| Study . | Description of study . | Main results . |
|---|---|---|
| Coresh [15] CKD Prognosis Consortium | Design: Patient-level meta-analysis Participants: ESKD analysis: 22 cohort studies, 1.5 million individuals Mortality analysis: 35 cohort studies, 1.7 million individuals Average eGFR (CKD-EPI Equation): Lower eGFR stratum 48 mL/min/1.73 m2 Higher eGFR stratum 92 mL/min/1.73 m2 Predictors: Lesser declines in eGFR (ranging from 0 to 40%) over a baseline period ranging from 1 to 3 years Primary outcome: ESKD (initiation of renal replacement therapy or death due to renal disease) during the subsequent follow-up after the initial baseline period Secondary outcome: Death | Lesser eGFR decline events occurred more frequently than 57% eGFR decline during the baseline period. Strong association between 30 and 40% eGFR decline over a 2-year baseline period and subsequent risks of ESKD and death. 30% eGFR decline over 2 years: HR for ESKD 5.4 and 6.7 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) HR for death 1.8 and 1.6 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) 40% eGFR decline over 2 years: HR for ESKD 10.2 and 15.3 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) HR for death 3.5 and 2.4 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) |
| Lambers Heerspink [18] | Design: Patient-level meta-analysis Participants: 9488 participants from 37 randomized controlled trials Mean ± SD baseline eGFR (CKD-EPI Equation): 49.2 ± 24.9 mL/min/1.73 m2 Predictors: 30 and 40% declines in eGFR from baseline to 12 months Primary outcome: Composite of ESKD, eGFR < 15 mL/min/1.73 m2 if baseline eGFR > 25 mL/min/1.73 m2, or doubling of serum creatinine during the subsequent follow-up Secondary outcome: Above composite end point plus death Median follow-up after the 12-month baseline period: 2.0 (IQR 1.2–3.1) | The events of 30 and 40% eGFR decline occurred more frequently than 57% eGFR decline during the baseline period. Strong association between 30 and 40% eGFR decline over a 1-year baseline period and subsequent risks of ESRD and death, after adjusting for age, sex, treatment assignment, baseline eGFR and proteinuria. 30% eGFR decline over 1 years: HR for ESKD 9.6 (reference 0% decline ∼ stable kidney function) HR for death 7.3 (reference 0% decline ∼ stable kidney function) 40% eGFR decline over 1 years: HR for ESKD 20.3 (reference 0% decline ∼ stable kidney function) HR for death 14.2 (reference 0% decline ∼ stable kidney function) |
| Inker [17] | Design: Patient-level meta-analysis Participants: 9488 participants from 37 randomized controlled trials Studies categorized into 5 types of interventions: RAS blockade versus control; RAS blockade versus calcium channel blocker; intensive blood pressure control; low-protein diet; and immunosuppressive therapy Index test: Alternative end points of lesser declines in eGFR (ranging from 30 to 40%) over a baseline period ranging from 12 to 24 months and throughout study duration Reference test: Established composite end point of ESKD, eGFR < 15 mL/min/1.73 m2 if baseline eGFR > 25 mL/min/1.73 m2, or doubling of serum creatinine Median follow-up: 3.62 years Analysis: Agreement between the established and alternative end points was calculated by Bayesian mixed models. | Treatment effects attenuated for lesser declines, particularly for 20 and 30% when compared with the established end points (suggestive of a weaker treatment effect). For the intervention of RAS blockade versus control, treatment effect increased for 30 and 40% declines at shorter interval (suggestive of a stronger treatment effect). For the intervention of low-protein diet, treatment effect increased for all alternative end points (suggestive of a stronger treatment effect). This result further amplified at shorter intervals. |
| Greene [16] | Design: Simulation study Index test: Alternative composite end point based on ESKD and either 30 or 40% eGFR decline Reference test: Established composite end point of ESKD or 57% eGFR decline Analysis: Comparison of the risk of type 1 errors for established and alternative end points. | Compared with a 57% eGFR decline, a 40% eGFR decline resulted in >20% reduction in the required sample size for a 2-year study. Use of 30% eGFR declined reduced the required sample size only in the absence of an acute treatment effect on eGFR. |
| Study . | Description of study . | Main results . |
|---|---|---|
