokalemia tau tshaj tawm hauv 20.8 feem pua ​​​​ntawm cov neeg mob noj abemaciclib.S10 Muab hais tiasCDK4/6 inhibitorsCov cheeb tsam uas cuam tshuam nrog QT ncua ntev, tshwj xeeb tshaj yog ribociclib, S11 nws yog ib qho tseem ceeb uas cov neeg mob tau txais kev saib xyuas ntawm cov ntshav electrolytes ua ntej kho thiab nrog txhua lub voj voog.

Txawm hais tias peb txoj kev tshawb fawb yog thawj zaug piav qhia txog kev kho mob thiab histopathology cuam tshuam nrogCDK4/6 inhibitors, muaj kev txwv. Peb muaj cov ntaub ntawv tsis tiav rau 2 tus neeg mob. Tsis tas li ntawd, peb tsis tuaj yeem tshem tawm qhov ua tau tias qhov kev tshwm sim AKI tshwm sim los ntawm cov tshuaj sib xyaw ua ke es tsis yog CDK4/6 inhibitor. Kev siv Tsoom Fwv Teb Chaws Tshuaj Txhaum Cai AdverseEvent Reporting System database muaj nws cov kev txwv ib yam; nws suav nrog txhua tus neeg muab kev pabcuam thiab tus neeg mob-kev tshaj tawm cov xwm txheej tsis zoo thiab yog li ntawd yuav tsis ntes tseebAKI. Tsis tas li ntawd, cov ntaub ntawv pej xeem thiab kev sib koom ua ke tsis tau yooj yim los txiav txim seb puas muaj lwm yam kev pheej hmoo nephrotoxic tuaj yeem ua rau.

Txawm tiasCDK4/6 inhibitorstej zaum yuav ua rau ib tug reversiblerise nyob rau hauv SCr yam tsis tau hloov lub glomerularfiltration tus nqi nyob rau hauv tej rooj plaub, peb tam sim no qhia tau hais tias lawv tuaj yeem ua rau muaj tseeb raum tubular toxicity. Muab qhov kev txheeb ze tshiab ntawm CDK4/6 inhibitors, muaj ntau yam uas tseem tsis tau paub txog ntawm cov txheej txheem tom qab AKIassociated nrog cov tshuaj no. Loj dua, cov kev tshawb fawb yav tom ntej yog xav tau kom nkag siab thiab ua tus yam ntxwv ntawm qhov xwm txheej thiab muaj feem cuam tshuam rau AKI hauv cov neeg mob tau txais CDK4 / 6 inhibitors.

Cistanche tuaj yeem tiv thaiv kab mob raum

Qhia tawm

KDJ tshaj tawm ua tus kws pab tswv yim rau Astex Pharmaceuticals, Natera, GlaxoSmithKline, ChemoCentryx, thiab Chinook; ua tus them nyiaj rau uptodate.com; tau txais kev qhuas los ntawm International Society rau Neurochemistry thiab American Society for Neurochemistry; thiab ua tus Thawj Saib Xyuas Haujlwm rau American Society for NeurochemistryLub raumXov xwm, ib ntu editor rau Onco nephrology rau Nephrology Dialysis Transplantation, thiab nyob rau hauv lub editorial board rau Phau ntawv Journal of Onconephrology, KI, Clinical Journal of the American Society of Nephrology, American Journal of Kidney Diseases, andClinicalLub raumPhau ntawv. Tag nrho lwm tus kws sau ntawv tshaj tawm tsis muaj kev sib tw txaus siab. KDJ thiab SG yog tus thawj coj ntawm American Society of Onconephrology.

TXOJ CAI

SG tau tshaj tawm tau txais nyiaj tshawb fawb los ntawm GE Healthcare thiab BTG International.

SMH tau txais nyiaj los ntawm National Institutes of Health, National Institute of Diabetes thiab Digestive thiabLub raumKab mob (K08 DK118120).

SUPPLEMENTARY KHOOM

Cov ntaub ntawv ntxiv (PDF)

Tab S1. Cov yam ntxwv ntawm lub hauv paus.

Tab S2. Cov tshuaj thaum lub sijhawm CDK4/6 inhibitor-associated AKI.

Tab S3. Summary of renal adverse events related withCDK4/6 inhibitors.

Supplementary References.STROBE Nqe Lus Qhia (PDF).