ovariates* | Category | CVD submodel† | CKD submodel | Probability of kidney transplant among those on dialysis in previous year | |||||
Vascular death | MAE or vascular death | MVE or vascular death | From any pre-RRT stage‡ | ||||||
CKD stage 3B versus CKD stage 4 | CKD stage 5, not RRT versus CKD stage 4 | Renal transplant versus CKD stage 4 | Dialysis versus CKD stage 4 | ||||||
Exponential PH HR (95% CI) | Gompertz PH HR (95% CI) | Gompertz PH HR (95% CI) | Multinomial logistic regression RRR2 (95% CI) | Logistic regression OR (95% CI) | |||||
Patient's characteristics at baseline | |||||||||
Sociodemographic characteristics | |||||||||
Sex | Male | 1.3 (1.1 to 1.6) | 1.4 (1.2 to 1.5) | 1.4 (1.2 to 1.5) | 1.2 (1.1 to 1.4) | 1.1 (1.0 to 1.2) | 1.2 (0.9 to 1.7) | 1.5 (1.3 to 1.7) | 1.2 (1.0 to 1.4) |
Ethnicity/country (ref: white) | Asian (China) | 3.5 (2.4 to 5.0) | 1.3 (1.0 to 1.7) | 1.4 (1.1 to 1.8) | 1.5 (1.2 to 1.9) | 2.1 (1.7 to 2.7) | 0.6 (0.2 to 1.9) | 1.6 (1.2 to 2.2) | 0.3 (0.2 to 0.6) |
Asian (other country) | 1.2 (0.9 to 1.5) | 0.7 (0.6 to 0.9) | 0.7 (0.6 to 0.9) | 0.9 (0.8 to 1.1) | 1.1 (0.9 to 1.2) | 0.1 (0.1 to 0.4) | 0.9 (0.7 to 1.1) | 0.1 (0.1 to 0.1) | |
Black | 0.9 (0.6 to 1.5) | 0.8 (0.6 to 1.1) | 0.9 (0.6 to 1.2) | 1.2 (0.9 to 1.7) | 1.1 (0.7 to 1.7) | 1.0 (0.2 to 4.4) | 1.9 (1.2 to 3.3) | 0.5 (0.4 to 0.8) | |
Other | 1.2 (0.8 to 1.8) | 0.7 (0.6 to 1.0) | 0.7 (0.6 to 1.0) | 1.0 (0.7 to 1.5) | 1.2 (0.9 to 1.7) | 2.7 (1.4 to 5.1) | 1.4 (0.9 to 2.1) | 0.6 (0.4 to 0.8) | |
Smoker (ref: never) | Former | 1.0 (0.8 to 1.2) | 1.1 (1.0 to 1.2) | 1.1 (1.0 to 1.2) | 1.0 (0.8 to 1.1) | ||||
Current | 1.4 (1.1 to 1.7) | 1.4 (1.2 to 1.6) | 1.4 (1.2 to 1.6) | 0.7 (0.6 to 0.9) | |||||
Adult dependants (ref: yes) | No | 0.7 (0.6 to 0.8) | |||||||
Missing | 0.8 (0.6 to 1.0) | ||||||||
Education level (ref: A-levels or above) | GCSE/vocational | 1.0 (0.9 to 1.2) | 1.1 (0.9 to 1.2) | 0.7 (0.5 to 1.0) | 1.2 (1.1 to 1.4) | 0.6 (0.5 to 0.8) | |||
Below secondary | 1.0 (0.9 to 1.2) | 0.8 (0.7 to 1.0) | 0.4 (0.2 to 0.7) | 0.9 (0.7 to 1.0) | 0.8 (0.6 to 1.0) | ||||
1.0 (0.8 to 1.1) | 1.1 (0.9 to 1.3) | 0.8 (0.5 to 1.2) | 1.1 (0.9 to 1.3) | 1.0 (0.8 to 1.2) | |||||
BMI, kg/m2 (ref: ≥25, <30) | <25 | 1.0 (0.9 to 1.2) | |||||||
