Nephrol Dial Transplant (2012) 27: 3182–3186 doi: 10.1093/ndt/gfs052 Advance Access publication 22 March 2012

Chronic kidney disease and life expectancy Tanvir Chowdhury Turin1, Marcello Tonelli2, Braden J. Manns1,3, Pietro Ravani1,3, Sofia B. Ahmed1 and Brenda R. Hemmelgarn1,3 1

Department of Medicine, University of Calgary, Calgary, Canada, 2Department of Medicine, University of Alberta, Edmonton, Canada and 3Department of Community Health Sciences, University of Calgary, Calgary, Canada Correspondence and offprint requests to: Brenda R. Hemmelgarn; E-mail: [email protected]

Keywords: chronic kidney disease; disease burden; epidemiology; life expectancy; population

Materials and methods Data source We studied adults 30 years of age and older in Alberta, Canada, who had at least one outpatient serum creatinine measurement between 1 May 2002 and 31 March 2008. We excluded those with end-stage renal disease at study entry [estimated glomerular filtration rate (eGFR) < 15 mL/min/1.73 m2, chronic dialysis or previous kidney transplant] for a final cohort of 1 542 957 participants (707 164 men and 835 793 women). Participants were followed until 31 March 2009. All-cause mortality was determined from Vital Statistics data of the Alberta Health and Wellness Registry file. Ethics approval for this study was obtained from the Institutional Review Board of the University of Calgary. Kidney function level We used the CKD-EPI equation [5] to estimate eGFR for each patient. Kidney function was categorized as ≥ 60, 45–59, 30–44 and 15–29 mL/ min/1 · 73.m2. Statistical analysis Age-specific mortality rates were calculated with the person-year method [6]. Age bands used in this calculation were set in 5 years, which began at age 30 years and the highest age category was set at age 85 years and over. The abridged life table was used to calculate the life expectancies from these age-group-specific mortality rates. Abridged life tables and associated variances, standard errors and 95% confidence intervals (95% CIs) were calculated according to Chiang’s method [7]. Consistent with prior studies, the fraction of the last interval of life lived by those dying in the interval was set to 0.5 for all age strata younger than the last age strata of 85 years and older [7, 8]. Differences in life expectancy between levels of eGFR as well as men and women were estimated with the 95% CI [8].

Introduction

Results

Chronic kidney disease (CKD) is recognized as a major public health problem affecting 13–16% of the adult population [1, 2] and is associated with increased risk of all-cause mortality [3, 4]. Life expectancy at different ages is a measure commonly used to estimate health status and impact of disease burden at a population level. This information can be used by policy makers to identify disease conditions with the greatest impact on overall life expectancy, which might be prioritized for specific health care programs or funding. We used a large population-based registry to estimate life expectancy of middle-aged men and women with varying levels of kidney function.

Among male participants, 90.7% had an eGFR ≥ 60, 6.2% had an eGFR 45–59, 2.3% had an eGFR 30–44 and 0.7% had an eGFR 15–29 (all eGFR in mL/min/1.73 m2). Among female participants, 92.4% had an eGFR ≥ 60, 5.3% had an eGFR 45–59, 1.7% had an eGFR 30–44 and 0.5% had an eGFR 15–29 (all eGFR in mL/min/1.73 m2). Table 1 shows life expectancy for participants by gender and level of eGFR in 5-year age bands (from 30 to 85 years of age and over). Within each age stratum, life expectancy was substantially shorter for people with lower eGFR (Appendix Figure A1). Men and women aged 40 years had a mean life expectancy of 30.5 and 34.6 years, respectively, at an eGFR of ≥ 60 and 24.5 and

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Abstract Background. Life expectancy is commonly used as an indicator of health and reflects disease burden in the population. The life expectancy for patients with lower levels of kidney function has not been reported. Methods. The abridged life table method was applied to calculate the life expectancies of men and women from age 30 to 85 years, by levels of kidney function as defined by estimated glomerular filtration rate (eGFR): ≥ 60, 45– 59, 30–44 and 15–29 mL/min/1.73 m2. Results. Men and women aged 40 years had a life expectancy of 30.5 and 34.6 years at eGFR ≥ 60 mL/min/1.73 m2, 24.5 and 28.7 years at eGFR 45–59 mL/min/1.73 m2, 14.5 and 16.5 years at eGFR 30–44 mL/min/1.73 m2 and 10.4 and 9.1 years at eGFR 15–29 mL/min/1.73 m2, respectively. Life expectancy was longer for women compared with men at all ages and eGFR categories, other than for eGFR 15–29 mL/min/1.73 m2 where there was no difference in life expectancy by gender. Conclusion. A lower level of kidney function is associated with a reduction in life expectancy for both men and women.

