Clinical Epidemiology

Lifetime Risk of ESRD

Tanvir Chowdhury Turin, Marcello Tonelli, Braden J. Manns, Sofia B. Ahmed, Pietro Ravani, Matthew James and Brenda R. Hemmelgarn
JASN September 2012, 23 (9) 1569-1578; DOI: https://doi.org/10.1681/ASN.2012020164

Abstract

Lifetime risk is the cumulative risk of experiencing an outcome between a disease-free index age and death. The lifetime risk of ESRD for a middle-aged individual is a relevant and easy to communicate measure of disease burden. We estimated lifetime risk of ESRD in a cohort of 2,895,521 adults without ESRD from 1997 to 2008. To estimate lifetime risk of ESRD by level of baseline kidney function, we analyzed a cohort of participants who had a serum creatinine measurement. We also estimated the sex- and index age-specific lifetime risk of incident ESRD and accounted for the competing risk of death. Among those individuals without ESRD at age 40 years, the lifetime risk of ESRD was 2.66% for men and 1.76% for women. The risk was higher in persons with reduced kidney function: for eGFR=44–59 ml/min per 1.73 m2, the lifetime risk of ESRD was 7.51% for men and 3.21% for women, whereas men and women with relatively preserved kidney function (eGFR=60–89 ml/min per 1.73 m2) had lifetime risks of ESRD of 1.01% and 0.63%, respectively. The lifetime risk of ESRD was consistently higher for men at all ages and eGFR strata compared with women. In conclusion, approximately 1 in 40 men and 1 in 60 women of middle age will develop ESRD during their lifetimes (living into their 90s). These population-based estimates may assist individuals who make decisions regarding public health policy.

ESRD is a chronic condition with significant health consequences and high-cost treatment options.1–3 Although estimates of incidence and prevalence provide important information about the burden of a disease in the community, they do not provide adequate information to understand risk at the individual level. Lifetime risk (which expresses the probability of an individual developing a disease condition during their remaining lifespan) may be more informative for both the general population and policy-makers, because it portrays overall risk burden over the course of a person’s life, thus allowing comparison of lifetime risks across diseases of interests. It has been suggested that lifetime risk estimates are useful for public education, because they are easier to comprehend than measures such as incidence, prevalence, or relative risk.4

Although estimates of lifetime risk are available for several chronic disease conditions, including coronary heart disease,5,6 stroke,7,8 hypertension,9 diabetes,10 breast cancer,11 dementia,12 and fractures,13,14 reports on the lifetime risk of ESRD are scarce and limited to an early-adult population.15 Furthermore, the lifetime risk of ESRD at middle age and the lifetime risk of ESRD by level of kidney function have not been reported. Given the high morbidity16 and cost17 associated with ESRD, an estimate of lifetime risk of ESRD would be important information for patients, health practitioners, and policy-makers.

Using a cohort of adults residing in a single Canadian province, we estimated the lifetime risk of ESRD by sex. We also estimated the lifetime risk of ESRD by level of kidney function among a cohort of adults with a serum creatinine measurement.

Results

During total follow-up of 25,985,361 person-years (see Figure 1 for cohort creation), 7107 participants experienced ESRD. The mean duration of follow-up was 8.97 years (SD=3.73). Table 1 presents the 10-, 20-, 30-, and 40-year risks of ESRD as well as the lifetime risk of ESRD for men and women by index ages of 40, 50, 60, and 70 years in Alberta, Canada (percentage). Adjustment for the competing risk of death attenuated the estimate of cumulative incidence for ESRD. Lifetime risk of ESRD for 40-year-old men was 4.14% when death was treated as a censoring event and 2.66% when the death was treated as a competing event. The lifetime risk of ESRD for 40-year-old women, without and with adjustment for the competing risk of death, was 2.28% and 1.76%, respectively. Similar differences between the two methods were observed for all strata defined by age and sex. As expected, there was a graded increase in the risk of ESRD over longer time horizons for all age and sex strata. For example, the risk of ESRD in a 40-year-old man was 0.15%, 0.46%, 1.08%, and 1.98% over 10-, 20-, 30-, and 40-year time horizons, respectively (Figure 2).

Figure 1.
Figure 1.

