Novel Therapies Rau Alport Syndrome

TSAB NTAWV

Alport syndrome (AS) yog ib hom kab mob hauv lub raum uas cuam tshuam nrog cov proteinuria, hematuria, thiab lub raum tsis ua haujlwm. Nws yog tus cwj pwm los ntawm qhov tsis zoo glomerular hauv qab daim nyias nyias los ntawm kev hloov pauv hauv hom IV collagen noob COL4A3 / A4 / A5 uas ua rau muaj qhov tsis zoo IV collagen 3, 4, lossis 5 chains, raws li. Alport syndrome muaj peb yam kev sib txawv ntawm cov qub txeeg qub teg: X-txuas, autosomal, thiab digenic. Hauv kev tshawb fawb ntawm CKD ntawm qhov tsis paub etiology hom IV collagen noob kev hloov pauv tau suav rau feem ntau ntawm cov xwm txheej ntawm cov kab mob glomerulopathies uas qhia tias AS feem ntau tsis lees paub. Lub ntuj keeb kwm thiab kev kwv yees hauv cov neeg mob AS yog qhov sib txawv thiab raug txiav txim los ntawm cov noob caj noob ces thiab ib puag ncig. Tam sim no, tsis muaj kev tiv thaiv lossis kev kho mob rau AS. Kev kho tam sim no suav nrog kev siv renin-angiotensin-aldosterone system inhibitors uas ua rau qeeb ntawm kev mob raum thiab ua rau lub neej ntev. Ramipril tau pom nyob rau hauv cov kev tshawb fawb rov qab los ncua qhov pib ntawm ESKD thiab tsis ntev los no tau pom tias muaj kev nyab xeeb thiab siv tau zoo rau cov menyuam yaus thiab cov tub ntxhais hluas, txhawb nqa qhov pib thaum ntxov ntawm Renin Angiotensin Aldosterone System (RAAS) blockade tseem ceeb heev. Mineralocorticoid receptor blockers tej zaum yuav zoo rau cov neeg mob uas tsim "aldosterone breakthrough." Thaum qhov kev sim DAPA-CKD qhia tau hais tias muaj txiaj ntsig zoo ntawm SGLT2 inhibitors hauv CKD ntawm cov neeg mob uas tsis yog metabolic, tsuas yog qee tus neeg mob tau Alport hauv pawg no, thiab yog li cov lus xaus tsis tuaj yeem raug ntxiv rau kev kho mob ntawm AS nrog SGLT2 inhibitors. Kev nce qib hauv peb txoj kev nkag siab ntawm pathogenesis ntawm Alport syndrome tau ua tiav hauv kev txhim kho cov txheej txheem kho tshiab uas tam sim no tab tom tshawb nrhiav. Peb yuav muab cov ntsiab lus luv luv ntawm cov hom phiaj kho tshiab los tiv thaiv kev mob raum hauv AS. Peb qhov kev tshuaj xyuas yuav suav nrog bardoxolone methyl, qhov ncauj NRf2 activator; lademirsen, anti-miRNA-21 molecule; spartan, dual endothelin type A receptor (ETAR) thiab angiotensin 1 receptor inhibitor; atrasentan, qhov ncauj xaiv ETAR inhibitor; lipid-modifying agents, suav nrog cov roj cholesterol efflux transporter ATP-binding cassette A1 (ABCA1) inducers, discoidin domain receptor 1 (DDR1) inhibitors thiab osteopontin blocking agents; cov tshuaj tiv thaiv kab mob malarial hydroxychloroquine; Cov tshuaj tiv thaiv glycemic tshuaj metformin thiab active vitamin D analog paricalcitol. Yav tom ntej genomic therapeutic tswv yim xws li chaperone therapy, genome editing, thiab qia cell therapy kuj tseem yuav tham txog.

KEYWORDS

Alport, Alport kab mob, Alport nephritis, Alport hereditary nephritis, COL4, hom IV collagen, collagen 4, kev kho mob.