≥30 | 0.7 (0.6 to 0.9) | ||||||||
Disease history, laboratory measurements and other risk factors | |||||||||
Diabetes | Yes | 1.4 (1.1 to 1.8) | 1.4 (1.2 to 1.7) | 1.4 (1.2 to 1.6) | 1.0 (0.8 to 1.2) | 0.9 (0.7 to 1.0) | 0.2 (0.1 to 1.0) | 1.2 (0.9 to 1.5) | 0.6 (0.4 to 0.9) |
Previous failed kidney transplant | Yes | 0.5 (0.4 to 0.7) | |||||||
Diastolic blood pressure, mm Hg (ref: ≥75, <85) | <75 | 0.8 (0.6 to 0.9) | |||||||
≥85 | 1.1 (0.9 to 1.3) | ||||||||
Systolic blood pressure, mm Hg (ref: ≥130, <150) | <130 | 1.2 (1.0 to 1.4) | 1.0 (0.9 to 1.2) | 1.0 (0.9 to 1.2) | 1.0 (0.9 to 1.2) | ||||
≥150 | 1.3 (1.1 to 1.6) | 1.2 (1.1 to 1.3) | 1.2 (1.1 to 1.4) | 0.8 (0.6 to 0.9) | |||||
Albumin, g/dL (ref ≥3.9, <4.2) | <3.9 | 1.3 (1.1 to 1.5) | 1.2 (1.1 to 1.4) | 1.2 (1.1 to 1.4) | 0.9 (0.8 to 1.0) | 1.1 (1.0 to 1.3) | 1.4 (0.9 to 2.2) | 1.4 (1.2 to 1.7) | |
≥4.2 | 0.8 (0.6 to 0.9) | 0.9 (0.8 to 1.0) | 0.9 (0.8 to 1.0) | 1.0 (0.9 to 1.1) | 1.0 (0.9 to 1.1) | 1.1 (0.7 to 1.5) | 0.9 (0.8 to 1.1) | ||
Missing | 1.1 (0.8 to 1.5) | 1.1 (0.9 to 1.3) | 1.1 (0.9 to 1.3) | 0.7 (0.6 to 0.9) | 1.1 (0.9 to 1.3) | 1.5 (0.8 to 2.8) | 1.4 (1.1 to 1.8) | ||
Haemoglobin, g/dL (ref: ≥11.6, <13) | <11.6 | 1.5 (1.2 to 1.8) | 1.3 (1.1 to 1.4) | 1.3 (1.1 to 1.4) | 1.0 (0.9 to 1.2) | 1.2 (1.0 to 1.3) | 1.0 (0.7 to 1.5) | 1.3 (1.1 to 1.6) | |
≥13 | 0.9 (0.7 to 1.2) | 1.0 (0.9 to 1.2) | 1.0 (0.9 to 1.1) | 1.3 (1.2 to 1.5) | 0.8 (0.7 to 0.9) | 0.6 (0.4 to 0.8) | 0.7 (0.6 to 0.8) | ||
Missing | 1.0 (0.7 to 1.5) | 1.1 (0.9 to 1.4) | 1.1 (0.9 to 1.4) | 1.1 (0.9 to 1.3) | 1.0 (0.8 to 1.3) | 1.0 (0.4 to 2.9) | 1.1 (0.8 to 1.6) | ||
Phosphate, mmol/L (ref: ≥1.2, <1.5) | <1.2 | 1.3 (1.1 to 1.4) | 0.7 (0.6 to 0.7) | 0.9 (0.6 to 1.3) | 0.6 (0.5 to 0.8) | ||||
≥1.5 | 0.8 (0.6 to 1.0) | 1.4 (1.2 to 1.6) | 1.3 (0.9 to 1.9) | 1.7 (1.5 to 2.1) | |||||
Missing | 1.5 (1.3 to 1.8) | 0.7 (0.6 to 0.9) | 0.5 (0.2 to 1.0) | 0.9 (0.7 to 1.1) | |||||
Urinary ACR (measured in pre-RRT participants only), mg/g (ref: <30) | ≥30, ≤300 | 1.0 (0.7 to 1.4) | 1.2 (1.0 to 1.5) | 1.2 (1.0 to 1.5) | 0.6 (0.5 to 0.7) | 1.7 (1.5 to 2.0) | 0.9 (0.5 to 1.5) | 1.7 (1.3 to 2.1) | |
>300 | 1.3 (0.9 to 1.8) | 1.4 (1.1 to 1.7) | 1.4 (1.1 to 1.7) | 0.3 (0.3 to 0.4) | 3.0 (2.5 to 3.5) | 2.8 (1.7 to 4.8) | 4.9 (3.8 to 6.3) | ||