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expectancy was shorter at lower levels of kidney function (compared to those with relatively higher levels of kidney function) across all age strata for both genders. Life

28.7 years at an eGFR 45–59. The life expectancy of both 40-year-old men and women with eGFR ≥ 60 was 5.9 years longer than those with eGFR 44–59 (Table 2). Life Table 1. Life expectancy by age, gender and level of eGFRa

Kidney function Age group (year)

eGFR ≥ 60

Men

30 35 40 45 50 55 60 65 70 75 80 85

Women

30 35 40 45 50 55 60 65 70 75 80 85

a

eGFR 45–59

eGFR 30–44

eGFR 15–29

39.1 (38.9–39.2) 34.7 (34.6–34.9) 30.5 (30.3–30.6) 26.2 (26.1–26.4) 22.3 (22.2–22.4) 18.6 (18.5–18.7) 15.1 (15.0–15.2) 11.9 (11.8–12.0) 9.0 (9.0–9.1) 6.7 (6.6–6.7) 4.6 (4.6–4.7) 2.7 (2.5–2.8)

28.4 (25.1–31.7) 28.0 (26.3–29.8) 24.5 (23.3–25.8) 21.3 (20.4–22.2) 18.3 (17.7–19.0) 16.0 (15.5–16.5) 13.6 (13.2–13.9) 10.9 (10.7–11.2) 8.4 (8.3–8.6) 6.2 (6.0–6.3) 4.3 (4.2–4.4) 2.3 (2.2–2.5)

20.1 (16.5–23.7) 16.3 (13.3–19.2) 14.5 (12.3–16.8) 12.5 (10.9–14.2) 10.6 (9.5–11.7) 8.7 (7.9–9.5) 7.8 (7.3–8.4) 6.6 (6.2–7.0) 5.9 (5.7–6.2) 4.7 (4.5–4.9) 3.4 (3.3–3.4) 1.8 (1.6–2.0)

15.3 (11.0–19.5) 13.8 (11.0–16.7) 10.4 (8.1–12.7) 8.8 (7.1–10.5) 7.4 (6.1–8.7) 6.6 (5.6–7.6) 5.6 (4.8–6.3) 4.6 (4.2–5.1) 3.9 (3.6–4.2) 3.1 (2.9–3.3) 2.5 (2.5–2.6) 1.4 (1.2–1.7)

43.8 (43.7–44.0) 39.2 (39.0–39.3) 34.6 (34.5–34.7) 30.2 (30.1–30.4) 26.0 (25.9–26.2) 22.0 (21.9–22.1) 18.2 (18.1–18.3) 14.6 (14.5–14.7) 11.3 (11.2–11.4) 8.4 (8.3–8.5) 5.6 (5.5–5.7) 3.0 (2.9–3.1)

33.6 (31.0–36.2) 30.8 (28.9–32.8) 28.7 (27.5–29.9) 25.4 (24.5–26.3) 22.3 (21.7–22.9) 19.1 (18.6–19.6) 16.5 (16.1–16.8) 13.4 (13.1–13.6) 10.5 (10.4–10.7) 7.9 (7.8–8.0) 5.3 (5.2–5.4) 2.8 (2.7–2.9)

21.4 (17.3–25.5) 17.6 (14.0–21.2) 16.5 (14.0–19.0) 14.9 (13.0–16.7) 13.2 (11.8–14.5) 11.3 (10.3–12.3) 10.6 (9.9–11.2) 9.4 (8.9–9.9) 7.9 (7.6–8.2) 6.0 (5.9–6.2) 4.5 (4.4–4.6) 2.2 (2.0–2.3)

12.7 (7.4–18.0) 13.1 (10.1–16.0) 9.1 (6.6–11.6) 7.4 (5.6–9.3) 7.4 (5.9–8.8) 6.7 (5.6–7.8) 6.2 (5.4–7.0) 4.7 (4.2–5.2) 4.1 (3.8–4.5) 3.9 (3.6–4.1) 3.1 (3.0–3.2) 1.6 (1.4–1.8)

Life expectancy is in years.

