Renal side effects of adefovir in hepatitis B virus-(HBV) positive kidney allograft recipients.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Kamar
N
N
Nephrology, Dialysis and Multiorgan Transplant Unit, CHU Rangueil, Toulouse, France.
Huart
A
A
Tack
I
I
Alric
L
L
Izopet
J
J
Rostaing
L
L
D000136:Acid-Base Equilibrium / Q000187:drug effects; D000225:Adenine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D024882:Drug Resistance, Viral; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D016030:Kidney Transplantation; D019259:Lamivudine; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies
D000998:Antiviral Agents; D063065:Organophosphonates; D019259:Lamivudine; C053001:adefovir; D000225:Adenine