Ekwasyon ki baze sou Cystatin C detekte maladi ren kache ak pronostik pòv nan pasyan ki fèk dyagnostike ak myelom miltip.

Objektif. Objektif etid sa a se te konpare ekwasyon kreyatinin yo ak ekwasyon sistatin C (CysC) pou defini enfimite ren (RI) nan pasyan ki fèk dyagnostike myelom miltip (MM) ak analize ekwasyon ki pèmèt pou idantifye pasyan ki gen plis ak pi mal pronostik. faktè.Metòd. Fonksyon ren yo te evalye potentiels nan 61 pasyan ki fèk dyagnostike MM ki pa trete.ZÈK-EPI ak CAPA ekwasyon. Konparezon te fèt lè l sèvi avèk grafik Bland-Altman ak estatistik Kappa Cohen a. Mann-WhitneyT akYo te itilize tès chi-kare, epi yo te fè analiz univarye ak miltivarye.

Rezilta yo. Dapre kritè IMWG yo, 26% nan pasyan yo te montre RI (3 fanm / 13 gason) pandan y ap itilize nan ekwasyon CysC pèmèt nou idantifye jiska 39% nan pasyan (7 fanm / 17 gason). ,Ekwasyon CAPA te mwens patipri ak dispèse ak pi sansib pase CKD-EPI-kreyatinin. Anplis de sa, analiz univarye te revele yon asosyasyon ant diminyeARD-EPI

CysC ak move pronostik ki baze sou R-ISS-3.Konklizyon. ,e kritè IMWG ka souzèstime maladi ren, sitou nan fanm, ki ta ka afekte dòz la resevwa kòm byen ke toksisite li yo. Ansanm, done nou yo sijere ke ekwasyon ki gen ladan CysC yo pi egzak nan detektemaladi ren kache, osi byen ke pasyan ki genpi plis ak pi mal faktè pronostik, nan MM ki fèk dyagnostike.

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

KLIKE LA POU JWENN CISTANCHE ÈRBAL POU REN

1. Entwodiksyon

Myeloma miltip (MM) karakterize pa ekspansyon klonal nan selil plasma malfezan nan mwèl zo. MM se dezyèm maladi ematolojik ki pi komen, ki reprezante apeprè 10% nan ka yo ak 1% nan tout dyagnostik kansè [1]. Avèk yon laj medyàn nan dyagnostik 65 ane, ensidans anyèl la se apeprè 3-5 ka pou chak 100,000 moun [2]. Dyagnostik MM fèt dapre kritè Gwoup Travay Entènasyonal Myeloma (IMWG) ki pèmèt klasifikasyon maladi evolisyonè sa a nan yon etap bonè asymptomatik, ke yo rekonèt kòm Gammopati monoklonal ki gen siyifikasyon endetèmine (MGUS), yon etap smoldering entèmedyè (sMM). ak sentòm 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%) nan evènman ki defini myeloma (MDE) yo konsidere tou pou terapi [3]. ,ese MDE gen ladan yo, pami lòt moun, ki enplike / ki pa enplike endèks chèn limyè ki pi wo pase 100, de oswa plis blesi fokal, ak enfiltrasyon mwèl zo pa selil plasma pi gwo pase oswa egal a 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) oswa clearance kreyatinin (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.

Objektif etid sa a se te konpare ekwasyon diferan ak sCr ak CysC pou defini RI dapre kritè IMWG ak konnen ekwasyon ki pi sansib nan detekte pasyan risk nan MM ki fèk dyagnostike ak trete.

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

2. Materyèl ak Metòd

2.1. Pasyan yo.

61 youn apre lòt ki fèk dyagnostike ak pasyan ki pa trete ak MM (24 fi ak 37 gason) te enskri nan etid la ant Desanm 2018 ak Avril 2021. ,Se yon etid epidemyolojik te apwouve pa komite etik lokal la ak Komite Rechèch la nan Hospital Universitario de Cabueñes ( Espay). MM te dyagnostike selon kritè klinik ak laboratwa estanda ki etabli pa direktiv entènasyonal [3]. Done klinik ak laboratwa yo te kolekte nan dosye medikal lopital yo. Tout pasyan yo te siyen konsantman enfòme pou yo patisipe nan etid la.

Mezi sCr yo te fèt apre yon metòd ki ka remonte nan yon pwosedi referans IDMS (isotope dilution mass spectrometry), yon metòd ki baze sou picrate (Advia 2400, Siemens). Valè CysC yo te detekte lè l sèvi avèk yon tès nefelometrik ki ka trase nan kalibratè entènasyonal la (Dimension Vista, Siemens). Konpozan monoklonal serom ak pipi yo te detèmine pa elektwoforèz kapilè (Capilarys 2, Sebia). Mezi turbidimetric nan nivo chèn limyè san serom yo te fèt apre tès Freelite a (SPA-Plus, Binding-Site).

