Kev tshuaj xyuas ntawm lub raum muaj nuj nqi thiab kev pheej hmoo mob qog noj ntshav siv Creatinine thiab Cystatin C hauv Kev Kawm Cohort

Hu rau: emily.li@wecistanche.com

Jennifer S. Lees, et al

Abstract:

Keeb kwm:Peb tau tshuaj xyuas seb puas muaj kev pheej hmoo ntawm kev mob qog noj ntshav thiab kev tuag muaj feem cuam tshuam nrograummuaj nuj nqithiab albuminuria thiab seb qhov kev pheej hmoo puas raug txheeb xyuas tau yooj yim dua thaum lub raum ua haujlwm tau kwv yees siv cystatin C.

Txoj kev:Cov neeg koom nrog yog los ntawm UK Biobank (kev nrhiav neeg ua haujlwm ntev 2007-2010), tsis suav nrog cov neeg mob qog noj ntshav ua ntej. Kwv yees glomerular filtration rate (ml/min/1.73m2) yog xam siv creatinine (eGFRcr), cystatin C (eGFRcys) thiab creatinine-cystatin C (eGFRcr-cys). Cox proportional hazards model tested Association of eGFR, urinary albumin: creatinine ratio (ACR), thiab mob qog noj ntshav thiab tuag.

Kev tshawb pom:In 431,263 participants over median follow-up of 11.3 (IQR 10.6-12.0) years, there were 41,745incident cancers and 11,764 cancer deaths. eGFRcys was most strongly associated with cancer incidence anddeath (HR 1.04 (95% CI 1.03- 1.04) and 1.06 (1.05-1.07) per 10 ml/min/1.73m2 decline, respectively). eGFRcrwas not associated with either outcome (incidence: HR 1.00 (1.00-1.01); death: HR 0.99 (0.98-1.01) per10 ml/min/1.73m2 decline). Relative to eGFRcys>90 o ua<3 mg/mmol,="" egfrcys60-89="" (hr="" 1.04="" (95%="" ci1.02-1.07)),=""><60 (hr="" 1.19="" (1.14-1.24))="" and="" uacr="">3 mg/mmol (HR 1.09 (1.06-1.12)) yog txuam nrog kev pheej hmoo ntawm mob qog noj ntshav. eGFRcys60-89 (HR 1.15 (1.10-1.21)); eGFRcys<60 (hr="" 1.48(1.38-1.59))="" and="" uacr="">3 mg / mmol (HR 1.17 (1.11 1.24)) yog txuam nrog kev mob qog noj ntshav.

Txhais lus:Kev pheej hmoo ntau dhau ntawm kev mob qog noj ntshav thiab mob qog noj ntshav tau yooj yim dua thaum ntxovmob ntevraum kab moblos ntawm eGFRcys dua los ntawm kev ntsuas tam sim no. Kev sib raug zoo ntawmraum muaj nuj nqi, ACR, thiab kev tuag mob qog noj ntshav, tshwj xeeb, yog hais txog thiab lav kev tshuaj xyuas ntxiv.

Nyiaj txiag:Chief Scientist Office; ANID Becas Chile; Pawg Neeg Saib Xyuas Kev Kho Mob; British Medical Association; British Heart Foundation.

Nyem qhov no kom tau txais cov ntaub ntawv ntxiv txog Cistanche

1. Taw qhia

Mob qog noj ntshav muaj ntau dua rau cov neeg uas muaj mob ntev heevraum kab mob(CKD) thiab/los yograumua tsis tiavxav tauraumKev hloov kho (KRT) [1]. Nws tsis paub meej thaum muaj kev pheej hmoo mob qog noj ntshav siab dua pib cuam tshuam nrog CKD txoj kev ua neej.

Raws liraum muaj nuj nqi, txhais los ntawm kwv yees glomerular filtration rate (eGFR), poob qis dua 60 ml / min / 1.73m2, muaj qhov piav qhia tau zoo txog kev pheej hmoo ntawm cov kab mob plawv [2] tab sis qhov no tsis tshua meej rau kev pheej hmoo mob qog noj ntshav. Ntau qhov kev tshawb fawb tau pom tias muaj kev sib koom ua ke ntawm cov cim ntawm CKD (hauv qab eGFR 60 ml / min / 1.73m2, ib leeg lossis ua ke nrog albuminuria) uas muaj kev pheej hmoo ntau dua ntawm kev tshwm sim thiab kev tuag ntawm tag nrho [3 6] thiab qhov chaw tshwj xeeb tso zis [3 ,7 9], ntsws[3] thiab hematological [10] mob qog noj ntshav. Txawm li cas los xij, cov ntaub ntawv tsis sib xws [1,4,7,11], tej zaum vim tias feem ntau cov kev tshawb fawb tau soj ntsuam cov koom haum nrog eGFR xam los ntawm cov ntshav creatinine [1,3,5,7 12], uas tau pom tias muaj U-shaped. kev sib raug zoo nrog mob qog noj ntshav [12]. Independent ntawm cov txiaj ntsig ntawm eGFR thiab ntshav qab zib, albuminuria tau cuam tshuam nrog kev pheej hmoo siab ntawm mob qog noj ntshav tag nrho [4,5,13], thiab tshwj xeeb hauv qhov chaw tshwj xeeb ntawm lub ntsws [4,5,13,14] thiab tso zis [4, 14] mob qog noj ntshav.

Piv nrog rau creatinine, cystatin C tsis cuam tshuam los ntawm cov leeg nqaij, hnub nyoog, haiv neeg, thiab poj niam txiv neej thiab, ua ke hauv kev sib npaug nrog creatinine, muaj peev xwm kwv yees qhov tseeb dua.raummuaj nuj nqicreatinine ib leeg [15] Rau cov kab mob plawv, kev pheej hmoo ntawm kev kwv yees hauv CKD yog txhim kho thaum cystatin C siv los kwv yeesraummuaj nuj nqi[2, 16]. Qhov no tsis tau tshawb pom yav dhau los rau cov txiaj ntsig mob qog noj ntshav.

