Chronic

Tubulointerstitial

NephritisCHENGKAIYUANChronic

TIN

is

a

frequent

cause

of

ESRD,

characterized

by

the

clinical

manifestation

of

tubular

dysfunction

and

progressive

chronic

renal

failure

and

pathological

changes

of

tubular

atrophy,

inflammatory

cell

infiltration

of

interstitial

nephritisandfibrosis.ContentEpidemiologyEtiologyPathophysiology診斷治療PrognosisEpidemiologyPrimarytubulointerstitialdiseases(ie,diseasesoftherenaltubulesandinterstitiumsparingtheglomeruli)constitute10-15%ofallkidneydiseasesbothintheUnitedStatesandaroundtheworld.Analgesicnephropathyis5-6timesmorecommoninwomen--womentakingmoreanalgesicsthanmen.--greatersensivityAlltoxicnephropathiesarerelatedtothecumulativeeffects,morefrequentlywithadvancingage.Metabolicdisorders--youngerindividuals.EtiologyDrugs(eg,analgesics,lithium,cyclosporine,tacrolimus)Heavymetals(eg,lead,cadmium,mercury)Infection(acute

pyelonephritis)Obstructiveuropathy,nephrolithiasis,refluxdiseaseImmunologicdiseases(eg,lupus,Sj?grensyndrome,primaryglomerulopathies,sarcoidosis,vasculitis,antineutrophilcytoplasmicantibody[ANCA]–associatedvasculitides,Wegenergranulomatosis,andchronictransplantnephropathy)Neoplasia(eg,myeloma,leukemia,amyloidosis)Metabolicdiseases(eg,hypercalcemia,cystinosis,potassiumdepletion,hyperoxaluria)Genetics(eg,Alportsyndrome,medullarycysticdisease)Miscellaneous(eg,Balkanendemicnephropathy,Chineseherb/aristolochicacidnephropathy)[5,6]PathophysiologyChronictubulointerstitialnephritisischaracterizedbyinterstitialscarring,fibrosis,andtubuleatrophy,resultinginprogressivechronicrenalinsufficiency.Activationofnucleartranscriptionfactors,suchNFκBininjuredkidneycells,withconsequenttranscriptionandreleaseofproinflammatorycytokinesintotheinterstitium,appearstobeamajormechanismPathophysiologycollagenproductiondegradationfibrogenesisTGF-β-+Kidneybiopsy.Thisimageshowschronictubulointerstitialnephritis.Theinterstitiumisexpandedbyfibrosis,withdistortionoftubulesandperiglomerularfibrosis.Glomerulidonotshowpathologicchanges(hematoxylinandeosin,20X).***Acute

vs

ChronicMorphology

featuresacutechronicinterstitiumCell

infiltration+~+++++~++edema+~+++++~++fibrosis-+~++++tubuleepitheliumInjury,

necrosisatrophyBasement

membraneInjury,breakagethickenessmorphologycompleteatrophyglomerulusNo

or

minimal

periglomerularFibrosis

or

sclerosisvesselMinimal,

reversiblesclerosis診斷——CIN臨床表現發(fā)病隱襲，常無癥狀；或僅有輕度乏力、夜尿增多病程進展中可出現貧血、高血壓和消化道癥狀（納差、惡心）等CIN實驗室檢查尿酸化功能障礙；尿濃縮功能障礙；腎小管轉運功能障礙；電解質代謝紊亂：如高鉀或低鉀血癥，高磷或低磷血癥等；腎小球濾過率下降：表現為血肌酐、BUN升高。診斷——懷疑慢性TIN的臨床線索原因不明性腎功能不全存在尿路梗阻或返流，有長期接觸腎毒性物質或服用腎毒性藥物病史伴有腎功能不全而無明顯水腫和高血壓輕度小分子蛋白尿，尿中β2微球蛋白、α1球蛋白及NAG等增加尚未確診的低磷血癥、高或低鉀血癥及代謝性酸中毒原因不明的骨軟化患者

明確有無腎小管功能損傷經常晨尿pH>6.0、比重<1.018血糖正常而尿糖陽性尿中β2微球蛋白、α1球蛋白及NAG、溶菌酶增加尿糖、氨基酸、磷酸鹽、尿鈉、尿氨異常、腎活檢確診明確引起慢性TIN的病因病損部位及功能受損情況病損部位病因小管功能不全近端小管重金屬，多發(fā)性骨髓瘤，免疫疾病，囊性病變重吸收功能↓酸化功能↓遠端小管免疫病，結節(jié)病，遺傳病，高鈣血癥，尿路梗阻，淀粉樣變泌H↓，泌K↓重吸收Na↓髓質止痛劑腎病，尿酸性腎病，高鈣血癥，感染，遺傳性疾病，結節(jié)病濃縮功能↓重吸收Na↓腎乳頭止痛劑腎病，糖尿病，感染，尿路梗阻，移植腎濃縮功能↓重吸收Na↓鑒別診斷小球or小管？尿蛋白比值，尿pH，尿比重急性or慢性？病因？治療——CIN治療原則針對病因進行治療；對癥治療：如糾正酸中毒，貧血，高血壓，電解質紊亂等；對已有腎功能損害者，按慢性腎功能不全處理。免疫抑制劑血液凈化治療PrognosisTubulointerstitialdiseasemayprogresstoend-stagerenaldisease(ESRD)andthusrequiredialysisortransplantation.

Much

slower

than

glomerular

diseas