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Abstract
Background: Increased albuminuria is associated with increased serum ferritin, insulin resistance, and non-alcoholic fatty liver disease (NAFLD). Liver iron accumulation is also related to hyperferritinemia, insulin resistance, and NAFLD; however, there is no evidence on its relationship with albuminuria. Aims: To assess the relationship between hepatic iron load and urine albumin-to-creatinine ratio (UACR) in patients with metabolic syndrome (MetS) and NAFLD. Methods: In total, 75 MetS and NAFLD patients (aged 40–60 years, BMI 27–40 kg/m2) were selected from a cohort according to available data on hepatic iron load (HepFe) by magnetic resonance imaging (MRI). Subjects underwent anthropometric measurements, biochemistry testing, and liver MRI. Increased albuminuria was defined by UACR. Results: UACR correlated with NAFLD, HepFe, triglycerides, serum ferritin, fasting insulin, insulin resistance (calculated using the homeostatic model assessment for insulin resistance—HOMA-IR- formula), and platelets (p < 0.05). Multiple regression analysis adjusted for gender, age, eGFR, HbA1c, T2DM, and stages of NAFLD, found that HepFe (p = 0.02), serum ferritin (p = 0.04), fasting insulin (p = 0.049), and platelets (p = 0.009) were associated with UACR (R2 = 0.370; p = 0.007). UACR, liver fat accumulation, serum ferritin, and HOMA-IR increased across stages of HepFe (p < 0.05). Patients with severe NAFLD presented higher HepFe, fasting insulin, HOMA-IR, and systolic blood pressure as compared to patients in NAFLD stage 1 (p < 0.05). Conclusion: Hepatic iron load, serum ferritin, fasting insulin, and platelets were independently associated with albuminuria. In the context of MetS, increased stages of NAFLD presented higher levels of HepFe. Higher levels of HepFe were accompanied by increased serum ferritin, insulin resistance, and UACR. The association between iron accumulation, MetS, and NAFLD may represent a risk factor for the development of increased albuminuria.
Highlights
Non-alcoholic fatty liver disease (NAFLD), considered the hepatic expression of the metabolic syndrome, affects more than 25% of the Western population, and its number continues to increase [1]
The aim of the present study was to explore whether liver iron accumulation independent of hereditary hemochromatosis (HHC) was associated with albuminuria in patients with non-alcoholic fatty liver disease (NAFLD), on the basis that conditions such as hyperferritinemia, insulin resistance, and NAFLD, which have been previously observed to be independently related to liver iron accumulation, contribute to albuminuria
NAFLD without hepatic iron load, could give a more confident answer to the possible relationship between the liver and kidney mediated by liver iron accumulation in patients with metabolic syndrome (MetS). This aim of the present secondary analysis was to assess whether a relationship exists between hepatic iron load and urine albumin-tocreatinine ratio (UACR) in the context of dysmetabolic iron overload syndrome (DIOS) and NAFLD
Summary
Non-alcoholic fatty liver disease (NAFLD), considered the hepatic expression of the metabolic syndrome, affects more than 25% of the Western population, and its number continues to increase [1]. A mild increase of liver iron accumulation and moderate hyperferritinemia in the context of the metabolic syndrome (MetS) have been detected in about half of patients with non-alcoholic fatty liver disease (NAFLD) [2,3]. Such condition has been named dysmetabolic iron overload syndrome (DIOS), and it is unrelated to hereditary hemochromatosis (HHC). Hyperferritinemia, besides being related to hepatic iron deposits, is a determinant of NAFLD [4,5] It has been described as an early marker of insulin resistance [6,7], and is associated with increased albuminuria in patients with prediabetes and diabetes [8,9,10].
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