Kev koom tes hauv lub raum hauv cov neeg mob uas muaj mob Myelomonocytic Leukemia lossis BCR-ABL-Negative Myeloproliferative Neoplasms

Taw qhia: Kev txheeb xyuas cov cim tshwj xeeb molecular thiab kev txhim kho ntawm cov tshuaj tshiab tau hloov pauv lub ntsiab lus ntawm co-nephrology, tam sim no tso cai rau ntau txoj hauv kev rau lub raum kev cuam tshuam nrog hematologic malignancies vam khom kev sib xyaw hematologic thiab molecular kev ntsuas. Hauv qhov kev tshawb fawb no, peb tsom mus kho cov kab mob ntawm lub raum tsis zoo uas cuam tshuam nrog mob myelomonocytic leukemia (CMML) lossis BCR-ABL-negative myeloproliferative neoplasms (MPNs), 2 yam tsis tshua muaj neeg piav qhia. Methods: Case series. Cov neeg mob uas muaj myeloid neoplasms uas raug xa mus rau Toulouse University Tsev Kho Mob Nephrology Unit thiab tau kuaj pom tias mob raum raug mob (AKI), kab mob raum ntev (CKD), lossis cov zis txawv txav tau rov qab suav nrog. Cov txiaj ntsig: Kaum yim tus neeg mob (txiv neej n¼13, CMML n¼8, qhov tseem ceeb thrombocytosis [ET] n¼7, polycythemia vera [PV] n¼1, thiab myelofibrosis n¼2) tsim kab mob raum 7.7 2 xyoo tom qab kuaj pom tus mob malignancy. Kaum ob tus neeg mob tau AKI ntawm kev nthuav qhia. Yim tus neeg mob muaj qhov kev nthuav qhia glomerular (high-range proteinuria 33 feem pua, microscopic hematuria 56 feem pua). Lub raum biopsy (n¼14) pom ntau yam qauv, suav nrog pauci-immune glomerulosclerosis (n¼5), extramedullary hematopoiesis (n¼6), lossis tubular atrophy thiab interstitial fifibrosis nrog polymorphic inflammation (n¼8). Immunostaining ntawm CD61 tau lees paub qhov kev nkag mus ntawm megakaryocytes hauv glomeruli lossis interstitium hauv 5 ntawm 8 tus neeg mob. Lwm cov duab ntawm glomerulopathy tau txheeb xyuas hauv 3 tus neeg mob (IgA nephropathy n¼2, AA amyloidosis n¼1). Lub raum infiltration loj heev los ntawm CMML tau txheeb xyuas hauv 1 tus neeg mob. Tom qab qhov kev soj ntsuam zoo li ntawm 24- 6 lub hlis, malignancy tau txiav txim siab ruaj khov hauv 11 tus neeg mob (61 feem pua), tab sis 22 feem pua ​​​​ntawm cov neeg mob tau nce mus rau theem kawg ntawm lub raum tsis ua haujlwm. Cov seem tau pheej txo lub raum ua haujlwm. Tsis muaj kev sib raug zoo ntawm tus kab mob malignancy thiab lub raum kev nthuav qhia thiab cov txiaj ntsig tau raug txheeb xyuas. Cov ntsiab lus: Cov teeb meem raum ntawm CMML / MPN yog heterogenous, thiab lub raum biopsy yuav pab txheeb xyuas cov hom phiaj tshiab molecular los tiv thaiv kev loj hlob ntawm lub raum fibrosis.

Nyem rau maca ginseng cistanche rau mob raum

Julie Belliere1,2,3, Magali Colombat3,4, Clément Kounde1, Christian Recher3,5, David Ribes1, Antoine Huart1, Dominique Chauveau1,2,3, Véronique Demas3,6, Isabelle Luquet6, Odile Beyne-Rauzyan3, thiab Stanislas Faguer1,2,3 1 Center Hospitalier Universitaire de Toulouse, Département de Néphrologie thiab Transplantation d'Organes, Center de reference des Maladies rénales rares, Toulouse, France; 2 INSERM U1048, Institut des maladies métaboliques thiab cardio-vasculaires, Toulouse, Fabkis; 3 Université Paul Sabatier, Toulouse, Fabkis; 4 Center Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse–Oncopole, Département d'Anatomopathologie, Toulouse, Fabkis; 5 Center Hospitalier Uni versitaire de Toulouse, Institut Universitaire du Cancer de Toulouse–Oncopole, Service d'Hématologie, Toulouse, Fabkis; 6 Center Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse–Oncopole, Laboratoire d'Hématologie, Toulouse, Fabkis; thiab 7 Center Hospitalier Universitaire de Toulouse, Institut Universitaire du Cancer de Toulouse– Oncopole, Service de Médecine interne, Toulouse, France

Lub spectrum ntawm lub raum mob nyob rau hauv cov neeg mob uas muaj hematologic malignancies yog heev heterogenous. Thaum lub raum teeb meem ntawm B cell- thiab plasma cell-related malignancies tau kawm dav, cov uas cuam tshuam nrog myeloid neoplasms tau piav qhia tsis zoo.

