Table 1:
Key inclusion and exclusion criteria, baseline characteristics and outcomes in the placebo arm in DAPA-CKD and EMPA-KIDNEY (data are from references [7] and [9], unless otherwise specified). Colored cells indicate major differences between the two trials.
| DAPA-CKD | EMPA-KIDNEY | |
|---|---|---|
| Key trial characteristics | ||
| Trial metrics | ||
| N | 4304 | 6609 |
| Median follow-up | 2.4 | 2.0 |
| Inclusion criteria | ||
| eGFR (mL/min/1.73 m2) | 25 to 75 | 20 to <90 |
| UACR (mg/g) | 200 to 5000 | ≥200 if eGFR 45 to <90 |
| No limit for eGFR <45 | ||
| CVD | Atherosclerotic CVD within 12 weeks prior to enrolment | Prior atherosclerotic CVD in T2DM participants with an eGFR >60 mL/min/1.73 m2 |
| RAS blockade | Yes, if not contraindicated | Yes; also included participants not on RAS blockade when RAS blockade not indicated or not tolerated |
| Exclusion criteria | ||
| PKD | Excluded | Excluded |
| Lupus nephritis, vasculitis | Excluded | Included |
| Kidney transplantation | Excluded | Excluded |
| T1DM | Excluded | Initially included (69 randomized), later excludeda |
| Baseline data | ||
| Clinical characteristics | ||
| Age (years) | 62 | 64 |
| Women (%) | 33 | 33 |
| Non-DM (%) | 32.5 | 54 |
| CVD (%) | 37 | 27 (36 in DM, 19 in non-DM) |
| HF (%) | 11 | 10 (14 in DM, 6 in non-DM) |
| Causes of CKD | (16) | (17) |
| DKD, n (%) | 2510 (58.3) | 2057 (31) |
| Glomerular, n (%) | 695 (16.1) | 1669 (25) |
| Hypertensive/renovascular, n (%) | 687 (16.0) | 1445 (22) |
| Tubulointerstitial, n (%) | 53 (1.2) | 468 (7) |
| Unknown/other, n (%) | 214 (5.0) | 630 (10) |
| Baseline CKD status | ||
| KDIGO risk category very high, n (%) | 2336 (54) [15] | 4911(74) |
| eGFR (mL/min/1.73 m2) | 43 (±12) | 37 (±14) |
| eGFR category G4, n (%) | 624(14.5) | 2280 (34.5) |
| UACR (mg/g)b | 934–965 | 330 |
| UACR category A1, n (%) | 0 (0) | 1332 (20) |
| UACR category A2, n (%) | 444 (10) [15] | 1862 (28) |
| UACR > 1000 mg/g (%) | 48 | ND |
| RAS blockade, n (%) | 4174 (97) | 3399 (85) |
| Outcomes | ||
| Outcomes in the placebo arm (events/100 patient-years) | ||
| Primary outcome (events/100 patient-years)c | 7.5 | 9.0 |
| Death (any cause) (events/100 patient-years) | 6.8 | 2.6 |
| CVD death (events/100 patient-years) | 1.7 | 1.1 |
| HF hospitalization or CVD death (events/100 patient-years) | 3.0 | 2.4 |
| CKD progression (events/100 patient-years)d | 5.8 | 8.1 |
| CKD progression similar definition in both trials (events/100 patient-years)e | DM 6.0, non-DM 5.3 | DM 5.9, non-DM 4.7 |
| Primary outcomec in the placebo arm in subgroups of interest (%) [15] | ||
| All (%) | 14.5 | 16.9 |
| UACR category A1–A2 (%) | 4.4 | 7.5 |
| UACR category A3 (%) | 15.6 | 25.7 |
| eGFR category G2/G3a (%) | 10.5 | 9.5 |
| eGFR category G3b (%) | 14.1 | 12.0 |
| eGFR category G4 (%) | 26.3 | 27.5 |
| KDIGO risk category low, moderate, high (%) | 9.8 | 4.9 |
| KDIGO risk category very high (%) | 18.44 | 20.91 |
| DM (%) | 15.78 [34] | 20.20 |
| No DM (%) | 11.84 [34] | 14.08 |
| Chronic eGFR slopes in the placebo arm in subgroups of interest (mL/min/1.73 m2/year) | ||
| All | –3.83 [35] | −2.75 (no differences DM vs non-DM) |
| eGFR <30, 30–<45, ≥45 | ∼−3.5 to ∼−4 [15] | −2.85, −2.50, −3.60f |
| UACR <1000, 1000–3500, >3500 | ∼−2, ∼−4.5, ∼−7.5 [15] | ND |
| UACR <30, 30–300, >300 | ND | −0.89, −1.69, −4.11 |
Note that the higher incident of primary endpoint events in EMPA-KIDNEY as opposed to DAPA-CKD appears to be driven by a less stringent definition of sustained decrease in eGFR (≥40% vs ≥50% decrease in eGFR), as when the same definition is used, the incidence rate of kidney events is actually lower for EMPA-KIDNEY than for DAPA-CKD.
aSponsor request, not because of safety concern.
bMedian.
cDAPA-CKD: composite of sustained decline of ≥50% in eGFR from randomization, kidney replacement therapy, sustained decrease in eGFR to <15 mL/min/1.73 m2 and renal or cardiovascular death. EMPA-KIDNEY: composite of kidney disease progression (a sustained decline of ≥40% in eGFR from randomization, kidney replacement therapy, sustained decrease in eGFR to <10 mL/min/1.73 m2 or renal death) and cardiovascular death. Both outcomes differ in the threshold to define kidney failure (<15 mL/min/1.73 m2 in DAPA-CKD vs <10 mL/min/1.73 m2 in EMPA-KIDNEY), which they term end-stage kidney disease, and in threshold for the sustained decline in eGFR (≥50% in DAPA-CKD vs ≥40% in EMPA-KIDNEY).
dDAPA-CKD: Composite of decline in estimated GFR of ≥50%, kidney replacement therapy, sustained decrease in eGFR to <15 mL/min/1.73 m2 or death from renal causes. EMPA-KIDNEY: a sustained decline of ≥40% in eGFR from randomization, kidney replacement therapy, sustained decrease in eGFR to <10 mL/min/1.73 m2 or renal death.
eThe kidney disease progression was defined as a sustained decrease in eGFR (≥50%) from randomization in both trials. Data from [11]. In this analysis, kidney failure continued to be defined differently (<15 mL/min/1.73 m2 in DAPA-CKD vs <10 mL/min/1.73 m2 in EMPA-KIDNEY).
fParticipants with eGFR >45 mL/min/1.73 m2 had UACR >200 mg/g.