Nyem qhov no kom paub seb cov txiaj ntsig ntawm Cistanche yog dab tsi

Taw qhia

Alport syndrome (AS), tseem hu ua hereditary nephritis, yog ib qho kab mob glomerular uas feem ntau cuam tshuam nrog kev hnov ​​​​lus tsis hnov ​​​​lus thiab qhov muag tsis pom kev. Nws nthuav tawm cov qauv kev tsis sib xws thiab kev ua haujlwm tsis zoo ntawm glomerular hauv qab daus daim nyias nyias (GBM) tshwm sim los ntawm kev hloov caj ces cuam tshuam rau hom IV collagen 3/4/5 chains (1). Hom IV collagen yog qhov tseem ceeb rau GBM kev ruaj ntseg thiab ua rau feem ntau ntawm tag nrho GBM protein ntau. Cov 1 txog 6 hom IV collagen chains yog cov caj ces sib txawv thiab lawv sib sau ua 3 hom heterotrimers: 1 1 2, 3 4 5, thiab 5 5 6 (2). Hauv AS, cov kab mob sib txawv hauv cov noob COL4A3 thiab COL4A4 (uas nyob rau ntawm chromosome 2) thiab COL4A5 (uas yog nyob rau ntawm X chromosome) tsim cov khoom tsis zoo IV collagen 3, 4 lossis 5 chains ntsig txog, uas cuam tshuam cov kev sib dhos tsim nyog ntawm lub cev. GBM (3, 4).

CLASSIFICATION

Cov txheej txheem kev faib tawm tshiab categorizes AS rau hauv 3 hom sib txawv raws li qhov cuam tshuam rau hom IV collagen noob koom nrog thiab hom kev qub txeeg qub teg: X-txuas AS, autosomal, lossis digenic (Table 1).

Raws li qhov kev faib tawm no, nws tsis tas yuav muaj keeb kwm zoo hauv tsev neeg, kev tshwm sim tsis zoo, lossis pov thawj ntawm cov kab mob hauv lub raum mus rau kev kuaj mob AS. Cov poj niam uas muaj heterozygous COL4A5 variants yog cais raws li muaj AS es tsis txhob raug sau tias yog "tus neeg nqa khoom" ntawm tus kab mob. Cov neeg mob uas muaj kev sib cais ntawm cov kab mob microscopic hematuria thiab heterozygous variants nyob rau hauv COL4A3 los yog COL4A4 raug suav hais tias muaj autosomal dominant Alport syndrome (ADAS), uas yog li tshem tawm qhov kev kuaj mob ntawm nyias hauv qab daim nyias nyias nephropathy (TBMN) (3). Nws yuav tsum raug lees paub tias lub ntsiab lus kawg no yog qhov tsis sib haum xeeb ntawm cov kws tshaj lij ntawm tus mob no thiab qhov no tsis yog kev pom zoo thoob ntiaj teb (5).

Genetic testing in AS is proposed for patients who have persistent dysmorphic hematuria for longer than 6 months; persistent proteinuria >0.5 g/g, tsev neeg keeb kwm ntawm hematuria lossis kab mob raum; tsis hnov ​​​​tsw sensorineural nrog hematuria; lenticonus, fleck retinopathy los yog temporal retinal thinning; biopsy-pov thawj focal segmental glomerulosclerosis (FSGS) lossis steroid-resistant nephrotic syndrome; GBM lamellation; Cov kab mob raum ntev uas tsis paub txog etiology nrog hematuria thiab tsev neeg IgA glomerulonephritis. Kev ntsuam xyuas caj ces kuj raug pom zoo hauv thawj qib cov txheeb ze ntawm cov neeg uas paub cov kab mob sib txawv hauv COL4A3-COL4A5 noob (6).