Myeloid neoplasms suav nrog myeloid leukemia, myelodysplastic syndromes, thiab MPNs1 thiab suav txog 30 feem pua ​​​​ntawm tag nrho cov tshiab hematologic malignancies.2 BCR-ABL-negative MPN qhia txog cov txheej txheem pathophysiological txhawb kev loj hlob ntawm ib qho kev txawv txav ntawm hematopoietic mucous membranes (tshwj xeeb tshaj yog cov kab mob hematopoietic. micro-environmental hloov).3,4 Li no, kev hloov pauv hauv JAK2 noob tau txheeb xyuas nyob rau hauv cov neeg mob feem ntau nrog PV, thiab tsawg dua ET thiab thawj myelofibrosis (PMF). CMML yog lwm qhov tsis tshua muaj BCR-ABL-negative myeloid neoplasm nrog cov txheej txheem sib txawv molecular. Dhau li ntawm cov teeb meem hematologic (cytopenia, thrombosis, splenomegaly, thiab kev loj hlob mus rau mob myeloid leukemia), BCR-ABL-negative MPN kuj tuaj yeem ua rau cov kab mob tsis zoo uas tshwm sim los ntawm qhov tsis zoo.5,6

Ntawm lwm tus, cov teeb meem ntawm lub raum cuam tshuam ncaj qha rau lub ntiaj teb kev kwv yees, thiab lub raum tsis ua haujlwm tseem ceeb txo qis kev muaj sia nyob tsis muaj sia nyob.7 Hauv kev tshawb nrhiav Kaus Lim Qab Teb ntawm 136 MPN cov neeg mob, qhov ntau ntawm CKD yog 11 feem pua.8 Txawm li cas los xij, thaj chaw ntawm lub raum tsis zoo cuam tshuam nrog MPN. thiab CMML tseem tsis tau paub ua ntej kev tswj hwm. Cov kev tshawb fawb ib leeg qhia txog ntau yam mob raum, suav nrog mob raum thiab / lossis mob raum raug mob los ntawm kev ncaj qha (piv txwv li, myeloid neoplasm infiltration, zis lysozyme, raum venous thrombosis) thiab indirect (xws li vasculitis, infarction, qog lysis syndrome) mechanisms. Tsis tshua muaj, extramedullary hematopoiesis tau raug tshaj tawm nyob rau hauv cov zis.9 Glomerular raug mob tau piav, tab sis cov ntaub ntawv pathologic tsawg heev. Qhov loj tshaj plaws, luam tawm xyoo 2011, suav nrog tsuas yog 11 tus neeg mob (PMF n¼8, ET n¼1, PV n¼1, mob myeloid leukemia n¼1). Nyob rau hauv cov ntaub ntawv no thiab cov ntaub ntawv sau tseg, focal segmental glomerulosclerosis (FSGS) yog qhov tseem ceeb ntawm pathologic nrhiav.10–12 Lub raum pathologies hauv cov neeg mob uas muaj CMML lossis ET tsis tau piav qhia ntau. cov ntaub ntawv luam tawm. Lub hom phiaj ntawm txoj kev tshawb fawb tam sim no yog los piav qhia qhov tob hauv chav kho mob ntawm cov neeg mob uas muaj ntaub ntawv MPN ​​lossis CMML thiab mob raum thiab ntsuas lawv cov txiaj ntsig hematologic thiab lub raum.

Cov txheej txheem

Hauv qhov kev tshawb nrhiav monocentric no, peb suav nrog txhua tus neeg mob MPN lossis CMML uas tau raug xa mus rau Lub Tsev Haujlwm Saib Xyuas Kev Kho Mob thiab Kev Hloov Pauv ntawm Lub Tsev Kho Mob University of Toulouse (Fabkis) thaum Lub Ib Hlis 2010 thiab Kaum Ob Hlis 2020.

