Therapeutic Insights in Chronic Kidney Disease Progression
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Amir Shabaka1, Clara Cases-Corona1, Gema Fernandez-Juarez1
1Nephrology Department, Hospital Universitario Fundación Alcorcón, Madrid, Spain.
Insights
Chronic kidney disease (CKD) is a major global health issue. New treatments targeting weight, inflammation, and epigenetic factors show promise for slowing CKD progression and improving kidney outcomes.
Area of Science:
- Nephrology
- Cardiovascular Medicine
- Endocrinology
Background:
- Chronic kidney disease (CKD) is a significant global health concern, contributing to morbidity and mortality through cardiovascular risk and end-stage kidney disease.
- Diabetes and obesity are major drivers of CKD, accounting for over half of the CKD burden.
- Current management focuses on blood pressure control, albuminuria treatment, avoiding nephrotoxins, and cardiovascular risk reduction.
Purpose of the Study:
- To review current and emerging therapeutic strategies for managing chronic kidney disease.
- To highlight novel pharmacological approaches and their potential benefits in slowing CKD progression.
- To emphasize the need for a holistic approach targeting early disease mechanisms.
Main Methods:
- Review of classical CKD management strategies.
- Analysis of new antihyperglycemic drugs (e.g., SGLT2 inhibitors) and their impact on GFR, weight, and cardiovascular outcomes.
- Evaluation of novel non-steroidal mineralocorticoid receptor antagonists and potassium-lowering therapies.
- Exploration of emerging therapeutic targets, including epigenetic regulators.
Main Results:
- Sodium-glucose-cotransporter 2 inhibitors demonstrate benefits in slowing GFR decline, promoting weight reduction, and improving cardiovascular and kidney outcomes.
- New mineralocorticoid receptor antagonists offer selective inhibition with reduced side effects like hyperkalemia, making them suitable for CKD patients.
- Novel potassium-lowering therapies enhance tolerance for renin-angiotensin system inhibitors, improving their nephroprotective effects.
- Emerging therapies targeting epigenetic regulators are in clinical trials and may offer coordinated regulation of CKD progression.
Conclusions:
- CKD management requires a multifaceted approach addressing its complex pathophysiology, including microvascular damage, oxidative stress, and inflammation.
- Early intervention targeting disease mechanisms is crucial, as established fibrosis is difficult to reverse.
- Novel therapeutic agents, including SGLT2 inhibitors, selective mineralocorticoid receptor antagonists, and epigenetic regulators, hold significant promise for improving CKD outcomes.
Abstract:
Chronic kidney disease (CKD) has been recognized as a leading public health problem worldwide. Through its effect on cardiovascular risk and end-stage kidney disease, CKD directly affects the global burden of morbidity and mortality. Classical optimal management of CKD includes blood pressure control, treatment of albuminuria with angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, avoidance of potential nephrotoxins and obesity, drug dosing adjustments, and cardiovascular risk reduction. Diabetes might account for more than half of CKD burden, and obesity is the most important prompted factor for this disease. New antihyperglycemic drugs, such as sodium-glucose-cotransporter 2 inhibitors have shown to slow the decline of GFR, bringing additional benefit in weight reduction, cardiovascular, and other kidney outcomes. On the other hand, a new generation of non-steroidal mineralocorticoid receptor antagonist has recently been developed to obtain a selective receptor inhibition reducing side effects like hyperkalemia and thereby making the drugs suitable for administration to CKD patients. Moreover, two new potassium-lowering therapies have shown to improve tolerance, allowing for higher dosage of renin-angiotensin system inhibitors and therefore enhancing their nephroprotective effect. Regardless of its cause, CKD is characterized by reduced renal regeneration capacity, microvascular damage, oxidative stress and inflammation, resulting in fibrosis and progressive, and irreversible nephron loss. Therefore, a holistic approach should be taken targeting the diverse processes and biological contexts that are associated with CKD progression. To date, therapeutic interventions when tubulointerstitial fibrosis is already established have proved to be insufficient, thus research effort should focus on unraveling early disease mechanisms. An array of novel therapeutic approaches targeting epigenetic regulators are now undergoing phase II or phase III trials and might provide a simultaneous regulatory activity that coordinately regulate different aspects of CKD progression.
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