Association Between Trimethylamine N-oxide and Adverse Kidney Outcomes and Overall Mortality in Type 2 Diabetes Mellitus.

CONTEXT: Type 2 diabetes (T2D) is the major contributor to chronic kidney disease and end-stage kidney disease (ESKD). The influence of trimethylamine N-oxide (TMAO) on kidney outcomes in T2D remains unclear. OBJECTIVE: To examine the association between fasting serum TMAO levels and adverse kidney outcomes in patients with T2D. METHODS: Between October 2016 and June 2020, patients with T2D were recruited and monitored every 3 months until December 2021. Serum TMAO levels were assessed using liquid chromatography-mass spectrometry. The primary kidney outcomes were doubling of serum creatinine levels or progression to ESKD necessitating dialysis; the secondary kidney outcome was a rapid 30% decline in estimated glomerular filtration rate within 2 years. All-cause mortality was also evaluated. RESULTS: Among the 440 enrolled patients with T2D, those in the highest serum TMAO tertile (≥0.88 µM) were older, had a longer diabetes duration, elevated blood urea nitrogen, and lower estimated glomerular filtration rate. Over a median follow-up period of 4 years, 26 patients (5.9%) had a doubling of serum creatinine level or progression to ESKD. After propensity score weighting, the patients in the highest serum TMAO tertile had a 6.45-fold increase in the risk of doubling of serum creatinine levels or progression to ESKD and 5.86-fold elevated risk of rapid decline in kidney function compared with those in the lowest tertile. Additionally, the stepwise increase in serum TMAO was associated with all-cause mortality. CONCLUSION: Patients with T2D with elevated circulating TMAO levels are at higher risk of doubling serum creatinine, progressing to ESKD, and mortality. TMAO is a potential biomarker for kidney function progression and mortality in patients with T2D.

Environmental melamine exposure and adverse kidney outcomes in patients with type 2 diabetes mellitus.

The impact of melamine exposure on kidney outcomes in type 2 diabetes mellitus (T2D) patients remains unclear. In this prospective cohort study, 561 T2D patients during October 2016 and June 2020 were enrolled and followed until December 2021. Baseline one-spot urinary corrected melamine levels were measured by LC-MS/MS. Average daily intake (ADI) of melamine represented environmental melamine exposure in daily life, and was estimated using urinary corrected melamine level by creatinine excretion (CE)-based model. Primary kidney outcomes were defined as doubling of serum creatinine levels or end stage kidney disease (ESKD), and secondary kidney outcomes included rapid decline in kidney function as estimated glomerular filtration rate (eGFR) decline >5 ml/min/1.73 m2/year. Baseline median urinary corrected melamine levels and estimated DI of melamine were 0.8 µg/mmol and 0.3 µg/kg/day in 561 T2D patients. During 3.7 years of follow-up, urinary corrected melamine level was positively correlated with reaching composite outcomes of either doubling of serum creation levels or ESKD and rapid decline in kidney function. Those with the highest quartile of urinary corrected melamine had 2.96-fold risk of composite outcomes of either doubling of serum creation levels or ESKD and 2.47-fold risk of eGFR decline >5 ml/min/1.73 m2/year. Estimated ADI of melamine also had significant correlation with adverse kidney outcomes. Furthermore, the positive relationship between melamine exposure and rapid decline in kidney function was only found in T2D patients with male, baseline eGFR ≥60 ml/min/1.73 m2 or glycated hemoglobin ≤7%. In conclusion, melamine exposure is significantly associated with adverse kidney outcomes in T2D patients, especially in those with male, well sugar control or good baseline kidney function.

The Relationship between Subtypes of Health Literacy and Self-Care Behavior in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a global public health issue that is associated with high rates of morbidity and mortality. Self-care behavior has been associated with clinical outcomes in chronic diseases, and adequate self-care behavior may mitigate adverse outcomes. Health literacy may be an important factor associated with self-care. The aim of this study was to examine the relationships between different domains of self-care behavior and health literacy in patients with CKD. This study enrolled 208 patients with CKD stages 1-5 who were not undergoing renal replacement therapy at Kaohsiung Medical University Hospital from April 2019 to January 2020. Health literacy was measured using a multidimensional health literacy questionnaire covering the following five dimensions: accessing, understanding, appraising, and applying health information, and communication/interaction. The CKD Self-Care scale, which is a 16-item questionnaire with five domains including medication adherence, diet control, exercise, smoking behavior, and home blood pressure monitoring was used to assess self-care behavior. Among the 208 patients, 97 had sufficient or excellent health literacy, and 111 had inadequate or limited/problematic health literacy. A higher health literacy score was significantly correlated with greater self-care behavior. Among the five domains of self-care behavior, the patients who had sufficient or excellent health literacy had higher diet, exercise, and home blood pressure monitoring scores than those who had inadequate or limited/problematic health literacy. This study demonstrated that health literacy was significantly and positively correlated with self-care behavior in patients with CKD.