Zinc Deficiency in Chronic Kidney Disease and Hemodialysis: Insights from Basic Research to Clinical Implications

Zinc is an essential trace element involved in diverse physiological processes in humans. Zinc deficiency is common in patients with chronic kidney disease (CKD), including those undergoing hemodialysis. This narrative review synthesizes both experimental and clinical findings on zinc status in CKD patients. Literature was primarily retrieved from PubMed using the keywords "zinc" AND ("CKD" OR "hemodialysis") AND at least one of the following: "cardiovascular disease (CVD)", "vascular calcification", "anemia", "blood pressure", OR "infection". In vitro, studies have shown that zinc suppressed phosphate-induced vascular calcification while zinc deficiency directly promoted calcification. Clinically, serum zinc levels were positively correlated with calcification propensity in patients with CKD. In vivo zinc deficiency has been implicated in elevated blood pressure, Moreover, zinc supplementation enhanced erythropoiesis and improved responsiveness to erythropoiesis-stimulating agents in both animal models and humans. We recently reported that low serum zinc levels are associated with increased mortality in hemodialysis patients with hypoalbuminemia. Previous randomized controlled trials (RCTs) suggest a daily dose of approximately 45 mg of zinc for 2 months mitigates inflammation, oxidative stress, and malnutrition in patients undergoing hemodialysis. Emerging evidence suggests that vascular calcification, hypertension, and renal anemia are newly recognized features of zinc deficiency and are established risk factors for CKD progression, CVD, and mortality. However, the impact of zinc supplementation on these clinical outcomes remains inconclusive. Further RCTs are required to establish zinc supplementation as an effective therapeutic strategy for improving various outcomes in patients with CKD including hemodialysis.