Missing | 1.2 (0.8 to 1.9) | 1.0 (0.8 to 1.4) | 1.1 (0.8 to 1.4) | 0.9 (0.8 to 1.1) | 1.6 (1.3 to 2.0) | 1.1 (0.5 to 2.5) | 1.9 (1.4 to 2.7) | ||
RRT | 1.2 (0.8 to 1.8) | 1.3 (1.0 to 1.8) | 1.4 (1.0 to 1.8) | ||||||
HDL cholesterol, mmol/L (ref: ≥0.9, <1.2) | <0.9 | 1.0 (0.9 to 1.1) | 1.1 (0.9 to 1.2) | 0.8 (0.5 to 1.2) | 1.1 (0.9 to 1.3) | ||||
≥1.2 | 1.1 (1.0 to 1.3) | 0.8 (0.7 to 0.9) | 0.9 (0.6 to 1.3) | 0.9 (0.8 to 1.1) | |||||
Cause of kidney disease (ref: other/unknown) | Diabetic nephropathy | 1.3 (1.0 to 1.7) | 1.4 (1.2 to 1.6) | 1.4 (1.2 to 1.6) | 0.8 (0.7 to 1.0) | 0.9 (0.7 to 1.1) | 2.1 (0.4 to 10.6) | 1.1 (0.8 to 1.5) | 0.8 (0.5 to 1.3) |
Cystic kidney disease | 0.8 (0.5 to 1.0) | 0.9 (0.7 to 1.0) | 0.9 (0.7 to 1.1) | 0.3 (0.3 to 0.4) | 2.6 (2.3 to 3.0) | 4.9 (3.5 to 6.9) | 4.9 (4.1 to 5.9) | 1.6 (1.3 to 1.8) | |
Characteristics updated on an annual basis | |||||||||
Age | Per 10 years older | 1.6 (1.5 to 1.7) | 1.4 (1.4 to 1.5) | 1.4 (1.3 to 1.5) | 0.8 (0.8 to 0.9) | 0.9 (0.9 to 1.0) | 0.4 (0.4 to 0.5) | 0.8 (0.7 to 0.8) | 0.6 (0.6 to 0.6) |
Time since CKD diagnosis | Per 10 years | 1.0 (0.9 to 1.0) | 1.1 (1.0 to 1.1) | 1.2 (1.1 to 1.3) | 1.1 (1.0 to 1.1) | ||||
Previous (most recent) CVD event (ref: no MVE within trial, no baseline vascular disease) | No MVE within trial, with baseline vascular disease | 1.7 (1.4 to 2.1) | 1.9 (1.7 to 2.2) | 1.9 (1.7 to 2.2) | 1.0 (0.9 to 1.2) | 1.0 (0.9 to 1.2) | 0.6 (0.3 to 1.2) | 1.0 (0.8 to 1.2) | 0.7 (0.5 to 0.9) |
MAE within trial, last year | 3.0 (2.2 to 4.0) | 4.3 (3.6 to 5.2) | 4.3 (3.5 to 5.1) | NA | NA | ||||
MAE within trial, 1–2 years ago | 2.6 (1.7 to 3.9) | 3.5 (2.7 to 4.6) | 3.5 (2.7 to 4.5) | ||||||
MAE within trial, >2 years ago | 1.5 (0.9 to 2.7) | 2.3 (1.6 to 3.3) | 2.3 (1.6 to 3.2) | ||||||
No MAE, but MVE within trial | 4.6 (1.7 to 12.5) | 3.4 (1.4 to 8.2) | 4.3 (1.8 to 10.0) | ||||||
MVE within trial§ | NA | 0.9 (0.7 to 1.2) | 1.6 (1.2 to 2.1) | 1.3 (0.3 to 5.1) | 3.0 (2.1 to 4.2) | 0.9 (0.7 to 1.3) | |||
CKD status at the end of the previous cycle (ref: CKD stage 3B) | CKD stage 4 | 1.7 (1.3 to 2.3) | 1.3 (1.1 to 1.5) | 1.3 (1.1 to 1.5) | 0.02 (0.02 to 0.02) | 10.8 (6.8 to 17.0) | 6.5 (0.9 to 48.2) | 2.6 (1.6 to 4.0) | NA |
