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American Journal of Kidney Diseases

Proteinuria and Life Expectancy

Published:December 10, 2012DOI:https://doi.org/10.1053/j.ajkd.2012.11.030
      To the Editor:
      Proteinuria, a marker of kidney disease, is associated strongly with risk of adverse outcomes, including all-cause mortality.
      • Perkovic V.
      • Verdon C.
      • Ninomiya T.
      • et al.
      The relationship between proteinuria and coronary risk: a systematic review and meta-analysis.
      • Grimm Jr, R.H.
      • Svendsen K.H.
      • Kasiske B.
      • Keane W.F.
      • Wahi M.M.
      Proteinuria is a risk factor for mortality over 10 years of follow-up MRFIT Research Group. Multiple Risk Factor Intervention Trial.
      • Hillege H.L.
      • Fidler V.
      • Diercks G.F.H.
      • et al.
      Urinary albumin excretion predicts cardiovascular and noncardiovascular mortality in general population.
      Life expectancy, a measure to estimate health status and disease burden at a population level, has not been reported for patients with different levels of proteinuria. This information could help policy makers recognize the health burden caused by proteinuria and prioritize health care programs or funding. We used a large population-based registry to estimate life expectancies of middle-aged men and women with varying levels of proteinuria.
      The study population included adults without end-stage renal disease in Alberta, Canada, who had at least one outpatient measurement of proteinuria between May 1, 2002, and December 31, 2006. A cohort of 812,386 patients (375,325 men, 437,061 women) was followed up until March 31, 2009, to identify all-cause mortality. Baseline proteinuria was estimated by urine albumin-creatinine ratio (ACR) or urine dipstick based on outpatient random spot urine measurements and categorized based on ACR (normal, <30 mg/g; mild, 30-300 mg/g; and heavy, >300 mg/g) or urine dipstick (normal, negative; mild, trace or 1+; and heavy, 2+).
      • Hemmelgarn B.R.
      • Manns B.J.
      • Lloyd A.
      • et al.
      Relation between kidney function, proteinuria, and adverse outcomes.
      • Lamb E.J.
      • MacKenzie F.
      • Stevens P.E.
      How should proteinuria be detected and measured?.
      Age-specific mortality rates were calculated with the person-year method,
      • Breslow N.E.
      • Day N.E.
      Statistical Methods in Cancer Research Volume II—The Analysis of Case-Control Studies.
      where age was considered in time scale. The abridged life table was used to calculate life expectancies.
      • Wilkins R.
      • Uppal S.
      • Finès P.
      • Senécal S.
      • Guimond E.
      • Dion R.
      Life expectancy in the Inuit-inhabited areas of Canada, 1989 to 2003.
      • Chiang C.L.
      The Life Table and Its Applications.
      (Details of the study methods have been published elsewhere
      • Turin T.C.
      • Tonelli M.
      • Manns B.J.
      • Ravani P.
      • Ahmed S.B.
      • Hemmelgarn B.R.
      Chronic kidney disease and life expectancy.
      and are provided in Item S1).
      Among men, 9.55% had mild proteinuria and 2.03% had heavy proteinuria. Corresponding proportions among women were 7.48% and 1.22%, respectively. Figure 1 shows mean life expectancy for participants by sex and level of proteinuria in 5-year age bands (from 30 to ≥85 years). Within each age stratum, life expectancy was substantially shorter for people with higher levels of proteinuria (Table S1). Life expectancy for men aged 40 years was 31.8 years for those without proteinuria, 23.2 years for those with mild proteinuria, and 16.6 years for those with heavy proteinuria. Life expectancies for women aged 40 years with normal, mild, and heavy proteinuria were 35.7, 25.2, and 18.2 years, respectively. Life expectancies of 40-year-old men and women with no proteinuria were 15.2 and 17.4 years longer, respectively, than for those with heavy proteinuria (Table 1). Life expectancy was shorter in the presence of mild and heavy proteinuria (compared with those with no proteinuria) across all age strata for both sexes. Life expectancy for men was consistently shorter than for women for all proteinuria categories, especially in the middle age strata (Table S2).
      Figure thumbnail gr1
      Figure 1Life expectancy for men and women with different levels of proteinuria at different index ages.
      Table 1Differences in Mean Life Expectancy
      Age Group (y)Normal vs Mild ProteinuriaNormal vs Heavy ProteinuriaMild vs Heavy Proteinuria
      Men
      309.7 (9.0 to 10.5)18.0 (16.3 to 19.7)8.3 (6.4 to 10.2)
      359.2 (8.5 to 9.8)16.6 (15.2 to 17.9)7.4 (5.9 to 8.9)
      408.5 (8.0 to 9.0)15.2 (14.1 to 16.3)6.7 (5.5 to 7.9)
      458.1 (7.6 to 8.5)13.9 (13.0 to 14.8)5.8 (4.9 to 6.8)
      507.1 (6.7 to 7.5)12.1 (11.4 to 12.8)5.0 (4.2 to 5.8)
      556.1 (5.8 to 6.5)10.2 (9.7 to 10.8)4.1 (3.5 to 4.7)
      605.1 (4.8 to 5.5)8.7 (8.2 to 9.1)3.5 (3.0 to 4.0)
      654.1 (3.9 to 4.4)6.6 (6.3 to 7.0)2.5 (2.1 to 2.9)