Cistanche tubulosa

PREVALENCE

Qhov tshwm sim ntawm Alport syndrome sib txawv heev nyob rau hauv cov ntaub ntawv sib txawv nrog kev kwv yees li ntawm ib ntawm 5, 000 mus rau ib qho ntawm 53, 000 cov neeg mob raum. X-txuas Alport syndrome (XLAS) yog tshwm sim los ntawm COL4A5 noob kev hloov pauv thiab tso nyiaj rau 70-80 feem pua ​​​​ntawm cov neeg mob AS. Autosomal recessive Alport syndrome (ARAS) yog tshwm sim los ntawm homozygous lossis compound heterozygous hloov pauv hauv COL4A3 thiab COL4A4 cov noob thiab suav rau ∼5 feem pua ​​​​ntawm cov neeg mob AS. Ib txoj kev tshawb fawb tsis ntev los no tau kwv yees qhov tshwm sim ntawm kev kwv yees kab mob COL4A3-COL4A5 sib txawv hauv cov neeg uas tsis muaj kab mob raum. Kwv yees kab mob COL4A5 variants tau pom nyob rau hauv ib qho ntawm 2,320 tus neeg. Kev kwv yees kab mob heterozygous COL4A3 thiab COL4A4 variants cuam tshuam rau ib qho ntawm 106 tus neeg, raws li kev tshawb pom ntawm TBMN hauv lub raum biopsies hauv cov neeg pub dawb uas tsis paub txog kab mob raum. Kev kwv yees kab mob sib xyaw ua ke heterozygous variants tshwm sim hauv ib qho ntawm 88, 866 cov neeg thiab digenic variants tsawg kawg ib ntawm 44,793 tus neeg. Txawm li cas los xij, cov pej xeem ntau zaus ntawm kev kwv yees COL4A3-COL4A5 cov kab mob sib txawv yuav tsum tau hloov kho raws li tus kab mob nkag mus ntawm tus neeg sib txawv (7).

Qhov tseeb prevalence ntawm AS yog yuav underestimated. Ib txoj kev tshawb fawb tsis ntev los no los ntawm Columbia University siv kev tshuaj ntsuam genetic testing cov neeg mob ntawm cov kab mob hauv lub raum tsis paub txog etiology qhia tias Mendelian nephropathies suav txog 21 feem pua ​​​​ntawm cov neeg mob. Monogenic glomerulopathies feem ntau tshwm sim thiab qhov no feem ntau yog tsav los ntawm kev hloov pauv hauv collagen IV noob uas suav txog ze li ib feem peb ntawm tag nrho cov kab mob hauv lub raum (8).

NATURAL HISTORY THIAB PROGNOSIS

AS suav nrog ntau hom phenotypic spectrum nrog ntau yam kev kho mob tshwm sim. Cov kab mob hauv lub raum histological hauv tus neeg mob uas tau tsim los ntawm AS tau piav qhia ntawm electron microscopy raws li qhov tsis xwm yeem thinning thiab thickening GBM nrog lub lamellated tsos uas muaj tus yam ntxwv "basket-weave" qauv (9). Thaum lub raum biopsy ua nyob rau hauv ib tug neeg mob nrog cais hematuria qhia tshwj xeeb tshaj yog ib tug nyias GBM nws tau raug thov kom siv cov ntsiab lus "benign familial hematuria" los yog "nyias hauv qab daus membrane nephropathy." Txawm li cas los xij, qhov no yog qhov kev xav yuam kev vim tias muaj pov thawj ntau ntxiv tias qee tus ntawm cov neeg mob no muaj kev pheej hmoo ntawm kev mob raum. Hauv cov neeg mob nrog AS, nyias GBM kuj tuaj yeem txheeb xyuas thiab yog li qhov kev tshawb nrhiav histological yuav tsum tsis txhob suav tias yog ib qho kev tsis sib haum xeeb. Ib tug nyias GBM los ntawm nws tus kheej tsis txaus los kwv yees kwv yees thaum tsis muaj kev kho mob ntxiv, kab mob, kab mob, thiab cov ntaub ntawv caj ces.