UK Biobank muaj ntau dua 500, 000 cov neeg koom thiab ze li 5 lab tus neeg koom nrog-xyoo ntawm kev soj ntsuam. Siv UK Biobank, peb tau sim qhov kev xav tias CKD cov cim (eGFR thiab albuminuria) cuam tshuam nrog kev pheej hmoo ntawm kev mob qog noj ntshav tag nrho thiab qhov chaw tshwj xeeb, mob qog noj ntshav thiab cov kev pheej hmoo no tsis muaj kev paub txog kev pheej hmoo rau mob qog noj ntshav. Tsis tas li ntawd, peb xav tias qhov ntawdraummuaj nuj nqiKev kwv yees suav nrog cystatin C, piv nrog creatinine ib leeg, yuav muaj kev cuam tshuam ntau dua nrog kev mob qog noj ntshav thiab cov txiaj ntsig mob qog noj ntshav.

2. Cov txheej txheem

2.1. Cov neeg koom nrog thiab sau cov ntaub ntawv hauv paus

Cov ntaub ntawv tau sau los ntawm 502,536 tus neeg koom nrog UK Biobank los ntawm 2007 txog 2010 thoob plaws cov chaw soj ntsuam hauv UK raws li tau piav qhia yav dhau los [17,18]. Txhua tus neeg koom nrog tau sau ntawv tso cai rau qhov pib phenotyping thiab ua raws (nrog cov ntaub ntawv txuas mus rau cov ntaub ntawv kho mob hauv hluav taws xob) txog thaum tuag lossis tshem tawm qhov kev tso cai. Lub UK Biobank tau txais kev pom zoo los ntawm North West Multi-Centre Research Ethics Committee (REC siv 11/NW/03/820). Txoj kev tshawb no tau ua nyob rau hauv UK Biobank qhov project code 7155 thiab tshaj tawm raws li STROBE cov hauv paus ntsiab lus.

Cov neeg koom nrog biochemistry muaj nyob rau hauv lub hauv paus thiab leej twg tau txais kev tso cai tsis tu ncua rau kev soj ntsuam tau suav nrog. Cov neeg koom nrog raug cais tawm yog tias lawv muaj kev kuaj mob ua ntej ntawm kev mob qog noj ntshav ntawm thawj UK Biobank kev ntsuam xyuas lossis yog tias lawv tsis muaj qhov ntsuas biochemistry hauv paus.

Biochemical sampling processes have been described and validated previously [19-22]. In brief, serum and spot urine samples were collected and analyzed at a central laboratory. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations using serum creatinine (eGFRcr), cystatin C (eGFRcys), or a combination of creatinine and cystatin C (eGFRcr-cys) [15]. CKD stage was categorised according to the Kidney Disease: Improving Global Outcomes standard classification [23]: -90 (Reference: eGFR-90), >60-89 (eGFR60- 89), >30 60, >1530-, 15 ml / min / 1.73m2 . Cov neeg koom nrog eGFR<60 ml/min/1.73m2="" were="" combined="" into="" one="" group="" for="" analysis=""><60) due="" to="" small="" numbers="" with="" egfr=""><30 ml/min/1.73m2="" .="" albuminuria="" was="" calculated="" as="" urine="" albumin:="" creatinine="" ratio="" (uacr)="" and="" categorized="" as=""><3 mg/mmol="" (normal)="" and=""
="" 3="" mg/mmol="" (abnormal)="" owing="" to="" small="" numbers="" of="" participants="" with="" uacr="">30 mg / mmol.

Hnub nyoog raug xam los ntawm hnub yug thiab kev ntsuam xyuas hauv paus. Lub cev qhov Performance index (BMI) yog xam los ntawm qhov hnyav (kg) / qhov siab (m) 2. Haiv neeg, kev haus luam yeeb, thiab cawv keeb kwm tau qhia tus kheej. Townsend deprivation index [24] tau suav los ntawm cov chaw nyob hauv tsev.

Kev ua raws li tau sau tseg los ntawm thawj UK Biobank hnub soj ntsuam mus txog rau hnub ntawm cov txiaj ntsig cuam tshuam. Qhov kawg ntawm kev taug qab tau txhais tias yog hnub tuag sai dua, thawj qhov kev kuaj mob qog noj ntshav, lossis qhov kawg ntawm kev sau cov ntaub ntawv (Lub Rau Hli 1, 2020 rau kev tuag (cov chaw hu xov tooj), 1st Lub Rau Hli 2020 rau kev nkag mus hauv tsev kho mob hauv tebchaws Askiv; 31st Lub Peb Hlis 2017 rau tsev kho mob nkag hauv Scotland thiab Wales).

2.2. Cov txiaj ntsig ntawm kev txaus siab

(i) Cov xwm txheej mob qog noj ntshav: los ntawm kev sib txuas mus rau kev sau npe mob qog noj ntshav hauv tebchaws, kev kuaj mob qog noj ntshav uas cuam tshuam tau siv tam sim no ICD10 codeclassififications thiab muab faib ua pawg raws li hauv qab no: mob qog noj ntshav tag nrho (C00-C97, tsis suav nrog cov qog nqaij hlav uas tsis yog melanoma (D44)), digestive kab mob (oesophagus, plab, hnyuv, hnyuv, hnyuv, rectosigmoid, rectum thiab qhov quav: C1521), lub taub hau thiab caj dab mob qog noj ntshav (di ncauj, nplaig, pos hniav, qhov ncauj, palate, parotid, qog qaub ncaug, tonsil, oropharynx, naso pharynx, sinus, hypopharynx, lwm qhov ncauj; C00- 14), ua pa (trachea, bronchus thiab ntsws: C33-34), plab hnyuv (lub siab, gallbladder, biliary tract, pancreas, lwm yam digestive: C2225), haematological cancer ( lymphoma, leukemia, ntau ple myeloma, kab mob immunoproliferative thiab lwm yam malignanthaematological mob (C8196), raum mob qog noj ntshav (lub raum, lub raum pelvis, ureter, zais zis: C6467), poj niam qog noj ntshav (mis, qhov chaw mos, qhov chaw mos, ncauj tsev menyuam: C6467) 50- 56), txiv neej mob qog noj ntshav (noov, prostate, testis: C60-62) thiab malignant melanoma (C43).