Table 2. Differences in life expectancy by age and gender and eGFR levelsa Difference in life expectancy (95% CI) Gender

Age group (year)

eGFR ≥ 60 versus 45–59

eGFR ≥ 60 versus 30–44

eGFR ≥ 60 versus 15–29

Men

30 35 40 45 50 55 60 65 70 75 80 85

10.7 (7.4–14.0) 6.7 (5.0–8.4) 5.9 (4.7–7.1) 4.9 (4.0–5.8) 4.0 (3.3–4.7) 2.6 (2.1–3.1) 1.5 (1.2–1.9) 1.0 (0.7–1.2) 0.6 (0.4–0.8) 0.5 (0.4–0.7) 0.3 (0.2–0.5) 0.3 (0.1–0.6)

19.0 (15.4–22.6) 18.5 (15.5–21.5) 15.9 (13.6–18.2) 13.7 (12.1–15.4) 11.7 (10.6–12.9) 9.9 (9.1–10.8) 7.3 (6.7–7.9) 5.2 (4.8–5.6) 3.1 (2.8–3.4) 2.0 (1.8–2.2) 1.3 (1.2–1.4) 0.9 (0.7–1.1)

23.8 (19.6–28.0) 20.9 (18.1–23.7) 20.1 (17.8–22.4) 17.5 (15.8–19.2) 14.9 (13.6–16.2) 12.0 (11.0–13.0) 9.6 (8.8–10.3) 7.2 (6.7–7.7) 5.2 (4.8–5.5) 3.6 (3.4–3.7) 2.1 (2.0–2.2) 1.3 (1.0–1.6)

Women

30 35 40 45 50 55 60 65 70 75 80 85

10.2 (7.6–12.8) 8.3 (6.4–10.3) 5.9 (4.7–7.1) 4.8 (4.0–5.7) 3.8 (3.1–4.4) 2.9 (2.4–3.4) 1.7 (1.3–2.0) 1.3 (1.0–1.5) 0.8 (0.6–1.0) 0.5 (0.3–0.6) 0.3 (0.1–0.4) 0.2 (0.0–0.4)

22.4 (18.3–26.5) 21.6 (17.9–25.2) 18.1 (15.7–20.6) 15.4 (13.6–17.2) 12.9 (11.5–14.2) 10.7 (9.8–11.7) 7.6 (6.9–8.3) 5.2 (4.8–5.7) 3.5 (3.2–3.8) 2.3 (2.1–2.5) 1.1 (1.0–1.3) 0.9 (0.7–1.0)

31.1 (25.8–36.4) 26.1 (23.1–29.1) 25.5 (23.0–28.0) 22.8 (20.9–24.7) 18.7 (17.2–20.1) 15.3 (14.2–16.4) 12.0 (11.2–12.8) 9.9 (9.4–10.5) 7.2 (6.9–7.6) 4.5 (4.3–4.8) 2.5 (2.4–2.7) 1.4 (1.2–1.7)

a

Difference in life expectancy is in years.

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Gender

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T.C. Turin et al.

expectancy for men was consistently shorter than for women for all age strata among the eGFR categories of ≥ 60, 45–59 and 30–44 mL/min/1.73 m2 (Table 3). For the eGFR 15–29, life expectancy did not differ between genders.

Discussion We found that both men and women with lower levels of kidney function had substantially reduced life expectancy, which was most notable in those with eGFR < 30. In Table 3. Difference in life expectancy among women and men by eGFR levelsa Difference in life expectancy (95% CI) Level of kidney function

eGFR 45–59

eGFR 30–44

eGFR 15–29

a

30 35 40 45 50 55 60 65 70 75 80 85 30 35 40 45 50 55 60 65 70 75 80 85 30 35 40 45 50 55 60 65 70 75 80 85 30 35 40 45 50 55 60 65 70 75 80 85