Txhais ntawm Hematological Disease

Kev kuaj mob rau myeloid neoplasms yog raws li 2016 kho WHO cov qauv.1 Myelodysplastic thiab myeloproliferative neoplasms suav nrog CMML thiab 4 lwm yam kab mob. MPNs yog ib pab pawg muaj 8 kab mob: mob myeloid leukemia, BCR-ABL1 (CML); PV; PMF nrog 2 theem: pov thawj PMF thiab precocious PMF (los yog profibrotic PMF); ET; mob neutrophic leukemia; mob eosinophilic leukemia, tsis tau teev tseg; systemic mastocytosis; thiab MPNs tsis raug cais tawm. Kev tshuaj xyuas Cytogenetic tau txiav txim siab siv cov txheej txheem txheej txheem thiab kev tshuaj xyuas molecular tau ua raws li tau piav qhia dhau los.13

Kev txhais cov kab mob raum

According to the National Kidney Foundation's Kidney Disease Outcome and Quality Initiative (KDOQI) guidelines, CKD was defined as renal damage or estimated glomerular filtration rate (eGFR) < 60 ml/min per 1.73 m2 for at least 3 months. CKD is classified into 5 stages. CKD stages 1 and 2 are defined by evidence of kidney damage (proteinuria, hematuria, abnormal imaging, or biopsy) and eGFR >90 thiab 60 txog 89 ml / min rau 1.73 m2, feem. CKD theem 3 txog 5 yog txhais raws li eGFR: theem 3, 4, thiab 5 yog tus cwj pwm los ntawm eGFRs hauv thaj tsam ntawm 30 txog 59, 15 txog 29, thiab<15 ml/min="" per="" 1.73="" m2,="" respectively.14="" egfr="" was="" calculated="" with="" the="" ckd-epi="" formula.15="" for="" aki,="" the="" following="" definition="" was="" used:="" an="" increase="" in="" serum="" creatinine="" (scr)="" by="" $0.3="" mg/dl="" ($26.5="" mmol/l)="" within="" 48="" hours;="" or="" an="" increase="" in="" scr="" to="" $1.5="" times="" baseline,="" which="" is="" known="" or="" presumed="" to="" have="" occurred="" within="" the="" prior="" 7="" days;="" or="" urine="" volume="" #0.5="" ml/kg/h="" for="" 6="" hours.="" aki="" was="" staged="" for="" severity="" according="" to="" the="" kdigo="" criteria.16="" egfr="" loss="" was="" calculated="" as="" the="" difference="" between="" egfr="" at="" diagnosis="" and="" gfr,="" at="" last,="">

Lub raum Biopsies

Kev ua ntawm lub raum biopsies suav nrog lub teeb microscopy thiab immunofluorescence. Rau lub teeb microscopy, txhua kis tau stained nrog hematoxylin thiab eosin, periodic acid-Schiff, Masson trichrome, thiab Jones methenamine nyiaj. Rau immunofluorescence, 0.3- hli cryostat seem tau stained nrog polyclonal antibodies rau IgG, IgM, IgA, C3, C1q, kappa, lambda, fibrinogen, thiab albumin-FITC (luav, polyclonal; Agilent, Santa Clara, CA). Cov kev tshawb fawb Immunoperoxidase tau ua tiav ntawm paraffin seem uas siv cov tshuaj tiv thaiv kab mob tiv thaiv CD61 (nas antihuman clone 2F2; Roche, Basel, Switzerland), myeloperoxidase (luv antihuman polyclonal; Roche), glycophorin C (nas antihuman clone Ret40f; Agilent), thiab luav polyclonal ; Roche).

Cov ntaub ntawv kho mob

Cov ntaub ntawv kho mob suav nrog cov pej xeem cov ntaub ntawv thiab cov kev kuaj mob niaj hnub thiab kuaj pom uas tau txais los ntawm cov ntaub ntawv kho mob.

Kev txheeb cais

Cov kev hloov pauv tsis tu ncua tau qhia tias txhais tau li cas thiab tus qauv kev ua yuam kev ntawm qhov nruab nrab thiab piv nrog Mann-Whitney U test. Cov kev hloov pauv tsis tu ncua tau nthuav tawm raws li tus lej thiab feem pua ​​​​thiab piv nrog Fisher qhov kev xeem.

Kev ncaj ncees

Txoj kev tshawb no tau ua raws li Helsinki tshaj tawm, raws li tau hloov kho hauv 2004, thiab ua tiav cov lus pom zoo ntawm Fabkis txoj cai lij choj hais txog kev tshawb fawb rov qab. Raws li cov lus pom zoo ntawm Pawg Saib Xyuas Kev Tshawb Fawb ntawm University Tsev Kho Mob ntawm Toulouse, sau ntawv tso cai raug zam.

Kev tshwm sim

Cov yam ntxwv ntawm cov neeg mob

Tshaj 11 xyoos, 18 tus neeg mob sib law liag (txiv neej poj niam txiv neej n¼13; txhais tau tias muaj hnub nyoog 70 5 xyoos) ua tiav cov txheej txheem suav nrog.