(ii) Kev tuag mob cancer: ua rau thiab hnub tuag tau txais los ntawm daim ntawv pov thawj kev tuag (National Health Service Information Center for England thiab Wales lossis NHS Central Register for Scotland).

2.3. Kev txheeb cais

Rau txhua qhov kev ntsuam xyuas, cov txiaj ntsig tau txais rau eGFR pawg siv eGFRcr, eGFRcys, eGFRcr-cys. Kev faib tawm ntawm cov teeb meem hauv paus thiab cov ntaub ntawv ploj lawm tau tshwm sim tag nrho thiab los ntawm pawg eGFR.

Cov hloov pauv tsis tu ncua tau tshwm sim raws li qhov nruab nrab (tus qauv sib txawv; SD) lossis nruab nrab (interquartile ntau) yog tias tsis yog ib txwm faib. Ib txwm raug kuaj los ntawm kev tshuaj xyuas qhov pom ntawm histograms thiab cov phiaj xwm ntau ntxiv rau tag nrho pawg thiab thoob plaws eGFR pawg. Categorical txaus ntshai yam tshwm sim tau tshwm sim raws li tus lej (feem pua). Kev ntsuam xyuas rau cov kev sib txawv ntawm txhua pawg tau soj ntsuam los ntawm ANOVA, chi-squared tests, lossis Wilcoxon rank-sum tests raws li qhov tsim nyog.

Cov ntaub ntawv ploj lawm tau muab ntau imputed los ntawm chained sib npaug, siv qhov nruab nrab ntawm tsib cais imputed datasets, piv txwv li cov ntaub ntawv uas ploj lawm ntawm random thiab hais tias qhov feem pua ​​ntawm cov ntaub ntawv uas ploj lawm.<>

Cov kab mob qog noj ntshav tau piav qhia nyob rau hauv tag nrho pawg ntawm 100, 000 cov neeg koom thiab ib 100, 000 tus neeg-xyoo. Tsis tas li ntawd, kev mob qog noj ntshav los ntawm cov kab mob qog noj ntshav kuj tau piav qhia siv tib txoj hauv kev rau 100, 000 cov neeg koom thiab ib 100, 000 tus neeg-xyoo.

Txhawm rau soj ntsuam kev sib raug zoo ntawm txhua qhov kev ntsuas eGFR thiab kev mob qog noj ntshav thiab mob qog noj ntshav (tag nrho), qhov raug nplua splines ntawm eGFRagainst txaus ntshai piv ntawm txhua qhov txiaj ntsig tau raug npaj, tom qab hloov kho hnub nyoog, poj niam txiv neej, kev haus luam yeeb thiab cawv keeb kwm, BMI, haiv neeg, deprivation Performance index, C -reactive protein, uACR, systolic thiab diastolic ntshav siab, tag nrho thiab tsawg-density lipoprotein (LDL) cov roj cholesterol, siv cov tshuaj tiv thaiv kab mob siab, siv cov tshuaj txo cov roj cholesterol, ntshav siab, ntshav qab zib, thiab kab mob plawv. eGFR 90 ml / min / 1.73m2 tau suav tias yog tus nqi siv rau txhua qhov tshwm sim.

Cox cov qauv kev phom sij tau tsim los ntsuas kev sib koom ua ke ntawm eGFR kev ntsuas thiab kev pheej hmoo ntawm kev mob qog noj ntshav (tag nrho thiab los ntawm subtype) thiab mob qog noj ntshav (tag nrho thiab los ntawm subtype) los ntawm 10 ml / min / 1.73m2 txo hauv eGFR, los ntawm ib qho kev sib txawv ntawm kev txo qis. hauv eGFR, thiab hla eGFR pawg (eGFR 90, eGFR60 89, eGFR<60). similar="" models="" were="" conducted="" to="" assess="" the="" effect="" of="" uacr="" on="" cancer="" incidence="" and="" death="" (overall="" and="" by="" subtype)in="" those="" with="" uacr=""><3 versus=""
="" 3="" mg/mmol.="" proportional="" hazard="" assumptions="" were="" checked="" by="" plotting="" schoenfeld="" residuals.="" cox="" models="" have="" adjusted="" for="" known="" risk="" factors="" for="" cancer="" development="" above.="" models="" to="" assess="" the="" impact="" of="" the="" uacr="" category="" were="" adjusted="" for="" egfrcys.="" evidence="" of="" multiplicative="" interaction="" effects="" was="" sought="" between="" age,="" sex,="" egfr,="" uacr,="" and="" type="" 2="" diabetes="" for="" all="" outcomes="" using="" all="" egfr="" measures.="" to="" attenuate="" the="" possibility="" of="" any="" observed="" associations="" between="" egfr="" and="" cancer="" outcomes="" being="" linked="" to="" reverse="" causality,="" we="" conducted="" exploratory="" analyses="" for="" cancer="" incidence="" and="" cancer="" death="" overall:="" (i)="" excluding="" participants="" who="" developed="" multiple="" myeloma="" and="" renal="" tract="" cancers;="" (ii)="" 1-year="" landmark="" analysis,="" excluding="" participants="" who="" developed="" cancer="" or="" died="" within="" 1="" year="" of="" enrolment.="" all="" survival="" models="" were="" censored="" for="" the="" competing="" risk="" of="" non-cancer="">

Tus qauv fifit ntawm Cox proportional txaus ntshai qauv los kwv yees mob qog noj ntshav thiab tuag (tag nrho thiab los ntawm subtype) tau soj ntsuam los ntawm C-statistics nrog ntxiv ntawm txhua qhov kev ntsuas eGFR raws li saum toj no, Akaike thiab Bayesian Cov Ntaub Ntawv Txheej Txheem (AIC thiab BIC raws li; qhov tseem ceeb ntawm kev ntsuas los ntawm kev ntsuas- kev muaj feem cuam tshuam)

Tus nqi nce qib (RAP): lub sijhawm uas qhov kev pheej hmoo siab dua piv rau 1 xyoos ntawm kev laus) tau kwv yees los ntawm kev rov qab coefficients (b) hauv cov qauv Cox uas tau hloov pauv tag nrho cov kev phom sij uas siv cov kev piav qhia yav dhau los [25]: RAP { {3}} bE/bA, qhov twg bE sawv cev rau qhov hloov kho coefficient ntawm qhov sib txawv ntawm qhov sib txawv, thiab bA sawv cev rau qhov regression coefficient rau hnub nyoog. Kev ntseeg siab tau kwv yees li hauv qab no [25]: bE/bA § 1.96 xvar(bE/bA). Rau kev ntsuas RAP, BMI thiab qhov ntsuas qhov tsis txaus ntseeg tau raug ntsuas raws li qhov cuam tshuam ntawm 5-unit increment.

