慢性肾小管间质肾炎

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诊断治疗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,Sjögrensyndrome,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诊断——CIN临床表现发病隐袭，常无症状；或仅有轻度乏力、夜尿增多病程进展中可出现贫血、高血压和消化道症状（纳差、恶心）等CIN实验室检查尿酸化功能障碍；尿浓缩功能障碍；肾小管转运功能障碍；电解质代谢紊乱：如高钾或低钾血症，高磷或低磷血症等；肾小球滤过率下降：表现为血肌酐、BUN升高。诊断——怀疑慢性TIN的临床线索原因不明性肾功能不全存在尿路梗阻或返流，有长期接触肾毒性物质或服用肾毒性药物病史伴有肾功能不全而无明显水肿和高血压轻度小分子蛋白尿，尿中β2微球蛋白、α1球蛋白及NAG等增加尚未确诊的低磷血症、高或低钾血症及代谢性酸中毒原因不明的骨软化患者

明确有无肾小管功能损伤经常晨尿pH>6.0、比重<1.018血糖正常而尿糖阳性尿中β2微球蛋白、α1球蛋白及NAG、溶菌酶增加尿糖、氨基酸、磷酸盐、尿钠、尿氨异常、肾活检确诊明确引起慢性TIN的病因病损部位及功能受损情况病损部位病因小管功能不全近端小管重金属，多发性骨髓瘤，免疫疾病，囊性病变重吸收功能↓酸化功能↓远端小管免疫病，结节病，遗传病，高钙血症，尿路梗阻，淀粉样变泌H↓，泌K↓重吸收Na↓髓质止痛剂肾病，尿酸性肾病，高钙血症，感染，遗传性疾病，结节病浓缩功能↓重吸收Na↓肾乳头止痛剂肾病，糖尿病，感染，尿路梗阻，移植肾浓缩功能↓重吸收Na↓鉴别诊断小球or小管？尿蛋白比值，尿pH，尿比重急性or慢性？病因？治疗——CIN治疗原则针对病因进行治疗；对症治疗：如纠正酸中毒，贫血，高血压，电解质紊乱等；对已有肾功能损害者，按慢性肾功能不全处理。免疫抑制剂血液净化治疗PrognosisTubulointerstitialdiseasemayprogresstoend-stagerenaldisease(ESRD)andthusrequiredialysisortransplantation.

Much

slower

than

glomerular

diseas