CKD stage 5, not on RRT | 2.2 (1.6 to 3.1) | 1.6 (1.3 to 2.0) | 1.6 (1.3 to 1.9) | 0.01 (0.01 to 0.02) | 737.1 (455.7 to 1192.4) | 1279.5 (174.2 to 9397.7) | 369.4 (233.5 to 584.3) | ||
On dialysis, RRT≤3 years | 2.8 (2.0 to 4.0) | 2.1 (1.7 to 2.7) | 2.1 (1.7 to 2.6) | NA | |||||
On dialysis, RRT>3 years | 4.1 (2.7 to 6.1) | 2.5 (1.9 to 3.3) | 2.5 (1.9 to 3.3) | 1.2 (1.1 to 1.4)¶ | |||||
Functioning kidney transplant | 0.9 (0.4 to 2.0) | 0.7 (0.5 to 1.2) | 0.8 (0.5 to 1.2) | NA | |||||
Intercept** | −14.8 (−15.5 to -14.1) | −12.4 (−12.8 to -12.0) | −12.4 (−12.8 to -11.9) | 9.3 (6.6 to 13.0) | 0.0 (0.0 to 0.0) | 0.1 (0.0 to 0.5) | 0.0 (0.0 to 0.0) | 3.0 (1.9 to 5.0) | |
Ancillary parameter (on the original scale) | NA | −0.0002 (−0.0003, −0.0001) | −0.0002 (−0.0003, −0.0001) | NA | NA |
*Missing data were either assigned into a separate category or, if data were missing for fewer than 5% of participants, to the middle group (online supplementary item S1 and table SM1), †Each risk equation included an adjustment for use of lipid-lowering therapy, ‡The coefficients represent the RRR for being in the respective CKD category versus the comparator category (CKD stage 4) per unit change in the covariate. For example, the RR of being in stage 3B relative to being in stage 4 in males is 1.2 times higher than in females. To calculate RR relative to another stage category, the corresponding RRRs need to be divided. For example, the RR of being on kidney transplant relative to being in CKD stage 5 in males is 1.2 (=1.3/1.1) times higher in males than in females; years in which deaths occurred were excluded from modelling, §In the CKD risk equations, all within-trial major vascular events were combined into one category, ¶Reference category is ‘on dialysis’, RRT≤3 years, **Intercept in the CVD submodel is presented on the original scale.
ACR, albumin:creatinine ratio; BMI, body mass index; CKD, chronic kidney disease; CVD, cardiovascular disease; MAE, major atherosclerotic event; MVE, major vascular event; NA, not applicable: covariate not included or specified through other covariates within category; PH, proportional hazards; RRR, relative risk ratio; RRT, renal replacement therapy.