Hematology Profile

Raws li tau piav qhia hauv Table 1, hematologic malignancies yog heterogenous: CMML n¼8, ET n¼7, PV n¼1, PMF n¼1, theem nrab myelofibrosis n¼1. Karyotype txawv txav thiab hloov pauv tau muaj nyob hauv 16 tus neeg mob.

Ntawm 8 tus neeg mob nrog CMML, cov kab mob subtypes yog cov hauv qab no: hom 1 ntawm 4 tus neeg mob, hom 0 hauv 3 tus neeg mob, thiab hom 2 hauv 1 tus neeg mob. Pom tau chromosomal thiab molecular abnormalities yog raws li nram no: deletion nyob rau hauv lub caj npab ntev ntawm chromosome 7 (del(7q); n¼1), taw tes kev hloov ntawm c-KIT (D816 mutation; n¼1), JAK2 (V617F mutation; n¼1), NRAs (n¼1). ), ASXL1 (n¼2), SRSF2 (n¼1), thiab X chromosome anomaly (n¼1). Qhov nruab nrab cov ntshav dawb suav ntawm kev nkag mus rau hauv lub raum yog 25 8 G / L. Qhov nruab nrab monocytes suav yog 4.9 2 G / L. Tsis muaj thrombocytosis tau sau tseg, txawm nyob hauv tus neeg mob nrog JAK2 kev hloov pauv. Kev kuaj pob txha pob txha tau ua tsuas yog hauv 2 tus neeg mob thiab qhia tias tsis muaj myelofibrosis. Ib qho kev nthuav dav monoclonal IgG kappa tau kuaj pom hauv 3 tus neeg mob thiab IgM kappa hauv 1 tus neeg mob CMML, ua rau kev kuaj mob ntawm monoclonal gammopathy ntawm qhov tsis paub qhov tseem ceeb. Ntawm 10 tus neeg mob nrog MPN, 5 ntawm 10 tus neeg mob kuaj tau muaj qhov rov ua dua V617F hloov pauv ntawm JAK2 noob (allelic zaus 10 feem pua ​​-88 feem pua). Kev hloov pauv kuj tau txheeb xyuas hauv DNMT3A thiab MPL (n¼1) lossis CALR (n¼1). Tsis muaj M-spike raug txheeb xyuas hauv MPN ​​cov neeg mob.

Lub raum thiab Cov Txheej Txheem Kev Koom Tes

Qhov ncua sij hawm ntawm kev kuaj mob ntawm myeloid neoplasms thiab qhov pib ntawm lub raum kab mob yog 7.7 2 xyoo. Cov ntaub ntawv ntawm keeb kwm kho mob muaj nyob rau hauv Cov Lus Qhia Ntxiv S1. Hauv 5 tus neeg mob, cov kab mob raum thiab hematological tau txheeb pom nyob rau tib lub sijhawm. Thaum nkag mus rau chav tsev xauj, 11 tus neeg mob tau kho hydroxyurea, cuam tshuam nrog kev kho mob hauv 1 kis. Tsis muaj tus neeg mob tau txais tshuaj nephrotoxic. Kaum ob tus neeg mob tau qhia nrog AKI (theem 1 ntawm 5, theem 2 hauv 3, thiab theem 3 hauv 5). Ob tug neeg mob yuav tsum tau lim ntshav thaum kuaj mob. Hauv 6 tus neeg mob uas tsis tsim AKI, qhov nruab nrab ntawm GFR yog 59 2 ml / min ib 1.73 m2. Ntshav siab tau sau tseg hauv 13 tus neeg mob (72 feem pua) thiab peripheral edema hauv 8 (50 feem pua). Autoimmunity tau txheeb xyuas hauv 8 ntawm 16 tus neeg mob kuaj (antinuclear antibodies n¼8, anti-RNA polymerase III antibodies n¼1, thiab anti-centromere antibodies n¼1). Tsib ntawm lawv muaj CMML. Plaub tus neeg mob tau kuaj pom hom 2 (n¼3) lossis hom 3 (n¼1) cryoglobulinemia, tab sis tsis muaj leej twg muaj ntshav qab zib tsawg C3 lossis C4. Lub raum profile yog heterogeneous, suav nrog ntau cov proteinuria (cov zis protein-rau-creatinine piv $ 3 g / g) hauv 4 tus neeg mob (22 feem pua), tag nrho cov mob nephrotic hauv 4 tus neeg mob (22 feem pua), thiab microscopic hematuria hauv 10 tus neeg mob ( 56 feem pua) (Table 1). Hauv 1 tus neeg mob, AKI tshwm sim los ntawm ureteral obstruction cuam tshuam rau ob qho tib si uric acid lithiasis thiab loj heev extramedullary hematopoiesis (Daim duab 1a qhia suav tomographic scan nrhiav). Tsis tas li ntawd, lub raum loj tau nce thiab lub raum biopsy tau lees paub qhov tshwj xeeb infiltration. Nco ntsoov, 2 tus neeg mob muaj keeb kwm ntawm uric acid lithiasis. Peb tus neeg mob tau nthuav tawm cov cim qhia ntxiv rau lub raum xws li vasculitic tshwm sim nrog rau purpura, arthralgia, lossis tawv nqaij tawg.

