Where Is the Epidemic in Kidney Disease?

There has been much discussion lately regarding the epidemic of kidney disease, mostly focusing on chronic kidney disease (CKD) and end-stage renal disease (ESRD).1,2 Much less attention has been paid to acute renal failure (ARF)/acute kidney injury (AKI). But this imbalance may not be justified on the basis of careful review of the epidemiologic evidence. ESRD According to the latest U.S. Renal Data System (USRDS) Annual Report, the annual incidence of ESRD in the United States is 354 per million person-years in 2007 (adjusted for age, gender, and race),3 representing a slight drop from the prior year. This secular trend is quite different from that observed in the 1980s and 1990s when the incidence of ESRD increased at a rapid rate. In fact, the adjusted incidence of ESRD has more or less reached a plateau in the 7 prior years (Figure 1).3 The corresponding unadjusted incidence rates are 334.2, 338.2, 342.8, 347.1, 353.8, 364.7, and 361.0 per million person-years in 2001, 2002, 2003, 2004, 2005, 2006, and 2007, respectively,4 which represents an increase of about 1% per year.Figure 1: Trend over time in the United States in adjusted rates of incidence ESRD. This rate (adjusted for age, gender, and race) had been relatively stable from 2000 through 2007. Adapted from reference 3, p 206, Figure hp.2.ii.It is notable that this slow growth in ESRD incidence is observed despite the fact that mean serum creatinine at the start of renal replacement therapy has dropped substantially in the past decade (Figure 2). This secular trend is almost certainly due to changes in practice pattern and more liberal initiation of dialysis, and hence would increase the number of ESRD patients even if there were no change in the underlying burden of kidney disease in the population.Figure 2: Mean serum creatinine (mg/dl) at the start of dialysis in the United States reported to the U.S. Renal Data System (by age groups). The drop in serum creatinine is almost certainly due to changes in secular changes in practice pattern and more liberal initiation of dialysis. Adapted from reference 3, p 246, Figure 3.8.ii.The encouraging flattening of incidence in ESRD may reflect success in retarding the progression of CKD with more aggressive control of BP and use of drugs that block the renin-angiotensin system.5 Improved glycemic control among patients with diabetes mellitus may also be contributory. The effect of such treatment is illustrated by a Finnish study that tracked outcome among patients with type 1 diabetes over several decades. In that study, those diagnosed in 1980 through 1999 has less than half the risk of developing ESRD compared with those diagnosed in 1965 through 1969.6 The stabilization of incidence of ESRD reported by the USRDS is consistent with data from other national ESRD registries such as Canada7 and the United Kingdom.8 This favorable trend in disease incidence rates in the United States, however, may not be apparent when data are presented as incidence count (Figure 3) since the absolute number of new ESRD patients will continue to increase because of increasing growth of the population even if incidence rate were held constant.Figure 3: Trend over time in the United States in absolute number (count) of patients with incident ESRD. Adapted from reference 3, p 233, Figure 2.1.ii.Stabilization is also not obvious when prevalence rate of disease is reported (Figure 4) because disease prevalence (number of patients living with the condition) depends not only on incidence (number of new cases) but also on survival after disease onset,9 which is influenced by factors such as availability of transplantation.10 Although annual mortality rate is still high in the United States,11 survival has improved for both dialysis and transplant patients; this will increase the prevalence of ESRD.Figure 4: Prevalence rates of ESRD in the Unites States (by age groups). Adapted from reference 3, p 236, Figure 2.13.ii.The bottom line for ESRD: The population incidence of ESRD is increasing slowly by only 0 to 1% per annum in recent years. Secular trends in incidence rates should be distinguished from secular trends in absolute counts or prevalence rates. CKD The best national level data regarding CKD epidemiology come from the National Health and Nutrition Examination Surveys (NHANES) in the United States, which provide data on disease prevalence. There are few reliable estimates of the incidence of CKD and no reliable data regarding temporal changes in CKD incidence. With use of data from the 1999 through 2004 NHANES, a widely quoted paper estimated that, among adults, the prevalence rate of CKD stages 1 to 4 was 131,000 per million persons (13.1%).12 This translated into an absolute number of 26.3 million individuals, or 2 orders of magnitude larger than the absolute number of incident ESRD patients (n = 104,962 in 2004). In addition, this paper reported that stages 1 to 4 CKD prevalence increased from 10.0% based on 1988 through 1994 NHANES III to 13.1% based on the 1999 through 2004 NHANES.12 However, accurately defining secular trends in CKD prevalence is difficult because of calibration problems with serum creatinine measurements.13–15 In the past 2 decades in NHANES, serum creatinine measurements were done in several different laboratories using different methodologies that introduce systematic biases (Figure 5). NHANES made substantial efforts to standardize serum creatinine measurements to traceable gold standards. To do this, it was necessary to multiply the original 1988 through 1994 serum creatinine values by 0.960 and subtract 0.184 mg/dl; it was necessary to multiply the original 1999 through 2000 serum creatinine values by 1.103 and add 0.147 mg/dl; values from 2001 through 2004 were left unchanged.16,12Figure 5: Selection factors and measurement techniques for serum creatinine and cystatin C in NHANES. Adapted from reference 17.After these maneuvers, it was found that for young participants (20 to 39 years) without diagnosed hypertension or diabetes—presumably a healthy stratum of the population—serum creatinine levels were 0.04 mg/dl lower in 1988 through 1994 than in 1999 through 2004 (P 7% per year. Conclusions To summarize, for ESRD requiring renal replacement therapy and ARF/AKI requiring dialysis, the population incidences are actually similar—343 versus 295 per million person-years in 2003, the latest year where there is overlapping data. But incidence of ARF/AKI is rising at a much higher rate than the incidence of ESRD (>7% per year versus 0 to 1%). The high mortality of patients with incident ESRD is well-known (24% per year).4,11 But the mortality rate of patients who developed dialysis-requiring ARF/AKI is even higher, being approximately 28% in the hospital,30 and on the order of 10% per year after hospital discharge (Table 1).39,40 To date, most discourse regarding the global burden of kidney disease has not included the epidemic of ARF.41–43 I hope future discussions in this area will be more balanced and reflect the actual distribution of kidney disease and its public health burden in the population.Table 1: Comparing kidney disease “epidemics”Disclosures None. Dr. Hsu has been supported by R01 DK67126, R01 DK70939, U01 DK82223, and U01 DK60902.