Overview of cohort creation. (A) The primary study cohort consisted of Alberta residents aged 18 years or older registered with Alberta Health and Wellness from April 1, 1997 to March 31, 2008. (B) Cohort of participants who had at least one outpatient serum creatinine measurement from May 1, 2002 to March 31, 2008.

Figure 2.
Figure 2.

Cumulative risk of ESRD (in percentage) with advancing age for men and women at the index age of 40 years.

View this table:
Table 1.

Age- and sex-specific 10-, 20-, 30-, and 40-year and lifetime risk estimates (in percentages) for ESRD in Alberta, Canada

In the cohort of participants who had at least one estimated GFR (eGFR) measurement during 2002–2008, there were 996,249 participants (416,576 men and 579,673 women) with baseline eGFR≥90 ml/min per 1.73 m2, 689,603 participants (335,387 men and 354,216 women) with baseline eGFR=60–89 ml/min per 1.73 m2, 89,662 participants (37,389 men and 52,273 women) with baseline eGFR=45–59 ml/min per 1.73 m2, and 31,755 participants (12,190 men and 19,565 women) with baseline eGFR=30–44 ml/min per 1.73 m2. During 7,504,339 person-years of follow-up, there were 2212 incident cases of ESRD. Table 2 shows the person-year of follow-up, incidence of ESRD, and mortality across age groups.

View this table:
Table 2.

Person-years of follow-up and number of events (ESRD and death) by sex and baseline kidney function across age groups

Table 3 presents the risk of ESRD in men and women over different time intervals by index ages and level of eGFR. After adjustment for the competing risk of death, the lifetime risk of ESRD for 40-year-old men with eGFR≥90 ml/min per 1.73 m2 was 0.72%, eGFR=60–89 ml/min per 1.73 m2 was 1.01%, eGFR=45–59 ml/min per 1.73 m2 was 7.51%, and eGFR=30–44 ml/min per 1.73 m2 was 55.54%. For women aged 40 years, the lifetime risk was 0.67% for those individuals with eGFR≥90 ml/min per 1.73 m2, 0.73% for those individuals with eGFR=60–89 ml/min per 1.73 m2, 3.21% for those individuals with eGFR=45–59 ml/min per 1.73 m2, and 28.81% for those individuals with eGFR=30–44 ml/min per 1.73 m2 (Figure 3). Differential trends were observed for the short-term risk estimates for the impaired and relatively preserved kidney function groups. The short-term risks for ESRD increased with higher index age for participants with eGFR>90 and 60–89 ml/min per 1.73 m2. However, short-term risks for ESRD decreased with higher index age for participants with eGFR=30–44 and 45–59 ml/min per 1.73 m2 (Table 3). A graded increase in the risk of ESRD over longer time horizons was observed for all age and sex strata across all levels of kidney function (Figure 3). Men had a consistently higher risk of ESRD compared with women in all analyses.

Figure 3.
Figure 3.

Competing risk of death-adjusted cumulative risk of ESRD (in percentage) with advancing age by eGFR category for men and women at the index ages of 40 and 70 years. eGFR was categorized as ≥90, 60–89, 45–59, and 30–44 ml/min per 1.73 m2.

View this table:
Table 3.

Age- and sex-specific 10-, 20-, 30-, and 40-year and lifetime risk estimates (in percentage) for ESRD by level of kidney function

Discussion

We estimated the lifetime risk of ESRD in a community-based cohort of nearly 3 million people from a provincial health registry. Lifetime risk is a measure of the cumulative risk of experiencing an outcome during the remainder of an individual’s life from a disease-free index age. Theoretical advantages of reporting lifetime risk include ease of comparison between studies and overall risk of an adverse outcome may be easier to understand than other commonly used epidemiologic measures of risk. The observed probabilities suggest that approximately 1 in 40 men and 1 in 60 women of middle age will develop ESRD over their remaining life (with the assumption that they will live to the age of 90 years). This risk was higher in persons with reduced kidney function compared with those individuals with preserved kidney function.