Histopathologic Nrhiav

Lub raum biopsy muaj nyob rau hauv 14 tus neeg mob. Raws li tau piav nyob rau hauv Table 1, tsis muaj kev sib raug zoo ncaj ncees yuav raug tsim los ntawm myeloid neoplasm subtypes thiab raum pathologic tshawb pom. Kev raug mob tubulointerstitial yog qhov feem ntau pom (n¼8; 57 feem pua) nrog rau mob ntev (n¼4; 29 feem pua) lossis mob (n¼4; 29 feem pua) . Tubular atrophy thiab inflammatory fifibrosis nrog polymorphic lymphocytic infiltration yog cov yam ntxwv tseem ceeb (Daim duab 2a). Lub cheeb tsam ntawm interstitial fifibrosis muaj li ntawm 10 feem pua ​​​​mus rau 50 feem pua. Cov qib ntawm mesangial hypertrophy thiab kev loj hlob yog sau tseg nyob rau hauv "mesangial sclerosis" kem nyob rau hauv Ntxiv Table S1

Glomerular lesions yog heterogeneous, FSGS yog qhov nquag nquag (n¼5; 36 feem pua), suav nrog 2 nrog kev tso tawm ntawm IgM, C3, thiab C1q. Tsis muaj thrombotic microangiopathy tau tshaj tawm. Qhov tsis muaj electron microscopy precluded tus yam ntxwv ntawm glomerular lesions. Glomerular immunostaining tsis zoo hauv 7 tus neeg mob. Ob tus neeg mob tau mob mesangial sclerosis (Daim duab 2b) nrog IgA mesangial deposits (polyclonal IgA n¼1; monoclonal IgA lambda n¼1). Ib tus neeg mob muaj SAA deposits nyob rau hauv glomeruli ua rau kev kuaj mob ntawm AA amyloidosis.

Lub xub ntiag ntawm megakaryocytes (zoo CD61 cim) tau txheeb xyuas hauv 5 ntawm 8 tus neeg mob kuaj (CMML n¼5; thawj ET n¼2, theem nrab myelofibrosis n¼1) nrog mob tubulointerstitial raug mob, FSGS, lossis ob qho tib si. Megakaryocytes tau txheeb xyuas hauv glomerular thiab interstitial compartments (Daim duab 2c). Extramedullary hematopoiesis tau pom ntawm lub raum biopsy ntawm 5 tus neeg mob (36 feem pua), txhua qhov zoo rau CD61 staining. Lysozyme staining tau zoo nyob rau hauv 4 ntawm 8 kuaj biopsies (ET n¼3 thiab theem nrab myelofibrosis n¼1; Daim duab 3). Raws li kev cia siab, 17 stainings raug txwv rau cov tubules ze ze. Hauv 2 tus neeg mob, lysozyme kuj tau kuaj pom hauv cov zis (cov ntsiab lus hauv Cov Lus Ntxiv S1). Ib tus neeg mob uas muaj CMML tau muaj cov hematopoiesis loj heev uas tsis suav nrog kev tsom xam glomerular (Daim duab 1b), raws li tau lees paub los ntawm CD61 (megakaryocytes; Daim duab 1c), glycophorin C (erythroid precursor cells; Daim duab 1d), thiab myeloperoxidase (myeloid dawb hlwb; Daim duab 1e).

