Cystatin C-raws li qhov sib npaug tshawb pom cov kab mob zais rau hauv lub raum thiab cov tsos mob tsis zoo hauv cov neeg mob tshiab uas muaj ntau tus mob myeloma

Lub hom phiaj. , e lub hom phiaj ntawm txoj kev tshawb no yog los sib piv cov creatinine sib npaug nrog cystatin C (CysC) sib npaug los txhais lub raum tsis zoo (RI) hauv cov neeg mob tshiab uas tau kuaj pom ntau tus neeg mob myeloma (MM) thiab txheeb xyuas qhov sib npaug uas tso cai rau txheeb xyuas cov neeg mob uas muaj ntau thiab tsis zoo. yam.Cov txheej txheem. Lub raum ua haujlwm tau raug tshuaj xyuas yav tom ntej hauv 61 tus neeg mob uas tau kuaj pom tshiab tsis tau kho MM ua haujlwmCKD- EPI thiab CAPA sib npaug. ,e kev sib piv tau ua los siv Bland-Altman cov duab thiab Cohen's Kappa statistic. Mann-WhitneyT thiabKev ntsuas Chi-square tau siv, thiab kev tshuaj xyuas tsis sib xws thiab ntau qhov sib txawv tau ua tiav.

Cov txiaj ntsig. Raws li IMWG cov qauv, 26% ntawm cov neeg mob pom RI (3 tus poj niam / 13 txiv neej) thaum siv CysC sib npaug tso cai rau peb txheeb xyuas txog 39% ntawm cov neeg mob (7 tus poj niam / 17 txiv neej). , e CAPA qhov sib npaug tsis tshua muaj kev ywj pheej thiab tawg thiab rhiab dua li CKD-EPI-creatinine. Tsis tas li ntawd, kev tshuaj ntsuam univariate tau nthuav tawm kev sib koom ua ke ntawm kev txo qisPEB-CKD

CysC thiab kev ua haujlwm tsis zoo raws li R-ISS-3.Cov lus xaus. , e IMWG cov txheej txheem tuaj yeem kwv yees cov kab mob raum tsis zoo, feem ntau ntawm cov poj niam, uas tuaj yeem cuam tshuam cov koob tshuaj tau txais nrog rau nws cov tshuaj lom. Ua ke, peb cov ntaub ntawv qhia tias qhov sib npaug uas suav nrog CysC yog qhov tseeb dua hauv kev txheeb xyuaszais raum kab mob, nrog rau cov neeg mob nrogntau thiab phem prognostic yam, nyob rau hauv tshiab kuaj MM.

CISTANCHE EXTRACT WITH 25% ECHINACOSIDE AND 9% ACTEOSIDE FOR KIDNEY

NYEM QHOV NO TUAJ SAIB HNUB NYOOG CISTANCHE FOR KIDNEY

1. Taw qhia

Ntau myeloma (MM) yog tus cwj pwm los ntawm kev nthuav dav ntawm cov qog ntshav ntshav hauv cov pob txha. MM yog qhov thib ob feem ntau hematological malignancy, sawv cev kwv yees li 10% ntawm cov neeg mob thiab 1% ntawm tag nrho cov mob qog noj ntshav [1]. Nrog rau lub hnub nyoog nruab nrab ntawm kev kuaj mob ntawm 65 xyoo, qhov tshwm sim txhua xyoo yog kwv yees li 3-5 tus neeg ntawm 100,000 neeg [2]. Kev kuaj mob ntawm MM yog ua raws li International Myeloma Working Group (IMWG) cov txheej txheem uas tso cai rau kev faib tawm ntawm cov kab mob sib kis no los ntawm cov theem asymptomatic thaum ntxov, hu ua monoclonal gammopathy ntawm qhov tseem ceeb (MGUS), theem nrab smoldering theem (sMM), thiab cov tsos mob MM [3, 4].

