Discussion
In this simulation study, the estimated lifetime risk of CKD stage 3a+ was >50%, lower than that of hypertension (83%-90% for a 55-year-old), but higher than those for diabetes (33%-39%), coronary heart disease (32%-49% for a 40-year-old), and invasive cancer (38%-45%). The lifetime risks of CKD stages 3b+ and 4+ and ESRD also were considerable at 33.6%, 11.5%, and 3.6%, respectively. Consistent with previous studies, the risk of CKD stage 3a+ increased dramatically with age, with approximately half the incident cases occurring after age 70 years, an observation even more pronounced in incident CKD stage 4+. In contrast, cases of ESRD developed earlier, reaching a plateau at older ages.
The strong relationship between age and incident CKD leads to an interesting result: those with the longest life expectancy had the highest risk of CKD stage 3a+. This observation, consistent with previous demonstrations of CKD incidence in older populations (eg, 20.5% incidence during a 24-month period in the Women's Health and Aging Study I), fuels the long-standing debate about whether eGFR decline is "normal aging" or a pathologic process. Although the present study was not designed to address this controversy, it relies on HRs from a recent meta-analysis that suggested that CKD-associated risks persist in older adults, albeit with diminished relative risks. In contrast to the relationship between age and CKD, the relationship between age and ESRD incidence was not monotonic: rates declined after age 75 years, perhaps reflecting a more frequent refusal of renal replacement therapy and a higher competing risk of pre-ESRD death for older adults.
Lifetime estimates of kidney disease risk differed substantially by sex and race. White women faced the highest risk of CKD stage 3a+, yet the lowest risk of treated ESRD, possibly reflecting the older onset of kidney disease (with respect to blacks), slower CKD progression, or differences in the acceptance of renal replacement therapy. Black individuals faced higher risks of kidney disease at earlier ages. For CKD stage 4+ and ESRD, the risk difference was dramatic and persistent over a lifetime, findings consistent with the seemingly paradoxical lower prevalence yet higher incidence of moderate CKD in the US black population. This may suggest a susceptibility to CKD progression, whether due to diminished access to medical care, genetic predisposition (eg, the prevalence of APOL1 high-risk variants), differences in disease cause, or lower competing risks of death in older age.
Our results expand upon the published literature in several ways. Models were based on the current US general population, stratified by sex and race, and they estimated the lifetime risk of not only ESRD, but also more moderate forms of CKD. Risk of CKD has been simulated for a study of cost-effectiveness in the United States. However, the forecasts were solely among the overall population, with no stratification by sex and race and few age groups. Previous studies of ESRD risk used different populations in nationality or era. Kiberd and Clase's study of ESRD risk provided useful US estimates based on mortality rates from 1998 and ESRD incidence in 1996–1998, but rates have changed significantly since that time. More recently published studies estimated ESRD risk among Canadian participants receiving medical care, in which the majority of the population is likely to be white. Our study updates risk estimates in US whites and US blacks, who shoulder a disproportionate amount of disease.
The estimate that >50% of the US population will develop CKD stage 3a+ is higher than that in a 2010 simulation study but consistent with the estimate that CKD prevalence nears 40% after age 70 years. Given that the average life expectancy is much older than 70 years for most individuals (black men being the exception), that the risk of low eGFR increases with older age, and that persons who develop CKD at younger ages have a much higher mortality risk than those without CKD, the previously published US population lifetime CKD risk estimate of 38.5% is too low to be consistent with current prevalence estimates. This discrepancy may be secondary to difficulties estimating CKD incidence rates: the simulation study estimated incidence using projections of eGFR decline, assuming a fixed multiplier for CKD-associated mortality irrespective of age. This method is highly sensitive to laboratory drift in serum creatinine assays, which influences eGFR decline and the modeled distribution of eGFR slopes. CKD incidence estimated from eGFR decline is driven primarily by those who rapidly experience progression, a tail of the distribution that can be difficult to estimate precisely.
Our estimates of lifetime ESRD risk, as well as the dramatic racial disparities in risk of kidney disease, are consistent with previous studies. Kiberd and Clase estimated lifetime risks of 7.3% and 7.8% for black men and women, respectively, compared with 2.5% and 1.8% for white men and women. Using current ESRD incidence rates, we demonstrate an even higher lifetime risk for all except black women. Somewhat surprisingly, ESRD risk estimates for white Americans were only slightly higher than those recently published from Alberta, Canada. In their cohort of insured patients, residual lifetime risks of ESRD were estimated at 2.7% and 1.8% for 40-year-old men and women, respectively, compared with our estimates of 3.2% and 2.2%. The small differences may reflect differences in disease progression, the competing risk of non-ESRD death, or practice patterns, including eGFR at renal replacement therapy initiation and the use of conservative (nondialysis) therapy, a practice that may be more prevalent in Canada.
Unlike those generated from a prospective cohort, our estimates of CKD incidence were modeled on US prevalence estimates. We chose this method for several reasons. First, national data for CKD incidence are sparse, and incidence estimates from a prospective cohort are extremely sensitive to laboratory drift, or instability in the serum creatinine assay over time. Our cross-sectional model is robust to this drift. Second, we need not extrapolate from follow-up times far shorter than the average lifetime, and we do not presume constant rates of eGFR decline. Third, using NHANES prevalence facilitates application to the general population. Our method relies on different assumptions but has the strength of providing lifetime CKD estimates that match the current US population prevalence. Reassuringly, in sensitivity analysis, our prevalence-based estimates of CKD incidence were very similar to those observed in the ARIC cohort, a population-based sample of middle-aged adults.
The central assumptions of our CKD models are: (1) a stable population (ie, no change in population structure, age-specific life expectancy, and CKD incidence rates) and (2) irreversibility of disease (ie, once CKD stage 3+ or 4+ develops, it is present until death). For a population with increasing life expectancy such as the United States, the equation we use provides a conservative estimate of CKD incidence. Similarly, an increase in CKD incidence, a real possibility given the projected increases in diabetes, hypertension, and obesity, would result in higher lifetime risk than we have presented. If CKD were to remit, we would underestimate CKD incidence, although estimates of lifetime risk might be less meaningful.
Additional limitations include the selection bias inherent in NHANES prevalence estimates; those with more severe disease may be less inclined to participate in the survey, particularly in older age groups, and a noted survey exclusion criterion is nursing home residence. However, this limitation also would apply to a prospective study and likely result in a conservative estimate of lifetime CKD risk. Finally, in estimating ESRD risk, we include those receiving dialysis or transplantation only, which may substantially underestimate those with untreated chronic kidney failure (eGFR <15 mL/min/1.73 m and death).
In summary, we estimate that >50% of Americans born today will develop CKD stage 3+ during their lifetime. Racial disparities, particularly in severe disease, are marked. Among whites, approximately 9%-11% will develop CKD stage 4+ and 2%-3% will develop ESRD; among blacks, the risks of CKD stage 4+ and ESRD are 16%-18% and 8%, respectively. Future research is needed in methods of preventing the development of CKD and ameliorating its associated morbidity.