title: Plasma Levels of Middle Molecules to Estimate Residual Kidney Function in Haemodialysis without Urine Collection.
abstract: BACKGROUND
  Residual Kidney Function (RKF) is associated with survival benefits in haemodialysis (HD) but is difficult to measure without urine collection. Middle molecules such as Cystatin C and β2-microglobulin accumulate in renal disease and plasma levels have been used to estimate kidney function early in this condition. We investigated their use to estimate RKF in patients on HD.
  
  
  METHODS
  Cystatin C, β2-microglobulin, urea and creatinine levels were studied in patients on incremental high-flux HD or hemodiafiltration(HDF). Over sequential HD sessions, blood was sampled pre- and post-session 1 and pre-session 2, for estimation of these parameters. Urine was collected during the whole interdialytic interval, for estimation of residual GFR (GFRResidual = mean of urea and creatinine clearance). The relationships of plasma Cystatin C and β2-microglobulin levels to GFRResidual and urea clearance were determined.
  
  
  RESULTS
  Of the 341 patients studied, 64% had urine output>100 ml/day, 32.6% were on high-flux HD and 67.4% on HDF. Parameters most closely correlated with GFRResidual were 1/β2-micoglobulin (r2 0.67) and 1/Cystatin C (r2 0.50). Both these relationships were weaker at low GFRResidual. The best regression model for GFRResidual, explaining 67% of the variation, was: GFRResidual = 160.3 · (1/β2m) - 4.2. Where β2m is the pre-dialysis β2 microglobulin concentration (mg/L). This model was validated in a separate cohort of 50 patients using Bland-Altman analysis. Areas under the curve in Receiver Operating Characteristic analysis aimed at identifying subjects with urea clearance≥2 ml/min/1.73 m2 was 0.91 for β2-microglobulin and 0.86 for Cystatin C. A plasma β2-microglobulin cut-off of ≤19.2 mg/L allowed identification of patients with urea clearance ≥2 ml/min/1.73 m2 with 90% specificity and 65% sensitivity.
  
  
  CONCLUSIONS
  Plasma pre-dialysis β2-microglobulin levels can provide estimates of RKF which may have clinical utility and appear superior to cystatin C. Use of cut-off levels to identify patients with RKF may provide a simple way to individualise dialysis dose based on RKF.
authors.affiliation: Renal Unit, Lister Hospital, Hertfordshire, Stevenage, United Kingdom.|Department of Postgraduate Medicine, University of Hertfordshire, United Kingdom.
authors.forename: Enric
authors.initials: E
authors.lastname: Vilar
authors.affiliation: Department of Pathology, Lister Hospital, Stevenage, United Kingdom.|University of the West of England, Bristol, United Kingdom.
authors.forename: Capella
authors.initials: C
authors.lastname: Boltiador
authors.affiliation: Renal Unit, Lister Hospital, Hertfordshire, Stevenage, United Kingdom.|Department of Postgraduate Medicine, University of Hertfordshire, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wong
authors.affiliation: Department of Pathology, Lister Hospital, Stevenage, United Kingdom.
authors.forename: Adie
authors.initials: A
authors.lastname: Viljoen
authors.affiliation: Renal Unit, Lister Hospital, Hertfordshire, Stevenage, United Kingdom.
authors.forename: Ashwini
authors.initials: A
authors.lastname: Machado
authors.affiliation: Renal Unit, Lister Hospital, Hertfordshire, Stevenage, United Kingdom.
authors.forename: Arani
authors.initials: A
authors.lastname: Uthayakumar
authors.affiliation: Renal Unit, Lister Hospital, Hertfordshire, Stevenage, United Kingdom.|Department of Postgraduate Medicine, University of Hertfordshire, United Kingdom.
authors.forename: Ken
authors.initials: K
authors.lastname: Farrington
mesh_terms: D055316:Cystatin C / Q000097:blood*; D005260:Female; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D007674:Kidney Diseases / Q000097:blood / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D016019:Survival Analysis; D001613:beta 2-Microglobulin / Q000097:blood*
chemical_list: D055316:Cystatin C; D001613:beta 2-Microglobulin