Study On The Correlation Between TCM Syndromes And Urinary MMP - 9 And TIMP - 1 In Patients With Chronic Kidney Disease

BackgroundChronic Kidney Disease (CKD) is a progressive disease, which have an increased incidence year by year, and most of whom are early-stage CKD patients. Therefore, the clinical diagnosis and treatment of early-stage CKD patients is very important. Renal fibrosis contributes to the final common pathway for almost all forms of kidney disease, and the imbalance of ECM synthesis and degradation is an important pathological process, which is related to "jusan xiaozhang" in "Shenluozhengjia" theory. So, it is significant to explore the relationship between TCM syndrome and ECM synthesis and degradation for the improvement of theory and guiding clinical diagnosis and treatment. MMP-9 and TIMP-1 have been shown to be important factors for the regulation of ECM synthesis and degradation. Through the detection of TCM syndrome and urinary levels of MMP-9/TIMP-1 in early CKD group and healthy control group, the correlation are analyzed between TCM syndrome and MMP-9, TIMP-1, MMP-9/TIMP-1 in patients with early CKD. And further explore the relationship between TCM syndrome and ECM synthesis and degradation in renal fibrosis.ObjectiveInvestigate and characteristic analysis of TCM syndrome in CKD1-2 group and control group, the distribution of TCM syndromes in patients with CKD are obtained. Explore the correlation between TCM syndrome and MMP-9, TIMP-1, MMP-9/TIMP-1 in early-stage CKD patients based on Shenluozhengjia theory, and provide basis for clinical treatment of early CKD patients by using the "Ju" and "San" in Shenluozhengjia theory as the core clue.Methods57 patients with stage 1-2 CKD were collected, while 24 healthy adults were concluded as the control group. The general information, clinical data and morning urine samples of the two groups were collected. While urinary levels of MMP-9/TIMP-1, difference of MMP-9, TIMP-1, MMP-9/TIMP-1 between the two groups were analyzed. And correlation between TCM syndrome and MMP-9, TIMP-1, MMP-9/TIMP-1 were analyzed.Results1. Symptom survey:Common symptoms of early-stage CKD patients are aching pains of loins and spine, fatigue, dry mouth and throat, susceptible to cold, spontaneous sweating, eye dryness, depression, dizziness, night urination, bitter taste in mouth, cold pain in the lumbar spine, sigh, foreign body sensation in throat, no desire to speak and aversion to cold.2. Distribution of syndrome:early-stage CKD patients with deficiency syndrome:Qi deficiency of lung and kidney (71.9%); Deficiency of both qi and yin(35.1%); Qi deficiency of spleen and kidney(33.3%); Yang deficiency of spleen and kidney(29.8%); Liver and kidney yin deficiency(29.8%).early-stage CKD patients with sthenia syndrome:Depression of Qi (47.4%); Dampness syndrome(28.1%); Damp heat syndrome(28.1%) and Blood stasis syndrome(12.3%).3.Correlation between TCM syndromes and common clinical indexes:There is positive correlation between Qi deficiency of spleen and kidney, Yang deficiency of spleen, Kidney Damp heat syndrome or dampness syndrome and uRBC (P <0.05). While there is negative correlation between Qi deficiency of spleen and kidney, Qi deficiency of lung and kidney, Yang deficiency of spleen and kidney and eGFR (P< 0.05).4. Changes of MMP-9 and TIMP-1 in early-stage CKD patients:Urinary MMP-9 and TIMP-1 content in early-stage CKD patients are higher than the control group (P<0.01),while MMP-9/TIMP-1 ratio is lower than normal people significantly (P<0.01).5. Correlation between MMP-9, TIMP-1, MMP-9/TIMP-1 and clinical data:There is a positive correlation between Utimp-1 and Scr, while the correlation between MMP-9/TIMP-1 ratio and Scr is negative.the study also shows that the level of MMP-9 and TIMP-1 have a negative correlation with eGFR,while MMP-9/TIMP-1 ratio shows positive relationship with eGFR.(all P<0.05)6.Correlation between MMP-9、TIMP-1 MMP-9/TIMP-1 ratio and TCM syndromes:There is a positive correlation between MMP-9 and Qi deficiency of lung and kidney, Qi deficiency of spleen and kidney, deficiency of both qi and yin,Damp heat syndrome or dampness syndrome (P<0.05).and there is a positive correlation between TIMP-1 and Qi deficiency of lung and kidney, Qi deficiency of spleen and kidney or deficiency of both qi and yin, the differences were significant(P<0.05).The correlation between the MMP-9/TIMP-1 ratio and Qi deficiency of lung and kidney or Qi deficiency of spleen and kidney shows negative significantly(P<0.05).Conclusions1. Most of early-stage CKD patients with deficiency syndrome are "deficiency of both qi"or "deficiency of qi and yin". While most of early-stage CKD patients with sthenia syndrome are "depression syndrome".2. The degradation effect of MMP-9 on ECM is enhanced in the early stage of CKD, while the inhibitory-degradation effect of TIMP-1 is also enhanced. The effect of TIMP-1 on the inhibitory-degradation of ECM was greater than degradation effect of MMP-9.3. Excessive pathogen possibily related to compensatory increase of degradation effect of MMP-9 on ECM. The deficiency syndrome is involved in the whole process of ECM synthesis and degradation. The deficiency of qi may be an important factor leading to the enhancement in inhibitory effect of ECM degradation and the additional accumulation of ECM.