Recurrence Of 2,8-dihydroxyadenine Crystalline Nephropathy nyob rau hauv Ib Lub raum Hloov Cov Neeg Tau Txais: Daim Ntawv Qhia Txog Cov Ntaub Ntawv thiab Kev Tshuaj Xyuas Cov Ntaub Ntawv Ⅱ

Kev sib tham

APRT tsis muaj peev xwmyog ib qho tsis tshua muaj autosomal recessive kab mob ntawmpurine metabolism tsis ua haujlwm. Adenine ib txwm hloov mus rau adenine monophosphate los ntawm APRT tab sis yog hloov pauv los ntawm xanthine dehydrogenase los ntawm 8- hydroxy intermediate mus rau 2,8-DHA vim qhov tsis txaus ntawm qhov khaws cia enzyme (6). Tus kab mob tam sim no tau kuaj pom tsis zoo vim tsis muaj kev paub txog tus kab mob no ntawm cov kws kho mob nrog rau qhov tsis muaj kev kho mob tshwj xeeb, uas tuaj yeem suav nrogcrystalline nephropathy, urolithiasis, raum colic, mob raum mob, thiaballograft tsis ua haujlwm(7, 19, 20).

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Urolithiasisyog qhov feem ntausoj ntsuam manifestation ntawm tus kab mob nothiab tuaj yeem tshwm sim thaum muaj hnub nyoog; tsawg kawg yog 50% ntawm cov neeg mob, cov tsos mob tsis tshwm sim txog thaum muaj hnub nyoog laus (19). Kev rov ua dua ntawm 2,8-dihydroxyadenine crystalline nephropathy hauv lub raum hloov tuaj yeem ua rau muaj kev ua haujlwm tsis zoo. Nees nkaum kis ntawm APRT tsis txaus hauv cov neeg mob lub raum hloov pauv tau raug tshuaj xyuas (Table). Urolithiasis thiab crystal deposition nyob rau hauv lub allograft ua rau graft dysfunction, mob nyob rau hauv tej rooj plaub thiab ntev nyob rau hauv lwm tus neeg. Huab tso zis tshwm sim los ntawm 2,8-DHA crystal excretion kuj yog ib qho kev tshwm sim tseem ceeb. Ib qho kev tshwm sim tseem ceeb ntawm kev ua haujlwm tsis zoo-anuria lossis oliguria- tau pom nyob rau hauv cov neeg mob no (4, 5, 11, 13, 14), thiab lawv cov kev kuaj pom pom crystal deposition nyob rau hauv lub raum tubules ua rau tubular obstruction. Yog li, cov neeg mob uas tau txais grafts thiab tso saib anuria lossis oliguria yuav tsum xav tias muaj 2, 8-DHA crystal deposition hauv lawv lub raum tubules.

Kev kuaj mob kom raug thiab kho raws sij hawm tuaj yeem feem ntautxhim kho txoj haujlwm graft, tab sis yog tias tsis tuaj yeem kuaj xyuas raws sijhawm lossis kev kho kom raug tsis tuaj yeem siv tom qab hloov lub raum, qhov teeb meem no tau ua rau kev poob qis. Nws tseem ceeb dua, txawm li cas los xij, txhawm rau txheeb xyuas tus kab mob no kom raug ua ntej hloov lub raum thiab tiv thaiv nws rov tshwm sim. APRT deficiency yuav tsum xav tias nyob rau hauv cov neeg mob uas tsis tau piav qhia lub raum tsis ua hauj lwm los yog recurrent urinary lithiasis ntawm undetermined muaj pes tsawg leeg, tshwj xeeb tshaj yog nyob rau hauv cov neeg uas muaj keeb kwm ntawm urolithiasis thaum yau los yog crystalline nephropathy los yog xav tias mob ntev tubulointerstitial nephritis ntawm tsis paub etiology, los yog nyob rau hauv cov neeg uas xav tias muaj autosomal recessive qub txeeg qub teg. tshwj xeeb tshaj yog rau cov neeg uas muaj keeb kwm ntawm kev sib yuav nrog ib tug kwv tij los yog txheeb ze.

