Department of Infectious Disease, Goethe University, Frankfurt/Main, Germany.
HIV Med. 2013 Nov;14(10):633-8. doi: 10.1111/hiv.12072. Epub 2013 Aug 28.
The renal elimination of tenofovir (TFV) may be subject to renal drug-drug interactions that may increase the risk of kidney injury. Case reports indicated that diclofenac might increase TFV-associated nephrotoxicity via a drug-drug interaction, leading to an increased intracellular TFV concentration in proximal tubular cells.
A retrospective analysis of data for all patients from the Frankfurt HIV Cohort (FHC) who had diclofenac prescriptions between January 2008 and June 2012 was carried out.
Among 89 patients with diclofenac use, 61 patients (68.5%) were treated with tenofovir disoproxil fumarate (TDF) and 28 patients (31.5%) were treated with TDF-sparing combination antiretroviral therapy (cART). Thirteen patients (14.6%) developed acute kidney injury (AKI) shortly after initiating diclofenac treatment. AKI occurred exclusively in TDF-treated patients, although all had previously stable renal function. All cases were accompanied by new onset of at least two parameters indicating proximal tubular damage, such as normoglycaemic-glucosuria and hypophosphataemia. TFV-associated nephrotoxicity was demonstrated by renal biopsy in four cases. Additionally, 11.5% of patients on TDF treatment developed new-onset proximal tubular damage, while having a preserved glomerular filtration rate. In contrast, diclofenac did not affect renal function in patients with TDF-sparing cART, as only one case of isolated hypophataemia was observed in these patients. In univariate analysis, risk factors for AKI were TDF-containing cART (P = 0.0076) and pre-existing hypophosphataemia (P = 0.0086).
Drug-drug interaction caused by diclofenac could exacerbate TFV-associated nephrotoxicity. Diclofenac should be used with caution in patients on TDF therapy, especially in those with hypophosphataemia. Our findings need to be confirmed in larger studies.
替诺福韦（TFV）的肾脏清除可能受到药物-药物相互作用的影响，这可能会增加肾损伤的风险。病例报告表明，双氯芬酸可能通过药物-药物相互作用增加 TFV 相关的肾毒性，导致近端肾小管细胞内 TFV 浓度增加。
对 2008 年 1 月至 2012 年 6 月期间法兰克福 HIV 队列（FHC）中所有使用双氯芬酸的患者进行回顾性数据分析。
在 89 例使用双氯芬酸的患者中，61 例（68.5%）接受了替诺福韦二吡呋酯（TDF）治疗，28 例（31.5%）接受了 TDF 节约型联合抗逆转录病毒治疗（cART）。13 例（14.6%）在开始使用双氯芬酸治疗后不久即发生急性肾损伤（AKI）。AKI 仅发生在 TDF 治疗的患者中，尽管所有患者的肾功能此前均稳定。所有病例均伴有至少两个表明近端肾小管损伤的新参数，如血糖正常性糖尿和低磷血症。4 例通过肾活检证实了与 TFV 相关的肾毒性。此外，在接受 TDF 治疗的患者中，有 11.5%出现了新的近端肾小管损伤，而肾小球滤过率保持不变。相比之下，双氯芬酸在接受 TDF 节约型 cART 的患者中并未影响肾功能，因为这些患者中仅观察到 1 例孤立性低磷血症。单因素分析显示，AKI 的危险因素为含 TDF 的 cART（P=0.0076）和预先存在的低磷血症（P=0.0086）。
双氯芬酸引起的药物-药物相互作用可能加重 TFV 相关的肾毒性。在接受 TDF 治疗的患者中，应谨慎使用双氯芬酸，特别是在存在低磷血症的患者中。我们的发现需要在更大的研究中得到证实。
