Patients with advanced chronic kidney disease (CKD) who have very low serum zinc levels are at higher risk for infection-related hospitalization compared with patients with higher levels, particularly users of proton pump inhibitors (PPI), a new study suggests.

Among 232 patients with stage 5 CKD, including 46 (20.6%) receiving maintenance dialysis, the rate of infection-related hospitalization was significantly higher for patients with low zinc levels (defined in this study as below a median of 50 µg/dL or less) compared with those who had higher levels (above 50 µg/dL) : 23.3% vs 12.6%, respectively. Further, patients with low zinc levels had a significantly higher rate of infection-related hospitalizations lasting more than 10 days: 23.3% vs 12.6%, investigators led by Yosuke Saka, MD, PhD, of Kasugai Municipal Hospital Takakicho in Aichi Prefecture, Japan, reported in the Journal of Renal Nutrition.

The normal range of serum zinc is 59-135 µg/dL. Serum zinc values were below the lower limit of the normal range, 59 µg/dL, in 77.6% of patients.

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During a median 36 months, 40 of the 232 patients were hospitalized for 60 infection events categorized as respiratory (17 events, 28.3%), soft tissue (11, 18.3%), abdominal (10, 16.7%), bacteremia (9, 15.0%), urinary tract (5, 8.3%), bone and joint (2, 3.3%), and other causes (6, 10%).

In adjusted Cox hazards models, zinc levels less than 50 µg/dL significantly and independently correlated with a 1.9-fold greater risk for infection-related hospitalization events compared with higher levels. For patients with low zinc currently taking PPIs, the risk was 2.7-fold greater.

According to the investigators, previous research indicate that changes in gastric pH caused by long-term term use of PPIs interfere with the absorption of micronutrients, including zinc.

“Patients with advanced CKD and low serum Zn concentration, especially when medicated with PPI, are at high risk of infection-related, and subsequent long-term, hospitalization,” Dr Saka’s team stated.

The cohort included 232 patients with stage 5 CKD with or without kidney replacement therapy who underwent laboratory testing for anemia but also had serum zinc values.

The researchers noted that, according to the International Zinc Nutrition Consultative Group, serum zinc concentrations are not reliable indicators of zinc status within an individual but are a useful indicator on a population level.. “Consequently, the present findings cannot be applied to identifying individual patients with a Zn deficiency,” the authors wrote. “On the other hand, our findings indicated that most patients with advanced CKD are at risk of infectious diseases due to a Zn deficiency, as this study reflected Zn status at the population level among patients with advanced CKD.”

The authors acknowledged some study limitations, including its having been conducted at a single center. In addition, they analyzed data only from patients with CKD whose serum zinc levels were measured to evaluate anemia. “Thus we did not measure Zn in all patients with CKD at our hospital. Nonetheless, we considered that Zn was measured in most patients, because anemia is a common complication of advanced CKD.”


Saka Y, Naruse T, Matsumoto J, et al. Low serum zinc concentration is associated with infection particularly in patients with stage 5 chronic kidney disease medicated with proton pump inhibitors. J Ren Nutr. 2021 Feb 25;S1051-2276(20)30287-9. doi:10.1053/j.jrn.2020.11.006