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肾移植术后3年观察中,移植前活检的组织病理学评估作为影响移植肾功能的一个因素。

Histopathologic evaluation of pretransplantation biopsy as a factor influencing graft function after kidney transplantation in 3-year observation.

作者信息

Sulikowski T, Tejchman K, Ziętek Z, Urasińska E, Domański L, Sieńko J, Romanowski M, Safranow K, Zukowski M, Ciechanowicz A, Ciechanowski K, Ostrowski M

机构信息

Department of General Surgery and Transplantation, Pomeranian Medical University, Szczecin, Poland.

出版信息

Transplant Proc. 2010 Nov;42(9):3375-81. doi: 10.1016/j.transproceed.2010.08.060.

Abstract

BACKGROUND

Many factors affect long-term results in kidney transplantation including histologic damage as a independent predictor, eg, chronic allograft dysfunction (CAD) in protocol biopsies and age-dependent lesions. Histopathologic findings correlate with the incidence of delayed graft function, eventual renal function, and allograft survival, allowing a rather precise prediction of graft outcomes.

PATIENTS AND METHODS

We analyzed 92 thick-needle preimplantation renal biopsies and 29 from grafts after explantation. They had been preserved in 4% formalin and immersed in paraffin. Evaluable specimens contained ≥10 glomeruli and ≥2 arterial cross-sections. We analyzed tubulitis, intensity of acute tubular necrosis (ATN), inflammatory infiltration, glomerulonephritis, arterial hyalinization, arteritis, fibrosis, tubular atrophy, arterial intimal fibrosis, increased mesangial matrix, and glomerulosclerosis percentage, although for comparative analysis not only optimal ones were taken into consideration. Over postoperative time, we analyzed patient condition, urine output, serum concentrations of creatinine, urea, uric acid, and ions as well as necessity for postoperative dialysis, ie, delayed graft function (DGF). During the 3-year observation we analyzed living recipients, graft loss, death with a functioning graft, incidence of dysfunction (CAD), and acute rejection episodes (ARE).

RESULTS

We observed significant correlations between immediate graft function (IGF) and lack of ATN in the pretransplantation biopsy. The presence of ATN significantly correlated with DGF and primary graft non-function. There was no correlation between renal function and arterial hyalinization or fibrosis, inflammatory infiltration, and tubular atrophy. Over postoperative time we observed significant correlations between IGF and the lack of interstitial fibrosis as well as significantly lower levels of creatinine, urea, and potassium as well as greater urine output early after transplantation. IGF correlated with shorter time to reach a creatinine level of 2 mg/dL, lower concentrations of creatinine, urea, and potassium, as well as greater diuresis during the first 5 days. In addition, lower creatinine and urea concentrations after 1 month and of urea at 6 and 36 months were associated with IGF. Female recipients showed lower concentration of creatinine over 3 months, of urea during the 1st day, and of potassium at 1 month; however, thereafter the differences were not significant. Better function of the right kidney was observed. The presence of severe ATN (ATN III) correlated with lower creatinine concentrations at 6 months and urea after 3 years. The presence of hyalinization in biopsies correlated with higher concentrations of urea at 1 year and of borderline significance after 3 years; surprisingly, potassium concentrations were lower after 2 and 3 years. The presence of inflammatory infiltrates correlated with higher creatinine concentrations after 1 and 3 years; similar correlations, albeit of borderline significance, were observed in tubular atrophy. Interstitial fibrosis correlated with creatinine concentrations during 10 days after the operation and after 12 months, also with potassium concentrations 5 days after the operation. Borderline correlations were observed between donor age and creatinine concentration in the first day after the operation, after 6 months, and time to achieve a creatinine concentration of 2 mg/dL. We observed that biopsies with greater numbers of glomeruli correlated with better graft function, namely, lower creatinine concentrations after 5 days as well as at 1 and 6 months, as well as lower urea concentrations after 5 days and 6 months. We also observed differences in renal function depending on gender. The presence of acute tubular necrosis, arterial fibrosis and a lack of inflammatory infiltration in pretransplantation biopsy correlated with worse late renal function. Explantation biopsies showed signs of CAD in 66.4% and histologic features of ARE in 38.51%.

摘要

背景

许多因素影响肾移植的长期结果,包括组织学损伤作为一个独立预测因素,例如,方案活检中的慢性移植肾功能障碍(CAD)和年龄依赖性病变。组织病理学发现与移植肾功能延迟的发生率、最终肾功能及移植肾存活相关,从而能相当精确地预测移植结果。

患者和方法

我们分析了92例移植前粗针肾活检标本以及29例移植肾切除后的标本。这些标本用4%甲醛固定并浸于石蜡中。可评估标本包含≥10个肾小球和≥2个动脉横断面。我们分析了肾小管炎、急性肾小管坏死(ATN)的严重程度、炎症浸润、肾小球肾炎、动脉玻璃样变、动脉炎、纤维化、肾小管萎缩、动脉内膜纤维化、系膜基质增加以及肾小球硬化百分比,不过在进行比较分析时并非仅考虑最佳指标。在术后随访期间,我们分析了患者状况、尿量、血清肌酐、尿素、尿酸和离子浓度以及术后透析的必要性,即移植肾功能延迟(DGF)。在3年观察期内,我们分析了活体受者、移植肾丢失、移植肾存活时的死亡情况、功能障碍(CAD)发生率以及急性排斥反应(ARE)发生率。

结果

我们观察到移植前活检中即时移植肾功能(IGF)与无ATN显著相关。ATN的存在与DGF及原发性移植肾无功能显著相关。肾功能与动脉玻璃样变或纤维化、炎症浸润及肾小管萎缩之间无相关性。在术后随访期间,我们观察到IGF与无间质纤维化显著相关,且移植后早期肌酐、尿素和钾水平显著较低以及尿量较多。IGF与达到肌酐水平2mg/dL的时间较短、肌酐、尿素和钾浓度较低以及术后前5天尿量较多相关。此外,术后1个月及6个月和36个月时较低的肌酐和尿素浓度与IGF相关。女性受者在3个月内肌酐浓度较低,术后第1天尿素浓度较低,术后1个月钾浓度较低;然而,此后差异不显著。观察到右肾的功能较好。严重ATN(ATN III)的存在与术后6个月时较低的肌酐浓度及术后3年时较低的尿素浓度相关。活检中玻璃样变的存在与术后1年时较高的尿素浓度相关,术后3年时具有临界显著性;令人惊讶的是,术后2年和3年时钾浓度较低。炎症浸润的存在与术后1年和3年时较高的肌酐浓度相关;在肾小管萎缩中观察到类似的相关性,尽管具有临界显著性。间质纤维化与术后10天及12个月时的肌酐浓度相关,也与术后5天的钾浓度相关。在术后第1天、术后6个月及达到肌酐浓度2mg/dL的时间方面,供体年龄与肌酐浓度之间观察到临界相关性。我们观察到肾小球数量较多的活检与较好的移植肾功能相关,即术后5天以及术后1个月和6个月时肌酐浓度较低,术后5天和6个月时尿素浓度较低。我们还观察到肾功能因性别而异。移植前活检中急性肾小管坏死、动脉纤维化的存在及无炎症浸润与较差的晚期肾功能相关。移植肾切除活检显示66.4%有CAD迹象,38.51%有ARE的组织学特征。

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