Department of Kidney Transplantation, The Second Xiangya Hospital of Central South University, Changsha, China.
Clinical Research Center for Organ Transplantation in Hunan Province, Central South University, Changsha, China.
Front Immunol. 2022 Aug 19;13:979983. doi: 10.3389/fimmu.2022.979983. eCollection 2022.
Patients after kidney transplantation need to take long-term immunosuppressive and other drugs. Some of these drug side effects are easily confused with the symptoms of Fanconi syndrome, resulting in misdiagnosis and missed diagnosis, and causing serious consequences to patients. Therefore, improving awareness, early diagnosis and treatment of Fanconi syndrome after kidney transplantation is critical.
This retrospective study analyzed 1728 cases of allogeneic kidney transplant patients admitted to the Second Xiangya Hospital of Central South University from July 2016 to January 2021. Two patients with Fanconi syndrome secondary to drugs, adefovir dipivoxil (ADV) and tacrolimus, were screened. We summarized the diagnostic process, clinical data, and prognosis.
The onset of Fanconi syndrome secondary to ADV after renal transplantation was insidious, and the condition developed after long-term medication (>10 years). It mainly manifested as bone pain, osteomalacia, and scoliosis in the late stage and was accompanied by obvious proximal renal tubular damage (severe hypophosphatemia, hypokalemia, hypocalcemia, hypouricemia, glycosuria, protein urine, acidosis, etc.) and renal function damage (increased creatinine and azotemia). The pathological findings included mitochondrial swelling and deformity in renal tubular epithelial cells. The above symptoms and signs were relieved after drug withdrawal, but the scoliosis was difficult to rectify. Fanconi syndrome secondary to tacrolimus has a single manifestation, increased creatinine, which can be easily confused with tacrolimus nephrotoxicity. However, it is often ineffective to reduce the dose of tacrolomus, and proximal renal failure can be found in the later stage of disease development. There was no abnormality in the bone metabolism index and imageological examination findings. The creatinine level decreased rapidly, the proximal renal tubule function returned to normal, and no severe electrolyte imbalance or urinary component loss occurred when the immunosuppression was changed from tacrolimus to cyclosporine A.
For the first time, drug-induced Fanconi syndrome after kidney transplantation was reported. These results confirmed that the long-term use of ADV or tacrolimus after kidney transplantation may have serious consequences, some of which are irreversible. Greater understanding of Fanconi syndrome after kidney transplantation is necessary in order to avoid incorrect and missed diagnosis.
肾移植患者需要长期服用免疫抑制剂等药物。这些药物的一些副作用容易与范可尼综合征的症状混淆，导致误诊和漏诊，给患者造成严重后果。因此，提高对肾移植后范可尼综合征的认识，做到早期诊断和治疗至关重要。
本回顾性研究分析了 2016 年 7 月至 2021 年 1 月中南大学湘雅二医院收治的 1728 例同种异体肾移植患者。筛选出阿德福韦酯（ADV）和他克莫司致药物相关性范可尼综合征 2 例患者，总结其诊断过程、临床资料及预后。
肾移植后 ADV 致范可尼综合征起病隐匿，长期服药（＞10 年）后发病，主要表现为后期出现骨痛、骨软化、脊柱侧弯，伴有明显近端肾小管损伤（严重低磷血症、低钾血症、低钙血症、低尿酸血症、糖尿、蛋白尿、酸中毒等）和肾功能损伤（肌酐、血氮升高）。病理表现为肾管状上皮细胞线粒体肿胀、变形。停药后上述症状、体征缓解，但脊柱侧弯难以矫正。他克莫司致范可尼综合征表现单一，以肌酐升高为主，易与他克莫司肾毒性混淆。但减少他克莫司剂量后往往效果不佳，后期疾病进展可出现近端肾衰竭，骨代谢指标及影像学检查无异常。改为环孢素 A 后，肌酐水平迅速下降，近端肾小管功能恢复正常，无严重电解质紊乱或尿成分丢失。
首次报道肾移植后药物相关性范可尼综合征，本研究结果证实，肾移植后长期应用 ADV 或他克莫司可能导致严重后果，部分为不可逆。为避免误诊和漏诊，需加深对肾移植后范可尼综合征的认识。
