title: Uraemia progression in chronic kidney disease stages 3-5 is not constant.
abstract: BACKGROUND
  Chronic kidney disease (CKD) is a progressive disease leading to loss of glomerular filtration rate (ΔGFR, measured in ml/min/1.73 m(2)/year). ΔGFR is usually assumed to be constant, but the hyperfiltration theory suggests that it accelerates in severe uraemia. A retrospective analysis of estimated GFR (eGFR) calculated from the Modification of Diet in Renal Disease equation was performed to evaluate whether ΔGFR is constant or accelerating.
  
  
  METHODS
  1,441 patients attending a nephrology clinic over a 21-year period, with an initial eGFR <60 ml/min/1.73 m(2) and an observation period ≥2 years, were included. eGFR was calculated from all creatinine measurements. 420 patients developed end-stage renal disease (ESRD). First- and second-order polynomial regression analysis of eGFR against time was performed for each patient individually. Patients had accelerating uraemia progression if the second-order term coefficient was negative.
  
  
  RESULTS
  The initial eGFR was 30.8 ±15.1 ml/min/1.73 m(2). The second-order coefficient was median -0.15 ml/min/1.73 m(2)/year(2) (interquartile range -0.92, +0.34). Significantly more patients had an accelerating loss (62%, p < 0.001). Acceleration was mainly seen when eGFR was <30 ml/min. ΔGFR was mean 1.47 ± 4.5 ml/min/1.73 m(2)/year (male 1.67, female 1.22). ESRD patients lost 5.4 ± 5.4 ml/min/year/1.73 m(2) during the last year before ESRD. Accelerating loss was seen for all diagnoses except polycystic disease. Diagnoses with higher ΔGFR were polycystic renal disease (3.3 ml/min/1.73 m(2)/year), hypertensive nephropathy (2.1 ml/min/1.73 m(2)/year) and diabetic nephropathy (2.6 ml/min/ 1.73 m(2)/year). There was no evidence of improvement in overall uraemia progression during the period of observation.
  
  
  CONCLUSIONS
  Uraemia progression in CKD stages 3-5 is not linear, but shows an accelerating trend. This suggests that hyperfiltration mechanisms play a role in CKD progression. ESRD cannot thus be predicted from previous ΔGFR alone.
authors.affiliation: Department of Nephrology B, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. heaf@dadlnet.dk
authors.forename: James Goya
authors.initials: JG
authors.lastname: Heaf
authors.forename: Leif Spange
authors.initials: LS
authors.lastname: Mortensen
mesh_terms: D000328:Adult; D000368:Aged; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005919:Glomerular Filtration Rate / Q000502:physiology; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014511:Uremia / Q000175:diagnosis* / Q000473:pathology* / Q000503:physiopathology