2,8-DHA yog cov protein-kho hauv cov ntshav plasma tab sis tsis zoo soluble hauv cov zis ntawm txhua lub cev pH thiab tsim cov muaju hauv tubular lumens, tubular epithelial cells, thiab interstitium, ua rau mob, necrosis, thiab fibrosis (15, 21-23). Qhov tseem ceeb, qhov mob yog tus cwj pwm los ntawm mononuclear cell infiltrates (23), thiab 2, 8-DHA crystals yog ib puag ncig los ntawm cov hlwb loj heev nrog rau cov macrophages ntawm lub raum biopsies (4, 15, 17, 22). Inflammation thiab necrosis nrog crystal deposition tuaj yeem tsis meej pem nrog kev tsis lees paub hauv cov neeg mob hloov pauv. Nyob rau hauv tus neeg mob tam sim no, qhov thib plaub biopsy tau pom muaj kev raug mob histological zoo ib yam li kev tsis lees paub, tab sis tsis muaj kev tiv thaiv kev tsis lees paub. Kev kho mob nrog allopurinol tau ua los txo qhov 2,8-DHA crystalline tsim, thiab tom qab ntawd, qib creatinine hauv cov ntshav poob qis. Qhov no tau qhia tias kev nkag mus ntawm cov hlwb inflammatory nyob rau hauv allograft tej zaum yuav raug ntxias los ntawm crystal deposition tshwm sim los ntawm 2, 8-DHA, ua rau tsis zoo li kev hloov pauv ntawm qhov thib ob biopsy. Nws yog ib qho tseem ceeb kom paub qhov txawv ntawm qhov kev hloov pauv uas tshwm sim los ntawm 2, 8-DHA los ntawm kev tsis lees paub.

Tsis tas li ntawd, qhov rov tshwm sim ntawm urolithiasis yuav tsum tau kuaj kom sai li sai tau. Kev txheeb xyuas tus yam ntxwv 2,8- DHA crystals nyob rau hauv cov zis los yog lub raum biopsy cov qauv yog tsim nyog rau kev kuaj mob, xws li qee kis, tsis muaj pob zeb tau txais. Hauv cov qauv crystalluria feem ntau, 2,8-DHA crystals yog puag ncig thiab xim liab-xim av thaum pom los ntawm cov zis microscopy thiab pom cov qauv hauv nruab nrab Maltese ntoo khaub lig qauv ntawm lub teeb pom kev zoo polarized. Hauv chaw kho mob, Fourier hloov pauv infrared microscopy tau lees paub tias yog ib txoj hauv kev los txheeb xyuas 2,8-DHA crystals (20, 22, 24). Txawm li cas los xij, kev kuaj mob ntawm APRT tsis txaus raws li kev soj ntsuam ntawm 2, 8-DHA crystals thiab urolithiasis tsis txaus. Kev ntsuas ntawm APRT kev ua ub no hauv cov cell liab lysates los yog kev ua haujlwm ntawm kev tshuaj ntsuam genetic molecular yog qhia kom paub meej tias qhov kev kuaj mob ntawm qhov teeb meem no. (20, 22) Kev soj ntsuam pob zeb thiab kev ua APRT hauv cov cell liab lysates tsis tau ua hauv peb tus neeg mob. Hloov chaw, kev tshuaj ntsuam genetic tau ua, qhia txog kab mob homozygous variant.

Txoj kev kho kom raug yuav tsum tau muab rau cov neeg mobkuaj pom tias tsis muaj APRT. Cov koob tshuaj tsawg ntawm allopurinol thiab/lossis febuxostat tsis zoo inhibit qhov tsim ntawm 2,8- DHA crystals (2, 7, 11, 13, 16, 18). Cov koob tshuaj ntau ntawm allopurinol (txog 600 mg, txawm tias 10 mg / kg / hnub) thiab / lossis febuxostat (80 mg) yuav tsum tau ua kom muaj txiaj ntsig zoo inhibition ntawm 2,8-DHA siv lead ua (2, 6, 16 , 18). Cov koob tshuaj ntawm allopurinol thiab febuxostat feem ntau yog empiric vim tsis muaj qhov chaw kuaj ntsuas ntawm 2,8-DHA rau kev kho ncaj qha. Raws li kev txwv cov ntaub ntawv qhia hauv Table thiab cov lus pom zoo ntawm Nasr li al. (11), koob tshuaj allopurinol (400 mg / hnub) thiab / lossis febuxostat (40 mg / hnub) yuav pab tau rau kev kho mob 2,8-DHA crystalline nephropathy. Qhov tseem ceeb, cov kev mob tshwm sim, xws li eosinophilia, ua pob liab liab, ua rau lub siab ua haujlwm tsis zoo, thiab cov tshuaj tiv thaiv kab mob plab, yuav tsum raug txiav txim siab thaum noj cov tshuaj allopurinol thiab / lossis febuxostat (18).

