Research Of Endogenous H₂S In Chronic Kidney Disease

ObjectiveHydrogen sulphide, H2S, is the third endogenous small molecule gas with cardiovascular properties, after nitric oxide(NO) and carbon monoxide(CO). It is involved in mediating several signaling and cytoprotective functions. H2S has been shown to exhibit potent vasodilator activity, by activating potassium channels in endothelia cells and vascular smooth muscle cells. In addition, it produced locally within the kidney stimulates natriuresis and diuresis by increasing glomeruar filtration and inhibiting tubular sodium reabsorption. Hypertension and cardio-cerebro vascular complications are comsidered as the most common long-term complications of chronic kidney disease(CKD)., and also important risk factors inducing death. Considering there are less researches about H2S in patients with chronic kidney disease, this study is designed to explore the distributing features of endogenous plasma H2S in patients with CKD before dialysis, and to discover the factors influencing it and the relationship between H2S and cardio-cerebro vascular complications.Methods(1)Plasma was obtained from patients with chronic kidney disease before dialysis and healthy subjects.(2)In a cross-sectional study, the levels of plasma H2S, NO, Carboxyhemoglobin and Vitamin B6were measured by enzyme-linked immunosorbant assay (ELISA). Uremic toxin Indole sulfate phenol was measured by High-performance liquid chromatography (HPLC). Blood sulphhaemoglobin was measured by Dual-wavelength spectrophotometry.(3)Patients’clinical data, laboratory results and auxiliary examination results were collected.(4)PASW Statistics software was used to assess the influencing factors of plasma endogenous H2S level, the relationship among the three small molecule gases, and the relationship between H2S and diseases like hypertension, diabetes, and cardio-cerebro vascular complications.Results(1)Plasma H2S level was significantly lower in CKD patients compared with controls(4.20(2.98-9.40) vs10.24(9.98～16.25)nmol/ml,P=0.000). Plasma H2S level in every stage of CKD was significantly lower compared with controls, and the results are6.59±4.78vs14.11±8.15nmol/ml(P=0.000),6.57±4.44vs14.11±8.15nmol/ml(P=0.000),5.98±4.52vs14.11±8.15nmol/ml(P=0.000),5.44±5.15vs14.11±8.15nmol/ml(P=0.001),5.39±3.40vs14.11±8.15nmol/ml(P=0.000).(2) Blood Sulphhaemoglobin(SHb) level in CKD patients correlated positively with estimated glomerular filtration rate (p=0.406, P=0.029), even as corrected by hemoglobin. And blood SHb level in CKD patients correlated negatively with plasma Indole sulfate phenol level (p=-0.393, P=0.043).(3) Plasma H2S level in CKD patients correlated negatively with low-density ipoprotein cholesterol(LDL-C) cholesterol(p=-0.184, P﹤0.05), and negatively with low-density ipoprotein cholesterol/high-density lipoprotein cholesterol(HDL-C) cholesterol(p=-0.248, P=0.008).(4) Plasma H2S level in CKD patients correlated negatively with left ventricular ejection fraction (LVEF)(p=-0.207, P=0.034). Blood SHblevel inCKD patients correlated positively with left ventricular posterior wall thickness (LVPWT)(p=0.437, P=0.020), and correlated negatively with cardiac troponin T (p=-0.376, P=0.034).(5) Plasma H2S level in CKD patients correlated negatively with blood pluse pressure (p=0.-0.187, P=0.049).(6) Plasma HbCO level was significantly lower in CKD patients compared with controls(41.28(34.33-54.24) vs93.27(61.30-170.08) ng/ml,P=0.000). Plasma HbCO level was significantly lower in CKD patients in stage1, stage2and stage5compared with controls. And plasma H2S level in CKD patients correlated positively with plasma HbCO level(p=0.221,P=0.042).(7) Plasma NO level was significantly lower in CKD patients compared with controls(18.49(13.40-19.96) vs53.90(47.69-60.22) ng/ml, P=0.000). and plasma NO level were significantly lower in every stage of CKD patients compared with controls.(8) Serum homocysteine level was siginificantly higher in CKD patients compared with controls(16.1(12.3-22.2) vs10.28(7.0-14.56) μmol/L, P=0.000), and was significantly different among patients in different stages of CKD, and further comparison revealed that Hey level significantly increased as renal function decreased. Plasma Vitamin B6level was significantly lower in CKD patients compared with controls(66.74(50.80-96.91) vs107.19(106.22-107.55)pg/ml,P=0.000).(9) There were no siginificantly differences revealed of plasma H2S level between CKD patients with or without smoking history, hypertension and cardio-cerebro vascular complications. And there were no siginificantly correlationship revealed of plasma H2S with renin system, blood glocuse, intima-media thichness, and N-terminal pro brain natriuretic peptide.Conclusion(1) Plasma H2S level is markedly reduced in CKD patients. Blood SHb is positively correlated with eGFR, and negatively correlated with plasma IS level.(2) The decrease of plasma H2S level in CKD patients is positively related with the significantly decrease of plasma VitB6level.(3) plasma H2S level in CKD patients is positively correlated with plasma HbCO level,and this reveals that the three endogenous small molecule gases have correlationship with each other.(4) Plasma H2S level in CKD patients has relation with some influencial factors of cardio-cerebro vascular complications, such as HDL-C, LDL-C, LVEF, cTnT and blood pressure.