Life Expectancy Gains for Patients with ESRD

• humans
• United States
• Nephrology
• renal dialysis
• life expectancy
• allografts
• drug labeling
• glomerular filtration rate
• survival analysis
• renal replacement therapy
• peritoneal dialysis
• proportional hazards models
• referral and consultation
• Centers for Disease Control and Prevention (U.S.)
• fistula
• kidney failure
• chronic
• hospitalization
• neoplasms
• hemoglobins

Mortality rates have been declining among patients with ESRD in the United States over the last two decades, particularly when the changing demographic characteristics of the ESRD population are taken into account (1). The decline in mortality rate (increase in life expectancy) has been observed among patients treated with hemodialysis, patients treated with peritoneal dialysis, and also, patients after receipt of a transplanted kidney. However, the mortality rate in the general United States population has also declined over the same period (2), which raises the question of whether the change in the ESRD population is something to celebrate or simply a reflection of overall trends.

In this issue of the Clinical Journal of the American Society of Nephrology, Foster et al. (3) set out to ascertain whether survival of patients with ESRD has improved relative to survival in the general population by examining excess mortality risk as a function of calendar year from 1995 to 2013. Using data from the US Renal Data System (USRDS), the authors calculated mortality rates during each calendar year for patients with ESRD in strata on the basis of age, sex, and race. Using data from the Centers for Disease Control and Prevention, they determined the expected number of deaths during each calendar year on the basis of patients’ demographic characteristics during that year and then calculated the rate of excess mortality among patients with ESRD in each year by simple subtraction. They then performed a relative survival analysis, in which excess risk in subsequent years was compared with excess risk at an earlier time, and they presented the results as the relative excess risk (akin to a hazard ratio) per 5 calendar years.

These analyses show that excess mortality has declined over time and that the decline occurred during time spent on dialysis as well as for patients who had functioning transplanted kidneys. A major aim of the study was to determine whether changes in life expectancy from 1995 to 2013 differed across the spectrum of age, and some interesting differences emerged. Older patients experienced less relative decline in mortality than younger patients. This pattern was particularly true for time spent after transplantation, whereas the declines in mortality rate showed less of a monotonic pattern across age groups during time on dialysis. However, the authors are careful to note that, because of the much higher mortality rates among older patients compared with younger patients, the absolute excess mortality risk declined most among older patients.

This type of temporal analysis is extremely useful as a way of understanding what is happening in the ESRD population. Specifically, the study by Foster et al. (3) adds to the data on mortality trends over time recently presented in the USRDS Annual Data Report (4), because improvements in care of patients with ESRD should be expected to improve ESRD-specific excess mortality and increase life expectancy in our patients relative to that of the general population. Accounting for changes in mortality in the general population can remove a source of “noise” that could impede attempts to assess the effect of changes in ESRD care on survival.

However, the study by Foster et al. (3) raises more questions than it answers and should serve as a place to start rather than as the end of the conversation on this topic. The potential causes for the observed trends are myriad. The authors speculate that technical advances in dialysis, new medications, and uptake of clinical practice guidelines might have contributed as well as increased access to transplant for some age groups and improved allograft survival (3). These are plausible explanations, but they are nonspecific and are not exhaustive. I can generate a longer but undoubtedly still noncomprehensive list of possibilities, but the exercise may nevertheless be worthwhile, because future investigations could use the analysis strategy set forth by Foster et al. (3) as a foundation to explore many of these possibilities in greater depth.

Overall hospitalization rates have also been declining among patients with ESRD in the United States over the last decade (4). The decline in hospitalization for cardiovascular events is particularly prominent, but infectious hospitalizations have also dropped. Understanding the extent to which declines in hospitalization may mediate the decline in mortality could be important given that some hospitalizations may be related to ESRD care and others may be less sensitive to ESRD-related practices.

It has been suggested that increasing use of fistulas and concomitant declines in catheter use or changes in dosing of erythropoiesis stimulating agents (ESAs) and hemoglobin levels could have contributed to the improvement in survival among patients on hemodialysis (5). The percentage of patients initiating dialysis with a functioning or maturing fistula has increased substantially since the dissemination of the Fistula First Breakthrough Initiative, and the increase in use of arteriovenous fistulas among prevalent hemodialysis patients has increased even more dramatically (4). ESA use and hemoglobin concentrations have declined markedly in the last decade (4), presumably in response to signals suggesting harm that led to a black box warning from the Food and Drug Administration. However, it should be noted that ESA doses and hemoglobin concentrations increased dramatically in the period from 1995 to 2007, during which time the mortality rate was declining to a similar extent as during the more recent period of declining ESA doses and hemoglobin concentration. The relatively constant decline in mortality rates in the setting of large increases and subsequent decreases in ESA dosing and hemoglobin concentrations tends to mitigate against these factors as major contributors.

We should also consider the possibility that pre-ESRD care or selection of patients for RRT might have contributed to changes in mortality. Earlier nephrology consultation before ESRD has been shown to improve survival after the onset of ESRD (6), and the percentage of patients receiving care >3 months before ESRD has been increasing (7). In addition, patients have been started on RRT at higher levels of eGFR in the modern era compared with the 1990s (4). Although this practice has not been associated with improved mortality (8), it could contribute to longer life expectancy during ESRD through lead time bias.

There are certainly other potential reasons for the changes in mortality among patients with ESRD, and in the final analysis, “the cumulative effect of multiple care advances may explain the decreases in excess mortality” (3). I believe that the results of the analyses by Foster et al. (3) represent a cause for cautious optimism. I do not recommend complacency or all out self-congratulation, because if we do not fully understand why the improvement occurred, it is not clear that we will be able to continue to improve or prevent future increases in mortality. This is especially relevant, because data from 2013 to 2015 show that the mortality rate among patients with ESRD has stabilized or even increased slightly (4). The facts that the mortality rate in the United States as a whole showed a similar uptick (9) and that the eGFR at initiation of RRT has also begun to decline (4) highlight the need for sophisticated analyses that consider survival of patients with ESRD relative to that of the general population and adjust for important changes in clinical care to fully understand changes in mortality. A final reason for restrained optimism is that, despite the increases in life expectancy over the last two decades, patients with ESRD still have a much shorter life expectancy than patients without ESRD (4), and 5-year survival remains lower among patients with ESRD than among those with cancer (4,10).

The analyses by Foster et al. (3) provide a framework for future studies that are needed to examine which changes in practice patterns and clinical care may be important contributors to changes in mortality in the ESRD population. The USRDS is a treasure trove of data that can be used to delve into these questions. Analyses of differences in outcomes over time and across geographic regions are powerful tools that we can apply to gain an understanding of the effect of changes or variations in practices on survival.

• Copyright © 2018 by the American Society of Nephrology