Integrating and Simplifying Evidence to Optimize Cardiorenal Guideline-Directed Therapies
Abstract
1. Introduction
2. Catching Chronic Kidney Disease Early: Why It Matters
3. GFR and UACR: The Dynamic Duo for Detecting, Staging and Tracking CKD
3.1. GFR
3.2. Albumin-to-Creatinine Ratio (uACR)
4. Renal Troubles: Sorting out Acute Kidney Injury (AKI) from Worsening Renal Function (WRF)
5. The GDMT Adoption Dilemma in HF with CKD
6. Therapies Delivering CV Gains in CKD
6.1. RAS Inhibitors: Angiotensin-Converting Enzyme Inhibitors (ACEis), Angiotensin II Receptor Blockers (ARBs)
6.2. Mineralocorticoid Receptor Antagonists (MRAs)
6.3. Angiotensin Receptor–Neprilysin Inhibitor (ARNI)
6.4. Sodium–Glucose Cotransporter-2 Inhibitors (SGLT2is)
6.5. Glucagon-like Peptide-1 Receptor Agonists (GLP-1RAs)
7. From Evidence to Impact: Challenges and Opportunities of Implementing Best Practices in CKD Management
7.1. Nonpharmacological Management of CKD and HF
7.2. Pharmacological Management of CKD and HF
8. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
ACEi | Angiotensin-converting enzyme inhibitors |
ADHF | Acute decompensated heart failure |
AKI | Acute kidney injury |
ARB | Angiotensin II receptor blockers |
ARNI | Angiotensin receptor-neprilysin inhibitor |
CKD | Chronic kidney disease |
CV | Cardiovascular |
CVOTs | CV outcome trials |
DM | Diabetes |
eGFRcr | Estimated GFR based on serum creatinine |
eGFRcr-cys | Cystatin C–based eGFR |
ESKD | End-stage kidney disease |
GDMT | Guideline directed medical therapy |
GFR | GFR glomerular filtration rate |
GLP-1RA | Glucagon-like peptide-1 receptor agonists |
HFH | Heart failure hospitalization |
HFmrEF | Heart failure with mildly reduced ejection fraction |
HFpEF | Heart failure with preserved ejection fraction |
HFrEF | Heart failure with reduced ejection fraction |
HTN | Hypertension |
KRT | Kidney replacement therapy |
MACE | Major adverse CV events |
RASi | Renin-angiotensin system inhibitors |
RAAS | Renin-angiotensin-aldosterone system |
SCr | Serum creatinine |
SGLT2i | Sodium–glucose cotransporter 2 inhibitors |
S/V | Sacubitril/valsartan |
T2DM | Type 2 diabetes mellitus |
uACR | Urine albumin-to-creatinine ratio |
WRF | Worsening renal function |
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Trial | Agent (Dose) | Median Follow-Up (yrs) | Composite Cardiovascular Endpoint | Exploratory Renal Composite Endpoint | Macroalbuminuria | Worsening eGFR | Renal Replacement Therapy |
---|---|---|---|---|---|---|---|
LEADER | Liraglutide 1.8 mg/d | 3.8 | 13% relative risk reduction HR: 0.87 (95% CI: 0.78–0.97) p = 0.01 | 0.78 [0.67–0.92] * | 0.74 [0.60–0.91] * | 0.89 [0.67–1.19] | 0.87 [0.61–1.24] |
REWIND | Dulaglutide 1.5 mg/wk | 5.4 | 11% relative risk reduction HR: 0.89 (95% CI: 0.79–0.99) p = 0.026 | 0.85 [0.77–0.93] * | 0.77 [0.68–0.87] * | 0.89 [0.78–1.01] | 0.75 [0.39–1.44] |
SUSTAIN-6 | Semaglutide 0.5/1 mg/wk | 2.1 | 26% relative risk reduction HR: 0.74 (95% CI: 0.58–0.95) p =< 0.001 | 0.64 [0.46–0.88] * | 0.54 [0.37–0.77] * | 1.28 [0.64–2.58] | 0.91 [0.40–2.07] |
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Singh, H.; Puckett, C.; Lucas, Y.Q. Integrating and Simplifying Evidence to Optimize Cardiorenal Guideline-Directed Therapies. J. Clin. Med. 2025, 14, 5883. https://doi.org/10.3390/jcm14165883
Singh H, Puckett C, Lucas YQ. Integrating and Simplifying Evidence to Optimize Cardiorenal Guideline-Directed Therapies. Journal of Clinical Medicine. 2025; 14(16):5883. https://doi.org/10.3390/jcm14165883
Chicago/Turabian StyleSingh, Harleen, Carrie Puckett, and Yennie Q. Lucas. 2025. "Integrating and Simplifying Evidence to Optimize Cardiorenal Guideline-Directed Therapies" Journal of Clinical Medicine 14, no. 16: 5883. https://doi.org/10.3390/jcm14165883
APA StyleSingh, H., Puckett, C., & Lucas, Y. Q. (2025). Integrating and Simplifying Evidence to Optimize Cardiorenal Guideline-Directed Therapies. Journal of Clinical Medicine, 14(16), 5883. https://doi.org/10.3390/jcm14165883