The finding of reduced estimated glomerular filtration rate is associated with increased mortality in a large UK population.
BACKGROUND
CKD as defined by KDIGO/KDOQI has been shown to affect ~ 8.5% of the UK population. The prevalence of CKD in the UK is similar to that in the USA, yet incident dialysis rates are dramatically different. This retrospective cohort study investigates the association between reduced kidney function and mortality in a large UK population.


METHODS
All serum creatinine results covering Northern Ireland's 1.7 million population were collected between 1 January 2001 and 31 December 2002. Estimated glomerular filtration rates (eGFR) were calculated for all serum creatinine measurements using four-variable MDRD equation (IDMS aligned). Patients were followed up for both all-cause and cardiovascular mortality data until the end of December 2006. Patients on renal replacement therapy were excluded. Subgroup analysis in the 75,345 subjects enrolled within a parallel primary care study permitted additional survival analysis with adjustment for traditional cardiovascular risk factors.


RESULTS
A total of 1,967,827 serum creatinine results from 533,798 patients were collected. During the period of follow-up, 59,980 deaths occurred. In multivariate survival analysis, using eGFR as a time-varying covariate, a graded association between CKD (defined by eGFR) and all-cause mortality was identified. Compared with participants with an eGFR of > 60 mL/min/1.73 m(2), the adjusted hazard ratios (and 95% confidence intervals) for participants with an eGFR of 45-59 mL/min/1.73 m(2) was 1.02 (0.99-1.04), an eGFR of 30-44 mL/min/1.73 m(2) was 1.44 (1.40-1.47), an eGFR of 15-29 mL/min/1.73 m(2) was 2.12 (2.05-2.20) and an eGFR of < 15 mL/min/1.73 m(2) was 3.46 (3.24-3.70). Significantly, increased all-cause mortality was associated with an eGFR < 45 mL/min/1.73 m(2) following adjustment for age and gender. The association between cardiovascular mortality and reduced renal function continued to be significant for participants with an eGFR of 45-65 mL/min/1.73 m(2). Subgroup analysis in 75,345 individuals with more detailed clinical information available confirmed this association following adjustment for traditional cardiovascular risk factors in addition to age and gender.


CONCLUSIONS
This study demonstrates a graded association between reduced renal function as represented by eGFR and mortality in a UK population. The all-cause and cardiovascular mortality risk increases sharply when estimated GFR falls < 45 mL/min/1.73 m(2). The association between an eGFR measured between 45 and 65 mL/min/1.73 m(2) and cardiovascular mortality persists in this cohort and highlights the ongoing uncertainty in accurately categorizing renal dysfunction.
Quinn
Michael P
MP
Nephrology Research Group, Centre for Public Health, Queen’s University and Regional Nephrology Unit, Belfast City Hospital, Lisburn Road, Belfast BT9 7AB, UK. mquinn05@qub.ac.uk
Cardwell
Christopher R
CR
Kee
Frank
F
Maxwell
Alexander P
AP
Savage
Gerard
G
McCarron
Peter
P
Fogarty
Damian G
DG
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000401:mortality* / Q000503:physiopathology; D002423:Cause of Death; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007676:Kidney Failure, Chronic / Q000401:mortality*; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009660:Northern Ireland; D006435:Renal Dialysis; D012189:Retrospective Studies; D012307:Risk Factors; D015996:Survival Rate; D014481:United States; D055815:Young Adult
D003404:Creatinine