Association Between Iron Metabolism and Acute Kidney Injury in Critically Ill Patients With Diabetes

Abstract

ObjectiveIron overload plays an important role in the pathogenesis of diabetes and acute kidney injury (AKI). The aim of this present study was to explore the relationship between iron metabolism and AKI in patients with diabetes.MethodsThe clinical data of diabetes patients from MIMIC-III database in intensive care unit (ICU) were retrospectively analyzed. Regression analyses were used to explore the risk factors of AKI and all-cause death in critical patients with diabetes. Area under the receiver operating characteristic curves (AUROCs) were used to analyze serum ferritin (SF), and regression model to predict AKI in critical patients with diabetes. All diabetes patients were followed up for survival at 6 months, and Kaplan–Meier curves were used to compare the survival rate in patients with different SF levels.ResultsA total of 4,997 diabetic patients in ICU were enrolled, with a male-to-female ratio of 1.37:1 and a mean age of 66.87 ± 12.74 years. There were 1,637 patients in the AKI group (32.8%) and 3,360 patients in the non-AKI group. Multivariate logistic regression showed that congestive heart failure (OR = 2.111, 95% CI = 1.320–3.376), serum creatinine (OR = 1.342, 95% CI = 1.192–1.512), Oxford Acute Severity of Illness Score (OR = 1.075, 95% CI = 1.045–1.106), increased SF (OR = 1.002, 95% CI = 1.001–1.003), and decreased transferrin (OR = 0.993, 95% CI = 0.989–0.998) were independent risk factors for AKI in critical patients with diabetes. Multivariate Cox regression showed that advanced age (OR = 1.031, 95% CI = 1.025–1.037), AKI (OR = 1.197, 95% CI = 1.011–1.417), increased Sequential Organ Failure Assessment score (OR = 1.055, 95% CI = 1.032–1.078), and increased SF (OR = 1.380, 95% CI = 1.038–1.835) were independent risk factors for 6-month all-cause death in critical diabetic patients. The AUROCs of SF and the regression model to predict AKI in critical patients with diabetes were 0.782 and 0.851, respectively. The Kaplan–Meier curve showed that the 6-month survival rate in SF-increased group was lower than that in SF-normal group (log-rank χ2 = 16.989, P < 0.001).ConclusionCritically ill diabetic patients with AKI were easily complicated with abnormal iron metabolism. Increase of SF is an important risk factor for AKI and all-cause death in critically ill patients with diabetes.

Association of serum ferritin and all-cause mortality in AKI patients: a retrospective cohort study

“…Previous studies have found that ferritin is not only an indicator of iron stores, but is also abnormally elevated in inflammatory responses, tumors, and other conditions. Studies of Sepsis ( 23 ), acute cardiac infarction ( 9 ), cerebrovascular disease ( 24 ), and rheumatoid disorders have suggested a correlation between elevated ferritin and poor disease prognosis ( 25 , 26 ). Therefore, our study does not imply that elevated serum ferritin is a specific manifestation of AKI, but rather the result of a combination of systemic diseases in critically ill patients.…”

Iron Chelation as a Potential Therapeutic Approach in Acute Lung Injury

“…For example, a clinical study showed that due to high glucose toxicity in diabetic patients, the release of serum iron was inhibited, which resulted in iron overload. What is more, by facilitating lipid peroxidation and catalyzing excess hydroxyl free radicals, the increase of serum iron can promote the occurrence of acute kidney injury (AKI); therefore, iron overload is considered an independent risk factor for AKI in critically ill patients with diabetes [ 48 ]. It is also reported that iron is necessary for the continuous and rapid proliferation of cancer cells, resulting in accelerated cancer cell growth and increased morbidity and mortality in cancer patients [ 22 ].…”

An update on essential micronutrients in critical illness

“…Iron overload with its potential prooxidant action has been associated with the pathogenesis of diabetes and acute kidney injury (AKI). Investigation of 4997 critically ill diabetic patients, including 32.8% presenting AKI [25], showed that high serum ferritin and low transferrin were independent risk factors for AKI. High ferritin is typical of inflammation and requires the additional biomarker hepcidin to correctly interpret the status.…”