Crude Associations With Subsequent Hospitalization
For 13,177 of 15,336 (86%) participants who completed the in-depth assessment, eGFR was calculated. Missing data included patient refusal of phlebotomy, poor veins, lost blood sample, or unknown. During the 2-year follow-up, 3,291 of 13,177 (25%) participants with eGFR data had at least 1 hospital admission; 2,310 (17%) had only 1 admission and 981 (7%) had 2 or more admissions. For those hospitalized at least once, the next admission occurred within a median of 98 (25th-75th percentile, 42-225) days. There were 12,371 participants who had both eGFR and dipstick proteinuria data. Six participants died on the day of admission to the hospital, and 2,279 died after being admitted to the hospital. There were 999 patients who died within 2 years of follow-up without entering the hospital; these were censored for the analysis at their death date.
Selected baseline characteristics and their associations with eGFR and proteinuria are listed in . Associations of baseline characteristics with subsequent hospital admissions are listed in . Hospitalization rates increased with increasing age, and men were more likely to be hospitalized than women. When investigating causes of admissions, 23.2% of all admissions were for circulatory reasons, 14.2% had infections as a contributing cause, and 11.6% had cancer or blood-related diseases as a contributing cause.
Baseline Characteristics for 12,371 Participants With Both eGFR and Urine Data
Rates of Subsequent Hospital Admission According to Selected Participants' Baseline Characteristics
Associations of eGFR and Proteinuria With Subsequent Hospitalization
Both decreasing categories of eGFR and dipstick-positive proteinuria had higher crude hospitalization rates (). Hospitalization rate ratios (age adjusted) stratified by sex and dipstick proteinuria results are listed in . For those hospitalized, there was no evidence for a trend across eGFR categories to have more infectious disease (P = 0.8) or cancer diagnoses (P = 0.5; adjusted for age and sex). However, for those hospitalized, in age- and sex-adjusted analyses, there was a trend (P < 0.001) for those with lower eGFRs to have more hospitalizations related to CVD, with odds ratios (ORs) of 1.86 (95% CI, 1.19-2.92), 1.58 (95% CI, 1.25-1.99), 1.29 (95% CI, 1.03-1.62), and 0.91 (95% CI, 0.72-1.15) for eGFRs <30, 30-44, 45-59, and ≥75 mL/min/1.73 m2, respectively, compared with eGFRs of 60-74 mL/min/1.73 m2. These associations were not confounded by dipstick proteinuria, which was not associated with infections, cancer, or circulatory reasons (data not shown).
Age-Adjusted Ratios of Hospital Admission Rates Across Categories of eGFR in Men and Women Stratified by Presence of Proteinuria
Subsequent analyses listed in were based on people with complete information for confounding variables (n = 10,977); results for analyses with all data with varying totals for each model are very similar (data not shown). Adjusting for age and sex of participants, we found a strong effect of eGFR <30 mL/min/1.73 m2, which was stronger in the first 6 months of follow-up compared with the subsequent 18 months (model 1). In age-adjusted analysis, there was no evidence for an interaction of eGFR and sex in up to 6 months' follow-up (P = 0.7) and during the subsequent 18 months of follow-up (P = 0.8). The association of eGFR <30 mL/min/1.73 m2 with hospitalization attenuated, but remained significant, when adjusting further for all cardiovascular risk factors and underlying CVD, as well as Jarman score (model 2). HRs for eGFR <30 mL/min/1.73 m2 during the first 6-month period were confounded weakly by dipstick positivity. There was no evidence for an interaction of eGFR and dipstick positivity in up to 6 months of follow-up (P = 0.7) and during the subsequent 18 months of follow-up (P = 0.6). There was no evidence of time-dependent effects of dipstick positivity, and the age- and CVD risk–adjusted HR was 1.29 (95% CI, 1.11-1.49) for the total 2-year follow-up.
Effects of Sequential Adjustments in Complete-Case Subset of Data on Associations of eGFR and Proteinuria With Subsequent Hospitalization
We then adjusted the model with both eGFR and proteinuria for hemoglobin, albumin, and phosphate levels (model 3), and the association of eGFR <30 mL/min/1.73 m2 was attenuated further by 12% (for eGFR <30 mL/min/1.73 m2; HR, 1.44 [95% CI, 1.04-1.98] in the first 6 months and 1.06 [95% CI, 0.81-1.40] in the subsequent 18 months; the reference group is eGFR of 60-74 mL/min/1.73 m2; other data not shown). Adjustment for hemoglobin, albumin, and phosphate levels did not appreciably alter the effects of dipstick proteinuria in the same models (HR, 1.23 [95% CI, 0.97-1.57] in the first 6 months and HR, 1.28 [95% CI, 1.06-1.53] in the subsequent 18 months).
Further adjustments for Mini-Mental State Examination scores, Geriatric Depression Scale scores, overall health perception, and ADLs attenuated the association of eGFR <30 mL/min/1.73 m2 with hospitalization (HR, 1.28 [95% CI, 0.91-1.80] for the first 6 months and HR, 1.01 [95% CI, 0.76-1.34] for the subsequent 18 months), whereas in the same analysis, the association of proteinuria with hospitalization remained very similar (HR, 1.21 [95% CI, 0.95-1.55] in the first 6 months and HR, 1.27 [95% CI, 1.05-1.53] for the subsequent 18 months; model 4; other data not shown).
Associations of eGFR and Proteinuria With Number of Hospitalizations
Compared with eGFR of 60-74 mL/min/1.73 m2, eGFR categories of 30-44 and <30 mL/min/1.73 m2 were associated with increased ORs for 2 or more hospitalizations during the 2-year follow-up. For those with eGFR <30 mL/min/1.73 m2 in particular, there was a more than doubled OR (). Adjustments for cardiovascular risk factors at baseline attenuated associations of eGFR with number of hospitalizations, with an increased OR remaining for only eGFR <30 mL/min/1.73 m2 and 2 or more admissions. Dipstick-positive proteinuria (not adjusted for eGFR) was associated with multiple hospitalizations during follow-up; adding potential cardiovascular confounding variables did not attenuate the association appreciably. In a model with both proteinuria and eGFR, we found that both dipstick-positive proteinuria and eGFR <30 mL/min/1.73 m2 were associated independently with the odds of multiple hospitalizations during the 2-year follow-up, even after adjustment for CVD ().
Effects of Sequential Adjustments in Complete-Case Subset of Data on Association of eGFR and Proteinuria (modeled separately) With Hospital Admissions During 2-Year Follow-up
Laboratory parameters (hemoglobin, phosphate, and albumin) attenuated the observed associations for eGFR <30 mL/min/1.73 m2 (OR, 1.21 [95% CI, 0.79-1.85] for 2 or more hospitalizations compared with none), whereas the effect for dipstick proteinuria was completely unchanged (model 3). Additional adjustments for other health factors (model 4) attenuated the association of number of hospitalizations with eGFR <30 mL/min/1.73 m2 (OR, 1.16 [95% CI, 0.73-1.85] for 2 or more hospitalizations compared with none), whereas the association with dipstick proteinuria was unchanged (OR, 1.34 [95% CI, 1.04-1.71] for 2 or more hospitalizations compared with none).