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Abstract：
BACKGROUND: Vancomycin, a commonly prescribed antibiotic particularly in the setting of multi-drug resistant infections, is limited by its nephrotoxicity. Despite its common occurrence, much remains unknown on the clinicopathologic profile as well as the pathogenesis of vancomycin nephrotoxicity. Clinical studies included patients often with severe comorbidities and concomitant polypharmacy confounding the causal pathogenesis. Animal models cannot recapitulate this complex clinical situation. Kidney biopsy was not commonly performed.
METHODS: To address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group.
RESULTS: Patients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity.
CONCLUSIONS: Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.
METHODS: To address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group.
RESULTS: Patients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity.
CONCLUSIONS: Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.
摘要：
背景：万古霉素，一种常用的抗生素，特别是在多重耐药感染的背景下，受其肾毒性的限制。尽管它很常见，万古霉素肾毒性的临床病理特征和发病机制仍不清楚。临床研究包括经常患有严重合并症和伴随的多重用药混淆了因果发病机制的患者。动物模型不能概括这种复杂的临床情况。通常不进行肾脏活检。
方法：为了解决此限制，我们研究了36例因怀疑万古霉素肾毒性而接受急性肾损伤(AKI)肾活检的患者.详细的肾活检评估，对临床资料进行细致的评估，和最新的随访允许对25例患者的万古霉素肾毒性（VNT）进行诊断分类，对11例患者无万古霉素肾毒性（NO-VNT）。为了仔细比较这两组，我们编制了每组特征性的临床病理和形态学资料.
结果：VNT患者具有特征性的临床特征，包括共同的临床背景，万古霉素的高血清谷水平，迅速发展和严重的急性肾损伤，和肾功能的恢复通常在停用万古霉素后不久。该临床过程与特征性肾活检结果相关，包括过敏性急性肾小管间质性肾炎，常见的肉芽肿性炎症，伴随和明显的急性肾小管坏死的肾毒性类型，和万古霉素模型，在没有明显的肾小管萎缩和间质纤维化的情况下。这种临床病理特征不同于NO-VNT患者，强调它在诊断中的作用，万古霉素肾毒性的管理和病因探讨。
结论：万古霉素肾毒性具有独特的形态学和临床特征，这应该有助于诊断，指导治疗和预后，并赋予致病性见解。
方法：为了解决此限制，我们研究了36例因怀疑万古霉素肾毒性而接受急性肾损伤(AKI)肾活检的患者.详细的肾活检评估，对临床资料进行细致的评估，和最新的随访允许对25例患者的万古霉素肾毒性（VNT）进行诊断分类，对11例患者无万古霉素肾毒性（NO-VNT）。为了仔细比较这两组，我们编制了每组特征性的临床病理和形态学资料.
结果：VNT患者具有特征性的临床特征，包括共同的临床背景，万古霉素的高血清谷水平，迅速发展和严重的急性肾损伤，和肾功能的恢复通常在停用万古霉素后不久。该临床过程与特征性肾活检结果相关，包括过敏性急性肾小管间质性肾炎，常见的肉芽肿性炎症，伴随和明显的急性肾小管坏死的肾毒性类型，和万古霉素模型，在没有明显的肾小管萎缩和间质纤维化的情况下。这种临床病理特征不同于NO-VNT患者，强调它在诊断中的作用，万古霉素肾毒性的管理和病因探讨。
结论：万古霉素肾毒性具有独特的形态学和临床特征，这应该有助于诊断，指导治疗和预后，并赋予致病性见解。
