When Kidneys and Joints Collide; Bidirectional Pathogenic Crosstalk in Ckd and Osteoarthritis; From Molecular Mechanisms to Clinical Management Publisher



Saberi K ; Mukhammadieva S ; Isirgapova S ; Khozhimetov D ; Mashrapov Q ; Nazarova M ; Xamdamova L ; Mengliyeva D ; Rahmonova S ; Kebriyaei E
Source: Journal of Nephropharmacology Published:2026

Abstract

Chronic kidney disease (CKD) and osteoarthritis frequently coexist, particularly in aging populations, imposing a significant burden on patients and healthcare systems. Emerging evidence reveals a complex, bidirectional pathogenic crosstalk between these conditions, extending beyond shared risk factors like aging and obesity. In CKD, the accumulation of uremic toxins, systemic inflammation driven by cytokines and disturbances in mineral bone disorder (CKD-MBD), characterized by dysregulated fibroblast growth factor-23 (FGF23), Klotho deficiency, hyperparathyroidism, and vascular calcification, actively contribute to accelerated articular cartilage degradation, synovitis, and subchondral bone sclerosis, thereby promoting osteoarthritis initiation and progression. Conversely, osteoarthritis-induced chronic pain, joint dysfunction, and reduced mobility lead to physical inactivity, sarcopenia, and metabolic dysregulation, potentially exacerbating CKD progression through strengthened inflammation, insulin resistance, and cardiovascular strain. This bidirectional relationship creates significant clinical challenges; since, standard osteoarthritis analgesics like non-steroidal anti-inflammatory drugs are nephrotoxic and contraindicated in chronic renal failure, since CKD-related complications complicate joint replacement surgery and rehabilitation. Effective management requires a paradigm shift towards integrated care. Treatment modalities include aggressive CKD-MBD control, cautious selection of joint-friendly analgesics, structured exercise programs tailored to renal and joint limitations, and early specialist collaboration. Identification of these intertwined molecular pathways is necessary for developing targeted therapies that simultaneously protect both renal and musculoskeletal health, eventually improving outcomes for this high-risk comorbid population. Copyright © 2026 The Author(s); Published by Society of Diabetic Nephropathy Prevention. This is an open-access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.