Despite novel therapeutic agents, including immunomodulatory drugs, small molecule inhibitors, or monoclonal antibodies, having revolutionized the landscape of MM therapy, it still remains as an incurable disease [5]. However, only patients with myeloma-related symptoms, such as anemia, hypercalcemia, bone disease, or renal impairment (RI), are considered for treatment initiation [2, 4]. In addition, those patients owning biomarkers predicting a high risk of progression (>80%) rau myeloma-defining events (MDE) kuj raug txiav txim siab rau kev kho mob [3]. , cov MDE suav nrog, nrog rau lwm tus, koom nrog / tsis koom nrog lub teeb pom kev zoo siab dua 100, ob lossis ntau qhov chaw focal, thiab cov pob txha pob txha infiltration los ntawm cov ntshav plasma ntau dua lossis sib npaug li 60%.

Importantly, MDE includes RI and it is considered as a poor prognosis factor. RI is a common complication in patients with MM and correlates with diminished time to treatment and overall survival [6]. In this context, the accurate identification of kidney disease is crucial, since recovery of RI is associated with response to therapy [6]. For defining RI (IMGW), serum creatinine (sCr) (>2 mg/dL) lossis creatinine clearance (CrCl) (<40 mL/min) is employed, although both parameters are considered to underestimate RI since sCr may vary depending on age or muscle mass [7–9]. Renal function is usually estimated using sCr using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)- based equation to estimate glomerular filtration rate (eGFR). Nevertheless, international guidelines recognize that equations based on sCr are imprecise and they do not represent the most accurate method for evaluating RI, especially in elderly patients owning malnutrition and fragility, very common characteristics of patients with MM [10]. In this context, the Kidney Disease Improving Global Outcomes (KDIGO) recommends equations based on the combination of sCr and cystatin C (CysC) (CKD-EPI-sCrCysC) to estimate GFR for chronic kidney disease or RI in patients under treatment using drugs with narrow therapeutic range [11]. ,ere are new equations that include CysC and could provide advantages (like CAPA equation (Caucasian and Asian pediatric and adult subjects)), but their validation is required before their widespread use in clinical practice.

, e lub hom phiaj ntawm txoj kev tshawb no yog los sib piv cov sib npaug sib txawv nrog sCr thiab CysC los txhais RI raws li IMWG cov qauv thiab kom paub qhov sib npaug rhiab tshaj plaws hauv kev tshawb nrhiav cov neeg mob pheej hmoo hauv MM tshiab thiab tsis kho.

CISTANCHE EXTRACT WITH 25% ECHINACOSIDE AND 9% ACTEOSIDE FOR KIDNEY

2. Cov ntaub ntawv thiab cov txheej txheem

2.1. Cov neeg mob.

61 sib law liag tshiab thiab tsis kho cov neeg mob nrog MM (24 poj niam thiab 37 txiv neej) tau tso npe rau hauv txoj kev tshawb fawb thaum lub Kaum Ob Hlis 2018 thiab Plaub Hlis 2021., yog qhov kev tshawb fawb txog kev kis kab mob tau pom zoo los ntawm Pawg Neeg Saib Xyuas Kev Ncaj Ncees hauv zos thiab Pawg Neeg Tshawb Fawb los ntawm Tsev Kho Mob Universitario de Cabueñes ( Spain). MM tau kuaj pom raws li cov txheej txheem kho mob thiab kuaj cov qauv tsim los ntawm cov txheej txheem thoob ntiaj teb [3]. Cov ntaub ntawv kho mob thiab chaw kuaj mob tau sau los ntawm cov ntaub ntawv kho mob hauv tsev kho mob. Txhua tus neeg mob tau kos npe rau daim ntawv pom zoo kom koom nrog hauv txoj kev tshawb no.

sCr ntsuas tau ua raws li ib txoj hauv kev uas tuaj yeem taug qab mus rau IDMS (isotope dilution mass spectrometry) cov txheej txheem siv, picrate-based method (Advia 2400, Siemens). CysC qhov tseem ceeb tau kuaj pom siv qhov kev ntsuam xyuas nephelometric traceable rau lub thoob ntiaj teb calibrator (Dimension Vista, Siemens). Ntshav thiab zis monoclonal Cheebtsam tau txiav txim los ntawm capillary electrophoresis (Capilarys 2, Sebia). Kev ntsuas Turbidimetric ntawm qib ntawm cov roj ntsha tsis muaj roj ntsha tau ua raws li Freelite assay (SPA-Plus, Binding-Site).