Qhov tshwm sim ntawm kev mob raum rau cov neeg mob cuam tshuam nrog AS yog qhov sib txawv thiab feem ntau yog txiav txim siab los ntawm hom kev hloov pauv ntawm cov noob. Kev tshem tawm loj, kev hloov pauv tsis tseem ceeb, thiab kev hloov pauv me me cuam tshuam rau kev nyeem ntawv uas ua rau txo qis lossis tsis tuaj yeem ua haujlwm tsis muaj protein ntau sawv cev rau kev pheej hmoo ntawm kev mob raum mus rau theem kawg (ESKD) thaum muaj hnub nyoog 30. Qhov kev pheej hmoo yog me me nrog kev tsis lees paub lossis qhov chaw sib hloov pauv ( 10). Tsis tas li ntawd, tej yam ib puag ncig tej zaum yuav ua rau muaj kab mob raum.

Cov txiv neej nrog XLAS thiab txhua tus neeg mob nrog ARAS feem ntau tsim "classic" AS cov yam ntxwv uas suav nrog cov kab mob hauv lub raum nrog hematuria thiab proteinuria, hnov ​​​​lus tsis hnov ​​​​lus, thiab qhov muag tsis pom kev (xws li lenticonus lossis maculopathy). Txawm hais tias tsawg dua kev lees paub tias yog ib qho kev ua haujlwm zoo, aortic aneurysms feem ntau pom tau hauv cov txiv neej nrog XLAS (11).

Nyob rau hauv rooj plaub ntawm XLAS, kev sib deev yog ib qho tseem ceeb prognostic yam txog CKD kev loj hlob. Ntawm cov txiv neej uas tsis kho nrog XLAS, nyob ib ncig ntawm 50 thiab 90 feem pua ​​​​nce mus rau ESKD los ntawm hnub nyoog 25 thiab 40, feem. Cov poj niam nrog XLAS nthuav tawm cov phenotype sib txawv vim cov txheej txheem ntawm X chromosome inactivation. Ntawm cov poj niam nrog XLAS, kwv yees li 12 feem pua ​​​​ntawm ESKD ua ntej hnub nyoog 40 thiab qhov kev faib ua feem no nce mus txog 30 feem pua ​​​​ntawm hnub nyoog 60 thiab 40 feem pua ​​​​ntawm hnub nyoog 80 (10). Cov neeg mob ARAS feem ntau nce mus rau ESKD thaum muaj hnub nyoog 40 tsis hais poj niam txiv neej (12).

Standardized Cistanche

Cov neeg mob nrog ADAS nthuav tawm ntau yam kev tshwm sim uas muaj xws li asymptomatic mus rau lub raum txwv tsis pub muaj kab mob microscopic hematuria lossis proteinuria thiab qee kis mus rau ESKD. Cov phenotype cuam tshuam nrog kev hloov pauv heterozygous hauv COL4A3 lossis COL4A4 tuaj yeem sib txawv heev txawm tias nyob hauv cov tswv cuab ntawm tib tsev neeg, thiab qhov kev hloov pauv ntawm qhov kev qhia no yuav muaj ntau yam. Qhov kev nkag mus tsis tiav no tuaj yeem cuam tshuam txog qhov muaj cov noob hloov pauv uas ua kom zoo lossis ua rau muaj kev cuam tshuam ntau dua los ntawm hom IV collagen noob hloov thiab lwm yam xws li ntshav siab, noj zaub mov sodium siab, rog, thiab haus luam yeeb uas tuaj yeem ua rau mob raum (3 , 13).

Hauv cov neeg mob nrog ADAS, kwv yees qhov kev pheej hmoo rau ESKD yog ntau dua lossis sib npaug li 20 feem pua ​​​​rau cov neeg uas muaj kev pheej hmoo rau kev loj hlob (proteinuria, FSGS, GBM thickening thiab lamellation, tsis hnov ​​​​lus tsis hnov ​​​​lus, genetic modifiers) thiab<1% in the absence of these risk factors (3).