| Coresh [15] CKD Prognosis Consortium | Design: Patient-level meta-analysis Participants: ESKD analysis: 22 cohort studies, 1.5 million individuals Mortality analysis: 35 cohort studies, 1.7 million individuals Average eGFR (CKD-EPI Equation): Lower eGFR stratum 48 mL/min/1.73 m2 Higher eGFR stratum 92 mL/min/1.73 m2 Predictors: Lesser declines in eGFR (ranging from 0 to 40%) over a baseline period ranging from 1 to 3 years Primary outcome: ESKD (initiation of renal replacement therapy or death due to renal disease) during the subsequent follow-up after the initial baseline period Secondary outcome: Death | Lesser eGFR decline events occurred more frequently than 57% eGFR decline during the baseline period. Strong association between 30 and 40% eGFR decline over a 2-year baseline period and subsequent risks of ESKD and death. 30% eGFR decline over 2 years: HR for ESKD 5.4 and 6.7 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) HR for death 1.8 and 1.6 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) 40% eGFR decline over 2 years: HR for ESKD 10.2 and 15.3 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) HR for death 3.5 and 2.4 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) |
| Lambers Heerspink [18] | Design: Patient-level meta-analysis Participants: 9488 participants from 37 randomized controlled trials Mean ± SD baseline eGFR (CKD-EPI Equation): 49.2 ± 24.9 mL/min/1.73 m2 Predictors: 30 and 40% declines in eGFR from baseline to 12 months Primary outcome: Composite of ESKD, eGFR < 15 mL/min/1.73 m2 if baseline eGFR > 25 mL/min/1.73 m2, or doubling of serum creatinine during the subsequent follow-up Secondary outcome: Above composite end point plus death Median follow-up after the 12-month baseline period: 2.0 (IQR 1.2–3.1) | The events of 30 and 40% eGFR decline occurred more frequently than 57% eGFR decline during the baseline period. Strong association between 30 and 40% eGFR decline over a 1-year baseline period and subsequent risks of ESRD and death, after adjusting for age, sex, treatment assignment, baseline eGFR and proteinuria. 30% eGFR decline over 1 years: HR for ESKD 9.6 (reference 0% decline ∼ stable kidney function) HR for death 7.3 (reference 0% decline ∼ stable kidney function) 40% eGFR decline over 1 years: HR for ESKD 20.3 (reference 0% decline ∼ stable kidney function) HR for death 14.2 (reference 0% decline ∼ stable kidney function) |
| Inker [17] | Design: Patient-level meta-analysis Participants: 9488 participants from 37 randomized controlled trials Studies categorized into 5 types of interventions: RAS blockade versus control; RAS blockade versus calcium channel blocker; intensive blood pressure control; low-protein diet; and immunosuppressive therapy Index test: Alternative end points of lesser declines in eGFR (ranging from 30 to 40%) over a baseline period ranging from 12 to 24 months and throughout study duration Reference test: Established composite end point of ESKD, eGFR < 15 mL/min/1.73 m2 if baseline eGFR > 25 mL/min/1.73 m2, or doubling of serum creatinine Median follow-up: 3.62 years Analysis: Agreement between the established and alternative end points was calculated by Bayesian mixed models. | Treatment effects attenuated for lesser declines, particularly for 20 and 30% when compared with the established end points (suggestive of a weaker treatment effect). For the intervention of RAS blockade versus control, treatment effect increased for 30 and 40% declines at shorter interval (suggestive of a stronger treatment effect). For the intervention of low-protein diet, treatment effect increased for all alternative end points (suggestive of a stronger treatment effect). This result further amplified at shorter intervals. |
| Greene [16] | Design: Simulation study Index test: Alternative composite end point based on ESKD and either 30 or 40% eGFR decline Reference test: Established composite end point of ESKD or 57% eGFR decline Analysis: Comparison of the risk of type 1 errors for established and alternative end points. | Compared with a 57% eGFR decline, a 40% eGFR decline resulted in >20% reduction in the required sample size for a 2-year study. Use of 30% eGFR declined reduced the required sample size only in the absence of an acute treatment effect on eGFR. |
CKD, chronic kidney disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; HR, hazard ratio; IQR, inter-quartile range; RAS, renin–angiotensin system.