2.2. Kev txheeb cais.

Peb siv CKD-EPI sib npaug raws li KDIGO cov lus qhia, thiab CKD-EPI-sCr-CysC tau raug suav hais tias yog "tus qauv kub," muab qhov tsis muaj kev ntsuas lwm yam, xws li inulin lossis Cr-EDTA, hauv tsev kho mob, raws li rau cov lus qhia no. , e CAPA kab zauv tau txhais los ntawm Grubbs li al. raws li nram no:

Rau kev txheeb xyuas cov ntaub ntawv, cov txiaj ntsig zoo sib xws rau qhov sib txawv tsis tu ncua tau piav qhia tias txhais tau li cas, nruab nrab, 95% CI, lossis feem pua, nyob ntawm qhov sib txawv. , e kev sib piv ntawm qhov sib npaug sib txawv tau ua nrog Bland-Altman cov duab, thiab los sib piv cov kev faib tawm hauv cov kab mob raum ntev, peb ua haujlwm rau Kappa tus nqi. Ib yam li ntawd, qhov kev sib piv ntawm qhov txawv tsis sib xws nrog eGFR txo qhov txiav txim siab nrog sCr lossis CysC raug soj ntsuam siv Tub Ntxhais Kawm T-test (ib txwm faib) lossis Mann–Whitney U test (nonparametric faib) rau qhov sib txawv ntawm qhov ntau thiab Chi-square lossis Fisher qhov kev xeem. rau qualitative variables. P tus nqi qis dua 0.05 tau suav tias yog qhov tseem ceeb. Txhawm rau txiav txim siab qhov sib raug zoo ntawm CKD-EPI txo qis (nrog CysC lossis sCr) txiav txim siab qhov tsis zoo ntawm cov neeg mob uas muaj MM, kev tshuaj xyuas ntau yam tau ua, suav nrog txhua qhov cuam tshuam kev kho mob raws li kev soj ntsuam ua ntej univariate. Txhua qhov kev txheeb xyuas txheeb cais tau ua los ntawm Med. Calc software (version 9.2.1.0) thiab SPSS (version 24).

CISTANCHE EXTRACT WITH 25% ECHINACOSIDE AND 9% ACTEOSIDE FOR KIDNEY

3. Cov txiaj ntsig

,e cov yam ntxwv ntawm cov neeg mob suav nrog hauv txoj kev tshawb fawb tau pom nyob rau hauv Table 1. Lub raum kev ua haujlwm tau soj ntsuam hauv ib pawg ntawm 61 cov neeg mob uas tau kuaj pom tshiab MM siv cov sib npaug sib txawv uas suav nrog sCr thiab / lossis CysC qhov tseem ceeb (Daim duab 1). Raws li IMWG cov qauv, 12 tus neeg mob (19.6%) muaj sCr ntau dua 2 mg/dL thiab 17 ntawm lawv (27.8%) pom CKDEPI-sCr-CysC qis dua 40 mL/min/1.73 m2. Hauv qhov sib piv, qhov sib npaug CKD-EPI-sCr tau ua rau 16 tus neeg mob (26.2%) nrog RI, whereas 24 (39.3%) thiab 23 (37.7%) tau kuaj pom siv CKD-EPI-CysC thiab CAPA sib npaug, raws li (Table 2) . , peb, cov kev sib npaug no suav nrog CysC kwv yees ntau dua ntawm cov neeg mob nrog RI ntau dua li cov kev sib npaug uas tsuas yog sCr qhov tseem ceeb. , qhov sib txawv no tau tshaj tawm rau cov poj niam (12% nrog CKD-EPI-sCr vs. 29% thiab 25% nrog CKD-EPI-CysC thiab CAPA, feem). Zuag qhia tag nrho, kev ua tau zoo ntawm qhov sib npaug sib txawv tau ntsuas los txhais RI raws li IMWG cov txheej txheem tau zoo heev rau CKD-EPI-sCr (Kappa index 0.958 (0.88–1, 95% CI)) thiab zoo rau CKD-EPI-CysC thiab CAPA ((Kappa index 0.747 (0.577–{54}}.917, 95% CI)) thiab Kappa index 0 .779 (0.619–0.939, 95% CI), ntsig txog).

