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Figure 1.1	Distribution of NHANES participants with diabetes, congestive heart failure, & markers of CKD, with GFR estimated by MDRD & CKD-EPI equations
Figure 1.2	Odds ratios of CKD in NHANES 2001–2008 participants, by risk factor & method used to estimate eGFR
Figure 1.3	Cumulative eGFR distribution curves of NHANES 2001–2008 participants, by method used to estimate GFR
Figure 1.4	Prevalence of comorbidity in NHANES 2001–2008 participants, by risk factor, eGFR, & method used to estimate GFR
Figure 1.5	Prevalence of comorbidity in NHANES 2001–2008 participants, by risk factor, expanded eGFR categories, & method used to estimate GFR
Figure 1.6	Distribution of NHANES 2001–2008 participants, by age, eGFR, & method used to estimate GFR
Figure 1.7	Prevalence of comorbidity in NHANES 2001–2008 participants, by risk factor & albumin/creatinine ratio
Figure 1.8	Predicting death: sensitivity & specificity of different eGFR thresholds: MDRD equation, NHANES 1988–1994 participants
Figure 1.9	Predicting death: sensitivity & specificity of different eGFR thresholds: CKD-EPI equation, NHANES 1988–1994 participants
Figure 1.10	Predicting death: sensitivity & specificity of different ACR thresholds, NHANES 1988–1994 participants
Figure 1.11	Mortality rates in NHANES 1999–2004 participants, by eGFR: MDRD equation
Figure 1.12	Mortality rates in NHANES 1999–2004 participants, by eGFR: CKD-EPI equation
Table 1.a	Prevalence & odds ratios of CKD in NHANES 2001–2008 participants, by ACR & method used to estimate GFR, age, gender, race/ethnicity, & risk factor (percent of participants)
Table 1.b	Awareness, treatment, & control of hypertension, hypercholesterolemia, HDL, total cholesterol, & diabetes, by ACR, eGFR, & method used to estimate GFR (percent of NHANES participants)

Chapter One

Chronic Kidney Disease in the General Population

In this chapter we use data from the National Health and Nutrition Examination Survey (NHANES), a valuable source of information for assessing disease burden and high-risk subsets among representative U.S. adults.

On the next page we begin by showing the overall burden and interactions of diabetes, congestive heart failure, and CKD — three interrelated chronic diseases of clear public health relevance — and compare prevalence estimates in 2001–2004 and 2005–2008. While the prevalence of diabetes has clearly increased, and the prevalence of congestive heart failure has remained stable, the prevalence of CKD appears to have declined slightly, from 15.8 percent to 15.1 percent when calculated with the MDRD formula, and from 14.7 percent to 14.5 percent when calculated with the CKD-EPI formula; prevalence estimates of CKD in 1988–1994 were 12.8 and 12 percent, respectively.

Estimates of CKD burden are partly dependent on the equation used to define the estimated glomerular filtration rate (eGFR): when the newer CKD-EPI equation is used, the prevalence of eGFR less than 60 ml/min/1.73 m2 is lowered by a factor of 0.88 (6.9 percent versus 7.8 percent) compared with the estimate from the older MDRD Study equation. Regardless of the method used to estimate GFR, low eGFR and high urinary albumin/creatinine ratio (ACR) are most likely to be found in the presence of age greater than 60, diabetes, hypertension, and cardiovascular disease.

Exploring the implications of CKD, diabetes, and cardiovascular disease in the general population, this chapter sets the stage for Chapter Two, in which we discuss the implications of CKD in datasets that are less well defined in terms of biochemical data, but that provide extensive information on morbidity, interventions, and costs not contained in the NHANES data or other samples.

Figure 1.1 Distribution of NHANES participants with diabetes, congestive heart failure, & markers of CKD, with GFR estimated by MDRD & CKD-EPI equations (see page 122 for analytical methods. NHANES participants age 20 & older)

Table 1.a Prevalence & odds ratios of CKD in NHANES 2001–2008 participants, by ACR & method used to estimate GFR, age, gender, race/ethnicity, & risk factor (percent of participants) (see page 122 for analytical methods. NHANES participants age 20 & older.)

With a single creatinine-based eGFR and the MDRD and CKD-EPI equations, 26 percent of NHANES participants age 60 or older have an eGFR of less than 60 ml/min/1.73 m2 (CKD Stages 3–5); 19.7 percent have a urinary albumin/creatinine ratio greater or equal to 30 mg/g. For all adults, multivariate associations of CKD for eGFR and ACR methodologies include older age, female gender, and self-reported diabetes, hypertension, and cardiovascular disease.

Figure 1.2 Odds ratios of CKD in NHANES 2001–-2008 participants, by risk factor & method used to estimate eGFR (see page 122 for analytical methods. NHANES participants age 20 & older. Odds ratios use populations without the risk factor as reference.)
Figure 1.3 Cumulative eGFR distribution curves of NHANES 2001–2008 participants, by method used to estimate GFR (see page 122 for analytical methods. NHANES 2001–-2008 participants age 20 & older)

In cumulative frequency distributions of eGFR in U.S. adults, the creatinine-based CKD-EPI methodology for eGFR calculations yields higher estimates of GFR than those achieved with the creatinine-based MDRD method.