Qhov kwv yees kev pheej hmoo rau kev nce mus rau ESKD hauv cov neeg mob uas muaj digenic AS yog qhov sib txawv thiab nyob ntawm cov noob cuam tshuam: rau COL4A3 thiab COL4A4 kev hloov pauv hauv trans simulating autosomal recessive qub txeeg qub tes qhov kev pheej hmoo yog mus txog 100 feem pua; rau COL4A3 thiab COL4A4 kev hloov pauv hauv cis simulating autosomal dominant qub txeeg qub teg qhov kev pheej hmoo yog nce txog 20 feem pua ​​thiab rau cov txiv neej cuam tshuam nrog kev hloov pauv hauv COL4A5 thiab COL4A3 thiab COL4A4 qhov kev pheej hmoo yog mus txog 100 feem pua ​​(3).

Hom IV collagen noob kev hloov pauv kuj tau cuam tshuam nrog FSGS thiab kev kuaj caj ces yuav tsum tau txiav txim siab tshwj xeeb hauv cov neeg mob uas muaj keeb kwm zoo ntawm FSGS thiab hnub nyoog yau ntawm kev nthuav qhia. Hom IV collagen noob kev hloov pauv tau pom nyob rau hauv 38 feem pua ​​​​ntawm cov neeg mob nrog tsev neeg FSGS thiab 3 feem pua ​​​​ntawm FSGS nrog ntau tshaj ib nrab ntawm cov kev hloov pauv tshwm sim hauv COL4A5. Lub xub ntiag ntawm hematuria, tsis hnov ​​​​lus, thiab GBM abnormalities yuav qhia tau tias muaj kev hloov pauv hauv COL4 (14). Nyob rau hauv ib pawg ntawm 193 tus neeg ntawm Toronto GN npe nrog feem ntau FSGS uas tau ua tiav tag nrho-exome sequencing, cov tshuaj ntsuam xyuas caj ces yog 11 feem pua ​​​​thiab los ntawm cov neeg mob no, 55 feem pua ​​​​tau muaj cov kab mob sib txawv hauv COL4 (A3 / A4 / A5) noob ( 15). Cov tib neeg uas muaj biopsy-pov thawj FSGS uas muaj cov kab mob sib txawv hauv hom IV collagen noob yuav tsum raug cais raws li cov neeg mob Alport syndrome. Nws yog ib qho tseem ceeb kom tsis txhob siv cov tshuaj tiv thaiv kab mob rau cov neeg mob no vim tias qhov no yuav ua tsis tau zoo thiab muaj feem cuam tshuam. Ua raws li cov kev soj ntsuam no, kev ntsuam xyuas caj ces yuav tsum tau txais hauv txhua tus neeg mob uas muaj FSGS pov thawj los yog steroid-resistant nephrotic syndrome (6).

KIDNEY TRANSPLANTATION

Cov neeg mob Alport syndrome uas tau nce mus rau ESKD feem ntau yog cov neeg sib tw zoo rau kev hloov lub raum. Preemptive raum hloov pauv yuav tsum tau ua raws thaum ua tau. Hauv cov neeg mob nrog AS, graft survival cov nqi sib npaug los yog zoo dua piv rau cov neeg uas pom hauv cov neeg mob uas muaj lwm yam ua rau ESKD. Nws raug pom zoo tias cov neeg hauv tsev neeg uas yog COL4A3 thiab COL4A4 heterozygotes tsis raug txiav txim siab rau lub raum pub dawb (6). Muaj pov thawj los ntawm cov tib neeg uas muaj hematuria los yog heterozygous pathogenic COL4A3 lossis COL4A4 variants uas ua raws li lub raum pub dawb uas tsim cov raum ua haujlwm tsis zoo lossis proteinuria dhau sijhawm (16-18). Thaum txoj kev loj hlob ntawm anti-GBM tshuaj tiv thaiv tsis muaj kev kho mob tshwm sim yog heev, posttransplant anti-GBM nephritis yog ib qho txawv txawv tab sis tej zaum yuav muaj kev puas tsuaj loj ntawm lub raum hloov hauv AS cov neeg mob (19).

