Electrolyte Disturbances in Chronic Kidney Disease: A Narrative Review of Hypophosphatemia and Hypocalcemia As Possible Contributors to Muscle Cramps and Knee Pain Publisher



Keshtkari S ; Shahrezaee MH ; Sharifzadeh SR ; Taheriazam A ; Heidari R ; Chamanara M ; Shahrezaee M
Source: SN Comprehensive Clinical Medicine Published:2026

Abstract

Background/Objective: Chronic kidney disease (CKD) is frequently complicated by disordered mineral metabolism and a high burden of neuromuscular and musculoskeletal symptoms. Muscle cramps and knee pain are common in advanced CKD and dialysis, yet their pathophysiology is multifactorial and incompletely understood. This narrative review examines how hypophosphatemia and hypocalcemia may contribute to these symptoms within the broader context of CKD–mineral bone disorder (CKD-MBD) and other established mechanisms. Methods: This narrative review was conducted on studies indexed in PubMed, Scopus and Google Scholar (January 2000–November 2025) that evaluated calcium and/or phosphate disturbances in CKD alongside neuromuscular outcomes and musculoskeletal manifestations. Heterogeneous study designs and populations precluded meta-analysis; instead, we synthesized mechanistic and clinical data qualitatively, explicitly distinguishing chronic CKD-related abnormalities from acute, dialysis-induced shifts. Results: Episodes of ionized hypocalcemia and hypophosphatemia, especially in the setting of dialysis-related alkalaemia, high-efficiency solute removal, or intensive phosphate-binding therapy, are biologically plausible contributors to neuromuscular hyperexcitability and impaired muscle energetics. Experimental and clinical data show that low ionized calcium lowers nerve depolarization thresholds, while phosphate depletion limits ATP synthesis and may prolong muscle contraction. Chronic mineral imbalance, together with vitamin D deficiency and secondary hyperparathyroidism, promotes renal osteodystrophy and can exacerbate knee pain via osteomalacia, osteitis fibrosa, and chondrocalcinosis. However, across CKD populations, muscle cramps and knee pain also arise from non-electrolyte mechanisms, including intradialytic hypotension and volume shifts, peripheral neuropathy, carnitine deficiency, and degenerative or dialysis-related joint disease, and cannot be attributed to electrolyte disturbances alone. Conclusions: Current evidence supports a contributory, rather than exclusive, role for hypocalcemia and hypophosphatemia in CKD-associated muscle cramps and knee pain. The available data are largely observational and mechanistic, and do not permit firm causal inference in stable dialysis cohorts. Clinically, careful attention to dialysate composition, avoidance of overtreatment with phosphate binders, and correction of vitamin D deficiency and hypocalcemia may benefit selected symptomatic patients, but should be integrated with strategies targeting volume management, neuropathy, carnitine deficiency and structural joint pathology. Prospective studies that quantify symptom responses to controlled changes in calcium and phosphate, while accounting for these co-factors, are needed before causal claims can be substantiated. © The Author(s), under exclusive licence to Springer Nature Switzerland AG 2026.