Kev tshuaj xyuas tau ua los ntawm kev siv tidyverse, zaum kawg haum, ggplot2, Hmisc, nephro, ciaj sia taus, paub tseeb miner, thiab rooj ib pob rau R statistical software (version 4.0.3) [26]

3. Lub luag haujlwm ntawm cov nyiaj txiag

JSL tau txais nyiaj los ntawm Tus Thawj Saib Xyuas Kev Tshawb Fawb (Scotland) PostdoctoralLectureship Scheme (PCL/20/10). SP-S. tau txais kev txhawb nqa nyiaj txiag

los ntawm Chilean Government rau ua lawv Ph.D. (ANID-Becas Chile). MKS tau txais nyiaj los ntawm Medical Research Council Clinical ResearchTraining Fellowship (MR/V001671/1). BDJ lub sijhawm yog ib feem nyiaj los ntawm Dawkins thiab Strutt cov nyiaj pab tshawb fawb los ntawm British Medical Association. NS tau txais kev txhawb nqa los ntawm British Heart Foundation CenterResearch Excellence Award (RE/18/6/34217).

4. Cov txiaj ntsig

Muaj 502,493 tus neeg koom nrog muaj nyob rau hauv tag nrho cov ntaub ntawv: 33,484 muaj cov ntaub ntawv biochemical uas ploj lawm thiab 37,746 tau kuaj mob qog noj ntshav ntawm lub hauv paus: 431,263 tus neeg koom tau suav nrog hauv kev tshuaj xyuas. Tshaj li kev soj ntsuam nruab nrab ntawm 11.3 (IQR 10.6 12.0) xyoo, muaj 41,745 tus mob qog noj ntshav tshiab, 23,525 tus neeg tuag los ntawm ib qho laj thawj uas 11,674 yog mob qog noj ntshav.

4.1. Kev faib tawm ntawm cov kev pheej hmoo hauv paus raws li eGFR pawg

Cov ntaub ntawv hauv paus los ntawm CKD theem tuaj yeem pom hauv Table 1 (eGFRcys), Cov Ntaub Ntawv Ntxiv 1 (eGFRcr) thiab 2 (eGFRcr-cys). Zuag qhia tag nrho, 53.4 feem pua ​​​​yog poj niam, qhov nruab nrab hnub nyoog tag nrho yog 57. 2.0% South Asian thiab 1.6% Dub). Nrog rau kev poob qis ntawm eGFR, cov teeb meem cardiometabolic pheej hmoo yuav nce ntxiv: piv rau pawg neeg siv, cov neeg koom nrog CKD G3- 5 yog laus dua (qhov nruab nrab hnub nyoog 64 (IQR 61 67) piv rau 52 (IQR 46 59) xyoo, p<0.001), with="" higher="" bmi="" (29.9="" (iqr="" 26.6-34.1)="" versus="" 25.7="" (iqr="" 23.4-="" 28.5)="" kg/m2,=""><0.001) and="" systolic="" blood="" pressure="" (142="" (sd="" 20)="" versus="" 135="" (sd="" 18)="" mmhg,=""><0.001). participants="" with=""><60 had="" a="" greater="" burden="" of="" cardiometabolic="" comorbidity="" at="" baseline="" compared="" to="" the="" reference="" group="" (hypertension="" 58.1="" versus="" 18.3%,=""><0.001; type="" 2="" diabetes="" 14.9="" versus="" 3.2%,=""><0.001; cardiovascular="" disease="" 20.6="" versus="" 3.6%,=""><>

4.2. Cov xwm txheej mob qog noj ntshav los ntawm qeb eGFR

Cov xwm txheej mob qog noj ntshav thiab qhov tshwm sim ntawm 100, 000 cov neeg koom thiab ib 100, 000 tus neeg-xyoo tau nthuav tawm tag nrho, los ntawm cov kab mob qog noj ntshav, thiab los ntawm eGFR pawg hauv Cov Lus Ntxiv 3 (eGFRcys), 4 (eGFRcr) thiab 5 (eGFRcr-cys). Thoob plaws tag nrho peb qhov kev ntsuas, tus nqi ntawm kev mob qog noj ntshav tag nrho thiab thoob plaws cov kab mob qog noj ntshav tau nce ntxiv nrog kev txo qis hauv eGFR. Qhov no tau tshaj tawm rau eGFRcys thiab eGFRcr-cys.

4.3. Kev tsom xam ciaj sia

The risk of cancer incidence and cancer death are displayed graphically across the spectrum of eGFRcr, eGFRcys, and eGFRcr-cys. The relationship between eGFR and both cancer outcomes was largely linear and negative below ~90 ml/min/1.73m2 for eGFRcys and eGFRcr-cys, and below ~75 ml/min/1.73m2 for eGFRcr, suggesting that eGFRcys and eGFRcr-cys can detect the heightened risk of cancer at an earlier stage. However, there was a J-shaped relationship for eGFRcr and eGFRcr-cys, with an elevated risk of cancer incidence and death >90 ml / min / 1.73 m2. Qhov no tau tshaj tawm rau eGFRcr. Rau txhua qhov kev txo qis hauv eGFR los ntawm 10 ml / min / 1.73m2 lossis los ntawm ib qho kev sib txawv ntawm tus qauv, muaj kev sib raug zoo ntawm kev mob qog noj ntshav thiab kev tuag tag nrho nrog eGFRcys dua li nrog eGFRcr lossis eGFRcr-cys (Table 2). Kev nce uACR tau zoo cuam tshuam nrog kev pheej hmoo ntawm ob qho kev mob qog noj ntshav, toj siab ntawm uACR ~ 90 mg / mmol rau kev mob qog noj ntshav thiab ~ 80 mg / mmol rau mob qog noj ntshav.

