Kamar N, Huart A, Tack I, Alric L, Izopet J, Rostaing L
Nephrology, Dialysis and Multiorgan Transplant Unit, CHU Rangueil, Toulouse, France.
Clin Nephrol. 2009 Jan;71(1):36-42. doi: 10.5414/cnp71036.
The purpose of this study was to evaluate the renal side-effects of adefovir therapy in kidney-transplant (KT) recipients with chronic hepatitis B virus (HBV) infection, who have become resistant to lamivudine therapy.
11 kidney-transplant (KT) patients (10 men, 1 woman, median age 54 (46 - 67) years) had lamivudine-resistant chronic HBV infection. With respect to HBV markers, all were HBs Ag-positive, 8 were HBe Ag-negative/HBe antibody- (Ab) positive, i.e. precore mutant, and 3 were HBe Ag-positive/HBe Ab-negative. They were all given adefovir at 10 mg/d (3 cases) or 5 mg/d (6 cases) or 2.5 mg/d (2 cases) according to creatinine clearance.
Compared to baseline without adefovir therapy, at last follow-up, adefovir therapy was associated, at 1 and 2 years post therapy, with a significant decrease in aspartate (AST) (28 (17 - 53), 28 (10 - 79) vs. 58 (24 - 1,282) IU/l, p = 0.001), alanine (ALT) (38 (13 - 55), 36 (17 - 92) vs. 72 (31 - 1,594) IU/l, p = 0.0032] aminotransferase levels, and gammaGT (31 (14 - 51), 25 (14 - 196) vs. 44 (25 - 742) IU/l, p = 0.03). With respect to HBV DNA, when compared to baseline, there was a significant decrease at both years 1 and 2 post therapy (p = 0.01). With respect to KT function at 2 years after starting adefovir, there was a significant increase in serum creatinine from 125 (+/- 35) to 141 (+/- 32) micromol/l, (p = 0.02) and a significant increase in 24-h proteinuria. With respect to renal tubular parameters, as compared to baseline without adefovir therapy, one year after adefovir therapy was commenced there was a significant decrease in urinary pH from 6.6 (+0.6) to 5.65 (+/- 0.7); p = 0.03, a significant decrease in bicarbonaturia (from 0.33 +/- 0.7 to 0.1 +/- 0.3 mmol/h, p = 0.01), an increase in urinary excretion of H+ (1.79 (+/- 1.33) to 2.44 (+/- 1.18) mmol/l (p = 0.03)), a significant decrease in phosphatemia (0.82 +/- 0.19 vs. 0.65 +/- 0.13 mmol/l, p = 0.04) and a significant decrease in phosphaturia threshold, a significant decrease in tubular phosphorus reabsorption (75.5 +/- 9.4% vs. 61.8 +/- 16%, p = 0.05), and a significant increase in the phosphorus index of excretion (0.18 +/- 0.114 vs. 0.35 +/- 0.164, p = 0.01).
We have demonstrated that low-dosage adefovir therapy in kidney-transplant patients is relatively safe as far as renal parameters are concerned, even though we observed a slight impairment of renal proximal-tubular function.
本研究旨在评估阿德福韦治疗对耐拉米夫定治疗的慢性乙型肝炎病毒（HBV）感染肾移植（KT）受者的肾脏副作用。
11例肾移植（KT）患者（10例男性，1例女性，中位年龄54（46 - 67）岁）患有耐拉米夫定的慢性HBV感染。关于HBV标志物，所有患者HBs Ag均为阳性，8例HBe Ag阴性/HBe抗体（Ab）阳性，即前C区突变，3例HBe Ag阳性/HBe Ab阴性。根据肌酐清除率，分别给予他们10mg/d（3例）、5mg/d（6例）或2.5mg/d（2例）的阿德福韦。
与未接受阿德福韦治疗的基线相比，在最后一次随访时，阿德福韦治疗在治疗后1年和2年与天冬氨酸转氨酶（AST）（分别为28（17 - 53）、28（10 - 79）与58（24 - 1282）IU/l，p = 0.001）、丙氨酸转氨酶（ALT）（分别为38（13 - 55）、36（17 - 92）与72（31 - 1594）IU/l，p = 0.0032）水平以及γ-谷氨酰转移酶（gammaGT）（分别为31（14 - 51）、25（14 - 196）与44（25 - 742）IU/l，p = 0.03）的显著降低相关。关于HBV DNA，与基线相比，治疗后1年和2年均有显著下降（p = 0.01）。关于开始阿德福韦治疗2年后的KT功能，血清肌酐从125（±35）显著升高至141（±32）微摩尔/升（p = 0.02），24小时蛋白尿显著增加。关于肾小管参数，与未接受阿德福韦治疗的基线相比，开始阿德福韦治疗1年后尿pH从6.6（±0.6）显著降至5.65（±0.7）；p = 0.03，重碳酸盐尿显著减少（从0.33±0.7至0.1±0.3毫摩尔/小时，p = 0.01），H⁺尿排泄增加（从1.79（±1.33）至2.44（±1.18）毫摩尔/升（p = 0.03）），血磷显著降低（0.82±0.19与0.65±0.13毫摩尔/升，p = 0.04），磷排泄阈值显著降低，肾小管磷重吸收显著降低（75.5±9.4%与61.8±16%，p = 0.05），以及磷排泄指数显著增加（0.18±0.114与0.35±0.164，p = 0.01）。
我们已经证明，就肾脏参数而言，肾移植患者的低剂量阿德福韦治疗相对安全，尽管我们观察到肾近端小管功能有轻微损害。