2.2. Estatistik.

Nou te itilize ekwasyon CKD-EPI yo dapre direktiv KDIGO, epi CKD-EPI-sCr-CysC te konsidere kòm yon "estanda lò," bay indisponibilite nan mezi altènatif, tankou inulin oswa Cr-EDTA, nan klinik la, dapre nan gid sa yo. Grubbs et al te defini ekwasyon CAPA. jan sa a:

Pou analiz done yo, yo dekri valè ki koresponn ak varyab kontinyèl yo kòm mwayen, medyàn, 95% CI, oswa pousantaj, tou depann de varyab la. ,E konparezon ant diferan ekwasyon yo te fè ak grafik Bland-Altman, epi konpare klasifikasyon an nan etap maladi ren kwonik, nou te anplwaye valè estatistik Kappa. Menm jan an tou, yo te evalye konparezon ant paramèt diferan ki asosye ak rediksyon eGFR yo detèmine ak sCr oswa CysC lè l sèvi avèk tès t Student a (distribisyon nòmal) oswa tès Mann-Whitney U (distribisyon non parametrik) pou varyab quantitative yo ak Chi-kare oswa tès egzak Fisher. pou varyab kalitatif. Valè P ki pi ba pase 0.05 yo te konsidere kòm estatistik enpòtan. Pou detèmine korelasyon ki genyen ant rediksyon CKD-EPI (ak CysC oswa sCr) konsidere faktè pronostik pòv nan pasyan ki gen MM, yo te fè analiz miltivarye, ki gen ladan tout varyab klinik ki enpòtan ki baze sou analiz univariate anvan an. Tout analiz estatistik yo te fèt lè l sèvi avèk Med. Lojisyèl Calc (vèsyon 9.2.1.0) ak SPSS (vèsyon 24).

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

3. Rezilta yo

,E karakteristik pasyan ki enkli nan etid la yo montre nan Tablo 1. Fonksyon ren yo te evalye nan yon kòwòt 61 pasyan ki fèk dyagnostike MM lè l sèvi avèk ekwasyon diferan ki gen ladan valè sCr ak / oswa CysC (Figi 1). Dapre kritè IMWG, 12 pasyan (19.6%) te gen nivo sCr ki pi wo pase 2 mg/dL ak 17 nan yo (27.8%) te montre CKDEPI-sCr-CysC pi ba pase 40 mL/min/1.73 m2. Kontrèman, ekwasyon CKD-EPI-sCr te rann 16 pasyan (26.2%) ak RI, tandiske 24 (39.3%) ak 23 (37.7%) pasyan yo te detekte lè l sèvi avèk ekwasyon CKD-EPI-CysC ak CAPA, respektivman (Tablo 2) . ,Nou, ekwasyon sa yo ki gen ladan CysC estime yon pi gwo kantite pasyan ki gen RI pase ekwasyon sa yo konsidere sèlman valè sCr. Diferans sa yo te plis pwononse nan fanm (12% ak CKD-EPI-sCr vs 29% ak 25% ak CKD-EPI-CysC ak CAPA, respektivman). An jeneral, pèfòmans diferan ekwasyon yo evalye pou defini RI selon kritè IMWG te trè bon pou CKD-EPI-sCr (Kappa endèks 0.958 (0.88-1, 95% CI) ak bon pou CKD-EPI-CysC ak CAPA ((Kappa endèks 0.747 (0.577–0.917, 95% CI) ak Kappa endèks 0 .779 (0.619-0.939, 95% CI), respektivman)).

ZÈK-EPI-sCr te tou mwens sansib pase ekwasyon yo ki gen ladan CysC nan deteksyon an nan pasyan ki gen maladi ren kwonik (etap 3), idantifye 21 pasyan kont pasyan 35 ak ekwasyon yo pi pito (Tablo 2). ,E ekwasyon ki gen ladan valè CysC estime menm kantite pasyan ki gen maladi ren kwonik (Kappa endèks 1). Anplis de sa, ekwasyon sa yo te pi sansib nan detekte 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

Figi 1: Pasyan miltip ki fèk dyagnostike ak andikap ren, dapre kritè gwoup k ap travay entènasyonal myeloma (kategorize pa sèks) lè l sèvi avèk kreyatinin serik ak sistatin C nan diferan ekwasyon.

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

Anplis de sa, nou konpare karakteristik pasyan ki gen MM ki soufri maladi ren (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).

Finalman, analiz univariate debouche yon asosyasyon enpòtan ant nivo eGFR redwi ke CKDEPI-CysC estime ak move pronostik pasyan ki fèk dyagnostike MM ki baze sou R-ISS-3 (HR 14.73; ranje 1.785-122.23, 95% CI, P). 0.013). Analiz miltivarye ki gen ladan laj, sèks, -2-mikroglobulin, emoglobin, albumin, ak proteinuri kòm varyab, te montre plis ke rediksyon CKDEPI-CysC se sèlman faktè pronostik endepandan pou move pronostik ki endike nan R-ISS la-3 nòt etap.

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