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Published on: November 10, 2021
Electron microscopic findings can support multiple etiologies of nephrotoxicity in renal tubules
Ping L Zhang1, Timothy Pancioli1, Wei Li1
1Division of Anatomic Pathology, Department of Pathology, Beaumont Labs, Beaumont Health System , Royal Oak, MI, USA.
Abstract:
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.
Insights
Electron microscopy (EM) reveals characteristic renal tubular changes, offering diagnostic or supportive evidence for drug-induced nephrotoxicity. This highlights the importance of examining tubules, not just glomeruli, for accurate diagnosis.
Area of Science:
- Nephrology
- Pathology
- Toxicology
Background:
- Electron microscopy (EM) is crucial for diagnosing glomerular diseases.
- Renal tubular changes identified by EM can offer significant diagnostic insights into nephrotoxicity.
- This study explores the utility of EM in diagnosing drug-induced kidney injury.
Observation:
- Review of multiple drug-induced nephrotoxicity cases, correlating clinical history, serum creatinine (sCr), and EM findings.
- Aminoglycoside antibiotics induced acute tubular injury with diagnostic myeloid bodies.
- Vancomycin and vedolizumab showed tubular changes (casts, tubulitis) as supportive evidence.
Findings:
- EM findings in renal tubules provide unique or additional diagnostic evidence for drug-associated nephrotoxicity.
- Myeloid bodies in tubules are diagnostic for aminoglycoside nephrotoxicity.
- Vancomycin casts and vedolizumab-induced tubulitis serve as supportive EM evidence.
Implications:
- EM examination of renal tubules is essential for diagnosing drug-induced nephrotoxicity.
- Integrating EM findings with clinical data enhances diagnostic accuracy.
- Understanding tubular EM changes aids in managing and predicting recovery from kidney injury.
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