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[骨髓瘤管型肾病和依赖透析的急性肾损伤患者肾脏对治疗反应的形态学和免疫组化预测指标]

[Morphological and immunohistochemical predictors of renal response to therapy patients with myeloma cast nephropathy and dialysis-dependent acute kidney injury].

作者信息

Rekhtina I G, Kazarina E V, Stolyarevich E S, Kovrigina A M, Dvirnyk V N, Kulikov S M, Mendeleeva L P

机构信息

National Research Center for Hematology.

Moscow City Nephrology Center, Moscow City Hospital 52.

出版信息

Ter Arkh. 2020 Sep 1;92(7):63-69. doi: 10.26442/00403660.2020.07.000776.

DOI:10.26442/00403660.2020.07.000776
PMID:33346446
Abstract

AIM

Reveal morphological and immunohistochemical predictors of reversibility of dialysis-dependent acute kidney injury (AKI) in patients with myeloma cast nephropathy (MCN) based on the study of kidney biopsy.

MATERIALS AND METHODS

Renal pathological findings were studied in 36 patients with MCN and dialysis-dependent stage 3 AKI (AKIN, 2012). The study of biopsy samples was performed by a semi-quantitative and quantitative analysis using computer morphometry. The expression of E-cadherin, vimentin and-smooth muscle actin was determined immunohistochemically in the tubular cells and interstitium. Induction therapy for 26 patients was carried out to bortezomib-based programs; in 10 patients other schemes were used. A comparative analysis of morphological changes in nephrobiopathy depending on the renal response was performed in patients with achieved hematologic remission.

RESULTS

Improved renal function was observed only in patients with hematologic response to therapy. There were no differences in the number of sclerotic glomeruli, protein casts, the area of inflammatory interstitial infiltration, and the degree of acute tubular damage in patients with and without renal response. In patients with renal response compared with patients without improving renal function, the area of interstitial fibrosis was less (24.9% and 45.9%, respectively;p=0.001), and the area of E-cadherin expression was larger (15.9% and 7.1%, respectively;p=0.006). Interstitial fibrosis of 40% or more and/or the area of expression of E-cadherin less than 10% of the area of tubulo-interstitium have an unfavorable prognostic value in achieving a renal response in MCN.

CONCLUSION

If the interstitial fibrosis area is 40% or more and the expression area of E-cadherin is less than 10%, the probability of the absence of a renal response is 93.3% (OR=24.5) even when a hematological response to induction therapy is achieved. The number of protein casts, the prevalence of acute tubular damage and inflammatory interstitial infiltration have not prognostic value.

摘要

目的

通过对肾活检的研究,揭示骨髓瘤管型肾病(MCN)患者中依赖透析的急性肾损伤(AKI)可逆性的形态学和免疫组化预测指标。

材料与方法

对36例MCN和依赖透析的3期AKI(AKIN,2012)患者的肾脏病理结果进行研究。活检样本的研究采用计算机形态计量学进行半定量和定量分析。通过免疫组化法测定肾小管细胞和间质中E-钙黏蛋白、波形蛋白和α-平滑肌肌动蛋白的表达。26例患者采用基于硼替佐米的方案进行诱导治疗;10例患者采用其他方案。对血液学缓解患者的肾病形态学变化根据肾脏反应进行比较分析。

结果

仅在对治疗有血液学反应的患者中观察到肾功能改善。有或无肾脏反应的患者在硬化肾小球数量、蛋白管型、炎性间质浸润面积和急性肾小管损伤程度方面无差异。与肾功能未改善的患者相比,有肾脏反应的患者间质纤维化面积较小(分别为24.9%和45.9%;p=0.001),E-钙黏蛋白表达面积较大(分别为15.9%和7.1%;p=0.006)。40%或更多的间质纤维化和/或E-钙黏蛋白表达面积小于肾小管间质面积的10%对MCN实现肾脏反应具有不良预后价值。

结论

如果间质纤维化面积为40%或更多且E-钙黏蛋白表达面积小于10%,即使诱导治疗获得血液学反应,无肾脏反应的概率仍为93.3%(OR=24.5)。蛋白管型数量、急性肾小管损伤的发生率和炎性间质浸润无预后价值。

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