3 Key Takeaways
Plain English Summary- 01Core Finding
We evaluated whether the impact of RASi-prescription on kidney outcomes was modified by APOL1 risk allele number or baseline albuminuria, using Cox models with inverse probability of treatment weighting and marginal structural models.
- 02Study Evidence
Tested in a observational cohort study (3418 participants) at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
What This Means for You
RASi-based therapy, addressed as a time-updated pooled treatment, provided similar benefit across APOL1 genotypes, driven by albuminuric participants. Among individuals with two APOL1 risk alleles, outcomes were similar regardless of baseline albuminuria. However, further studies are needed due to small sample sizes and the inability of statistical methods to capture clinical variables that may have affected prescription changes.
The Discovery
We included Black participants with APOL1 genotyping on first-line anti-hypertensive therapy from the Chronic Renal Insufficiency Cohort (CRIC) and Systolic Blood Pressure Intervention Trial (SPRINT). We evaluated whether the impact of RASi-prescription on kidney outcomes was modified by APOL1 risk allele number or baseline albuminuria, using Cox models with inverse probability of treatment weighting and marginal structural models. A total of 3418 participants (62% from SPRINT), 40%, a clinically meaningful level and 16% carrying zero, one and two APOL1 risk alleles, respectively, were included. RASi-use compared to other first-line antihypertensive therapy was associated with a comparably lower risk of the kidney outcome in individuals with zero (hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.44-0.87]), one (HR 0.68 [95% CI 0.49-0.94]) or two risk alleles (HR 0.59 [95% CI 0.40-0.86]). This benefit was driven by albuminuric participants, but estimates were similarly low for RASi-use compared to other antihypertensive therapy in albuminuric (HR 0.62, 95% CI [0.41-0.93]) and non-albuminuric (HR 0.37, 95% CI [0.13-1.08]) participants with two APOL1 risk alleles, although the estimate was imprecise in non-albuminuric participants.
How It Works, Simply
This nephrology research focuses on glomerular filtration & renal tubular preservation. Researchers evaluated it using an observational cohort study (3418 participants) at the real-world cohort stage of medical research.
3 Key Takeaways
Clinical Takeaways- 01Core Finding
We evaluated whether the impact of RASi-prescription on kidney outcomes was modified by APOL1 risk allele number or baseline albuminuria, using Cox models with inverse probability of treatment weighting and marginal structural models.
- 02Study Evidence
Tested in a observational cohort study (3418 participants) at the real-world cohort stage.
- 03Practical Meaning
Observational cohort findings reveal real-world links, though lifestyle or unmeasured factors cannot be fully ruled out without an RCT.
Key Numbers
Biological Mechanism & Study Design
Study Design & Cohort
Observational cohort study
Observational cohort study (3418 participants) · Real-World Cohort
Biological Pathway & Modality
Glomerular filtration & renal tubular preservation
Intervention: Pooled cohort analysis of renin-angiotensin system inhibition and the risk of kidney
Experimental Findings & Endpoints
We included Black participants with APOL1 genotyping on first-line anti-hypertensive therapy from the Chronic Renal Insufficiency Cohort (CRIC) and Systolic Blood Pressure Intervention Trial (SPRINT).
We evaluated whether the impact of RASi-prescription on kidney outcomes was modified by APOL1 risk allele number or baseline albuminuria, using Cox models with inverse probability of treatment weighting and marginal structural models. A total of 3418 participants (62% from SPRINT), 40%, a clinically meaningful level and 16% carrying zero, one and two APOL1 risk alleles, respectively, were included.
RASi-use compared to other first-line antihypertensive therapy was associated with a comparably lower risk of the kidney outcome in individuals with zero (hazard ratio (HR) 0.62 [95% confidence interval (CI) 0.44-0.87]), one (HR 0.68 [95% CI 0.49-0.94]) or two risk alleles (HR 0.59 [95% CI 0.40-0.86]). This benefit was driven by albuminuric participants, but estimates were similarly low for RASi-use compared to other antihypertensive therapy in albuminuric (HR 0.62, 95% CI [0.41-0.93]) and non-albuminuric (HR 0.37, 95% CI [0.13-1.08]) participants with two APOL1 risk alleles, although the estimate was imprecise in non-albuminuric participants.
Clinical Translation & Practice Context
RASi-based therapy, addressed as a time-updated pooled treatment, provided similar benefit across APOL1 genotypes, driven by albuminuric participants.
Among individuals with two APOL1 risk alleles, outcomes were similar regardless of baseline albuminuria. However, further studies are needed due to small sample sizes and the inability of statistical methods to capture clinical variables that may have affected prescription changes.
The Bottom Line · Clinical Pearl
“RASi-based therapy, addressed as a time-updated pooled treatment, provided similar benefit across APOL1 genotypes, driven by albuminuric participants.”
Published in Kidney International · Current Stage: Real-World Cohort