4.3.1. Cancer tshwm sim-tag nrho

Ntawm kev txheeb xyuas ntau yam sib txawv, nce hnub nyoog, txiv neej poj niam txiv neej, siab dua BMI, C-reactive protein, haus luam yeeb thiab cawv keeb kwm, haiv neeg, nce deprivation, tag nrho thiab LDL cholesterol, txo cov roj cholesterol thiab tshuaj tiv thaiv kab mob, thiab keeb kwm ntawm hom 2 mob ntshav qab zib yog tag nrho ntawm nws tus kheej cuam tshuam. nrog kev pheej hmoo ntau dua ntawm kev mob qog noj ntshav (p<0.05 for="">

Tom qab kev hloov pauv ntau yam, muaj qhov me me tab sis pom tau tias muaj mob qog noj ntshav hauv cov neeg muaj eGFRcys60- 89 (HR 1.04(95 feem pua ​​​​CI 1.02-1.07), p<0.001) and="" a="" higher="" increase="" in="" risk="" in="" people="" with=""><60 (hr="" 1.19="" (1.14
="" 1.24),=""><0.001). this="" increase="" in="" risk="" was="" not="" detected="" by="" egfrcr.="" uacr-3="" mg/mmol="" was="" independently="" associated="" with="" an="" increased="" risk="" of="" cancer="" incidence="" (hr="" 1.09(1.06
="" 1.12),=""><>

4.3.2. Cancer tuag-tag nrho

Ua kom muaj hnub nyoog, txiv neej pw, siab BMI, C-reactive protein, haus luam yeeb thiab cawv keeb kwm, haiv neeg, nce deprivation, uACR, C-reactive protein, systolic ntshav siab, tshuaj rau cov cholesterol thiab ntshav siab, tag nrho thiab LDL cholesterol, thiab keeb kwm ntawm Hom 2 mob ntshav qab zib mellitus thiab kab mob plawv yog tag nrho ntawm nws tus kheej cuam tshuam nrog kev pheej hmoo siab ntawm kev tuag qog noj ntshav (p<0.05 for="">

Tom qab hloov kho, muaj kev mob qog noj ntshav nce nruab nrab hauv cov neeg uas muaj eGFRcys60- 89 (HR 1.15 (1.10- 1.21), p<0.001) and="" a="" more="" pronounced="" increase="" in="" risk="" in="" people="" with=""><60 (hr1.48="" (1.38
="" 1.59),=""><0.001). this="" increase="" in="" risk="" was="" not="" detected="" byegfrcr.="" uacr
="" 3="" mg/mmol="" was="" independently="" associated="" with="" an="" increased="" risk="" of="" cancer="" death="" (hr="" 1.17="" (1.11-1.24),=""><>

Muaj kev sib txuam sib luag ntawm lub hnub nyoog thiab poj niam txiv neej rau txhua qhov kev ntsuas eGFR nrog rau ob qho tib si mob qog noj ntshav thiab mob qog noj ntshav (p<0.001), with="" older="" men="" demonstrating="" the="" highest="" increase="" in="" cancer="" risk.="" statistical="" interactions="" between="" egfr="" and="" uacr,="" type="" 2="" diabetes,="" age,="" and="" sex="" were="" variable="" according="" to="" the="" egfr="" measure="" and="" cancer="" outcome="" (supplementary="" table="" 6).="" exploratory="" analyses="" (tables="" 3="" and="" 4)="" suggest="" that=""><60 may="" be="" more="" strongly="" associated="" with="" cancer="" outcomes="" in="" those="" without="" type="" 2="" diabetes="" (incidence:="" hr="" 1.20="" (1.14-1.25)="" versus="" 1.14="" (1.01-1.30);="" death:="" 1.53="" (1.41-1.65)="" versus="" 1.28="" (1.04-1.57)).="" uacr="" -="" 3="" mg/mmol="" may="" be="" more="" strongly="" associated="" with="" cancer="" death="" in="" younger="" compared="" with="" older="" participants="" (table="" 4).="" similar="" associations="" between="" egfr="" and="" risk="" of="" cancer="" incidence="" were="" observed="" between="" younger="" men="" and="" women="" (table="" 4).=""><60 may="" be="" associated="" with="" a="" higher="" incidence="" of="" cancer="" death="" in="" younger="" compared="" with="" older="" women="" (hr="" 1.49="" (1.271.75)="" versus="" hr="" 1.34="" (1.12-1.60);="" table="">

Qhov sib ntxiv ntawm eGFRcys thiab eGFRcr-cys, tab sis tsis yog eGFRcr, txhim kho qauv fifit rau kev mob qog noj ntshav tag nrho (SupplementaryTables 7 thiab 8). Qhov kev txhim kho loj tshaj plaws tau pom nrog GFRcys.

4.3.3. Cancer tshwm sim-subtypes

eGFRcys60 89 tau cuam tshuam nrog kev pheej hmoo ntawm hematological malignancies (HR 1.24 (1.14 1.33): 25.1 feem pua ​​​​mob myeloma) thiab mob qog noj ntshav ntawm lub plab zom mov (HR 1.12 (1.01-1.25)), lub raum (HR 1.11 (1.<60 -.="" egfrcr60
="" 89="" was="" not="" associated="" with="" an="" increased="" risk="" of="" any="" of="" these="" cancer="" subtypes="" but=""><60 was="" associated="" with="" an="" increased="" risk="" of="" hematological="" (hr="" 1.19="" (1.00-1.41))="" and="" renal="" (hr="" 1.30="" (1.10-1.53))="" cancers.="" uacr="" -3="" mg/mmol="" was="" convincingly="" associated="" with="" an="" increased="" risk="" of="" hematological="" (hr="" 1.13="" (1.02-1.24)),="" abdominal="" (hr="" 1.40="" (1.23-1.58)),="" renal="" (hr="" 1.40="" (1.27-1.54))="" and="" respiratory="" (hr="" 1.20="" (1.09-1.32))="" cancers,="" with="" weaker="" associations="" with="" digestive="" and="" head="" and="" neck="">

Qhov sib ntxiv ntawm eGFRcys txhim kho tus qauv fifit rau kev mob qog noj ntshav hauv lub ntsws thiab lub raum, lub plab zom mov, thiab cov qog nqaij hlav hematological tab sis tsis yog lub taub hau thiab caj dab, plab zom mov, txiv neej / poj niam cov qog nqaij hlav tshwj xeeb, lossis melanoma (Table 7 Ntxiv).

4.3.4. Cancer tuag-subtypes

eGFRcys60 89 tau cuam tshuam nrog kev pheej hmoo ntawm kev tuag los ntawm hematological malignancies (HR 1.40 (1.20 1.64): 20.8 feem pua ​​​​kev tuag los ntawm ntau yam myeloma), digestive (HR 1.22 (1.10-1.35), thiab mob qog noj ntshav (HR. 1.15 (1.03 kuaj pom rau eGFRcys<60. egfrcys="" 1.27))="" with="" stronger="" associations=""><60 was="" further="" associated="" with="" risk="" of="" death="" from="" the="" abdominal="" solid="" organ="" (hr="" 1.36="" (1.11-1.66)),="" head="" and="" neck="" (hr="" 2.50="" (1.40-="" 4.47)),="" male-specifific="" (hr="" 1.46="" (1.08-1.96))="" and="" renal="" (hr="" 1.77="" (1.34-="" 2.35))="" cancers.=""><60 was="" associated="" with="" an="" increased="" risk="" of="" death="" from="" renal="" tract="" cancers="" only="" (hr="" 1.50="" (1.06-2.12)),="" though="" egfrcr60-89="" was="" associated="" with="" a="" reduced="" risk="" of="" death="" from="" abdominal="" solid="" organ="" and="" malespecifific="" cancers.="" uacr="" -3="" mg/mmol="" was="" associated="" with="" an="" increased="" risk="" of="" death="" from="" abdominal="" (hr="" 1.22="" (1.06-1.41)),="" digestive="" (hr="" 1.14="" (1.01-="" 1.30),="" renal="" (hr="" 1.73="" (1.42-="" 2.11)="" and="" respiratory="" (hr="" 1.19="" (1.06=""
="" 1.34)="">

Qhov sib ntxiv ntawm eGFR cys txhim kho tus qauv fifit rau kev tuag ntawm plab hnyuv, ua pa, plab, lub taub hau thiab caj dab, hematological, thiab mob raum mob qog noj ntshav (Table 8).

4.3.5 ib. Cov txiaj ntsig tsis suav nrog cov neeg koom nrog ntau yam myeloma lossis mob raum mob qog noj ntshav

Tom qab tsis suav nrog 4524 tus neeg koom nrog kuaj pom muaj mob qog noj ntshav hauv lub raum lossis mob raum, eGFRcys tseem cuam tshuam nrog kev pheej hmoo ntawm kev mob qog noj ntshav (eGFRcys 60- 89: HR 1.03(1.01- 1.05), p=0. 016); eGFRcys<60: hr="" 1.15="" (1.10
=""><0.001) and="" cancer="" death="" (egfrcys60
="" 89:="" hr="" 1.14="" (1.09
=""><0.001);><60 hr="" 1.44="" (1.34
="" 1.56),=""><0.001; supplementary="" table="">

4.3.6. Kev tshuaj xyuas ib xyoos ib zaug

Tom qab tsis suav nrog 6386 tus neeg koom nrog uas tau kuaj pom muaj mob qog noj ntshav lossis tuag hauv ib xyoos ntawm kev tso npe, eGFRcys tseem nyob nrog kev pheej hmoo ntawm kev mob qog noj ntshav (eGFRcys 60 89: HR1.04 (1.02 1.07), p<0.001);><60: hr="" 1.20="" (1.15
=""><0.001) and="" cancer="" death="" (egfrcys60
="" 89:="" hr="" 1.16="" (1.11
=""><0.001);><60 hr="" 1.51="" (1.40
="" 1.63),=""><0.001); supplementary="" table="">

4.3.7 ib. Ntsuas cov sij hawm nce qib

Tom qab kev hloov pauv ntau yam, eGFRcys<60 was="" associated="" with="" a="" rap="" of="" 2.8="" (
="" 2.5=""
="" 8.1)="" years,="" i.e.,="" an="" advance="" in="" risk="" of="" cancer="" incidence="" equivalent="" to="" an="" average="" of="" 2.8="" years="" of="" additional="" age.="" this="" is="" similar="" to="" that="" observed="" for="" previous="" smoking="" (rap="" 2.3="" (
="" 1.6=""
="" 6.1)="" years)="" and="" greater="" than="" observed="" for="" type="" 2="" diabetes="" (rap="" 0.9="" (
="" 3.7=""
="" 5.6)="" years;="" table="" 5).="" current="" smoking="" is="" associated="" with="" the="" greatest="" rap="" (6.8="" (
="" 0.9=""
="" 14.5)="" years).=""><60 is="" associated="" with="" rap="" of="" 4.5="" (
="" 1.3
="" 10.3)="" years="" for="" cancer="" death,="" suggesting="" that="" a="" person="" with="" more="" advanced="" ckd="" has="" a="" risk="" of="" cancer="" death="" equivalent="" to="" a="" person="" without="" ckd="" who="" is="" (on="" average)="" 4.5="" years="" older.="" the="" effect="" is="" greater="" than="" that="" observed="" for="" greater="" deprivation:="" rap="" 1.8="" (
="" 1.0=""
="" 4.6)="" years="" per="" 5-unit="" increase="" in="" deprivation="" score="" (equivalent="" to="" a="" transition="" up="" at="" least="" one="" deprivation="">

