Table 2.
Multivariable associations of time-updated eGFR, time-updated clinical factors, baseline demographic factors, and baseline laboratory markers of mineral metabolism, anemia, and inflammation with risk of incident moderate-to-severe pruritus among Chronic Renal Insufficiency Cohort (CRIC) Study participants
| Risk Factors | N Events | Unadjusted IR, per 100 Person-Years (95% CI) | Model 1 HR (95% CI) | Model 2: Main Model HR (95% CI) | Model 3A: Additional Analysis HR (95% CI) | Model 3B: Additional Analysis HR (95% CI) |
|---|---|---|---|---|---|---|
| eGFR (time-updated) per 10 ml/min per 1.73 m2 lower | — | — | 1.20 (1.13 to 1.26) | 1.16 (1.10 to 1.23) | 1.16 (1.08 to 1.23) | 1.14 (1.07 to 1.21) |
| Demographic factors (baseline only) | ||||||
| Age, yr | ||||||
| ≤44 | 82 | 4.2 (3.4 to 5.3) | 0.86 (0.67 to 1.10) | 0.94 (0.73 to 1.21) | 0.96 (0.74 to 1.25) | 0.93 (0.72 to 1.21) |
| 45–64 | 380 | 4.8 (4.4 to 5.4) | 1.0 Ref | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| ≥65 | 198 | 5.6 (4.9 to 6.5) | 1.20 (1.00 to 1.43) | 1.31 (1.09 to 1.57) | 1.33 (1.10 to 1.60) | 1.29 (1.08 to 1.56) |
| Sex | ||||||
| Male | 341 | 4.5 (4.1 to 5.0) | 1.0 Ref | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Female | 319 | 5.6 (5.0 to 6.2) | 1.25 (1.06 to 1.46) | 1.15 (0.98 to 1.36) | 1.14 (0.96 to 1.35) | 1.15 (0.97 to 1.36) |
| Race/ethnicity | ||||||
| Non-Hispanic White | 282 | 4.2 (3.7 to 4.7) | 1.0 Ref | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Non-Hispanic Black | 284 | 5.8 (5.1 to 6.5) | 1.31 (1.11 to 1.56) | 1.13 (0.94 to 1.35) | 1.03 (0.85 to 1.25) | 1.09 (0.91 to 1.32) |
| Hispanic | 69 | 6.2 (4.9 to 7.8) | 1.12 (0.80 to 1.55) | 0.92 (0.66 to 1.28) | 0.86 (0.61 to 1.20) | 0.89 (0.63 to 1.25) |
| Other | 25 | 4.9 (3.3 to 7.2) | 1.09 (0.71 to 1.66) | 1.11 (0.73 to 1.71) | 1.07 (0.69 to 1.65) | 1.10 (0.71 to 1.69) |
| Clinical factors (time-updated) | ||||||
| BMI, per 5 kg/m2 higher | — | — | — | 1.10 (1.04 to 1.16) | 1.09 (1.04 to 1.15) | 1.08 (1.02 to 1.15) |
| Diabetes | ||||||
| No | 339 | 4.1 (3.7 to 4.6) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Yes | 321 | 6.3 (5.7 to 7.1) | — | 1.24 (1.05 to 1.46) | 1.24 (1.04 to 1.47) | 1.18 (0.99 to 1.40) |
| Hypertension | ||||||
| No | 90 | 4.0 (3.3 to 4.9) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Yes | 570 | 5.2 (4.8 to 5.6) | — | 0.89 (0.66 to 1.21) | 0.89 (0.65 to 1.21) | 0.93 (0.68 to 1.27) |
| Coronary artery disease | ||||||
| No | 528 | 4.8 (4.4 to 5.2) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Yes | 132 | 5.9 (5.0 to 7.0) | — | 1.03 (0.85 to 1.25) | 1.01 (0.83 to 1.24) | 1.01 (0.83 to 1.23) |
| Peripheral vascular disease | ||||||
| No | 621 | 4.8 (4.5 to 5.2) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Yes | 39 | 8.5 (6.2 to 11.7) | — | 1.22 (0.89 to 1.66) | 1.10 (0.79 to 1.53) | 1.16 (0.85 to 1.60) |
| Congestive heart failure | ||||||
| No | 615 | 4.8 (4.5 to 5.2) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Yes | 45 | 7.7 (5.7 to 10.3) | — | 1.13 (0.84 to 1.52) | 1.17 (0.87 to 1.58) | 1.10 (0.82 to 1.47) |
| Lung disease | ||||||
| No | 568 | 4.9 (4.5 to 5.3) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Yes | 92 | 5.7 (4.7 to 7.0) | — | 1.10 (0.90 to 1.35) | 1.09 (0.89 to 1.34) | 1.08 (0.88 to 1.33) |
| Opioid use | ||||||
