title: Macroenzyme creatine kinase (CK) type 2 in HIV-infected patients is significantly associated with TDF and consists of ubiquitous mitochondrial CK.
abstract: OBJECTIVE
  To evaluate the prevalence and origin of macroenzyme creatine kinase type 2 (Macro CK2) in HIV-1-infected patients on antiretroviral treatment.
  
  
  METHODS
  CK, CK-MB activity and protein weight, electrophoretic behaviour, glomerular filtration rate (GFR), aspartate aminotransferase (AST), alanine aminotransferase (ALT), bone alkaline phosphatase (AP), beta2-microglobulin serum levels and proteinuria were analysed in 468 HIV-infected outpatients. Sera with detectable Macro CK2 were further analysed using immunoblotting.
  
  
  RESULTS
  CK-MB isoenzyme activity and mass concentration revealed the presence of Macro CK2 in 32/408 (7.8%) outpatients. Tenofovir DF (TDF) treatment was a prominent common feature in these patients. Prospective examination of sera from 41 patients collected prior to and during TDF exposure showed Macro CK2 in 20/41 (48%) TDF-treated patients and in 0/19 control sera from patients with TDF-free regimens. Macro CK2 was not present prior to TDF exposure. Patients with Macro CK2 showed a significant elevation of serum beta2-microglobulin levels. GFR, AST/ALT ratio, bone AP and proteinuria remained unchanged. Electrophoresis and immunoblotting demonstrated that the Macro CK2 in TDF-treated patients consisted of the ubiquitous (uMtCK) and not the sarcomeric type (sMtCK) of mitochondrial CK (MtCK).
  
  
  CONCLUSIONS
  Macro CK2 consisting of uMtCK is associated with the use of TDF-containing regimens. Whether the appearance of uMtCK in these patients reflects mitochondrial damage remains to be clarified.
authors.affiliation: Medizinische Poliklinik, Ludwig Maximilians University Munich, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Schmid
authors.forename: Dieter
authors.initials: D
authors.lastname: Mühlbayer
authors.forename: Jörg
authors.initials: J
authors.lastname: Röling
authors.forename: Thomas
authors.initials: T
authors.lastname: Sternfeld
authors.forename: Boris
authors.initials: B
authors.lastname: Jülg
authors.forename: Uwe
authors.initials: U
authors.lastname: Schlattner
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Nelson
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Bogner
authors.forename: Theo
authors.initials: T
authors.lastname: Wallimann
authors.forename: Frank D
authors.initials: FD
authors.lastname: Goebel
mesh_terms: D000225:Adenine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D015331:Cohort Studies; D052281:Creatine Kinase, Mitochondrial Form / Q000737:chemistry* / Q000378:metabolism*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000201:enzymology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000009:adverse effects* / Q000627:therapeutic use; D000068698:Tenofovir
chemical_list: D019380:Anti-HIV Agents; D063065:Organophosphonates; D000068698:Tenofovir; D052281:Creatine Kinase, Mitochondrial Form; D000225:Adenine