5. Kev sib tham

Peb tau pom tias muaj kev pheej hmoo ntau ntxiv ntawm kev mob qog noj ntshav thiab mob qog noj ntshav tuaj yeem kuaj pom thaum ntxov hauv CKD, thiab pom tau yooj yim dua siv eGFRcys, uas yog qhov nkag siab thiab nkag siab ntau dua li eGFRcr lossis eGFRcr-cys. eGFRcys thiab uACR cuam tshuam nrog kev pheej hmoo ntawm qhov chaw tshwj xeeb hematological, lub raum, ua pa thiab mob qog noj ntshav. eGFRcys zoo li ua rau muaj kev pheej hmoo ntawm kev mob qog noj ntshav thiab mob qog noj ntshav mus rau qib zoo ib yam li lwm yam kev pheej hmoo paub, xws li ntshav qab zib hom 2, BMI siab dua, kev tsis txaus siab ntau dua, thiab kev haus luam yeeb yav dhau los.

Rau peb txoj kev paub, qhov no yog thawj txoj kev tshawb fawb los sib piv eGFRcr, eGFRcys, thiab eGFRcr-cys rau kev pheej hmoo mob qog noj ntshav. Nyob rau hauv sib piv rau cov kev tshawb fawb uas soj ntsuam cov koom haum ntawm eGFRcr[3,5,7 11,27] los yog eGFRcr-cys [4] nrog mob qog noj ntshav thiab tuag, peb tau pom tias eGFRcys 60 89 ml / min / 1.73m2 yog txuam nrog me me. tab sis qhov tseem ceeb nce hauv kev mob qog noj ntshav, thiab muaj kev sib raug zoo nrog kev mob qog noj ntshav.

Lub koom haum muaj zog ntawm CKD thiab cov qog nqaij hlav hematological [10] yuav yog vim muaj kev pheej hmoo sib koom nrog rau kev kis kab mob (hepatitis B, C, HIV, Epstein-Barr, thiab cytomegalovirus) thiab cov teebmeem ntawm kev tiv thaiv kab mob [28]. Qee qhov hematological malignancies (piv txwv li, ntau yam myeloma) tuaj yeem ua rau lub raum tsis ua haujlwm ncaj qha: txo lub raum tsis ua haujlwm tuaj yeem sawv cev rau qhov tshwm sim ntxov ntawm malignancy. Peb tau ua qhov kev soj ntsuam rhiab heev (tsis suav cov neeg koom nrog uas tsim cov qog nqaij hlav hauv lub raum thiab ntau yam myeloma, thiab kev tshuaj ntsuam xyuas ib xyoos) hauv kev sim ntsuas thiab txo qhov cuam tshuam ntawm kev mob qog noj ntshav ua ntej ntawm kev ntsuas eGFR. Peb cov lus xaus tsis hloov pauv, tab sis peb lees paub tias tseem muaj peev xwm rau qee qhov ntawm peb qhov kev tshawb nrhiav tau txuas mus rau qhov rov qab ua rau muaj kev puas tsuaj.

Kev sib koom ua ke ntau dua yog pom ntawm CKD thiab cov qog nqaij hlav hauv lub cev [1,3,7 9,29], uas muaj feem cuam tshuam nrog, xws li metabolic syndrome, haus luam yeeb, ua ntej nephrectomy, cov kab mob caj ces (xws li tuberous sclerosis), kev raug ua hauj lwm, thiab siv tshuaj. Mob raum raug mob (AKI) paub tias yuav pab txhawb rau CKD txoj kev loj hlob [30] thiab feem ntau yuav tshwm sim rau cov neeg uas muaj CKD. Kev puas tsuaj ntawm tes los ntawm AKI tau pom tias yuav txhawb nqa clonal proliferation ntawm lub raum progenitors raws li ib feem ntawm kev kho cov lus teb, ua rau kev loj hlob ntawm lub raum cell carcinoma subtypes nrog rau cov kab mob metastatic [31]. Cov tswv yim los tiv thaiv ob qho tib si AKI thiab CKD (raws li qhov muaj feem cuam tshuam rau AKI) tuaj yeem txo qhov kev pheej hmoo ntawm mob qog noj ntshav hauv cov neeg no.

Mob ntsws cancer yav dhau los tau cuam tshuam nrog txo eGFR [3] thiab ntau ntxiv nrog albuminuria [3 5,14]. Cov nyhuv no yog me ntsis txo qis thaum coj mus rau hauv tus account keeb kwm ntawm kev haus luam yeeb [4,14], qhia tias albuminuria tej zaum yuav yog ib qho cim ntawm kev raug mob rau mob qog noj ntshav lossis cov ntaub so ntswg puas cuam tshuam nrog kev haus luam yeeb. Mob qog noj ntshav thiab albuminuria tau cuam tshuam nrog cov xeev o [32,33], thiab albuminuria tsuas yog ib qho cim ntawm kev mob ntxiv thiab kev ua haujlwm endothelial. Txawm li cas los xij, albuminuria tseem cuam tshuam nrog kev pheej hmoo ntawm tag nrho thiab qhov chaw tshwj xeeb hematological, plab, lub raum, thiab ua pa thiab tsis muaj zog ntxiv nrog rau plab hnyuv thiab mob qog noj ntshav, txawm tias tom qab hloov kho rau C-reactive protein ua tus cim ntawm kev mob. Kev tshawb nrhiav ntxiv ntawm cov txheej txheem hauv qab ntawm lub koom haum no tau lees paub.