Qhov tseem ceeb,hloov raumCov neeg tau txais kev kho nrog allopurinol yuav tsum tsis txhob raug pom zoo kom noj azathioprine thiab mercaptopurine (19). Cov kua dej alkalization tsis muaj txiaj ntsig vim tias 2, 8-DHA tseem nyob tsis tau ntawm cov zis pH. Nco ntsoov, cov koob tshuaj ntawm cov tshuaj no yuav tsum tsis tu ncua hauv cov neeg mob lub raum tsis ua haujlwm (19). Tsis tas li ntawd, kev kho mob nrog xanthine dehydrogenase yuav tsum tau txuas ntxiv mus thoob plaws hauv tus neeg mob lub neej, vim tias qhov teeb meem no cuam tshuam rau lub neej tsis muaj peev xwm ntawm APRT. Hauv peb cov ntaub ntawv (Fig. 4), tom qab ob lub raum biopsy, tus neeg mob muaj cov qib uric acid siab thiab tau kho nrog allopurinol kom txo tau cov qib siab no. Lub raum ua haujlwm tau ruaj khov nyob rau xyoo tom ntej, nrog rau qib uric acid tseem nyob li qub. Kev saib xyuas mus sij hawm ntev nrog allopurinol hauv peb tus neeg mob tau cuam tshuam qhov tsim ntawm 2,8-DHA. Txawm li cas los xij, tom qab tus neeg mob tsis noj allopurinol, cov ntshav creatinine qib nce ntxiv, nrog cov pov thawj ntawm cov khoom siv lead ua pom nyob rau hauv cov tubule thiab qhov kev tsis pom zoo tau sau tseg ntawm peb thiab plaub lub raum allograft biopsies. Tshwj xeeb, thaum tus neeg mob tau ntsib qhov pom tseeb tsis lees paub ntawm qhov kev kuaj ntshav thib peb thiab tau txais kev kho mob tiv thaiv kev tsis lees paub nrog cov ntshav creatinine txo qis hauv lub sijhawm luv luv, biopsy (plaub biopsy) tau ua ob lub hlis tom qab tsis pom qhov pom tseeb tsis lees paub, ib sab ntawm crystal deposition. nyob rau hauv lub lumen, thiab tus neeg mob tau txais txiaj ntsig los ntawm kev kho mob ntawm allopurinol txawm tias tsis muaj tshuaj tiv thaiv kev tsis lees paub. Qhov no qhia txog qhov tseem ceeb ntawm kev kho mob mus ib txhis nrog allopurinol.

Hauv cov ntsiab lus, APRT tsis muaj peev xwm raug kuaj pom tsis zoo raws li etiology ntawm allograft tsis ua haujlwm vim tsis muaj kev paub txog tus kabmob no. Cov ntaub ntawv no thiab cov ntaub ntawv tshuaj xyuas tau piav qhia txog qhov rov tshwm sim ntawm 2, 8-DHA crystalline nephropathy hauv lub raum hloov pauv. Kev soj ntsuam pob zeb thiab kuaj caj ces yuav tsum tau ua sai sai rau kev kuaj mob. Kev paub txaus yuav tsum muaj rau qhov kev kho mob tsis zoo no, vim tias mob raum mob hnyav tuaj yeem tiv thaiv tau los ntawm kev kuaj mob raws sij hawm, raug thiab kev tswj xyuas sai.

Sau ntawv tso cai rau kev tshaj tawm cov ntaub ntawv kho mob thiab cov duab kho mob tau txais los ntawm tus neeg mob thiab muaj rau kev tshuaj xyuas thaum thov.