Figure 1.4 Prevalence of comorbidity in NHANES 2001–2008 participants, by risk factor, eGFR, & method used to estimate GFR (see page 122 for analytical methods. NHANES 2001–2008 participants age 20 & older)
Figure 1.5 Prevalence of comorbidity in NHANES 2001–2008 participants, by risk factor, expanded eGFR categories, & method used to estimate GFR (see page 122 for analytical methods. NHANES 2001–-2008 participants age 20 & older)
Figure 1.6 Distribution of NHANES 2001–2008 participants, by age, eGFR, & method used to estimate GFR (see page 122 for analytical methods. NHANES 2001–-2008 participants age 20 & older)
Figure 1.7 Prevalence of comorbidity in NHANES 2001–2008 participants, by risk factor & albumin/creatinine ratio (see page 122 for analytical methods. NHANES 2001-–2008 participants age 20 & older)

With both creatinine-based MDRD and CKD-EPI estimates, prevalence estimates of diabetes, hypertension, cardiovascular disease (CVD, not including CHF), and CHF are noticeably higher in participants with eGFRs below 60 ml/min/1.73 m2. Approximately 64–68 percent of NHANES participants with an eGFR less than 60, for example, have hypertension, compared to 26 percent of those with an eGFR of 60 or greater, and their prevalence of CVD is nearly five-fold greater.

The prevalence of disease rises with CKD severity. In participants with eGFRs less than 30, 30–<45, and 45–<60, for example, 40, 27, and 18 percent have diabetes, compared to 7 percent of those with an eGFR of 60 or above. And in participants with an eGFR less than 30, 84–85 percent have hypertension and 35–36 percent have CHF, compared to 5.0 and 1.5 percent, respectively, of participants with an eGFR of 60 or greater.

Slightly more than 75 percent of NHANES participants with an MDRD-estimated eGFR less than 60 ml/min/1.73 m2 are age 60 years or older, compared with 85 percent when eGFR is calculated with the CKD-EPI equation.

The prevalence of comorbid illness among NHANES participants rises with albumin/creatinine ratio (ACR). Four percent of participants with an ACR less than 10 mg/g have diabetes, compared to 26 percent of those whose ACR is 30 or greater. Hypertension and CVD are present in 24 and 4.5 percent of participants with an ACR below 10, compared to 51 and 13.5 percent of those with an ACR of 30 or greater.

Table 1.b Awareness, treatment, & control of hypertension, hypercholesterolemia, HDL, total cholesterol, & diabetes, by ACR, eGFR, & method used to estimate GFR (percent of NHANES participants) (see page 123 for analytical methods. NHANES 1999-–2008 participants age 20 & older; those with Stage 5 CKD excluded)

Here we use NHANES data from two time periods to evaluate awareness, treatment, and control of disease conditions, using estimates of glomerular filtration rate (eGFR) from the MDRD and CKD-EPI methods (both creatinine-based).

In 1999-–2004, using the MDRD method, 81 percent of participants with an eGFR less than 60 ml/min/1.73 m2 had hypertension; only 15 percent, however, were aware of their condition and on a successful treatment regime. In 2005–2008 participants, 80 percent were hypertensive and 21 percent were being treated successfully. With the CKD-EPI method, 85 percent of the 1999–-2004 cohort were hypertensive and 15 percent were being treated sucessfully, compared to 85 and 23 percent in 2005–2008. Among 1999–2004 participants with eGFRs of 60 or greater (both MDRD and CKD-EPI formulas), 28 percent had hypertension and approximately 7 percent were being successfully treated compared to 30 and 11 percent in 2005–2008.

With both the MDRD and CKD-EPI formulas, 81 percent of 1999–2004 participants with eGFRs less than 60 had hypercholesterolemia (based on elevated LDL), but only 18–21 percent were successfully treated. The proportion of participants with hypercholesterolemia in the later period was lower, at 66–69 percent, but little improvement was observed in rates of successful treatment.

In 2005–-2008, approximately 15 percent of participants with CKD had a high total cholesterol level, while 40–50 percent had glycohemoglobin levels above the recommended 7 percent.

Figure 1.8 Predicting death: sensitivity & specificity of different eGFR thresholds: MDRD equation, NHANES 1988–-1994 participants (see page 123 for analytical methods. NHANES III (1988-–1994) participants age 20 & older)
Figure 1.9 Predicting death: sensitivity & specificity of different eGFR thresholds: CKD-EPI equation, NHANES 1988-–1994 participants (see page 123 for analytical methods. NHANES III (1988-–1994) participants age 20 & older)
Figure 1.10 Predicting death: sensitivity & specificity of different ACR thresholds, NHANES 1988-–1994 participants (see page 123 for analytical methods. NHANES III (1988-–1994) participants age 20 & older)
Figure 1.11 Mortality rates in NHANES 1999-–2004 participants, by eGFR: MDRD equation (see page 123 for analytical methods. NHANES 1999-–2004 participants age 20 & older)
Figure 1.12 Mortality rates in NHANES 1999-–2004 participants, by eGFR: CKD-EPI equation (see page 123 for analytical methods. NHANES 1999-–2004 participants age 20 & older)

For screening purposes, it can be useful to know the efficacy of different threshold levels for predicting death or survival in patients with CKD. For death within a finite time interval, a threshold where individuals classified as "normal" show low mortality rates (a high proportion of true negatives, with high specificity for predicting death) and those classified as "abnormal" show high mortality rates (a high proportion of true positives, with high sensitivity for predicting death) might be attractive for defining subgroups in which intensive follow-up and treatment may be appropriate, and for classification purposes as well.
Figures 1.8 - 1.–10 show sensitivity and specificity values for different threshold renal values among NHANES III participants (1988-–1994) followed through 2006. Conventionally used thresholds — like <60 ml/min/1.73 m2 for eGFR and =30 mg/g for ACR — exhibit low sensitivity and high specificity values for predicting death.
Here we show annual mortality rates in 1994-–2004 NHANES participants. For eGFR below 90 ml/min/1.73 m2, mortality rates are higher with the CKD-EPI formula; for eGFRs above 90, rates are lower.