PHARMACOLOGICAL MODULATION OF RENAL BIOCHEMICAL PATHWAYS IN CHRONIC KIDNEY DISEASE: A SYSTEMATIC REVIEW

Abstract

Background: Chronic kidney disease (CKD) is a complex, progressive disorder driven by interconnected hemodynamic, metabolic, inflammatory, and fibrotic pathways. Traditional therapies largely emphasize risk reduction rather than direct modulation of underlying biochemical mechanisms. Increasing evidence indicates that pathway-targeted pharmacological interventions may offer disease-modifying benefits, necessitating a systematic evaluation of both clinical and mechanistic data.

Methods: A systematic literature review was conducted across peer-reviewed sources published between 2016 and 2025 to assess pharmacological modulation of renal biochemical pathways in CKD. Eligible studies included randomized controlled trials, observational studies, narrative and systematic reviews, experimental investigations, computational analyses, and one doctoral dissertation. Studies involving CKD populations or relevant models and reporting renal clinical or mechanistic outcomes were synthesized using a pathway-based analytical framework.

Results: Twenty-two studies were included, encompassing diabetic and non-diabetic CKD contexts. Pharmacological modulation of the renin–angiotensin–aldosterone system, oxidative stress and fibrotic signalling, and metabolic–mitochondrial pathways was consistently associated with renal protection. SGLT2 inhibitors and non-steroidal mineralocorticoid receptor antagonists demonstrated pleiotropic effects, including attenuation of inflammation, reduction of fibrosis, and slowing of kidney function decline. Evidence also supported combination pharmacotherapy, particularly strategies integrating metabolic and hemodynamic pathway modulation, which showed additive or synergistic reno-protective effects.

Conclusions: This review highlights a transition toward mechanism-informed, multi-pathway pharmacological strategies in CKD management. Targeting convergent biochemical pathways, rather than isolated risk factors, may enhance disease modification. Future research should focus on biomarker-guided precision approaches to optimize therapeutic selection, sequencing, and long-term renal outcomes.