NHANES III included 15,488 participants and NHANES rounds 1999-2004 included 13,233 participants over the age of 20 years with serum creatinine measurements. During the time period between the surveys the US population became older and included a smaller proportion of Non-Hispanic Whites (). The shift in age distribution was less pronounced above 60 years where CKD is more common. At the same time, the prevalence of self reported diabetes and hypertension increased as did the mean body mass index and proportion of the population that is overweight and obese, all risk factors for CKD. Mean albuminuria increased across the surveys but mean ACR was not different among young healthy individuals (12.2 mg/g in 1988-1994 and 12.3 in 1999-2004). The mean serum creatinine was higher in 1999-2004 compared to 1988-1994 corresponding to a lower mean estimated GFR in 1999-2004. The conservative trends analysis which added 0.04 mg/dl to the serum creatinine in NHANES III resulted in nearly identical mean serum creatinine and mean estimated GFR across surveys.
Population Characteristics of U.S. Adults Age 20 Years or Older Based on NHANES 1988-1994 and NHANES 1999-2004
The proportion of the US population with mild, moderate or severely reduced estimated GFR increased from 1988-1994 to 1999-2004. The combined prevalence estimate for 1999-2004 had similar precision to the 1988-1994 estimate while prevalence estimates from each of the three two year surveys had relatively wide confidence intervals (). Moderately reduced GFR increased in prevalence from 5.4% to 7.7% (P<0.001) and severely reduced GFR increased from 0.21% to 0.35% (P=0.02). Similarly, the proportion of the overall population with microalbuminuria on a single occasion increased from 7.1% to 8.2% (P=0.01). The prevalence of macroalbuminuria rose somewhat from 1.1% to 1.3% but this difference was well within the limits of random variation (P=0.4). Subdividing the prevalence of albuminuria by different levels of estimated GFR showed that the prevalence of microalbuminuria rose significantly among individuals with normal estimated GFR while all other subgroups showed no significant rise or fall in albuminuria.11
Figure 1 Trends in the prevalence of CKD stages 3 and 4 between NHANES 1988-1994 and 1999-2004 (full squares) as well as the three component surveys for the later NHANES (empty squares for 1999-2000, 2001-2002 and 2003-2004). Error bars denote 95% confidence intervals. (more ...)
The prevalence estimate for each stage of CKD was higher in 1999-2004 than in 1988-1994 with the difference being statistically significant for CKD stages 2 to 4 and overall (). Stratified analyses by sex and race showed similar trends. The overall prevalences of CKD in 1988-1994 and 1999-2004 among men were 8.2% and 11.1%. Among women they were 12.1% and 15.0%. By ethnicity the change was from 10.5% to 13.8% among Non-Hispanic whites, 10.2% to 11.7% among non-Hispanic Blacks, and from 6.3% to 8.0% among Mexican Americans. After age adjustment prevalence odds ratios for estimated GFR < 60 ml/min/1.73 m2
between 1999-2004 and 1988-1994 were of similar magnitude (between 1.4 and 1.5) and statistically significant in men, women, non-Hispanic whites and non-Hispanic blacks and Mexican-Americans. The association was somewhat weaker in the smaller number of individuals of other ethnicity. Trends over time were also similar within age categories indicating the trends were not due to age differences in the population (data not shown11
Prevalence of CKD Stages in US Adults Age 20 Years or Older Based on NHANES 1988-1994 and NHANES 1999-2004
Differences in prevalence of decreased GFR and albuminuria between 1988-1994 and 1999-2004 remain substantial after adjustment for changes in the age, sex and race/ethnic composition of the US population over this time period (). The higher prevalence of diagnosed diabetes, hypertension, and higher body mass index explained some of the higher prevalence. For albuminuria trends, the higher prevalence was partly explained by the older age and high proportion of minority groups (odds ratio declined from 1.18 to 1.12 after adjustment). Further adjustment for the higher prevalence of diagnosed diabetes and hypertension and higher body mass index explained practically all of the difference (odds ratio declined to 1.03). In the fully adjusted models, the prevalence of albuminuria was strongly associated with diagnosed diabetes (OR 3.58; 95% CI 3.12-4.12) and hypertension (OR 1.70; 95% CI 1.1-1.92) as well as older age, and all race-ethnicity groups other than non-Hispanic whites (P<0.001) but not higher body mass index (P=0.1). The prevalence odds ratio of estimated GFR less than 60 ml/min/1.73 m2 in 1999-2004 compared to 1988-1994 was 1.47. Age adjustment had little impact, likely because the increase in the number of older individuals was offset by a similar increase in the number of younger individuals leading the percentage of individuals aged 60+ years to remain relatively unchanged (). The prevalence odds ratio increased further to 1.53 after adjustment for age, sex and race due to the lower prevalence of decreased GFR among minority groups. The odds ratio decreased to 1.43 with additional adjustment for diagnosed diabetes and hypertension and body mass index. In the fully adjusted model, the prevalence of low GFR was strongly associated with diagnosed diabetes (OR 1.54; 95% CI 1.28-1.80) and hypertension (OR 1.98; 95% CI 1.73-2.67) as well as higher body mass index (OR 1.08; 95% CI 1.02-1.15 per 5 kg/m2) and older age but was lower among men, non-Hispanic blacks, and Mexican-Americans compared to non-Hispanic whites (P<0.001).
