急性腎盂腎炎之回溯分析與追蹤

泌尿道感染為最常見的人類細菌感染之一，急性腎盂腎炎，屬其中較嚴重的類別，一般以臨床症狀為診斷依據，主要含發燒、腰痛及菌尿，病程通常會進展到系統性炎症反應症候群，可能合併菌血症，敗血性休克，甚至死亡。泌尿道感染的致病機轉，致病菌的角色很早就被確立，但宿主因素近幾年正受積極的研究，解剖構造、環境、行為都已獲證明，尚未明瞭的是宿主免疫反應的差異。小鼠的動物模式證明，嗜中性白血球在泌尿道感染的易感性及細菌清除具決定性角色，而介白質-8為其中最重要的趨化物質。介白質-8受器 knock out 小鼠，急性期常合併菌血、敗血症甚至死亡，存活小鼠則呈現腎臟的慢性纖維化。在人類小兒患者，有泌尿道發炎病史的，其嗜中性白血球上介白質-8受器的表現，比未曾有過泌尿道發炎病史者低，結果和上述缺乏受器小鼠泌尿道感染易感性符合。本研究的目的在試圖分析，成人急性腎盂腎炎患者，有無任何宿主因素(如:介白質-8受器表現)，和急性疾病的嚴重度，與慢性腎臟損傷，或持續菌尿有相關。方法:以社區感染的，非阻塞性的，尿液培養陽性的，曾於200401-200412期間於高醫住院之成人女性病患，以及，未曾有過急性腎盂腎炎病史的志願者，做一非感染期的追蹤檢查，並回溯住院期間病歷做記錄，追蹤檢查包含:血液及尿液生化檢查，尿液培養，以及腎臟超音波，並測量腎臟血管阻力係數，並以流體細胞儀，計測患者在非感染期時，嗜中性白血球上介白質-8受器(CXCR1, CXCR2)的表現，統計分析何項參數和疾病病程嚴重度(以有無合併菌血症、治療後發燒日數、住院日數代表) 相關，何項參數和腎臟慢性變化(以肌酸酐清除率、尿白蛋白/肌酸酐比例代表)及持續菌尿症相關。結果:共26個成人急性腎盂腎炎患者，及32個年齡相對應的志願者，參與實驗。回溯研究部分:急性腎盂腎炎患者住院天數和糖尿病相關，而有合併菌血症和疾病時CRP數值相關。追蹤研究部分:CCr及ACR和急性感染發生時的尿蛋白價數有關；目前有菌尿，易發生於APN患者，糖尿病患者及急性感染有菌血症者；mean RI在糖尿病的有或無，以及目前菌尿症有或無有差異。嗜中性白血球上介白質8受器之表現，在病患組和志願者之間沒有差異。結論:社區感染的，非阻塞性的，尿液培養陽性的，成人女性急性腎盂腎炎患者，其急性感染期的預後很好，然而，針對急性感染時尿蛋白價數多的，合併菌血症的，以及糖尿病患者，應該特別注意追蹤，有無潛藏持續的菌尿，以及腎功能的變化。Mean RI在本研究，雖未能區分病患與對照組，但未來研究時可試圖在急性感染期及追蹤期操作，分析其差異變化以及預後。嗜中性白血球上介白質8受器，在成人急性腎盂腎炎有無角色，本研究結果是沒有差異，但是，由於CXCR1及CXCR2表現，在個體間或同個體不同時間之差異很大，且過去很少研究討論CXCR1及CXCR2在追蹤期卅非感染期的基準值，因此可能須多次研究，並提高個數才能得到較明確的結果。

關鍵字

急性腎盂腎炎；回溯分析；追蹤

並列摘要

Urinary tract infection (UTI) is one of the most common infectious diseases in human. There are important medical and financial implications associated with UTIs. Acute pyelonephritis (APN) is clinical syndrome of flank pain, renal tenderness, fever, and chills, accompanied by bacteriuria, and represent severe form of UTIs. It may combined bacteremia and can progress to the systemic inflammatory response syndrome, septic shock, and death. Research during the last few decades has established that the site of infection and the disease severity are influenced by bacterial virulence. Other anatomic, behavior, and environment host risk factors had also been discussed. Confirmed by murine UTI model, neutrophil-dependent “innate” defense mechanisms are more important than specific immunity for resistance to UTI. Interleukin (IL)-8 is the critical chemotatic factor. Neutrophil recruitment is the pivotal pathophysiological event underlying the bacterial clearance but also tissue damage and renal scarring associated with UTI. In mIL-8Rh KO mice, the neutrophil influx was delayed and neutrophils failed to transverse the epithelium. These mice were shown to develop acute, lethal disease accompanied by bacteremia. Survived animals developed chronic infection and progressively destructive inflammation of the kidneys. And UTI-prone children have reduced neutrophil IL-8R expression. In our study, we use retrospective APN data collection and a follow up examination try to answer: is any host factors, such as IL-8R (CXCR1, CXCR2) expression, or other clinical parameter associated with APN acute disease severity or follow up chronic renal damage. Method: We enrolled community-acquired, non-obstructive, adult, female who had been hospitalized for APN at KMUH during 200401-200412, and a age-matched, control group who had no APN history to participate the study. We will retrospectively record date during hospitalization, and analyze what clinical parameter associated with acute APN severity (longer hospital days, longer febrile days after treatment, combined bacteremia). With the follow up visit, we performed blood, urine, and renal sonographic examination, The analysis focused on chronic renal damage (low creatinine clearance, more urine albumin/creatinine ratio, persist bacteriuria ). Renal interlobar artery resistive index (RI) were measured by sonography. And neutrophil’s CXCR1 and CXCR2 expression were checked by flow cytometry. Result: total 26 APN cases and 32 volunteers were examined. Retrospective study showed: DM patients had longer hospital stay than non-diabetic patient. Bacteremia had higher CRP level at admission than patient without bacteremia. Follow up study showed: acute pyelonephritis patients’ in their follow up examination: lower creatinine clearance and higher urine albumin/creatinine ratio were associated with urine protein during acute APN. Positive follow-up urine culture (possible indicated persist chronic infection) associated with diabetic mellitus and bacteremia during acute APN. Mean RI, CXCR1 and CXCR2 expression showed no significant between APN group and volunteers. Conclusion: community-acquired, non-obstructive, culture-proven APN has good acute disease survival. But when APN patient has significant proteinuria, combined with bacteremia, or had diabetic mellitus, serial follow up should be performed due to increase chances of chronic renal damage and persistent bacteriuria. Is adult baseline neutrophil CXCR1 and CXCR2 expression has association with APN? It may be need more case number and further study.

並列關鍵字

acute pyelonephritis ； retrospective analysis ； follow up

參考文獻

1. Foxman B. Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am J Med. 2002; 113(1A): 5S-13S.

Google Scholar

2. Foxman B, Klemstine KL, Brown PD. Acute pyelonephritis in US hospitals in 1997: hospitalization and in-hospital mortality. Ann Epidemiol. 2003; 13: 144-50.