title: Risk of Chronic Kidney Disease among Patients Developing Mild Renal Impairment during Tenofovir-Containing Antiretroviral Treatment.
abstract: BACKGROUND
  Tenofovir (TDF) can cause kidney injury through tubular dysfunction, with or without drop of estimated glomerular filtration rate (eGFR). Whether mild eGFR reductions during treatment should be considered a reason for prompt TDF discontinuation, however, remains unclear.
  
  
  METHODS
  Patients with normal pre-TDF eGFR levels, who had developed mild renal impairment (i.e., two consecutive eGFR results between 89-60 ml/min) on TDF, were observed until onset of chronic kidney disease (CKD), defined as two eGFR<60 ml/min 3 to 6 months apart. Multivariable Poisson regression analysis was used to investigate whether outcome was associated with current and cumulative use of TDF (modeled as time-varying covariates).
  
  
  RESULTS
  2023 (29%) out of 6984 patients developed mild renal impairment on TDF. Among them, 191 progressed to CKD. The incidence of CKD did not significantly differ during TDF treatment (2.6 per 100 PYFU; 95%CI 2.2-3.2) or after its discontinuation (2.2 per 100 PYFU; 95%CI 1.8-2.6). However, the rate of CKD was significantly higher among patients continuing with TDF treatment compared to those who had discontinued it within 6 months of occurrence of mild renal impairment (aIRR 4, 95%CI 2.4-6.8). In contrast, among patients who had maintained TDF >6 months despite mild renal impairment, current TDF use was not associated with a significantly higher rate of CKD. Other significant predictors of CKD were older age, intravenous drug use, diabetes, hypertension, lower pre-TDF eGFR, higher eGFR drop since TDF introduction and longer exposure to TDF.
  
  
  CONCLUSIONS
  Prompt discontinuation of TDF among patients developing mild renal impairment may prevent further progression of renal damage.
authors.affiliation: "San Gerardo" Hospital, Monza, Italy.
authors.forename: Giuseppe
authors.identifier: http://orcid.org/0000-0002-9976-8102
authors.initials: G
authors.lastname: Lapadula
authors.affiliation: University of Milano-Bicocca, Milan, Italy.
authors.forename: Davide Paolo
authors.initials: DP
authors.lastname: Bernasconi
authors.affiliation: University of Brescia, Brescia, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Casari
authors.affiliation: Papa Giovanni XXIII Hospital, Bergamo, Italy.
authors.forename: Franco
authors.initials: F
authors.lastname: Maggiolo
authors.affiliation: Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Cauda
authors.affiliation: Ospedale S. Maria Annunziata, Florence, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Di Pietro
authors.affiliation: Ospedale Policlinico, Bari, Italy.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Ladisa
authors.affiliation: Ospedale Sant'Anna, Ferrara, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Sighinolfi
authors.affiliation: Istituti Ospitalieri, Cremona, Italy.
authors.forename: Sarah
authors.initials: S
authors.lastname: Dal Zoppo
authors.affiliation: "San Gerardo" Hospital, Monza, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Sabbatini
authors.affiliation: "San Gerardo" Hospital, Monza, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Soria
authors.affiliation: University of Brescia, Brescia, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Pezzoli
authors.affiliation: Università Cattolica del Sacro Cuore, Rome, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Mondi
authors.affiliation: "San Gerardo" Hospital, Monza, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Costarelli
authors.affiliation: University of Milano-Bicocca, Milan, Italy.
authors.forename: Maria Grazia
authors.initials: MG
authors.lastname: Valsecchi
authors.affiliation: University "Magna Graecia", Catanzaro, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Torti
authors.affiliation: "San Gerardo" Hospital, Monza, Italy.|University of Milano-Bicocca, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Gori
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000009:adverse effects*; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000009:adverse effects*
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir