Relationship Between Plasma Trimethylamine N-oxide Levels And Renal Dysfunction In Patients With Hypertension

Objective: Trimethylamine-N-oxide(TMAO)is influenced by alien cholinerich foods,which is digested by the innate intestinal flora to trimethylamine(TMA),and then oxidated by liver flavin monooxygenase3(FOM3).It has been confirmed that raising TMAO succeed in making of diseases and is a amplificated agent for poor prognosis.Our focus is to explicate plasma TMAO rise is a causative factor to hypertension(HTN)and renal dysfunction in HTN patients by adjustment covariates,and it is aide to the severity of the disease.Whether TMAO be united with closely related indicators of renal tubular injury,β 2-microglobulin(β 2-MG)in the diagnosis of early renal impairment in hypertensive patients.Methods: This is a cross-sectional examine on 239 subjects.According to the inclusion and exclusion criteria,the subjects were divided into three groups: HTN-CKD group(n=143),simple HTN group(n=46)and healthy control group(n=50).The blood pressure was graded according to the highest blood pressure.Renal function was evaluated by glomerular filtration rate(eGFR),plasma TMAO level was measured by high performance liquid chromatography tandem-mass spectrometry(HPLC-MS/MS).Binary Logistic regression analysis and ordered Logistic regression analysis were used to evaluate the relationship between plasma TMAO level and HTN,renal dysfunction and its severity.Determine the ratio(OR)and 95% confidence interval(95%CI)before and after adjusting the confounding factors.Spearman correlation analysis was used to test the correlation between plasma TMAO levels and traditional and new markers of renal function damage.the receiver operating characteristic(ROC)curve was used to analyze the area under the curve(AUC),the optimal critical value,sensitivity and specificity of plasma TMAO and β 2-MG for predicting renal dysfunction in patients with HTN.Results: There were giant differences in plasma TMAO levels among the three groups.The plasma TMAO level in the HTN group increased than that in the normal control group(1.00 [0.73,1.27]mg/L)versus(2.01 [1.58,2.49]mg/L,P<0.01).Similarly,compared with the level of plasma TMAO in HTN group,HTN-CKD group was also significantly higher(2.01 [1.58,2.49]mg/L)versus(2.99 [2.08,3.55] mg/ L,P<0.01).Binary Logistic regression analysis showed that plasma TMAO was not only an independent risk factor for HTN,but also an independent risk factor for renal function damage in patients with HTN.Ordered logistic regression model showed that compared with the lowest quartile of TMAO,the highest quartile TMAO had a higher risk in CKD5 stage(OR 5.47,95%CI 2.16-13.87,P<0.01).Plasma TMAO was not only correlated with traditional renal function damage indexes(creatinine and urea),but also positively correlated with β 2-MG,a specific renal tubular damage marker.The working characteristic curve of the subjects showed that the optimal critical values of TMAO and β 2-MG for predicting renal function injury in patients with HTN were 2.62 mg/L and 2.93 mg/L respectively,the sensitivity were 62.2% and 72%,the specificity were 87% and 91.3% respectively,and the area under the curve was 0.76,95%CI scope from 0.68 to 0.84 and 0.83,95%CI scope from 0.77 to 0.88,respectively.The AUC of TMAO combined with β 2-MG in predicting renal dysfunction in HTN patients was 0.85,95%CI scope from 0.80 to 0.90,the best critical value was 0.79 mg/L,the sensitivity was 67.8%,and the specificity was 93.5%.All in all,TMAO is an independent risk factor for HTN and HTN-CKD.TMAO combined with β 2-MG may assist early diagnosis and improve CKD staging.Conclusion: the increase of plasma TMAO is a risk factor for hypertension,and it can also cause and aggravate renal insufficiency in patients with hypertension.In addition,the level of plasma TMAO in HTN patients increased significantly when eGFR decreased slightly,which can be used as a pioneering plasma marker to predict early renal function injury in patients with hypertension.