CKD muaj feem xyuam nrog cov kab mob plawv: qhov kev pheej hmoo siab tau pom ua ntej thiab muaj zog dua los ntawm eGFRcys lossis eGFRcr-cys piv rau eGFRcr [2,16,34]. Mendelian randomization kev tshawb fawb qhia tau hais tias kev sib koom ua ke ntawm cystatin C thiab kab mob plawv tsis yog qhov ua rau, tab sis yog kho los ntawm eGFR [35]. Mob qog noj ntshav, kab mob plawv, thiab kab mob raum muaj feem cuam tshuam xws li hnub nyoog nce, haus luam yeeb, mob, thiab metabolic syndrome. eGFRcys zoo nkaus li ntes cov kab mob metabolic thiab cov kab mob ua npaws uas cuam tshuam nrog cov kab mob ntev nyob rau hauv ib txoj hauv kev uas cuam tshuam thiab ncaj nraim rau cov kws kho mob kuaj thiab txhais. Muab qhov kev pheej hmoo siab ntawm cov kab mob plawv thiab mob qog noj ntshav, kev txhim kho kev paub txog lub raum ua haujlwm tuaj yeem pab nrog kev pheej hmoo stratification thiab kev npaj kho mob, tshwj xeeb tshaj yog nyob rau hauv ib qho mob uas muaj mob asymptomatic mus txog thaum lig ntawm cov kab mob.

Muaj ntau qhov kev piav qhia txog kev mob qog noj ntshav ntau dhau tau pom hauv CKD. Cov neeg uas muaj CKD tuaj yeem raug kuaj pom tias muaj mob qog noj ntshav nyob rau theem uas muaj kev cuam tshuam ntau dua, los ntawm kev paub txog cov tsos mob zoo tshaj plaws lossis kab mob hnyav dua. Cov neeg uas muaj CKD yog qhov tsis txaus ntseeg nyob rau hauv kev sim tshuaj kho mob qog noj ntshav [36 38]: cov pov thawj-piv rau kev kho mob qog noj ntshav hauv CKD tsis tshua tsim tau zoo, thiab cov neeg mob CKD tuaj yeem tau txais kev kho mob qog noj ntshav uas tsis tshua muaj txiaj ntsig lossis tsis muaj zog. Hauv CKD, cov kev mob tshwm sim (tshwj xeeb tshaj yog mob raum nrog rau AKI [39]) tej zaum yuav muaj ntau dua, thiab cov neeg mob CKD yuav tsis tuaj yeem zam qhov koob tshuaj lossis lub sijhawm ntawm kev kho mob qog noj ntshav kom kho tau zoo. Cov tshuaj siv rau hauv kev kho mob ntawm CKD tuaj yeem cuam tshuam nrog kev kho mob qog noj ntshav, txwv lawv cov txiaj ntsig. Kev tshawb nrhiav cov teeb meem no tau lees paub hauv cov ntaub ntawv nrog cov ntaub ntawv qhia ntxaws ntxiv ntawm kev mob qog noj ntshav thiab kev kho mob hauv cov neeg koom nrog CKD.

Peb lees paub qee qhov kev txwv rau txoj haujlwm no. Ua ntej, lub raum kev ua haujlwm yog kwv yees raws li tus nqi hauv paus ntawm creatinine lossis cystatin C, tsis muaj ntaub ntawv qhia txog kev mob raum mus ntev. Qhov thib ob, UK Biobank tsis tuav cov ntaub ntawv hais txog cov tsos mob qog noj ntshav, kev kuaj mob, lossis kev kho mob, yog li peb tsis tuaj yeem ntsuas qhov cuam tshuam ntawm CKD cov cim ntawm kev kho mob thiab cov txiaj ntsig. Qhov thib peb, qhov ua rau tuag tau raug txheeb xyuas los ntawm kev sib txuas mus rau cov ntaub ntawv sau npe tuag, tsis yog raws li cov ntsiab lus txiav txim siab: nws muaj peev xwm hais tias kev faib tawm tsis zoo ntawm qhov ua rau tuag tuaj yeem tshwm sim ua rau ntau tshaj lossis qis dua ntawm kev pheej hmoo cuam tshuam nrog eGFR lossis albuminuria. . Plaub, peb tsis tau hloov kho rau hormonal influences nyob rau hauv cov poj niam, txawm li cas los xij, CKD cuam tshuam nrog kev cuam tshuam ntawm hormonal signaling thiab fertility [40] thiab eGFR kev ntsuas yuav tau ntes qee qhov cuam tshuam no. Tsis tas li ntawd, cov tshuaj hormone profiles yuav tsis raug ntsuas txhua zaus hauv kev saib xyuas thawj zaug. Qhov thib tsib, muaj tsawg tus neeg koom nrog eGFR<30 ml/min/1.73m2,="" so="" we="" are="" unable="" to="" comment="" on="" the="" impact="" of="" more="" advanced="" ckd.="" sixth,="" the="" included="" participants="" were="" relatively="" young="" (all="" under="" 74="" years="" old),="" therefore="" we="" cannot="" be="" confident="" the="" same="" associations="" would="" be="" observed="" in="" more="" elderly="" people,="" in="" whom="" cancer="" and="" lower="" egfr="" are="" more="" common.="" seventh,="" a="" small="" representation="" of="" non-white="" ethnic="" groups="" may="" limit="" the="" generalisability="" of="" the="" fifindings.="" last,="" uk="" biobank="" is="" not="" representative="" of="" the="" uk="" population="" in="" terms="" of="" lifestyles.="" cancer="" incidence="" in="" uk="" biobank="" is="" around="" 30%="" lower="" than="" in="" the="" general="" population="" [41]="" and="" absolute="" risk="" may="" not="" be="" generalizable.="" however,="" hazard="" ratios="" should="" still="" be="" applicable="" to="" the="" general="" uk="" population="">

Muaj kev pheej hmoo ntau dhau ntawm kev mob qog noj ntshav thiab mob qog noj ntshav hauv CKD uas tau kuaj pom ua ntej thiab yooj yim dua los ntawm eGFRcys dua li kev ntsuas tam sim no. Qhov kev pheej hmoo siab ntxiv cuam tshuam nrog eGFR<60 is="" at="" least="" as="" important="" as="" other="" recognized="" risk="" factors="" such="" as="" obesity,="" type="" 2="" diabetes,="" deprivation,="" and="" previous="" smoking.="" the="" impact="" of="" ckd="" markers="" on="" cancer="" death,="" in="" particular,="" is="" concerning="" and="" warrants="" further="">

Nyiaj txiag

Chief Scientist Office; ANID Becas Chile; Pawg Neeg Saib Xyuas Kev Kho Mob; British Medical Association; British Heart Foundation.

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