Incidence of and risk factors for tenofovir-induced nephrotoxicity: a retrospective cohort study.
OBJECTIVE
Despite the recent publication of case reports describing various manifestations of tenofovir-related nephrotoxicity, data regarding the incidence of and risk factors for this adverse effect are currently lacking.


METHODS
A retrospective cohort study of patients from four centres in Toronto, Canada, enrolled in the tenofovir expanded access programme with a minimum of 3 months follow up, was carried out.


RESULTS
A total of 172 patients receiving tenofovir disoproxil fumarate (TDF) for a median of 16 months (range 3-25 months) were included in the study. Seven (4%) patients developed grade 1 (>44 micromol/L from baseline) increases in serum creatinine (SCr) during follow up; no patient developed grade 2 or higher nephrotoxicity. Fifteen (8.7%) patients had an increase in SCr of greater than 1.5 times baseline values during follow up. Four (2.3%) patients discontinued TDF because of an increase in SCr and/or abnormal urinalysis. Of 62 patients with a urinalysis, grade 1 or higher proteinuria (< 3 g/L) was observed in 27 (43%) patients. Only baseline SCr [odds ratio (OR)=0.51 per 10 micromol/L increase; P=0.0005] and baseline creatinine clearance (1.26 per 10 mL/min increase; P=0.01) were significantly associated with ever having a 1.5-fold increase in serum creatinine. Twenty-eight (16%) and 11 (6%) patients developed grade 1 (serum phosphorus < or = 0.71 mmol/L) and grade 2 (serum phosphorus < or = 0.61 mmol/L) hypophosphataemia during follow-up, respectively.


CONCLUSIONS
Although slight increases in SCr did occur after starting TDF, clinically significant nephrotoxicity was rare. The clinical significance of TDF-related hypophosphataemia and proteinuria requires further study.
Antoniou
T
T
University of Toronto, Toronto, Ontario, Canada. tantoniou@smh.toronto.on.ca
Raboud
Jm
J
Chirhin
S
S
Yoong
D
D
Govan
V
V
Gough
K
K
Rachlis
A
A
Loutfy
Mr
M
D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives*; D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D003404:Creatinine / Q000097:blood / Q000493:pharmacokinetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D017674:Hypophosphatemia / Q000150:complications / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology; D007674:Kidney Diseases / Q000139:chemically induced* / Q000150:complications / Q000378:metabolism; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects*; D011507:Proteinuria / Q000150:complications / Q000378:metabolism; D012189:Retrospective Studies; D012307:Risk Factors; D000068698:Tenofovir; D016482:Urinalysis / Q000379:methods
D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D003404:Creatinine; D000225:Adenine