Division of Anatomic Pathology, Department of Pathology, Beaumont Labs, Beaumont Health System , Royal Oak, MI, USA.
Ultrastruct Pathol. 2020 Nov 20;44(4-6):481-488. doi: 10.1080/01913123.2020.1839152. Epub 2020 Nov 1.
Electron microscopy (EM) has been mainly used for identifying ultrastructural abnormalities such as fusion of foot processes and immune complex deposits in glomeruli. However, electron microscopic findings in renal tubules can provide either diagnostic evidence (unique finding) or supportive evidence (additional finding) for final diagnosis. Here we present multiple situations that EM can be used for drawing conclusions of various drug-associated nephrotoxicity. Multiple cases with drug-induced nephrotoxicity are reviewed, including clinical history, EM findings, and serum creatinine (sCr) levels, prior to renal biopsy and during follow-up. Two cases with nephrotoxicity by aminoglycoside antibiotics showed acute tubular injury with EM findings of myeloid bodies, characterized by laminated dense materials in lysosomes in both proximal and distal tubular epithelium (diagnostic evidence). Five cases of vancomycin associated nephrotoxicity presented with acute tubular injury and vancomycin casts in distal tubules, characterized by central laminated casts in the lumina of distal tubules (supportive evidence). Vedolizumab, a humanized monoclonal antibody used in treating Crohn's disease, can cause T-cell dominant acute interstitial nephritis, with EM revealing lymphocytic infiltration into tubules as tubulitis (supportive evidence). Four of Seven cases (5/8) cases had renal functional recovery upon follow-up check for sCr. EM findings of characteristic changes in renal tubules can be particularly useful as either diagnostic or supportive evidence, in correlation with clinical history and etiologies of nephrotoxicity. Therefore, EM should not only focus on glomerular changes, but renal tubular changes as well.
电子显微镜(EM)主要用于识别超微结构异常,如足突融合和肾小球内免疫复合物沉积。然而,肾小管的电子显微镜检查结果可以为最终诊断提供诊断证据(独特发现)或支持证据(附加发现)。在这里,我们提出了多种可以用于得出各种药物相关性肾毒性的结论的情况。我们回顾了多个药物引起的肾毒性病例,包括临床病史、EM 发现和血清肌酐(sCr)水平,这些病例在肾活检前和随访期间均有记录。两例氨基糖苷类抗生素引起的肾毒性表现为急性肾小管损伤,EM 发现髓样小体,特征为近端和远端肾小管上皮细胞溶酶体中分层致密物质(诊断证据)。五例万古霉素相关性肾毒性表现为急性肾小管损伤和远端肾小管中的万古霉素管型,特征为远端肾小管管腔中中央分层管型(支持证据)。用于治疗克罗恩病的人源化单克隆抗体Vedolizumab 可引起 T 细胞占主导地位的急性间质性肾炎,EM 显示淋巴细胞浸润到肾小管中,表现为肾小管炎(支持证据)。在对 sCr 进行随访检查后,7 例中有 4 例(5/8)肾功能恢复。与肾毒性的临床病史和病因相关,肾小管的 EM 特征性改变可以作为诊断或支持证据特别有用。因此,EM 不仅应关注肾小球变化,还应关注肾小管变化。