Kev kho mob

Tam sim no, tsis muaj kev kho mob rau Alport syndrome. Kev siv renin-angiotensin-aldosterone system (RAAS) inhibition (RAASi) yog tus qauv tam sim no ntawm kev saib xyuas kom qeeb kev loj hlob ntawm cov kab mob raum.

Cistanche capsules

RAAS Inhibition

Tag nrho thiab cov npoj yaig luam tawm xyoo 2012 uas siv cov tshuaj angiotensin-hloov enzyme inhibitors (ACEi) hauv ib pawg ntawm 174 cov neeg mob nrog AS (feem ntau txiv neej nrog XLAS) tau cuam tshuam nrog qhov pib ntawm kev kho lub raum hloov pauv thiab lub neej ntev dua piv rau cov pab pawg ntawm cov neeg mob. 109 tsis kho AS cov txheeb ze dhau qhov kev soj ntsuam ntawm ntau tshaj ob xyoo lawm. Qhov txiaj ntsig no tau zoo dua rau cov neeg mob uas pib kho thaum ntxov, tshwj xeeb tshaj yog rau cov neeg mob uas tau cais hematuria lossis microalbuminuria thaum lub sijhawm pib kho (20). Cov ntaub ntawv los ntawm European Alport Registry tau qhia tias kev siv RAAS blockade hauv heterozygous Alport cov neeg nqa khoom yog cuam tshuam nrog kev mob raum qeeb. Lub hnub nyoog nruab nrab ntawm qhov pib kho yog 28 xyoo thiab lub sijhawm nruab nrab ntawm kev kho yog 5.8 xyoo hauv qhov kev tshuaj ntsuam no. Qhov pib ntawm kev kho lub raum hloov (RRT) tshwm sim tsawg zaus thiab tom qab ntawd tshwm sim hauv cov neeg mob uas tau kho nrog RAAS blockade (21). Yamamura thiab cov npoj yaig tau tshuaj xyuas ib pawg neeg Nyij Pooj cov neeg mob nrog XLAS nrog cov pov thawj COL4A5 variants thiab pom tias lub raum tiv thaiv cov nyhuv ntawm RAAS blockade yog tam sim no tsis hais hom COL4A5 gene variant (truncating vs. non-truncating) (22).

Most ACE Inhibitors are currently authorized by the Food and Drug Administration (FDA) for the treatment of hypertension in adults or children ≥6 years old (23). However, the EARLY PROTECT trial showed that the use of ramipril in children with AS aged ≥2 years when there is either isolated microscopic hematuria or microalbuminuria (defined as 30– 300 mg albumin/g creatinine) is safe and effective at slowing kidney disease progression compared to placebo. Ramipril was initiated at a mean age of 8.8 ± 4.2 years. In this study, ramipril therapy reduced the risk of disease progression by almost 50%. Disease progression was defined as progression to the next disease stage according to the extent of renal damage and loss of function. These stages were defined as (0) microhematuria without microalbuminuria, (I) microalbuminuria [30–300 mg albumin/g creatinine], (II) proteinuria [>300 mg albumin/g creatinine], (III) >25 feem pua ​​​​kev poob qis ntawm lub raum tsis ua haujlwm (CrCl), (IV) kab mob raum kawg. Ib qho kev phom sij ntawm 0.51 txhais tau tias yog 5.4 tus menyuam yaus uas yuav tsum tau kho nrog ramipril rau 3 xyoos txhawm rau tiv thaiv kev kis tus kabmob hauv ib tus menyuam (24).

Cov lus pom zoo ntawm kev kho mob tshiab txhawb kev pib ua ntej ntawm ACEi hauv cov neeg mob cuam tshuam nrog AS. Kev kho mob yuav tsum tau pib thaum lub sijhawm kuaj mob hauv cov txiv neej nrog XLAS thiab txhua tus neeg mob ARAS yog tias muaj hnub nyoog ntau dua lossis sib npaug li 24 lub hlis. Hauv cov poj niam nrog XLAS thiab txiv neej thiab poj niam nrog ADAS, kev kho tuaj yeem pib thaum pib ntawm microalbuminuria (25).