      703.0 (2.7 to 3.2)5.0 (4.7 to 5.2)2.0 (1.7 to 2.3)
      752.2 (2.0 to 2.3)3.3 (3.1 to 3.5)1.1 (0.9 to 1.3)
      801.3 (1.2 to 1.5)2.0 (1.9 to 2.1)0.7 (0.6 to 0.8)
      850.8 (0.5 to 1.0)1.0 (0.6 to 1.4)0.2 (−0.2 to 0.6)
      Women
      3011.1 (10.4 to 11.8)19.9 (18.3 to 21.6)8.8 (7.0 to 10.6)
      3510.8 (10.2 to 11.5)19.0 (17.4 to 20.5)8.1 (6.5 to 9.7)
      4010.4 (9.8 to 11.0)17.4 (16.2 to 18.7)7.0 (5.7 to 8.4)
      459.8 (9.3 to 10.4)16.2 (15.1 to 17.3)6.4 (5.2 to 7.6)
      508.9 (8.3 to 9.4)14.8 (13.9 to 15.8)6.0 (4.9 to 7.0)
      557.7 (7.2 to 8.1)13.0 (12.2 to 13.8)5.3 (4.4 to 6.2)
      606.6 (6.1 to 7.0)11.1 (10.5 to 11.8)4.6 (3.8 to 5.3)
      655.5 (5.1 to 5.8)9.0 (8.4 to 9.5)3.5 (2.9 to 4.1)
      704.4 (4.1 to 4.7)6.7 (6.3 to 7.1)2.3 (1.8 to 2.7)
      752.7 (2.5 to 3.0)4.6 (4.3 to 4.9)1.9 (1.6 to 2.2)
      801.7 (1.5 to 1.8)2.7 (2.5 to 2.8)1.0 (0.8 to 1.2)
      851.0 (0.8 to 1.2)1.4 (1.0 to 1.7)0.4 (0.0 to 0.8)
      Note: Difference in life expectancy is reported in years (95% confidence interval).
      These results mirror our recent report of the life expectancy of patients across different levels of estimated glomerular filtration rate, in which we observed that lower levels of kidney function were associated with a decrease in life expectancy for both men and women.
      • Turin T.C.
      • Tonelli M.
      • Manns B.J.
      • Ravani P.
      • Ahmed S.B.
      • Hemmelgarn B.R.
      Chronic kidney disease and life expectancy.
      Our study is strengthened by its population-based sample and large size, but also has limitations. First, life expectancy for the middle-aged population with no proteinuria in our study was approximately 7-8 years shorter than the overall life expectancy during the same period in Alberta.
      Statistics Canada
      Life Tables, Canada, Provinces and Territories Life expectancy at birth, by sex, by province 2006-2008 (Catalogue 84-537-XIE).
      This difference may be due to the selective nature of our cohort, including that it comprised individuals who had outpatient proteinuria measurements as part of routine care and excluded presumably healthier individuals who did not access medical services and receive proteinuria testing. This might have selected patients with comorbid conditions associated with kidney disease and increased the overall risk of mortality for the cohort. Second, proteinuria categorization was based on a single measurement at baseline. Thus, misclassification due to transient proteinuria could not be ruled out. Third, our study provides information for only the crude association between proteinuria and life expectancy. These estimates of life expectancy were not adjusted for coexistent comorbid conditions, and in particular, for level of kidney function, and therefore the projected decreases in life expectancy associated with proteinuria may be due partly to conditions such as hypertension and diabetes or more severely decreased kidney function. Also, the age effects on life expectancy should not be interpreted as in a longitudinal study. Finally, it is important to note that current methods for the estimation of life expectancy cannot account for changes in risk factor status over time due to aging, changes in lifestyle, or medication. Regardless, our estimates accurately reflect life expectancy for people with proteinuria in a developed country and are useful to decision makers.
      In conclusion, we found a substantial and progressive decrease in life expectancy for men and women with the presence and severity of proteinuria.

      Acknowledgements

      Support: T.C.T. is supported by Fellowship Awards from the Canadian Institutes of Health Research (CIHR), Canadian Diabetes Association, and the Interdisciplinary Chronic Disease Collaboration team grant funded by Alberta Innovates–Health Solutions (AI-HS). B.R.H., M.T., B.J.M., and S.B.A. are supported by AI-HS Salary Awards. S.B.A. is supported by a salary award from CIHR; B.R.H., by the Roy and Vi Baay Chair in Kidney Research; M.T., by a Canada Research Chair, and M.J., by a KRESCENT new investigator award.
      Financial Disclosure: The authors declare that they have no other relevant financial interests.

      Supplementary Material

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      Linked Article

      • Overestimation of Life Expectancy in CKD
        American Journal of Kidney DiseasesVol. 62Issue 2
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          Turin et al1 reported life expectancies for patients with mild or heavy proteinuria. Their results must be viewed as overestimates. The authors properly excluded persons with end-stage renal disease at baseline, classified the rest as having mild or heavy proteinuria, and followed them up for 3-7 years to determine survival. However, their life expectancies for the mild and heavy groups come from life tables constructed using age- and group-specific mortality rates computed over the 3-7 year period.
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