title: Cystatin C as a marker of renal function is affected by HIV replication leading to an underestimation of kidney function in HIV patients.
abstract: BACKGROUND
  Broad use of tenofovir and an ageing HIV- infected population have created an interest in renal function in HIV patients. Serum cystatin C is a newer marker of renal function and might be more sensitive than creatinine.
  
  
  METHODS
  Patients were enrolled consecutively in an observational study. HIV-seropositive patients naive to antiretroviral therapy (n = 261) were compared with healthy volunteers undergoing check-up procedures (n = 193). Estimated glomerular filtration rate (eGFR) was derived using creatinine-based Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formulas or cystatin C-based calculations. HIV-seropositive patients starting antiretroviral therapy (n = 92) were followed prospectively after enrolment.
  
  
  RESULTS
  MDRD showed a higher median eGFR in antiretroviral-naive HIV-seropositive patients compared with controls (104 versus 93 ml/min; P < 0.001). Cockcroft-Gault gave similar results (118 versus 106 ml/min; P < 0.001). By contrast, cystatin C levels in HIV-seropositive individuals were higher, resulting in a lower median eGFR compared with controls (99 versus 120 ml/min; P < 0.001). Cystatin C was positively correlated with HIV RNA (r = 0.33, P < 0.01) and inversely correlated with CD4+ T-cell count (r = -0.29, P < 0.01). Initiating antiretroviral therapy (n = 92) decreased cystatin C levels and led to an increased cystatin C-based eGFR from median 84 to 103 ml/min at week 24 (P < 0.001). Serum creatinine was not substantially altered.
  
  
  CONCLUSIONS
  Correlation of cystatin C with HIV RNA and CD4+ T-cell count, plus decrease of cystatin C after suppression of HIV replication, suggest an increase of cystatin C levels by active HIV infection. This might result in overestimation of renal impairment, particularly in treatment-naive patients. Therefore, use of cystatin C to calculate GFR in HIV-seropositive individuals should not be recommended without further validation.
authors.affiliation: Center for HIV and Hepatogastroenterology, Duesseldorf, Germany. stefan.mauss@center-duesseldorf.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.forename: Florian
authors.initials: F
authors.lastname: Berger
authors.forename: Dieter
authors.initials: D
authors.lastname: Kuschak
authors.forename: Julia
authors.initials: J
authors.lastname: Henke
authors.forename: Petra
authors.initials: P
authors.lastname: Hegener
authors.forename: Eva
authors.initials: E
authors.lastname: Wolf
authors.forename: Stephan
authors.initials: S
authors.lastname: Schauseil
authors.forename: Guenther
authors.initials: G
authors.lastname: Schmutz
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D055316:Cystatin C / Q000097:blood*; D005260:Female; D015658:HIV Infections / Q000097:blood* / Q000821:virology; D006801:Humans; D007668:Kidney / Q000502:physiology* / Q000821:virology*; D008297:Male; D008875:Middle Aged; D014779:Virus Replication / Q000502:physiology*
chemical_list: D015415:Biomarkers; D055316:Cystatin C