Mineralocorticoid Receptor Blockers

Cov ntshav aldosterone tseem nce siab hauv qee cov neeg mob kho nrog ACEi thiab / lossis ARBs, qhov tshwm sim hu ua "aldosterone breakthrough" uas tau cuam tshuam nrog sab laug ventricular hypertrophy thiab ntau dua ntawm albuminuria (26). Rubel thiab cov npoj yaig tau soj ntsuam yog tias kev siv spironolactone sib xyaw rau saum ramipril hauv COL4 3 −/− nas muaj txiaj ntsig ntxiv piv rau ramipril monotherapy. Ob txoj kev kho mob ua rau muaj kab mob raum qeeb qeeb thiab txo qis proteinuria thiab fibrosis. Txawm li cas los xij, kev ciaj sia tsis hloov. Qhov no tshwm sim vim kev tuag ntxov ntxov los ntawm kev mob tshwm sim ntawm ob txoj kev kho mob xws li hyperkalemia (27). Spironolactone cov teebmeem hauv tib neeg cov ntsiab lus tau raug tshuaj xyuas hauv kev soj ntsuam soj ntsuam [NCT02378805] (28). Cov txiaj ntsig tau pom zoo ntawm cov non-steroidal mineralocorticoid receptor blocker finer enone ntawm kev ncua CKD kev loj hlob hauv cov neeg mob ntshav qab zib mellitus (DKD) (29, 30) qhia tias yuav tsum tau kuaj nws cov txiaj ntsig hauv cov tsis muaj ntshav qab zib CKD.

SODIUM-GLUCOSE COTRANSPORTER-2 INHIBITORS (SGLT2I)

SGLT2i blocks renal glucose absorption in the proximal convoluted tubule which promotes glucosuria and lowers blood glucose. These drugs have nephroprotective properties which are independent of glycemic control and are thought to be mediated by glucose-induced osmotic diuresis and concomitant natriuresis leading to afferent arteriole vasoconstriction and a reduction in intraglomerular pressure and reduction in albuminuria (31). There is extensive evidence about the benefit of these drugs to slow the progression of CKD of diabetic and non-diabetic origin (32, 33). In a cohort of 5 pediatric patients with Alport syndrome (mean age 10.4 years) with an eGFR >60 ml / min / 1.73 m2 kev siv dapagliflozin tau txais txiaj ntsig zoo thiab ua rau 22 feem pua ​​​​ntawm cov proteinuria txo los ntawm 12 lub lis piam (34).

Hauv cov nas mob ntshav qab zib, SGLT2i kuj tseem txo qis kev mob plawv ntawm cov lipids lom thiab pub dawb fatty acid uptake (35). Hauv cov neeg mob uas muaj cov kab mob tsis zoo rau lub siab thiab hom 2 mob ntshav qab zib mellitus (T2DM) siv SGLT2i txo cov rog rog thiab txhim kho ALT qib (36). Yog li ntawd, nws muaj peev xwm pom tau tias cov nyhuv nephroprotective ntawm SGLT2i kuj tseem kho tau los ntawm kev txo qis lipotoxicity ntawm lub raum, uas peb tau pom tias muaj kab mob hauv kev sim AS (37). Thaum qhov kev sim DAPA-CKD qhia tau hais tias muaj txiaj ntsig zoo ntawm SGLT2 inhibitors hauv CKD ntawm cov neeg mob uas tsis yog metabolic, tus naj npawb ntawm cov neeg mob Alport syndrome suav nrog hauv pawg no tsawg, thiab yog li cov lus xaus tsis tuaj yeem ntxiv rau cov pej xeem nyob rau lub sijhawm no. Txawm li cas los xij, qhov ua tau zoo ntawm SGTL2 inhibitors hauv kev kho mob ntawm AS yuav tsum tau tshawb xyuas (38).