| No | 577 | 4.7 (4.3 to 5.1) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Yes | 83 | 8.0 (6.5 to 9.9) | — | 1.27 (1.01 to 1.59) | 1.30 (1.03 to 1.64) | 1.27 (1.01 to 1.60) |
| Current smoking | ||||||
| No | 560 | 4.7 (4.3 to 5.1) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Yes | 100 | 7.9 (6.5 to 9.6) | — | 1.60 (1.27 to 2.01) | 1.59 (1.26 to 2.01) | 1.55 (1.23 to 1.96) |
| Depressive symptomsa | ||||||
| None (BDI 0–10) | 500 | 4.4 (4.0 to 4.8) | — | 1.0 Ref | 1.0 Ref | 1.0 Ref |
| Moderate (BDI 11–13) | 49 | 6.9 (5.2 to 9.1) | — | 1.41 (1.04 to 1.92) | 1.50 (1.10 to 2.04) | 1.46 (1.08 to 1.99) |
| Severe (BDI ≥14) | 111 | 9.6 (8.0 to 11.6) | — | 2.01 (1.61 to 2.51) | 2.03 (1.61 to 2.55) | 1.98 (1.57 to 2.48) |
| Markers of mineral metabolism (baseline only) | ||||||
| Serum calcium,a mg/dl | ||||||
| <9 | 167 | 4.1 (3.5 to 4.8) | — | — | 0.80 (0.66 to 0.97) | — |
| 9–9.4 | 320 | 5.3 (4.8 to 6.0) | — | — | 1.0 Ref | — |
| ≥9.5 | 164 | 5.4 (4.6 to 6.3) | — | — | 0.94 (0.78 to 1.15) | — |
| Serum phosphate,a mg/dl | ||||||
| <3 | 66 | 3.9 (3.1 to 5.0) | — | — | 0.94 (0.71 to 1.24) | — |
| 3–3.9 | 394 | 4.8 (4.3 to 5.3) | — | — | 1.0 Ref | — |
| ≥4.0 | 186 | 6.0 (5.2 to 6.9) | — | — | 1.10 (0.92 to 1.33) | — |
| Intact PTH,a pg/ml | ||||||
| 0–64 | 410 | 4.4 (4.0 to 4.8) | — | — | 1.0 Ref | — |
| ≥65 | 233 | 6.2 (5.5 to 7.1) | — | — | 1.30 (1.08 to 1.55) | — |
| Markers of anemia and inflammation (baseline only) | ||||||
| Hemoglobina | ||||||
| M: <12 g/dl; F: <11 g/dl | 153 | 6.9 (5.9 to 8.1) | — | — | — | 1.19 (0.97 to 1.46) |
| M: 12–14 g/dl; F: 11–13 g/dl | 503 | 4.6 (4.2 to 5.0) | — | — | — | 1.0 Ref |
| hsCRP,a mg/L | ||||||
| 0–3.0 | 359 | 4.5 (4 to 4.9) | — | — | — | 1.0 Ref |
| >3 | 300 | 5.7 (5.1 to 6.4) | — | — | — | 1.03 (0.87 to 1.23) |
| Serum albumin,a g/dl | ||||||
| <3.5 | 75 | 7.3 (5.8 to 9.2) | — | — | — | 1.31 (1.00 to 1.73) |
| 3.5–3.9 | 238 | 5.8 (5.1 to 6.5) | — | — | — | 1.20 (1.01 to 1.43) |
| ≥4.0 | 338 | 4.3 (3.8 to 4.8) | — | — | — | 1.0 Ref |
| IL-6,a pg/ml | ||||||
| 0–3.0 | 492 | 4.5 (4.1 to 4.9) | — | — | — | 1.0 Ref |
| >3 | 158 | 7.2 (6.2 to 8.5) | — | — | — | 1.17 (0.95 to 1.43) |
Bold font denotes a P value <0.05. Results shown above are from joint modeling of linear mixed effects models and proportional hazards survival models. Models were also adjusted for clinical center site. Model 2, the main model, included 1951 participants with complete covariate data. Model 3A included 1876 CRIC participants and model 3B included 1893 CRIC participants because of a small percentage of missing values for either calcium, phosphate, PTH or hemoglobin, hsCRP, albumin, or IL-6, respectively, at the baseline visit. Unadjusted incidence rates were calculated using the value of the variable at the baseline visit; however, some of these variables (e.g., clinical factors) were included as time-updated variables in joint models. IR, incidence rate; 95% CI, 95% confidence interval; HR, hazard ratio; BMI, body mass index; BDI, Beck's Depression Inventory; PTH, parathyroid hormone; M, male; F, female; hsCRP, high-sensitivity C-reactive protein; IL-6, interleukin-6.
To reduce biases in our estimates that can result from controlling for sequelae of changing eGFR, only baseline values of these variables were included in models. All other variables included as time-updated variables in models.