Logistic Regression of Albuminuria and Decreased Estimated GFR comparing 1999-2004 to 1988-1994 Before and After Adjustment
The conservative trends analysis showed that the difference in mean serum creatinine between surveys accounts for much but possibly not all of the higher prevalence of lower GFR in 1999-2004. In this analysis, the prevalence of CKD in 1988-1994 was higher (1.5%, 2.8%, 6.7%, and 0.23% for CKD stages 1 to 4 for a total of 11.3%). The prevalence odds ratio of estimated GFR less than 60 ml/min/1.73 m2 comparing 1999-2004 to 1988-1994 was 1.17 (95% CI 1.02-1.34). After full adjustment in the conservative trends analysis the prevalence odds ratio of decreased GFR between surveys was 1.08 (0.94-1.24) indicating that the differences in mean serum creatinine, demographics, diagnosed diabetes, hypertension, and body mass index between surveys explain nearly all of the difference in prevalence of low GFR between 1988-1994 and 1999-2004 (P=0.3).
Since CKD Stage 3 includes a large number of individuals we examined the distribution of individuals in this stage across different characteristics (). As expected, the majority of individuals had a higher estimated GFR (45-59 ml/min/1.73 m2 included 78.8% of all CKD stage 3 individuals adding the percentages across sex, age and albuminuria categories). Further, 61.5% of all individuals in CKD stage 3 had an estimated GFR between 45-59 ml/min/1.73 m2 with no evidence of albuminuria. The table also shows the distribution of albuminuria, with 25.7% of CKD stage 3 individuals with and 74.3% without albuminuria, and age, where 22.1%, 22.7% and 55.2% were age <60, 60-69 and 70+ years. A total of 16.6% of individuals in CKD stage 3 had previously diagnosed diabetes, and slightly less than half of these had evidence of albuminuria (7.5% of all individuals in stage 3).
Distribution of individuals with CKD stage 3 by estimated GFR < 45 ml/min/1.73 m2, age, sex, presence of albuminuria, and diabetes: Combined NHANES 1988-1994 and 1999-2004
An analysis estimating what proportion of individuals with CKD stage 3 would be eligible for referral to a nephrologist using one proposed referral recommendation suggested that 18.6% of individuals should be referred to a nephrologist while the other 81.4% could be managed by their internists (). Under this scenario, the largest proportion of referrals in CKD stage 3 was due to macroalbuminuria, type II diabetes with presence of albuminuria, or diabetic retinopathy. Independently of other criteria for referral, macroalbuminuria accounted for 20.5% (SE 4.0%) of referrals, type II diabetes with albuminuria for 32.9% (SE 5.6%), and diabetic retinopathy for 23.1% (SE 4.5%). Hyperkalemia (0.5%, SE 0.3%) and resistant hypertension (11.5%, SE 4.2%) accounted for less, and 11.5% of individuals would be referred for more than one criterion. The suggested referral rate was lower for Whites than other groups because of a lower rate of albuminuria and diabetes (). However, retinopathy data are limited to NHANES III making many of the specific referral groups relatively small and estimated rates imprecise.
Proportion of individuals with CKD stage 3 and whether they meet proposed criteria for referral to a nephrologist by age, sex, race, and diabetes status: NHANES 1988-1994
Proportion of individuals with CKD Stage 3 according to proposed criteria for referral to a nephrologist by race: NHANES 1988-1994