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Baseline Urinary Angiotensinogen Excretion Predicts Deterioration ntawm lub raum ua hauj lwm nyob rau hauv cov neeg mob uas muaj mob raum kab mob Ⅱ

Jan 11, 2024

Cov yam ntxwv ntawm tus neeg mob

Rau caum-obcov neeg mob nrog CKDuas tau mus rau hauv peb lub tsev kho mob thaum lub sijhawm kawm tau suav nrog hauv qhov kev tshawb fawb no. Lawv cov yam ntxwv tseem ceeb tau nthuav tawm hauv Table 1. Vim tias cov neeg mob feem ntau tau txais kev kuaj mob raum rau cov kab mob glomerulonephritis, cov neeg mob feem ntau yog cov hnub nyoog nruab nrab (48.5 ± 17.7 xyoo), thiab lawv.lub raum ua haujlwmtau khaws cia (ntshav creatinine: 1.05 ±{13}}.45 mg/dL; eGFR: 59.8 ± 22.6 mL / min / 1.73 m2), nrog logarithmic urinary albumin excretion ntawm 2.42 ± 0.60 mg / hnub. Tus naj npawb ntawm cov neeg mob tau tswj hwm RAS blockers yog 17 [Ang II receptor blockers (ARBs), n=16; angiotensin-hloov enzyme inhibitors (ACE-Is), n=1] thaum pib ntawm txoj kev tshawb no thiab 35 (ARBs, n=33; ACE-Is, n=2) thoob plaws txoj kev tshawb no .

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Kev hloov pauv txhua xyoo hauv eGFR hauv txhua tus neeg mob

Lub sijhawm nruab nrab ntawm kev soj ntsuam yog 3.4 ± 1.5 xyoo, thiab qhov nruab nrab txhua xyoo hloov pauv hauveGFRyog -0.93±6.16 mL/min/1.73 m2 nyob rau lub sijhawm no.

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Kev sib raug zoo ntawm kev hloov pauv txhua xyoo hauv eGFR thiabob peb lub chaw kho mob, suav nrog cov hauv paus ntsiab lus tso zis AGT

Peb thawj zaug soj ntsuam kev sib raug zoo ntawm kev hloov pauv txhua xyoo hauv lubeGFRthiab ntau qhov chaw kho mob, suav nrog kev tso zis AGT hauv qab. Cov kev sib raug zoo tsis zoo tau pom nyob nruab nrab ntawm qhov kev hloov pauv txhua xyoo hauv eGFR thiab hnub nyoog (r=-0.35, p<0.01), systolic BP (r=-0.36, p <0.01), and daily urinary albumin excretion (r=-0.32, p= 0.011) (Table 2). In addition, the annual change in the eGFR was significantly and negatively correlated with the baseline urinary AGT excretion (r=-0.31, p=0.015) (Fig. 2). However, no significant relationships were found between the annual change in the eGFR and plasma Ang II (r=0.22, p=0.10) (Table 2). We also performed multiple linear regression analyses between the annual change in the eGFR and baseline urinary AGT excretion after adjusting for the age, sex, BMI, and baseline eGFR. A significant negative relationship was found between them after adjusting in this manner (β=- 0.27, p=0.032) (Table 3).

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Kev sib piv ntawm kev hloov pauv txhua xyoo hauv lubeGFRntawm cov quartiles raws li lub hauv paus urinary AGT excretion

Peb mam li faib cov neeg mob mus rau hauv quartiles raws li lub hauv paus urinary AGT excretion thiab muab piv rau theem ntawm kev kho mob tsis nyob rau hauv lub quartiles. Cov systolic thiab diastolic BPs nyob rau hauv lub siab tshaj plaws quartile ntawm lub hauv paus urinary AGT excretion (Pab 4) (systolic BP: 124.9 ± 12.7 mmHg thiab diastolic BP: 77.5 ± 10.4 mmHg) yog ho ntau dua li cov nyob rau hauv pawg 1 (11.9 ± 9.2 mmHg): mmhg ;p< 0.05 and diastolic BP: 66.3±4.6 mmHg; p<0.01). In addition, the logarithmic daily urinary albumin excretion (2.99± 0.31 mg/day) in the highest quartile (Group 4) was higher than that in the other groups (Group 1: 1.98±0.43 mg/day; p<0.05, Group 2: 2.43±0.55 mg/day; p<0.05, and Group 3: 2.34±0.63 mg/day; p<0.05) (Supplementary material 1). TheKev hloov pauv txhua xyoo hauv eGFRnyob rau hauv lub siab tshaj plaws quartile ntawm lub hauv paus urinary AGT excretion (Pawg 4; -5.48 ± 7.14 mL/min/ 1.73 m2 / xyoo) yog ho txo ​​qis dua li hauv Pawg 2 (1.41 ± 3.39 mL / min / 1.73 m2 / xya; p<0.01) and Group 3 (0.46±5.50 mL/min/1.73 m2 /year; p=0.023). In addition, a similar tendency was found between the lowest quartile of baseline urinary AGT excretion (Group 1: -0.31±6.11 mL/ min/1.73 m2 /year) and Group 4 (p=0.073) (Fig. 2).