Women versus men 4.7 (4.5–4.9) 4.4 (4.2–4.6) 4.2 (4.0–4.3) 4.0 (3.8–4.2) 3.7 (3.5–3.9) 3.4 (3.2–3.6) 3.1 (2.9–3.2) 2.7 (2.6–2.9) 2.3 (2.2–2.4) 1.7 (1.6–1.8) 1.0 (0.8–1.1) 0.3 (0.1–0.5) 5.2 (1.0–9.4) 2.8 (0.2–5.4) 4.2 (2.4–5.9) 4.1 (2.8–5.3) 3.9 (3.0–4.9) 3.1 (2.4–3.8) 2.9 (2.4–3.4) 2.4 (2.1–2.8) 2.1 (1.9–2.4) 1.7 (1.5–1.9) 1.0 (0.9–1.2) 0.5 (0.2–0.7) 1.3 (−4.1 to 6.8) 1.3 (−3.4 to 6.0) 1.9 (−1.4 to 5.3) 2.3 (−0.1 to 4.8) 2.6 (0.8–4.3) 2.6 (1.3–3.9) 2.7 (1.8–3.6) 2.8 (2.2–3.4) 2.0 (1.6–2.4) 1.4 (1.1–1.6) 1.1 (1.0–1.3) 0.4 (0.1–0.6) −2.6 (−9.3 to 4.2) −0.8 (−4.9 to 3.3) −1.3 (−4.7 to 2.1) −1.4 (−3.9 to 1.1) −0.1 (−2.0 to 1.8) 0.1 (−1.3 to 1.6) 0.7 (−0.4 to 1.7) 0.0 (−0.6 to 0.7) 0.2 (−0.2 to 0.6) 0.8 (0.5–1.0) 0.6 (0.5–0.6) 0.2 (−0.2 to 0.5)

Difference in life expectancy is in years.

Acknowledgements. Dr T.C.T. is supported by Fellowship Awards from the Canadian Institutes of Health Research (CIHR), Canadian Diabetes Association (CDA) and the Interdisciplinary Chronic Disease

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eGFR ≥ 60

Age group (year)

general, women had longer life expectancy than men across all levels of eGFR and age, except for those with eGFR 15–29 where the reduction in life expectancy was similar for both men and women. Previous studies estimating life expectancy in people with kidney disease have focused on those with kidney failure [9–15]. To our knowledge, this is the first population-based study to estimate life expectancy for people with different levels of kidney functions. Prior studies have estimated the reduction in life expectancy associated with other chronic conditions. Lidia et al. [16] recently reported that middle-aged patients with hypertension had a reduction in life expectancy of 2–3 years. Similar results have been reported in the Finnish populations [17] and among participants in the Framingham Heart Study [18]. People with diabetes have a large reduction in life expectancy. For instance, among participants from the Framingham Heart Study, men and women aged 50 years with diabetes had on average 7.5 and 8.2 years shorter life expectancy than their non-diabetic equivalents [19]. Similarly, Gu et al. [20] observed that the median life expectancy was 8 years shorter for diabetic subjects aged 55–64 years. While hypertension and diabetes are important chronic diseases, in our study participants with lower levels of kidney functions also showed substantial reductions in life expectancy. This underscores the importance of CKD as a public health problem and illustrates the potential impact of effective primary and secondary prevention activities aimed at CKD. Our study has potential limitations that should be recognized. Firstly, life expectancy among the middleaged population with kidney function level of ≥ 60 mL/ min/1.73 m2 in our study was ∼8 years shorter than the overall life expectancy for men and women during the same time period in Alberta [21]. This difference is attributed to the selective nature of our study cohort, which was limited to individuals who had outpatient serum creatinine measurements as part of routine care. Secondly, our estimates of life expectancy were not adjusted for concomitant comorbid conditions—and therefore, the projected reductions in life expectancy associated with lower levels of kidney function may be partially due to conditions such as hypertension and diabetes. Regardless, our estimates accurately reflect life expectancy for people with CKD in a developed country and will be useful to decision makers. Thirdly, participants’ kidney function status was classified based on serum creatinine measurement at one point in time, with 32% of study participants having a repeated measurement of serum creatinine 3–12 months after the baseline measurement. Given the reduction in life expectancy associated with lower eGFR, the estimates presented here may in fact be an overestimate of the actual life expectancy for patients with progressive CKD. In conclusion, we found a substantial and progressive reduction in life expectancy for men and women with lower levels of kidney function, reflective of CKD.

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Figure A1. Life expectancy for men and women with different levels of kidney function as different index ages.

