Among 177 570 subjects followed up for a total of 5 275 957 person-years, there were 842 cases of treated ESRD identified. Among ESRD cases, the mean (SD) duration between the baseline examination and the development of ESRD was 24.5 (6.8) years (median, 25.7 years; interquartile range, 20.2–29.7 years). The baseline characteristics of subjects are given in .
Baseline Characteristics of Subjects Who Did and Did Not Develop End-Stage Renal Disease (ESRD) Based on Kaiser Permanente of Northern California Multiphasic Health Checkup, 1964–1973
As summarized in , potential novel risk factors that were associated on univariate analysis with the development of ESRD included the following: history of stroke, gout, kidney disease, kidney or bladder stones, nocturia, and kidney surgery; left ventricular hypertrophy on electrocardiogram; higher serum cholesterol, lower hemoglobin, and higher uric acid levels; family history of kidney disease; selected occupational exposures (to lead or other metal fumes; asbestos, cement or grain dust; ammonia, chlorine, ozone or nitrous gas; chemicals, cleaning fluid or solvents; engine exhaust fumes [>2 h/d]; extreme heat; insect or plant spray; silica, sandblasting, grinding or rock dust); current smoking; and lack of consumption of alcohol (compared with consumption of 1–2 alcoholic drinks a day).
Novel Risk Factors Associated With End-Stage Renal Disease on Univariate Survival Analysis
Based on differences in the likelihood ratio statistic between the base model that included only established risk factors, independent information was contributed by the novel clinical risk factors (P
<.001) and by family history of kidney disease (P
=.02). Therefore, occupational novel risk factors (P
=.14) and behavioral novel risk factors (P
=.11) were not considered further. Of note, the same conclusion about types of risk factors to include in our final model was reached when history of coronary artery disease was forced into the novel clinical risk factors model9,10
=.17) or when pack-years of smoking were used in alternate analysis of behavioral novel risk factors (P
Among the novel clinical risk factors, only hemoglobin level, history of nocturia, and serum uric acid level demonstrated P<.05 in multivariate analyses; therefore these, along with family history of kidney disease, were included in the final model. The results of the final multivariate model are shown in the . Persons in the highest quartile of serum uric acid level had a more than 2-fold higher adjusted risk of developing ESRD compared with those in the lowest quartile (adjusted hazard ratio [HR], 2.14; 95% confidence interval [CI], 1.65–2.77). Independent associations with ESRD were also observed for lower hemoglobin level (HR, 1.33; 95% CI, 1.08–1.63 for lowest vs highest quartile), self-reported history of nocturia (1.36; 1.17–1.58), and family history of kidney disease (1.40; 1.02–1.90).
Adjusted relative risks among independent risk factors for end-stage renal disease (adjusted for all factors shown). To convert serum creatinine level to micromoles per liter, multiply by 88.4.
The importance of established risk factors was confirmed in this comprehensive evaluation (). These included proteinuria (HR, 7.90 [95% CI, 5.35–11.67] for 3 to 4+ on urine dipstick, 3.59 [2.82–4.57] for 1 to 2+, and 2.37 [1.79–3.14] for trace vs negative on urine dip-stick); excess weight (HR, 4.39 [95% CI, 3.38–5.70] for class 2 and 3 obesity, 3.11 [2.51–3.84] for class 1 obesity, and 1.65 [1.39–1.97] for overweight vs normal weight); elevated serum creatinine (HR, 4.25 [95% CI, 2.49–7.25] for a level of >2.00 mg/dL, 3.16 [2.11–4.73] for a level of 1.60–2.00 mg/dL, and 1.24 [1.05–1.45] for a level of 1.10–1.59 mg/dL vs a level of <1.10 mg/dL); African American race (HR, 3.02 [95% CI, 2.58–3.54] vs white race); higher blood pressure (HR, 2.94 [95% CI, 2.21–3.92] for stage 2 hypertension, 2.33 [1.78–3.05] for stage 1 hypertension, and 1.72 [1.32–2.24] for prehypertension vs normal); DM (HR, 2.53 [95% CI, 1.97–3.25] presence vs absence); older age (HR, 0.55 [95% CI, 0.37–0.83] for age >60 years, 1.51 [1.17–1.96] for age 51–60 years, 2.23 [1.79–2.79] for age 41–50 years, and 1.91 [1.52–2.38] for age 31–40 years vs age ≤30 years); lower educational attainment (HR, 1.55 [95% CI, 1.21–2.00] for no college and 1.45 [1.11–1.90] for some college vs college graduate or higher); and male sex (HR, 1.22 [95% CI, 1.02–1.45]).
Results were unchanged in sensitivity analyses when we added a linear term for serum creatinine level to the model to minimize residual confounding within categories of serum creatinine level. Results were also unchanged when estimated glomerular filtration rate was used instead of serum creatinine level to measure renal function.