Cov txiaj ntsig

Cov txiaj ntsig tau muab sau tseg rau hauv Table 2. Ua raws li kev txheeb xyuas cov kab mob myeloid neoplasm-mob raum, kev kho mob tau pib lossis hloov kho hauv 11 tus neeg mob (61 feem pua) thiab suav nrog kev qhia lossis hloov ntawm hydroxyurea mus rau anagrelide (n¼1), azacytidine (n¼4) , decitabine (n¼1), lossis ruxolitinib (n¼1). Plaub tus neeg mob tau txais qhov ncauj steroids. Tom qab qhov kev soj ntsuam zoo li ntawm 24- 6 lub hlis, 2 ET cov neeg mob tau nce mus rau theem nrab myelofibrosis. Kev kuaj mob ntawm atypical mastocytosis thaum kawg tau tsim nyob rau hauv ib qho kev kuaj mob yav dhau los CMML. Tsuas yog tus neeg mob nrog PV tsim mob myeloid leukemia tom qab 26 xyoo tom qab. Hematologic malignancy tau pom tias ruaj khov hauv 11 tus neeg mob (61 feem pua), tab sis tsuas yog 8 tus neeg mob tseem muaj sia nyob ntawm qhov kev soj ntsuam zaum kawg (tus ciaj sia taus ntawm 44 feem pua). Hauv txhua tus neeg mob tshwj tsis yog ib qho, lub raum ua haujlwm tsis zoo nrog lub sijhawm, nrog qhov poob qis ntawm -{17}} ml / min ib 1.73 m2. eGFR poob tsis txawv ntawm pawg CMML thiab ET (–21 vs –18 ml/min ib 1.73 m2, P > 0.05).

Kev sib tham

Raws li kev txhim kho cov phiaj xwm tshiab nrog lawv cov tshuaj lom, onconephrology tau tshwm sim los ua qhov kev tshawb fawb loj hauv nephrology.18 Piv txwv li, qhov tseeb tus yam ntxwv ntawm cov kab mob hauv lub raum cuam tshuam nrog hematologic malignancies tso cai rau tus kheej ntawm kev kho mob hauv cov neeg mob monoclonal gammapathies ntawm lub raum tseem ceeb thiab Lwm cov kab mob B cell-related raum.19,20 Hauv qhov sib piv, cov lus piav qhia ntawm lub raum mob cuam tshuam nrog myeloid neoplasms yog qhov tsawg heev, tshwj xeeb tshaj yog rau cov neeg mob uas muaj CMML, tsis suav nrog cov tswv yim kho tus kheej.21–23 Txawm hais tias kev txhim kho raum kab mob feem ntau qeeb ( 7.7 xyoo nyob rau hauv peb series thiab 7.2 xyoo nyob rau hauv lub cohort qhia los ntawm Said li al.12), 5 cov neeg mob muaj concomitant raum kev koom tes ntawm kev kuaj mob ntawm hematologic malignancy, qhia tias lub raum pathology tshwm sim los ntawm ntau yam mechanisms. Myeloid neoplasm clones tuaj yeem tsim cov caj ces txawv txav ntxiv uas ua rau kev tsim cov molecules tsav lub raum fibrosis. Interestingly, ob peb cov kev tshawb fawb pom tau hais tias MPN hlwb muaj peev xwm secrete loj npaum li cas ntawm soluble daim ntawv ntawm urokinase plasminogen activator receptor (suPAR).24

suPAR yog ib qho kev qhia glycoprotein koom nrog hauv kev tsim cov kab mob raum. Cov qib siab ntawm suPAR circulating yog txuam nrog kev loj hlob ntawm CKD thiab tuaj yeem tiv thaiv lub raum rov qab rau cov neeg mob AKI.25,26 Lwm cov kev tshawb fawb kuj tau tshaj tawm tias megakaryocytes tuaj yeem tsav cov pob txha pob txha thiab spleen fifibrosis los ntawm kev tso tawm ntawm kev hloov pauv kev loj hlob-b27. Siv CD61 immunostaining ntawm lub raum biopsies, peb tuaj yeem ua kom pom tias megakaryocytes tuaj yeem nkag mus rau lub raum ntawm cov neeg mob uas muaj cov kab mob myeloid neoplasm ntsig txog raum, yog li qhia tias cov kab mob tshwm sim thaum myeloid neoplasm megakaryocytes tau txais lub peev xwm mus rau hauv lub raum. Txoj kev loj hlob ntawm TGF-bb inhibitors tshiab hauv myelofibrosis thiab myelodysplastic syndromes28 tam sim no ua txoj hauv kev los kuaj cov molecules hauv cov neeg mob uas muaj mob raum ntawm MPN thiab pov thawj raum infiltration los ntawm megakaryocytes. Ntxiv mus, ob lub tswv yim no tsis yog tshwj xeeb thiab tej zaum yuav yog additive, CD61 (los yog integrin-b3) yog tus receptor ntawm suPAR. Raws li peb qhov kev tshawb pom, CD61–/– nas muaj kev tiv thaiv los ntawm glomerulosclerosis vim yog overproduction ntawm suPAR isoform.29 Raws li cov kev xav no, qhov tseem ceeb ntawm glomerular pathologic nrhiav hauv peb cov neeg mob thiab cov uas yav tas los tau tshaj tawm yog mesangial sclerosis thiab hypercellularity.12 Hauv Ib pawg ntawm cov neeg mob, kev raug mob glomerular culminate nyob rau hauv overt FSGS, raws li yav tas los tau piav nyob rau hauv cov neeg mob nrog ET los yog MPN.30 Intracapillary hematopoietic hlwb kuj tau txheeb xyuas nyob rau hauv 23 feem pua ​​​​rau 36 feem pua ​​​​ntawm cov neeg mob, 12 tab sis peb tsis tau soj ntsuam cov tsos mob ntawm cov mob thrombotic microangiopathy, sib piv nrog cov kev tshawb pom uas tau tshaj tawm los ntawm Said et al.12 Hauv pawg tom kawg, MPN yog PMF hauv 8 ntawm 11 (73 feem pua) piv rau ET hauv 7 ntawm 10 (70 feem pua) hauv peb li. Hauv kev tshawb fawb ntxiv, kev sib piv ntawm cov secretome ntawm PMF thiab ET clonal hlwb yuav pab txheeb xyuas cov neeg tshiab hauv cov kab mob ntawm myeloid neoplasm-txog glomerular capillary lesions tab sis kuj thrombotic microangiopathy.