Cov kws sau ntawv hais tias lawv tsis muaj qhov tsis sib haum xeeb ntawm kev txaus siab (COI). Kev them nyiaj yug

Txoj kev tshawb no tau txais kev txhawb nqa nyiaj txiag los ntawm Lub Tsev Haujlwm Saib Xyuas Kev Tshawb Fawb thiab Tshuab ntawm Zhejiang Xeev (Grant No. 2019C 03029), Bethune Charitable Foundation (GX-2019-0101-12), thiab National Natural Science Foundation of China (Grant Nos. 81870510).

Cov ntaub ntawv

1. Zaidan M, Palsson R, Merieau E, et al. Rov ua dua 2,8- dihydroxyadenine nephropathy: qhov tsis tshua muaj tab sis tiv thaiv tau ua rau lub raum tsis ua haujlwm. Am J Hloov 14: 2623-2632, 2014.

2. Glicklich D, Gruber HE, Matas AJ, et al. 2,8-dihydroxyadenine urolithiasis: daim ntawv qhia txog ib rooj plaub thawj zaug tom qab hloov lub raum. QJ Med 68: 785-793, 1988.

3. Gagné ER, Deland E, Daudon M, Noël LH, Nawar T. Mob raum tsis ua hauj lwm theem nrab mus rau 2, 8-dihydroxyadenine deposition: thawj daim ntawv qhia txog kev rov tshwm sim hauv lub raum hloov. Am J Raum Dis 24: 104-107, 1994.

4. De Jong DJ, Assmann KJM, De Abreu RA, et al. 2,8- Dihydroxyadenine pob zeb tsim nyob rau hauv lub raum hloov pauv vim yog adenine phosphoribosyltransferase Deficiency. J Urol 156: 1754-1755, 1996.

5. Brown HA. Kev rov ua dua ntawm 2,8-dihydroxyadenine tubulointerstitial lesions hauv lub raum hloov pauv nrog rau thawj qhov kev nthuav qhia ntawm lub raum tsis ua haujlwm. Nephrol Dial Transplant 13: 998-1000, 1998.

6. Benedetto B, Madden R, Kurbanov A, Braden G, Freeman J, Lipkowitz GS. Adenine phosphoribosyltransferase deficiency thiab lub raum allograft tsis ua haujlwm. Am J Raum Dis 37: E37, 2001.

7. Cassidy MJ, McCulloch T, Fairbanks LD, Simmonds HA. Diagno sis ntawm adenine phosphoribosyltransferase deficiency raws li lub hauv paus ua rau lub raum tsis ua hauj lwm nyob rau hauv lub raum hloov pauv. Nephrol Dial Transplant 19: 736-738, 2004.

8. Micheli V, Massarino F, Jacomelli G, et al. Adenine phosphoribosyltransferase (APRT) deficiency: ib qho kev hloov pauv caj ces tshiab nrog cov kab mob raum pob zeb thaum ntxov hauv kev hloov raum. NDT Plus 3: 436-438, 2010.

9. Stratta P, Fogazzi GB, Canavese C, thiab al. Txo lub raum ua haujlwm thiab crystal deposition hauv tubules tom qab hloov lub raum. Am J Raum Dis 56: 585-590, 2010.

10. Bertram A, Broecker V, Lehner F, Schwarz A. Kev hloov pauv hauv lub raum hauv tus neeg mob uas muaj adenine phosphoribosyl transferase deficiency: obstacles thiab pitfalls. Transpl Int 23: e56-e58, 2010.

11. Nasr SH, Sethi S, Cornell LD, et al. Crystalline nephropathy vim 2,8-dihydroxyadeninuria: ib qho tsis pom zoo ua rau lub raum tsis ua haujlwm. Nephrol Dial Transplant 25: 1909-1915, 2010.

12. Sharma SG, Moritz MJ, Markowitz GS. 2, 8-Dihydroxyadeninuria tus kab mob. Raum Int 82: 1036, 2012.

13. Kaartinen K, Hemmilä U, Salmela K, Räisänen-Sokolowski A, Kouri T, Mäkelä S. Adenine phosphoribosyltransferase deficiency raws li qhov tsis tshua muaj ua rau lub raum tsis ua haujlwm. J Am Soc Nephrol 25: 671-674, 2014.