| Study . | Description of study . | Main results . |
|---|---|---|
| Coresh [15] CKD Prognosis Consortium | Design: Patient-level meta-analysis Participants: ESKD analysis: 22 cohort studies, 1.5 million individuals Mortality analysis: 35 cohort studies, 1.7 million individuals Average eGFR (CKD-EPI Equation): Lower eGFR stratum 48 mL/min/1.73 m2 Higher eGFR stratum 92 mL/min/1.73 m2 Predictors: Lesser declines in eGFR (ranging from 0 to 40%) over a baseline period ranging from 1 to 3 years Primary outcome: ESKD (initiation of renal replacement therapy or death due to renal disease) during the subsequent follow-up after the initial baseline period Secondary outcome: Death | Lesser eGFR decline events occurred more frequently than 57% eGFR decline during the baseline period. Strong association between 30 and 40% eGFR decline over a 2-year baseline period and subsequent risks of ESKD and death. 30% eGFR decline over 2 years: HR for ESKD 5.4 and 6.7 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) HR for death 1.8 and 1.6 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) 40% eGFR decline over 2 years: HR for ESKD 10.2 and 15.3 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) HR for death 3.5 and 2.4 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) |
| Lambers Heerspink [18] | Design: Patient-level meta-analysis Participants: 9488 participants from 37 randomized controlled trials Mean ± SD baseline eGFR (CKD-EPI Equation): 49.2 ± 24.9 mL/min/1.73 m2 Predictors: 30 and 40% declines in eGFR from baseline to 12 months Primary outcome: Composite of ESKD, eGFR < 15 mL/min/1.73 m2 if baseline eGFR > 25 mL/min/1.73 m2, or doubling of serum creatinine during the subsequent follow-up Secondary outcome: Above composite end point plus death Median follow-up after the 12-month baseline period: 2.0 (IQR 1.2–3.1) | The events of 30 and 40% eGFR decline occurred more frequently than 57% eGFR decline during the baseline period. Strong association between 30 and 40% eGFR decline over a 1-year baseline period and subsequent risks of ESRD and death, after adjusting for age, sex, treatment assignment, baseline eGFR and proteinuria. 30% eGFR decline over 1 years: HR for ESKD 9.6 (reference 0% decline ∼ stable kidney function) HR for death 7.3 (reference 0% decline ∼ stable kidney function) 40% eGFR decline over 1 years: HR for ESKD 20.3 (reference 0% decline ∼ stable kidney function) HR for death 14.2 (reference 0% decline ∼ stable kidney function) |
| Inker [17] | Design: Patient-level meta-analysis Participants: 9488 participants from 37 randomized controlled trials Studies categorized into 5 types of interventions: RAS blockade versus control; RAS blockade versus calcium channel blocker; intensive blood pressure control; low-protein diet; and immunosuppressive therapy Index test: Alternative end points of lesser declines in eGFR (ranging from 30 to 40%) over a baseline period ranging from 12 to 24 months and throughout study duration Reference test: Established composite end point of ESKD, eGFR < 15 mL/min/1.73 m2 if baseline eGFR > 25 mL/min/1.73 m2, or doubling of serum creatinine Median follow-up: 3.62 years Analysis: Agreement between the established and alternative end points was calculated by Bayesian mixed models. | Treatment effects attenuated for lesser declines, particularly for 20 and 30% when compared with the established end points (suggestive of a weaker treatment effect). For the intervention of RAS blockade versus control, treatment effect increased for 30 and 40% declines at shorter interval (suggestive of a stronger treatment effect). For the intervention of low-protein diet, treatment effect increased for all alternative end points (suggestive of a stronger treatment effect). This result further amplified at shorter intervals. |
| Greene [16] | Design: Simulation study Index test: Alternative composite end point based on ESKD and either 30 or 40% eGFR decline Reference test: Established composite end point of ESKD or 57% eGFR decline Analysis: Comparison of the risk of type 1 errors for established and alternative end points. | Compared with a 57% eGFR decline, a 40% eGFR decline resulted in >20% reduction in the required sample size for a 2-year study. Use of 30% eGFR declined reduced the required sample size only in the absence of an acute treatment effect on eGFR. |
| Study . | Description of study . | Main results . |
|---|---|---|