The magnitude of the lifetime risks for ESRD may seem higher than expected. However, a few key issues must be considered when interpreting our results. First, our estimates by levels of kidney function are based on people who obtained a serum creatinine measurement as part of clinical care. Because physicians may be less likely to measure serum creatinine in healthy individuals with no risk factors for ESRD, our estimates by levels of kidney function may be most relevant to people accessing medical care with a perceived clinical need rather than the general population. Second, given the average age of our cohort, the lifetime risks predominantly reflect the risks in people who have survived to middle age, and they exclude individuals dying because of causes that disproportionately affect young individuals, such as childhood illnesses or trauma. With these caveats in mind, our results are consistent with prior reports. A simulation study based on the US population reported the lifetime risk of ESRD to be 1 in 40 for white men and nearly 1 in 50 for white women.15

Our estimates take into account all-cause mortality and the competing risk of death in a community-based population. Adjustment for the competing risk of death clearly attenuated the estimate of cumulative ESRD incidence, especially over longer time horizons, for those individuals with relatively preserved kidney function. Adjusting for the competing risk of death did not have any marked effect among the participants with impaired kidney function. Attenuation of lifetime risk estimates after adjusting for the competing risk of death has also been reported in studies of cardiovascular disease.5,7

Sex differences in studies of CKD progression have been reported, with higher rates of progression for men.18–20 We also observed that women had a lower lifetime risk of ESRD compared with men of similar age strata. Our results are consistent with prior reports, with lifetime risk of ESRD for 20-year-old white men reported to be higher than white women.15 Interestingly, the lifetime risk of ESRD was reported to be the same for black men and women at approximately 1 in 12.15

The cumulative risk of ESRD increased across the time horizons for all age strata for both men and women and reflects the contribution of the age time scale, which has also been reported for cardiovascular disease.5–8 We also observed that the lifetime risk of ESRD decreased for increasing age strata, which is also consistent with other reports of similar estimation for other chronic disease conditions.5–8 The decrease in lifetime risk of ESRD with older age reflects the shorter life expectancy and period at risk for older participants. Also at older ages, competing causes of death will increase in importance, because older people may not live long enough to develop ESRD, and people susceptible to ESRD would have developed ESRD at an earlier age.

Adjustment of competing risk of death led to attenuation for lifetime risk of ESRD in the overall estimates. Similar attenuation was observed regarding competing risk adjustment for the estimates reported for other chronic disease conditions.5–8 Not accounting for mortality (i.e., competing risk) during risk estimation in studies with prospective capturing of incidence may introduce bias in risk estimates.21 Thus, adjusting for competing risk of death will provide more robust lifetime risk estimates.

The lifetime risk estimates are useful for public education, because they are easier to comprehend than measures such as incidence, prevalence, or relative risk.4 These estimates provide a more coherent approach to health education, because low statistical numeracy and/or quantitative literacy are common.22 A study with the objective to elicit patient preferences for the presentation and framing of risk information concluded that patients preferred health risks to be framed in absolute terms and lifetime estimates with a scale of x of 100.23 The benefits of reporting lifetime risk estimates have also been observed. The widely publicized lifetime risk of breast cancer, estimated to be one in eight (12.6%) for women in the United States,11 is believed to have contributed to the increase in screening mammogram for early disease detection.24 Although lifetime risk lacks the detail and precision required for clinical consultation, the lifetime estimates presented here provide a useful and understandable summary of risk in a population that will be useful for researchers and policy-makers in envisaging the population burden of ESRD.

Strengths of our study include the use of a population-based cohort and the completeness of ESRD and mortality ascertainment. We were also able to analyze a cohort stratified by level of kidney function to estimate the lifetime risk of ESRD by stage of kidney function.

This study examines the lifetime risk of ESRD among the general population and by level of kidney function. However, our estimates reported should be interpreted within the context of the study limitations common to this type of methodology—including an inability to directly validate the results.5–7,11–13 Lifetime risks estimates are population-based results, and therefore they have limited prognostic use at the patient level, where the lifetime risk would also depend on individual risk factors for ESRD. Furthermore, lifetime risk estimates are based on assumptions of a fixed age and demographic structure for the general population as well as stable ESRD incidence rates and mortality. As in our study, lifetime risks are estimated from a defined study period (rather than the full lifespan), with the assumption that the incidence and mortality rates of the older age groups will be applicable to the participants from the younger age when they reach the corresponding older age groups (for example, the mortality or incidence rate at age 70 years will be applicable when participants of age 40 years reach age 70 years). Thus, time period and birth cohort effects of our study population, therefore, could limit the external validity of our results. Also, severity of the measure of exposure was categorized based on a single point in time (baseline kidney function). Consequently, temporal trends in the prevalence of risk factors and the sensitivity of diagnostic tests could also alter the lifetime risk of ESRD. Finally, our estimates describe the risk of ESRD treated with renal replacement therapy but do not address the risk of untreated renal failure. Therefore, the ESRD risks that we report are likely to be conservative estimates of the true population burden.