Collaboration (ICDC) team grant funded by Alberta Innovates-Health Solutions (AI-HS). Drs B.R.H., M.T., B.J.M. and S.B.A. are supported by AI-HS Salary Awards. Dr S.B.A. is supported by a salary award from CIHR. Dr B.R.H. is supported by the Roy and Vi Baay Chair in Kidney Research and Dr M.T. is supported by a Canada Research Chair.

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Conflict of interest statement. None declared. (See related article by Stevens and Farmer. Chronic kidney disease and life expectancy. Nephrol Dial Transplant 2012; 27: 3014–3015.)

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statement from Kidney Disease Improving Global Outcomes. Kidney Int 2007; 72: 247–259 Coresh J, Selvin E, Stevens LA et al. Prevalence of chronic kidney disease in the United States. JAMA 2007; 298: 2038–2047 Chronic Kidney Disease Prognosis Consortium. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. The Lancet 2010; 375: 2073–2081 Tonelli M, Wiebe N, Culleton B et al. Chronic kidney disease and mortality risk: a systematic review. J Am Soc Nephrol 2006; 17: 2034–2047 Levey AS, Stevens LA, Schmid CH et al. A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150: 604–612 Breslow NE, Day NE Statistical Methods in Cancer Research Volume II—The Analysis of Case-control Studies. Lyon, France: International Agency for Research on Cancer, 1980, pp. 41–81

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Available at http://www.usrds.org/2008/view/default.asp. Accessed on 25-01-2012 Lidia L, Chris W, Bernard C Health-adjusted life expectancy among Canadian adults with and without hypertension. Cardiol Res Pract 2011; 2011: 612968 Kiiskinen U, Vartiainen E, Puska P et al. Long-term cost and lifeexpectancy consequences of hypertension. J Hypertens 1998; 16: 1103–1112 Franco OH, Peeters A, Bonneux L et al. Blood pressure in adulthood and life expectancy with cardiovascular disease in men and women: life course analysis. Hypertension 2005; 46: 280–286 Franco OH, Steyerberg EW, Hu FB et al. Associations of diabetes mellitus with total life expectancy and life expectancy with and without cardiovascular disease. Arch Intern Med 2007; 167: 1145–1151 Gu K, Cowie CC, Harris MI Mortality in adults with and without diabetes in a national cohort of the US population, 1971–1993. Diabetes Care 1998; 21: 1138–1145 Statistics Canada. Life Tables, Canada, Provinces, Territories. Life Expectancy at Birth, by Sex, by Province 2006–2008 (Catalogue 84537-XIE). Available at http://www.statcan.gc.ca/bsolc/olc-cel/olc-cel? catno=84-537-XIE&langeng. Accessed December 16, 2011

Received for publication: 22.12.2011; Accepted in revised form: 30.1.2012

Nephrol Dial Transplant (2012) 27: 3186–3190 doi: 10.1093/ndt/gfr750 Advance Access publication 9 January 2012

Renal biopsy criterion in children with asymptomatic constant isolated proteinuria Taketsugu Hama1, Koichi Nakanishi1, Yuko Shima1, Hironobu Mukaiyama1, Hiroko Togawa1, Ryojiro Tanaka2, Kiyoshi Hamahira3, Hiroshi Kaito4, Kazumoto Iijima4 and Norishige Yoshikawa1 1 Department of Pediatrics, Wakayama Medical University, Wakayama, Japan, 2Department of Nephrology, Hyogo Prefectural Kobe Children’s Hospital, Kobe, Japan, 3Department of Pediatrics, Himeji Red Cross Hospital, Himeji, Japan and 4Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan

Correspondence and offprint requests to: Koichi Nakanishi; E-mail: [email protected]

Abstract Background. The criterion of a renal biopsy in children with asymptomatic persistent isolated proteinuria is controversial. Methods. To determine an adequate renal biopsy criterion in children with asymptomatic constant isolated proteinuria, the optimal cutoff maximum urinary protein/ creatinine ratio (uP/Cr) to separate minor glomerular abnormalities (MGA) and other significant glomerular changes was obtained by receiver operating characteristic analysis in 44 children with asymptomatic constant isolated proteinuria (uP/Cr ≥0.2 g/g) screened from 1167 patients who underwent a renal biopsy between September 2000 and April 2010. Patients were divided into two groups according to the cutoff value to verify its validity.

Results. The optimal uP/Cr was 0.5 g/g. In Group 1 (uP/ Cr