Monteiro Nadine, Branco Margarida, Peres Susana, Borges Fernando, Mansinho Kamal
Infectious Diseases and Tropical Medicine, Hospital Egas Moniz, Lisbon, Portugal.
J Int AIDS Soc. 2014 Nov 2;17(4 Suppl 3):19565. doi: 10.7448/IAS.17.4.19565. eCollection 2014.
With improvements in survival and disease progression in the era of combined antiretroviral therapy, complications such as kidney disease are becoming increasingly prevalent in HIV-infected patients. Tenofovir disoproxil fumarate (TDF) has been associated with nephrotoxicity, including decline in glomerular filtration rate, proximal tubular damage and acute kidney injury.
Characterize kidney safety of TDF-containing antiretroviral treatment (ART) regimens in HIV-infected patients.
Non-controlled, observational, retrospective study was based on the clinical files registry of HIV patients who started TDF between January and December 2008. We assessed outpatients followed at a single Portuguese center. Demographic, clinical, virological and immunological data at baseline were collected. Serum creatinine, estimated glomerular filtration rate (eGFR) and creatinine clearance (CrCL) were assessed at baseline, after six months and every year up to four years. CrCL and eGFR were calculated by Cockroft-Gault and Modification of Diet in Renal Disease equations, respectively.
A total of 176 patients (71.6% males) with a mean age of 43 years were enrolled. Ninety-six (52%) were ART-naive patients at TDF initiation. At baseline 12.5% had hypertension, 4% diabetes, 25% chronic hepatitis C and 9% chronic hepatitis B infections; 58% had normal renal function (eGFR ≥90 ml/min/1.73 m(2)), 36% had mild (eGFR 60-89 ml/min/1.73 m(2)) renal dysfunction and 2.3% had moderate (eGFR 30-59 ml/min/1.73 m(2)) renal dysfunction at initiation of TDF. Eighty-three (47%) patients were on protease inhibitors and the remaining on NNRTIs containing regimens. During 48 months follow-up, 5% experienced moderate renal dysfunction and 1.7% severe renal dysfunction. Twenty-one (12%) patients met the definition criteria of rapid decline of renal function (annual decline of eGFR ≥3 ml/min/1.73 m(2) in two consecutive years). The development of kidney events was associated with age above 50 years, presence of comorbidities and advanced stage HIV infection (p>0.05 in univariate analysis).
These data reveal a favourable renal safety profile of TDF, during a four-year follow-up. Screening for kidney disease markers, regular follow-up and control and prevention of risk factors for renal failure are crucial for adequate management of HIV-infected patients.
在联合抗逆转录病毒治疗时代，随着生存率的提高和疾病进展，肾病等并发症在HIV感染患者中越来越普遍。富马酸替诺福韦二吡呋酯（TDF）与肾毒性有关，包括肾小球滤过率下降、近端肾小管损伤和急性肾损伤。
描述含TDF的抗逆转录病毒治疗（ART）方案在HIV感染患者中的肾脏安全性。
非对照、观察性、回顾性研究基于2008年1月至12月开始使用TDF的HIV患者的临床档案登记。我们评估了在葡萄牙一个中心随访的门诊患者。收集了基线时的人口统计学、临床、病毒学和免疫学数据。在基线、六个月后以及每年直至四年时评估血清肌酐、估计肾小球滤过率（eGFR）和肌酐清除率（CrCL）。CrCL和eGFR分别通过Cockcroft-Gault方程和肾脏病饮食改良方程计算。
共纳入176例患者（71.6%为男性），平均年龄43岁。96例（52%）在开始使用TDF时为初治ART患者。基线时，12.5%患有高血压，4%患有糖尿病，25%患有慢性丙型肝炎，9%患有慢性乙型肝炎感染；58%的患者肾功能正常（eGFR≥90 ml/min/1.73 m²），36%患有轻度（eGFR 60 - 89 ml/min/1.73 m²）肾功能不全，2.3%在开始使用TDF时患有中度（eGFR 30 - 59 ml/min/1.73 m²）肾功能不全。83例（47%）患者使用蛋白酶抑制剂，其余患者使用含非核苷类逆转录酶抑制剂的方案。在48个月的随访期间，5%的患者出现中度肾功能不全，1.7%的患者出现重度肾功能不全。21例（12%）患者符合肾功能快速下降的定义标准（连续两年eGFR年下降≥3 ml/min/1.73 m²）。肾脏事件的发生与50岁以上的年龄、合并症的存在以及晚期HIV感染有关（单因素分析中p>0.05）。
这些数据显示在四年的随访期间TDF具有良好的肾脏安全性。筛查肾脏疾病标志物、定期随访以及控制和预防肾衰竭的危险因素对于HIV感染患者的适当管理至关重要。