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Kev ntsuam xyuas kev sib txawvnruab nrab ntawm lub quartiles ntawm lub hauv paus urinary AGT excretion thiab txhua xyoo hloov nyob rau hauv eGFR tom qab hloov

Kev soj ntsuam Covariance kuj tau ua los tshuaj xyuas kev sib koom ua ke ntawm cov quartiles ntawm lub hauv paus urinary AGT excretion thiab kev hloov pauv txhua xyoo hauv eGFR hloov kho rau hnub nyoog, poj niam txiv neej, BMI, thiab lub hauv paus eGFR. Covariance tsom xam pom tau tias cov quartiles ntawm lub hauv paus urinary AGT excretion txawv heev txog kev hloov txhua xyoo hauv eGFR tom qab kev hloov kho (Model 1: Group 1 vs. Group 4, p=0.11; Pawg 2 vs. Pawg 4, p<0.01; and Group 3 vs. Group 4, p=0.011; and Model 2: Group 1 vs. Group 4, p= 0.09; Group 2 vs. Group 4, p<0.01; and Group 3 vs. Group 4, p=0.031) (Fig. 3 and Table 4).

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Ntshav siab yog txuam nrog kev pheej hmoo ntawm kev loj hlob ntawm CKD. Kanno et al. tshuaj xyuas 2,150 tus neeg uas tsis muaj CKD los ntawm cov pej xeem nyob rau hauv lub sij hawm nruab nrab ntawm kev soj ntsuam ntawm 6.5 xyoo, thiab 461 qhov xwm txheej ntawm CKD tau sau tseg. Lawv tau qhia tias qhov kev hloov pauv txaus ntshai ntawm CKD tau nce siab dua rau kev mob ntshav siab ua ntej (1.49, p.<0.003), Stage 1 (1.83, p<0.001), and Stage 2 (2.55, p<0.001) hypertension in the study than normotension (21).

Hauv qhov sib piv, Kiriyama et al. tshuaj xyuas 2,739 tus neeg uas tau kuaj xyuas kev noj qab haus huv dua, thiab lawv pom tias qhov kev poob qis eGFR feem ntau pom nyob rau hauv cov neeg uas muaj proteinuria ntawm lub hauv paus dua li cov uas tsis muaj proteinuria ntawm lub hauv paus (cov neeg uas muaj proteinuria: 3.3% piv rau cov neeg tsis muaj proteinuria: {{4} }.8%, p<0.001) (22). These previous reports coincide with our data indicating that systolic BP and urinary albumin excretion were predictors of lub raum tsis ua haujlwmnyob rau hauv txoj kev tshawb no. Tsis tas li ntawd, nws kuj tau ua pov thawj tias urinary AGT yog ib qho cim npe ntawm intrarenal RAS kev ua (2, 5, 6, 9-13) thiab cov zis AGT yog txuam nrog rau theem ntawm lub raum puas thiab BPs ({{4}). }). Yog li, peb xav tias cov theem pib ntawm cov zis AGT tau kwv yees lub raum tsis ua haujlwm hauv txoj kev tshawb no.

Nws yuav tsis muaj txiaj ntsig los ntsuas cov qib AGT ntawm cov zis, vim tias qib AGT cov zis tuaj yeem hloov pauv rau lub raum puas lossis kub siab. Txawm li cas los xij, peb tau tshaj tawm tias systolic BP tau nce zuj zus hauv ob lub transgenic nas qhia tib neeg renin systemically ntxiv rau tib neeg AGT hauv lub raum (23). Saito et al. qhia tau hais tias kev nce qib hauv cov zis AGT ua ntej nce qib ntawm cov zis albumin hauv cov neeg mob ntshav qab zib hom 1 (11). Peb yav dhau los tau qhia tias qhov intrarenal RAS tau qhib rau hauv cov neeg hloov lub raum tam sim tom qab pub raum, ua ntej nce qib ntawm cov zis albumin (24). Cov kev tshawb pom no qhia tau hais tias kev ua kom lub raum RAS ua rau lub raum puas, xws li microalbuminuria thiab kub siab. Yog li ntawd, qib AGT tso zis tsis yog tsuas yog qhia txog kev puas tsuaj rau lub raum thiab kub siab; Nws yog qhov tsim nyog los ntsuas qib AGT cov zis.