| Coresh [15] CKD Prognosis Consortium | Design: Patient-level meta-analysis Participants: ESKD analysis: 22 cohort studies, 1.5 million individuals Mortality analysis: 35 cohort studies, 1.7 million individuals Average eGFR (CKD-EPI Equation): Lower eGFR stratum 48 mL/min/1.73 m2 Higher eGFR stratum 92 mL/min/1.73 m2 Predictors: Lesser declines in eGFR (ranging from 0 to 40%) over a baseline period ranging from 1 to 3 years Primary outcome: ESKD (initiation of renal replacement therapy or death due to renal disease) during the subsequent follow-up after the initial baseline period Secondary outcome: Death | Lesser eGFR decline events occurred more frequently than 57% eGFR decline during the baseline period. Strong association between 30 and 40% eGFR decline over a 2-year baseline period and subsequent risks of ESKD and death. 30% eGFR decline over 2 years: HR for ESKD 5.4 and 6.7 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) HR for death 1.8 and 1.6 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) 40% eGFR decline over 2 years: HR for ESKD 10.2 and 15.3 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) HR for death 3.5 and 2.4 for lower and higher eGFR strata, respectively (reference 0% decline ∼ stable kidney function) |
| Lambers Heerspink [18] | Design: Patient-level meta-analysis Participants: 9488 participants from 37 randomized controlled trials Mean ± SD baseline eGFR (CKD-EPI Equation): 49.2 ± 24.9 mL/min/1.73 m2 Predictors: 30 and 40% declines in eGFR from baseline to 12 months Primary outcome: Composite of ESKD, eGFR < 15 mL/min/1.73 m2 if baseline eGFR > 25 mL/min/1.73 m2, or doubling of serum creatinine during the subsequent follow-up Secondary outcome: Above composite end point plus death Median follow-up after the 12-month baseline period: 2.0 (IQR 1.2–3.1) | The events of 30 and 40% eGFR decline occurred more frequently than 57% eGFR decline during the baseline period. Strong association between 30 and 40% eGFR decline over a 1-year baseline period and subsequent risks of ESRD and death, after adjusting for age, sex, treatment assignment, baseline eGFR and proteinuria. 30% eGFR decline over 1 years: HR for ESKD 9.6 (reference 0% decline ∼ stable kidney function) HR for death 7.3 (reference 0% decline ∼ stable kidney function) 40% eGFR decline over 1 years: HR for ESKD 20.3 (reference 0% decline ∼ stable kidney function) HR for death 14.2 (reference 0% decline ∼ stable kidney function) |
| Inker [17] | Design: Patient-level meta-analysis Participants: 9488 participants from 37 randomized controlled trials Studies categorized into 5 types of interventions: RAS blockade versus control; RAS blockade versus calcium channel blocker; intensive blood pressure control; low-protein diet; and immunosuppressive therapy Index test: Alternative end points of lesser declines in eGFR (ranging from 30 to 40%) over a baseline period ranging from 12 to 24 months and throughout study duration Reference test: Established composite end point of ESKD, eGFR < 15 mL/min/1.73 m2 if baseline eGFR > 25 mL/min/1.73 m2, or doubling of serum creatinine Median follow-up: 3.62 years Analysis: Agreement between the established and alternative end points was calculated by Bayesian mixed models. | Treatment effects attenuated for lesser declines, particularly for 20 and 30% when compared with the established end points (suggestive of a weaker treatment effect). For the intervention of RAS blockade versus control, treatment effect increased for 30 and 40% declines at shorter interval (suggestive of a stronger treatment effect). For the intervention of low-protein diet, treatment effect increased for all alternative end points (suggestive of a stronger treatment effect). This result further amplified at shorter intervals. |
| Greene [16] | Design: Simulation study Index test: Alternative composite end point based on ESKD and either 30 or 40% eGFR decline Reference test: Established composite end point of ESKD or 57% eGFR decline Analysis: Comparison of the risk of type 1 errors for established and alternative end points. | Compared with a 57% eGFR decline, a 40% eGFR decline resulted in >20% reduction in the required sample size for a 2-year study. Use of 30% eGFR declined reduced the required sample size only in the absence of an acute treatment effect on eGFR. |
CKD, chronic kidney disease; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration equation; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; HR, hazard ratio; IQR, inter-quartile range; RAS, renin–angiotensin system.
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