In conclusion, the observed probabilities indicate that approximately 1 in 40 men and 1 in 60 women of middle age will develop ESRD in their lifetime in Alberta, Canada. The risk was higher in those individuals with reduced kidney function compared with those individuals with relatively preserved kidney function (eGFR>60 ml/min per 1.73 m2). These measures can be used in both assisting healthcare planners and decision-makers in setting priorities and increasing public awareness and interest in prevention of kidney disease.

Concise Methods

Study Sample

The primary study cohort consisted of 2,895,521 (1,459,937 men and 1,435,584 women) Alberta residents ages 18 years or older registered with Alberta Health and Wellness from April 1, 1997 to March 31, 2008 (Figure 1A). All Alberta residents are eligible for insurance coverage by Alberta Health and Wellness, and >99% participate in this coverage. Participants with ESRD (dialysis or transplantation) were excluded. To estimate the lifetime risk of ESRD by level of baseline kidney function, we included a cohort of participants (Figure 1B) who had at least one outpatient creatinine measurement from May 1, 2002 to March 31 200825 and used their first serum creatinine measurement of eGFR using the CKD Epidemiology Collaboration equation.26 Participants with eGFR<30 ml/min per 1.73 m2 at the time of the first creatinine measurement were excluded. We estimated the lifetime risk of ESRD for people with baseline eGFR categorized as ≥90, 60–89, 45–59, and 30–44 ml/min per 1.73 m2.

Outcome Ascertainment

The primary outcome was development of ESRD, which was defined as the date of registration for chronic dialysis or renal transplantation as determined from the databases of Northern Alberta and Southern Alberta Renal Programs and administrative data using a validated algorithm.27,28 Death was identified using Vital Statistics data from the Alberta Health and Wellness Registry file.

Statistical Analyses

Age (in years) was used as the time scale. The index age categories started at age 40 years and increased by decade to age 70 years. Risk estimation began at an index age—participants who were below the index age of interest at the beginning of the study period entered the analysis when they reached the required age. For example, for risk estimation at an index age of 40 years, participants ages 40 years and older were included. Participants who were <40 years of age at the beginning of the study period began contributing to the risk estimation at their 40th birthday.

Follow-up ended at ESRD occurrence, death, migration from the province, or study end (March 31, 2009), whichever came first. We estimated cumulative ESRD incidence conditional on survival to ages of 50, 60, 70, 80, and 90 years. We estimated lifetime risk of ESRD (conditional on survival to ages of 40, 50, 60, and 70 years) with and without adjustment for competing risk of death. The estimates were calculated using a modified technique of survival analysis29 from previously reported analyses.9,30 All statistical analyses were done using SAS version 9.1 (SAS Institute, Cary, NC). The study was approved by the institutional ethics review board of the University of Calgary.

Disclosures

None.

Acknowledgments

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). M.T., B.J.M., S.B.A., and B.R.H. are supported by AI-HS Salary Awards. M.J. is supported by a KRESCENT new investigator award. M.T. is supported by a Canada Research Chair. S.B.A. is supported by a salary award from CIHR. B.R.H. is supported by the Roy and Vi Baay Chair in Kidney Research.

The authors declare that they have no relevant financial interests or any conflicts of interests.

Footnotes

  • Published online ahead of print. Publication date available at www.jasn.org.

  • See related editorial, “Lifetime Risk of ESRD: A Meaningful Concept?,” on pages 1444–1446.

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Lifetime Risk of ESRD
Tanvir Chowdhury Turin, Marcello Tonelli, Braden J. Manns, Sofia B. Ahmed, Pietro Ravani, Matthew James, Brenda R. Hemmelgarn
JASN Sep 2012, 23 (9) 1569-1578; DOI: 10.1681/ASN.2012020164
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