Txawm hais tias lub koom haum tseem ceeb tau tsim los ntawm CMML thiab autoimmunity (ob leeg vasculitis31 thiab autoantibodies32), peb tsis tau pom muaj qhov tshwm sim ntau ntawm ob qho tib si extrarenal manifestations lossis lub raum vasculitis. Tseeb, polymorphic interstitial fifibrosis nrog tubular atrophy yog lub raum pathologic hloov pauv loj (75 feem pua), tom qab ntawd FSGS (25 feem pua) hauv cov neeg mob CMML. Interestingly, overt infiltration los ntawm CMML tau pom nyob rau hauv tsuas yog 1 tus neeg mob thiab yog li tsis yog lub ntsiab ua rau lub raum tsis ua hauj lwm. Extramedullary hematopoiesis yog qhov loj heev hauv 1 tus neeg mob kuj nthuav qhia nrog obstructive AKI ntsig txog uric acid lithiasis. Monocytic thiab myelomonocytic neoplasms, tshwj xeeb tshaj yog CMML, cuam tshuam nrog kev tsim tawm ntau dhau ntawm lysozyme, cov protein uas tsis muaj molecular-yuag dawb lim los ntawm glomerulus, thiab tuaj yeem cuam tshuam nrog nephrotic-ntau lysozymuria. Lysozyme accumulates nyob rau hauv proximal tubular hlwb, thiab muaj ib tug pib ntawm qhov tsub zuj zuj yog txuam nrog toxic proximal tubular raug mob thiab AKI.17 Nyob rau hauv peb series, ntawm 4 cov neeg mob uas zoo staining rau lysozyme, tsuas yog 1 muaj ib tug tubulointerstitial raum raug mob qauv, hos lwm tus muaj FSGS.

Tsis muaj kev sib raug zoo ntawm lysozyme staining thiab hauv qab hematologic malignancy. Yog li, lysozyme raum staining qhia ntau yam pathogenesis hauv myeloid neoplasm-induced raum kab mob. Txog niaj hnub no, cov neeg mob loj tshaj plaws ntawm MPN (tsis suav nrog myelodysplastic neoplasms) tau tshaj tawm 11 tus neeg mob thiab tsom mus rau cov kab mob glomerular, tab sis kev soj ntsuam tau luv dua.12 Ob tug neeg mob tuag (hli 3 thiab 62) thiab 4 mus txog rau theem kawg ntawm lub raum tsis ua haujlwm. . Hauv peb cov koob, cov neeg tuag tau siab (56 feem pua) txawm tias ruaj khov hematologic malignancy hauv 61 feem pua ​​​​ntawm cov neeg mob. Lub raum ua haujlwm tsis zoo rau txhua tus tsuas yog 1 tus neeg mob. Plaub tus neeg mob (22 feem pua) yuav tsum tau lim ntshav mus ntev. Cov neeg mob uas xav tau kev lim ntshav tsis tau txais kev hloov kho, tsuas yog 1 tus uas tau txais hydroxyurea pib. Qhov tsis muaj lub raum kev txhim kho tom qab kev kho cytoreductive hauv peb cov koob sib piv nrog cov txiaj ntsig ntawm kev sib koom ua ke yav dhau los uas suav nrog 136 tus neeg mob uas muaj BCR-ABL-tsis zoo MPN (ET, PV, thiab PMF).8 Hauv txoj kev tshawb no, cov neeg mob feem ntau tau maj mam nce ntxiv. CKD, thaum cov neeg mob suav nrog hauv peb feem ntau muaj AKI uas tuaj yeem tshwm sim los ntawm cov txheej txheem pathophysiological sib txawv. Yog li, cov neeg mob lub raum tsis zoo ntawm MPN yuav tau txais txiaj ntsig los ntawm cov tshuaj tshwj xeeb (xws li ruxolitinib rau PMF) tseem yuav txiav txim siab.33

