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Non-Pharmacological Activation of the Renal Kallikrein–Kinin System: Dietary Potassium as a Novel Renoprotective Approach

Year: 2026

Type: article

Abstract: Chronic kidney disease (CKD) is a growing global health burden for which there are no curative treatments; therefore, it is essential to implement preventive and kidney-protective strategies. The renal kallikrein-kinin system (KKS) is a vasodilator, anti-inflammatory, and antifibrotic pathway located in the distal nephron, whose decline contributes to hypertension and CKD progression. A thorough evaluation of both experimental and clinical data was undertaken to ascertain the interactions between dietary potassium, renal KKS activity, and kidney protection. A particular focus was placed on animal models of proteinuria, tubulointerstitial damage, and salt-sensitive hypertension, in conjunction with human studies on potassium intake and renal outcomes. Experimental models show that potassium-rich diets stimulate renal kallikrein synthesis, increase urinary kallikrein activity, and up-regulate kinin B₂ receptor expression, leading to reduced blood pressure, oxidative stress, apoptosis, inflammation, and fibrosis. These effects are lost with B₂ receptor blockade. In humans, higher potassium intake enhances kallikrein excretion and lowers cardiovascular and renal risk, independently of aldosterone, and low potassium intake has the potential to exacerbate CKD progression. Notwithstanding the concerns that have been raised regarding the potential necessity of increasing potassium intake in cases of advanced CKD, extant evidence would appear to indicate that potassium excretion persists until late disease stages. Activation and preservation of the renal KKS through a potassium-rich diet represents a rational, low-cost renoprotective strategy. Combined with sodium reduction and nutritional education, this approach could mitigate CKD progression and improve cardiovascular health on a population scale.

Source: Drugs and Drug Candidates

DOI: 10.3390/ddc5010013

Authors: Leopoldo Ardiles, Carlos D. Figueroa

Institution: Austral University of Chile

Language: English

Topic: Coagulation, Bradykinin, Polyphosphates, and Angioedema

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,207