Table 1.
Definition of the reported renal outcomes in each of the CVOTs for SGLT-2 inhibitors, DPP4 inhibitors and GLP-1 analogues
| Trial | Renal composite outcome | Albuminuria | eGFR/creatinine | ESRD |
|---|---|---|---|---|
| EMPA-REG OUTCOME [19, 20] | Progression to macroalbuminuria, doubling of serum creatinine with eGFR ≤ 45 ml/min/1.73 m2, ESRD, renal death |
Incident microalbuminuria (urinary ACR 30–300 mg/g) Incident macroalbuminuria (urinary ACR > 300 mg/g) |
Doubling of serum creatinine and eGFR < 45 ml/min/1.73 m2 | Need for RRT |
| CANVAS Program [21, 22] | Sustained ≥ 40% decrease in eGFR, ESRD or renal death | New microalbuminuria, or new macroalbuminuria with ≥ 30% increased urinary ACR | Sustained 40% reduction in eGFR for ≥ 30 days | Sustained eGFR < 15 ml/min/1.73 m2 for > 30 days, dialysis ≥ 30 days or renal transplant |
| CREDENCE trial [23] | Doubling of serum creatinine, ESRD, or death from renal or cardiovascular disease | Comparison of urinary ACR versus placebo | Sustained doubling of serum creatinine | Sustained eGFR < 15 ml/min/1.73 m2 for > 30 days or need for dialysis for ≥ 30 days or renal transplant |
| DECLARE-TIMI 58 [24, 26] | Sustained ≥ 40% decrease in eGFR to ≤ 60 ml/min/1.73 m2, ESRD, renal or cardiovascular death | Comparison of urinary ACR versus placebo | Sustained ≥ 40% decrease in eGFR to ≤ 60 ml/min/1.73 m2 | Sustained eGFR < 15 ml/min/1.73 m2, or dialysis for ≥ 90 days, or renal transplant |
| DAPA-HF study [27] | Sustained ≥ 50% decrease in eGFR, ESRD, renal death | Not reported | Sustained ≥ 50% decrease in eGFR | Sustained eGFR < 15 ml/min/1.73 m2 ≥ 28 days, or need for continuous RRT |
| EXAMINE trial [44] | Not reported | Not reported | Changes in eGFR over the study | Need for renal dialysis |
| SAVOR-TIMI 53 [45, 46] | Doubling of serum creatinine or ESRD | Categorical change in urinary ACR from baseline | Doubling of serum creatinine | Need for renal dialysis, transplant or serum creatinine > 530 µmol/L |
| TECOS trial [47, 48] | Not reported | Comparison of urinary ACR versus placebo | Changes in eGFR over the study | Not reported |
| CARMELINA trial [49] | Sustained ≥ 40% decrease in eGFR and eGFR ≤ 60 ml/min/1.73 m2, ESRD, renal death | Microalbuminuria (ACR 30–300 mg/g) or macroalbuminuria (urinary ACR ≥ 300 mg/g) | Sustained ≥ 40% decrease in eGFR and eGFR ≤ 60 ml/min/1.73 m2 | Need for renal dialysis ≥ 30 days or renal transplant |
| ELIXA trial [50, 51] | Not reported | Mean percentage change in urinary ACR, progression to macroalbuminuria | Doubling of the serum creatinine, changes in eGFR | Not reported |
| LEADER trial [52, 53] | New macroalbuminuria, doubling of serum creatinine with eGFR ≤ 45 ml/min/1.73 m2, need for continuous RRT or renal death | New macroalbuminuria (urinary ACR > 300 mg/g or urinary albumin > 300 mg/24 h) | Doubling of the serum creatinine with eGFR ≤ 45 ml/min/1.73 m2 | Need for continuous RRT |
| SUSTAIN-6 trial [54] | New macroalbuminuria, doubling of serum creatinine with eGFR ≤ 45 ml/min/1.73 m2, need for continuous RRT or renal death | New macroalbuminuria (urinary ACR > 300 mg/g or urinary albumin > 300 mg/24 h) | Doubling of the serum creatinine with eGFR ≤ 45 ml/min/1.73 m2 | Need for continuous RRT |
| PIONEER-6 [55] | Not reported | Not reported | Changes in eGFR ratio from baseline to end of treatment | Not reported |
| EXSCEL trial [56, 57] | New macroalbuminuria, sustained ≥ 40% decrease in eGFR or RRT or renal death | New macroalbuminuria | Sustained ≥ 40% decrease in eGFR | Need for RRT |
| HARMONY Outcomes study [58] | Not reported | Not reported | Changes in eGFR over the study | Not reported |
| REWIND study [59] | New macroalbuminuria, sustained ≥ 30% decrease in eGFR or chronic RRT | New macroalbuminuria (urinary ACR > 33.9 mg/mmol) | Sustained ≥ 30% decrease in eGFR | Need for continuous RRT |
eGFR estimated glomerular filtration rate, ESRD end-stage renal disease, ACR albumin-to-creatinine ratio, RRT renal replacement therapy