Cistanche hmoov

Kev sib tham

Alport Syndrome yog ib hom kab mob hauv lub raum uas niaj hnub no tsis muaj kev kho mob. Cov kev kho mob ib txwm ua kom qeeb qhov kev loj hlob ntawm lub raum tsis ua haujlwm siv RAASi. Kev tsim tshuaj yeeb hauv AS tam sim no tab tom ua nrog cov hom phiaj tshuaj ntawm ntau theem ntawm tus kab mob. Kev sim tshuaj tuaj yeem tsom qhov hloov pauv ntawm GBM lossis kev sib cuam tshuam ntawm GBM nrog podocytes thiab endothelial hlwb. Lwm cov tshuaj tshiab tsom rau tubular cell raug mob los yog qhov mob thiab fibrosis pom nyob rau hauv cov theem kawg ntawm tus kab mob. Targeting puas collagen chains ntxov nyob rau hauv tus kab mob los ntawm noob kev kho tej zaum yuav yog txoj kev kho nrog lub siab tshaj plaws peev xwm los thim qhov teeb meem no. Kev tshawb fawb nce qib ntawm cov txheej txheem kho tshiab rau tus mob no yog qhov zoo siab thiab tuaj yeem ua rau muaj kev cia siab rau ntau lab tus neeg mob cuam tshuam.

Yuav Ua Li Cas Cistanchis Txhim Kho Raum Ua Haujlwm

Cistanches, tseem hu ua Rou Cong Rong hauv Suav tshuaj, yog ib hom tshuaj ntsuab uas tau siv rau ntau pua xyoo los kho ntau yam mob. Ib qho txiaj ntsig tseem ceeb tshaj plaws ntawm Cistanches yog lawv lub peev xwm los txhim kho lub raum ua haujlwm.

Ua ntej, Cistanches muaj phytochemicals xws li echinacoside thiab Acteoside uas tau raug pov thawj tias muaj txiaj ntsig zoo rau lub raum. Cov tshuaj no muaj cov tshuaj tiv thaiv kab mob antioxidant thiab tiv thaiv kab mob uas pab txo qhov mob thiab oxidative kev nyuaj siab hauv lub raum. Qhov no yuav pab tiv thaiv lub raum hlwb los ntawm kev puas tsuaj thiab txhim kho lub raum ua haujlwm.

Thib ob, Cistanches kuj txhawb cov ntshav khiav thiab ncig hauv lub raum. Qhov no yog qhov tseem ceeb vim tias cov ntshav txaus kom lub raum tau txais cov as-ham tseem ceeb thiab cov pa oxygen xav tau rau kev ua haujlwm zoo. Thaum lub raum cov ntshav khiav tsis zoo, nws tuaj yeem ua rau mob raum mob thiab lwm yam mob uas cuam tshuam rau lub raum.

Tsis tas li ntawd, Cistanches tau siv ib txwm siv los kho lub raum tsis zoo, xws li qis zog, tso zis ntau zaus, thiab mob nraub qaum. Cov tshuaj ntsuab no tau pom tias ua rau lub raum tonify thiab muab cov khoom noj uas tsim nyog rau kev ua haujlwm zoo.

Hauv kev xaus, Cistanches yog ib qho tshuaj zoo rau kev txhim kho lub raum. Nrog nws cov tshuaj tiv thaiv kab mob thiab antioxidant, nws pab tiv thaiv ob lub raum thiab txhawb cov ntshav txaus. Nws yog ib qho tshuaj ntsuab zoo thiab muaj txiaj ntsig uas txhua tus tuaj yeem siv los txhawb lawv lub raum noj qab haus huv.

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Efren Chavez 1, Juanly Rodriguez 1, Yelena Drexler 1, thiab Alessia Fornoni 1,2

1 Katz Family Division of Nephrology and Hypertension, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL, United States,

2 Peggy thiab Harold Katz Family Drug Discovery Center, University of Miami Miller Tsev Kawm Ntawv Tshuaj, Miami, FL, United States