title: Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study.
abstract: BACKGROUND
  No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011.
  
  
  METHODS
  Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated.
  
  
  RESULTS
  22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years' follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD.
  
  
  CONCLUSIONS
  Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals.
authors.affiliation: Research Dept, of Infection and Population Health, University College London, London, United Kingdom. d.kamara@ucl.ac.uk.
authors.forename: David A
authors.initials: DA
authors.lastname: Kamara
authors.forename: Lene
authors.initials: L
authors.lastname: Ryom
authors.forename: Michael
authors.initials: M
authors.lastname: Ross
authors.forename: Ole
authors.initials: O
authors.lastname: Kirk
authors.forename: Peter
authors.initials: P
authors.lastname: Reiss
authors.forename: Philippe
authors.initials: P
authors.lastname: Morlat
authors.forename: Olivier
authors.initials: O
authors.lastname: Moranne
authors.forename: Christoph A
authors.initials: CA
authors.lastname: Fux
authors.forename: Amanda
authors.initials: A
authors.lastname: Mocroft
authors.forename: Caroline
authors.initials: C
authors.lastname: Sabin
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
authors.forename: Colette J
authors.initials: CJ
authors.lastname: Smith
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D003936:Diagnosis, Computer-Assisted / Q000379:methods*; D018450:Disease Progression; D005260:Female; D005919:Glomerular Filtration Rate; D015658:HIV Infections / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D038622:Internationality; D008297:Male; D008875:Middle Aged; D051436:Renal Insufficiency, Chronic / Q000150:complications* / Q000175:diagnosis*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index