Tsis tas li ntawd, azacytidine (n¼4) thiab decitabine (n¼1) tau siv los ua ob txoj kab kev kho mob tom qab kev txheeb xyuas ntawm lub raum raug mob nrog kaw kev saib xyuas ntawm qhov muaj peev xwm ntxiv rau lub raum tsis zoo, vim lawv paub tias qee zaum nephrotoxic, tshwj xeeb tshaj yog rau tubules.34,35 Kev txwv. ntawm no ua ntej thiab foremost cia siab rau nws retrospective tsim thiab qhov me me ntawm pawg neeg txawm tias qhov no yog qhov loj tshaj plaws luam tawm txoj kev kawm nyob rau hauv lub tshav pob. Tias yog vim li cas nws tsis tuaj yeem txiav txim siab tag nrho cov kev xav ntawm kev sib raug zoo ntawm lub raum kab mob nrog cov kab mob hematologic. Piv txwv li, 1 tus neeg mob tau nthuav tawm nrog amyloidosis AA thiab raug kev txom nyem los ntawm ankylosing spondylitis rau 28 xyoo thiab los ntawm ET rau 12 xyoo. Cov kab mob ntev tubulointerstitial pom ntawm lub raum biopsy tuaj yeem raug ntaus nqi rau ob qho tib si ET thiab mob ntev uas cuam tshuam nrog amyloidosis. Qhov thib ob, peb tsis tuaj yeem ua kom tsis muaj zog tiv thaiv kab mob, suav nrog CD61 thiab CALR staining, 30 hauv txhua qhov kev kuaj pom, tab sis peb cov txiaj ntsig tsis ntev los no tau qhia txog qhov xav tau kom nkag siab zoo dua li cas myeloid clonal hlwb tuaj yeem ua rau lub raum fifibrosis. Nws tau raug pom tias muaj clonal hematopoiesis nyob rau hauv peripheral-ntshav hlwb cuam tshuam nrog ze li ob npaug ntawm qhov kev pheej hmoo ntawm cov kab mob plawv hauv tib neeg thiab nrog rau kev ceev atherosclerosis hauv cov nas, 36,37 qhia tias clonal monocytes tuaj yeem koom nrog raum mob. Thib peb, electron microscopy tsis muaj. Plaub, kev kuaj mob ntawm atypical mastocytosis thaum kawg tau tsim nyob rau hauv ib qho kev kuaj mob yav dhau los CMML. Thib tsib, peb txoj kev tshawb fawb tsis tau tsim los ntsuas qhov tshwm sim ntawm AKI thiab CKD hauv cov neeg mob uas muaj myeloid neoplasms tab sis pom tau tias (i) kev kho mob raum tsis zoo yog qhov tsis tshua muaj tshwm sim: nrog rau 18 tus neeg muaj hnub nyoog 11 xyoos, qhov tshwm sim txhua xyoo mus txog 1.6, uas yog tsawg heev. ; thiab (ii) nws yuav tsum tau tshawb nrhiav tsis tu ncua rau cov neeg mob uas muaj cov ntaub ntawv tshwj xeeb ntawm myeloid malignancies. Thaum kawg, tib tus neeg mob uas muaj PMF thiab lub raum kev koom tes hauv peb txoj kev tshawb fawb tsis muaj lub raum biopsy. Tab sis, raws li tau hais, pathology ntawm PMF cov neeg mob twb tau piav qhia los ntawm Said li al.12,38,39

Hauv cov ntsiab lus, peb qhia tau hais tias lub raum tsis zoo ntawm CMML thiab MPN yog qhov tsis tshua muaj tab sis tus cwj pwm los ntawm lub raum tsis zoo thiab kev mob thoob ntiaj teb. Glomerulosclerosis thiab interstitial fifibrosis thiab tubular atrophy yog cov kab mob hauv lub raum loj thiab tej zaum yuav raug tsav los ntawm megakaryocyte infiltration hauv ob lub raum, qhib lub qhov rais kho tshiab. Kev tshuaj xyuas cov proteinuria tsis tu ncua thiab cov neeg mob raum tsis raug rau txhua tus neeg mob myeloid neoplasms nyob rau hauv thiaj li yuav ntes tau tus mob raum thaum ntxov thiab hloov kho kev kho mob ntawm malignancy.

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