CKD-EPI-sCr kuj tsis tshua muaj siab dua qhov sib npaug nrog rau CysC hauv kev tshawb nrhiav cov neeg mob uas muaj kab mob raum ntev (theem 3), txheeb xyuas 21 cov neeg mob thiab 35 cov neeg mob uas muaj qhov sib npaug nyiam (Table 2). , e sib npaug uas suav nrog CysC qhov tseem ceeb kwv yees tib tus naj npawb ntawm cov neeg mob uas muaj kab mob raum ntev (Kappa index 1). Tsis tas li ntawd, cov kev sib npaug no tau nkag siab ntau dua hauv kev kuaj xyuas eGFR<60 mL/min/1.73 m2 , corresponding to chronic kidney disease stage 3, compared to CKD-EPI-sCr. Particularly, the CAPA equation was less biased (−7.5 mL/min/1.73 m2 ) and dispersed (−19.4 to 4.4 mL/min/1.73 m2 , 95% CI), while CKD-EPI-sCr showed the highest bias (+9.5 mL/min/ 1.73 m2 ) and imprecision (−10.7 to 29.6 mL/min/1.73 m2 ) (Figure 2).

CISTANCHE EXTRACT WITH 25% ECHINACOSIDE AND 9% ACTEOSIDE FOR KIDNEY

Daim duab 1: Kev kuaj mob tshiab tshiab ntau tus neeg mob myeloma nrog lub raum tsis zoo, raws li cov txheej txheem ua haujlwm thoob ntiaj teb myeloma (categorized los ntawm kev sib deev) siv cov ntshav creatinine thiab cystatin C hauv ntau qhov sib npaug.

CISTANCHE EXTRACT WITH 25% ECHINACOSIDE AND 9% ACTEOSIDE FOR KIDNEY

Tsis tas li ntawd, peb piv cov yam ntxwv ntawm cov neeg mob uas muaj MM muaj mob raum (eGFR<60 mL/min/ 1.73 m2 ) estimated by CKD-EPI-sCr and by CKD-EPI-CysC, unveiling similar profiles in these individuals (Table 3). Compared to patients with normal eGFR, the cohort of patients with RI estimated using both equations was older and displayed significantly higher β-2-microglobulin, serum urate, proteinuria, and serum monoclonal component levels and lower values of hemoglobin. Moreover, the majority of these patients showed advanced MM (R-ISS stage 3). Of note, patients with chronic kidney disease estimated with CKD-EPI-CysC had lower levels of albumin (34.1 g/L versus 38.05 g/L; P 0.0137) (Table 3), a risk factor associated to MM. Fourteen patients with CKD-EPI-CysC reduction, but no CKD-EPI-sCr, have distinctively low albumin levels as well (32 g/L). No significant differences were observed in the rest of the variables analyzed. Among these high-risk patients, three died within ten months from diagnosis (2 men and 1 woman) due to COVID-19, sudden death, and sepsis (CKDEPI-CysC 35, 41, and 25 mL/min/1.73 m2 versus CKD-EPIsCr 88, 83, and 64 mL/min/1.73 m2 , respectively).

Thaum kawg, univariate tsom xam unraveled ib tug tseem ceeb kev koom tes ntawm txo eGFR theem kwv yees los ntawm CKDEPI-CysC thiab tsis zoo prognosis ntawm cov neeg mob uas tshiab MM kuaj raws li R-ISS -3 (HR 14.73; range 1.785–122.23, 95% CI, P 0.013). Kev txheeb xyuas ntau yam suav nrog hnub nyoog, poj niam txiv neej, -2-microglobulin, hemoglobin, albumin, thiab proteinuria raws li qhov sib txawv, ntxiv qhia tias kev txo qis CKDEPI-CysC tsuas yog ib qho kev ywj pheej rau kev kuaj mob tsis zoo qhia los ntawm R-ISS-3 staging qhab nia.

CISTANCHE EXTRACT WITH 25% ECHINACOSIDE AND 9% ACTEOSIDE FOR KIDNEY