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Tsis ntev los no, Lee et al. tau tshaj tawm tias kev hloov pauv hauv cov zis AGT cuam tshuam nrog kev poob qis hauvlub raum ua haujlwmhauv cov neeg mob nrogmob ntshav qab zib hom 2(14), thiab Sawaguchi et al. qhia tias nce qib ntawm cov zis AGT hauvhom 2 mob ntshav qab zibCov neeg mob uas muaj albuminuria yog ib qho kev pheej hmoo ua rau mob raum thiab mob plawv (15). Tsis tas li ntawd, peb yav dhau los tau qhia tias kev ua haujlwm ntawm lub raum RAS yog qhov ua tau zoo thiab muaj feem cuam tshuam nrog rau lub raum puas thiab kub siab hauvcov neeg mob nrog CKD, suav nrog cov neeg mob ntshav qab zib nephropathy (2). Qhov no qhia tau hais tias theem pib ntawm cov zis AGT tau kwv yees kev ua haujlwm tsis zoo ntawm lub raum hauv txhua tus neeg mob CKD hauv txoj kev tshawb no. Txawm li cas los xij, AGT qhia hauv glomerular mesangial hlwb tau tshaj tawm los ntawm qib qabzib siab (25, 26). Tsis tas li ntawd, AGT qhia nyob rau hauv cov tubular cov hlwb proximal yog txhawb los ntawm qib qabzib siab. Tam sim ntawd tom qab siv tshuaj sodium-glucose co-transporter 2 (SGLT2) inhibitor, urinary AGT theem tau nce los ntawm kev nce qib ntawm cov piam thaj hauv cov tubular lumen. Txawm li cas los xij, thaum cov piam thaj txo qis los ntawm SGLT2 inhibitor, cov piam thaj hauv cov tubular lumen txo qis, ib yam li AGT qhia hauv cov cell tubular proximal (27). Raws li tau hais dhau los, qib ntawm intrarenal RAS ua kom sib txawv ntawm qee yam mob, xws li raws li qib qabzib thiab kev siv tshuaj kho mob. Yog li ntawd, qhov tshwm sim ntawm tag nrho covcov neeg mob nrog CKDhauv txoj kev tshawb fawb tam sim no yuav txawv ntawm cov neeg mob ntshav qab zib nkaus xwb hauv cov kev tshawb fawb yav dhau los. Txawm li cas los xij, peb tau txais cov txiaj ntsig zoo ib yam li cov kev tshawb fawb yav dhau los, qhia tias qib AGT tso zis kwv yeeslub raum tsis ua haujlwmnyob rau hauv txoj kev tshawb no.

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Ntau qhov kev txwv cuam tshuam nrog kev tshawb fawb tam sim no hais txog. Ua ntej, nws cov qauv loj me me, thiab cov neeg mob raug xaiv los ntawm ib lub chaw. Qhov thib ob, lub sijhawm ua raws yog 3.4 ± 1.5 xyoo, thiab lub sijhawm luv luv. Thaum kawg, txawm hais tias qee qhov kev cuam tshuam nrog kev noj zaub mov, xws li kev noj zaub mov qis, tau ua thaum lub sijhawm rov qab los hauv peb lub chaw kho mob sab nraud, cov kev cuam tshuam tsis sib npaug rau txhua tus neeg mob CKD. Tsis tas li ntawd, kev noj ntsev tsis tau ntsuas los ntawm kev sau cov zis txhua hnub rau txhua tus neeg mob. Yog li ntawd, nws nyuaj rau peb ntsuas qhov cuam tshuam ntawm kev noj zaub mov ntawm qhov kev tshawb pom. Txawm li cas los xij, peb muaj peev xwm ua kom pom tau tias cov neeg mob CKD nrog nce qib hauv cov zis AGT, zoo ib yam li cov neeg uas muaj qib urinary albumin thiab BP qhov tseem ceeb, pom tias lub raum tsis ua haujlwm sai piv nrog rau lwm tus neeg mob.

Hauv kev xaus, qhov kev hloov pauv txhua xyoo hauv eGFR yog qhov cuam tshuam loj heev thiab cuam tshuam nrog cov theem pib ntawm cov zis AGT. Tsis tas li ntawd, cov neeg mob nyob rau hauv lub siab tshaj plaws quartile ntawm lub hauv paus urinary AGT theem qhia ib tug zuj zus poob rau hauv eGFR. Cov txiaj ntsig no qhia tias qhov nce qib hauv cov zis AGT kwv yees sailub raum tsis ua haujlwmhauvcov neeg mob nrog CKD. Nyob rau hauv lub neej yav tom ntej, kev tshawb fawb loj thiab ntev ntev yuav tsum tau ua kom peb cov kev tshawb pom ntxiv.



Cov ntaub ntawv

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10. Nishiyama A, Konishi Y, Ohashi N, et al. Urinary angiotensinogen qhia txog kev ua haujlwm ntawm intrarenal renin-angiotensin system hauv cov neeg mob IgA nephropathy. Nephrol Dial Hloov26: 170-177, 2011. 

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