Effect Of Ursodeoxycholic Acid On Patients With Early Diabetic Nephropathy

Background and Objective:Diabetic nephropathy(DN)is one of the major complications that are gradually forming along with the continuous development of diabetes mellitus(DM).It is the main cause of the end stage renal failure caused by diabetes.Epidemiological survey data show that with the increasing incidence of diabetes,the high mortality rate rising rapidly in patients with diabetic nephropathy.The data show that more than 30% of the diabetic patients develop into clinical diabetic nephropathy at 10-20 years’ course of disease.However,the pathogenesis of diabetic nephropathy is still unclear,and the effective measures to treat and delay the progress have been lacking.In addition to lower blood sugar,we can only treat related risk factors such as hypertension,hyperlipidemia and so on,even if the drug angiotensin converting enzyme inhibitor(Renin-angiogenin-system inhibitors,RASI)recommended by the K/DOQI,the effect is to reduce proteinuria and retard the rate of decline in renal function,but there are high risk of hyperkalemia and acute kidney injury,it is inconvenience to clinical.The study found that the inflammatory cascade reaction mediated by endoplasmic reticulum stress is an important pathogenesis of diabetic nephropathy,using molecular chaperones of endoplasmic reticulum stress regulation can effectively reduce the urinary protein excretion of diabetic nephropathy rats.And regulation of endoplasmic reticulum stress may be an important drug targets for the treatment of diabetic nephropathy.Ursodeoxycholic acid is the main component of bear’s pharmacological effects,recent studies have found that UDCA is a kind of natural molecular chaperones help endoplasmic reticulum protein folding,can effectively control the endoplasmic reticulum stress ability,including not only reduce the inflammation of endoplasmic reticulum stress and apoptosis signal coupling activation,and increase the effective transmission of XBP1 signal pathway-insulin metabolism.The purpose of this study is to observe the clinical efficacy of ursodeoxycholic acid in the treatment of phase III patients with diabetic nephropathy,and to provide clues for finding new ways to treat diabetic nephropathy.Methods:From May 2016 to December 2016,a total of 40 patients with early DN(Mogensen stage Ⅲ)were diagnosed in the Nephrology Department of Xinqiao Hospital,aged 30 to 59 years,were divided into 2 groups: irbesartan treatment group.Irbesartan Tablets oral 0.15g/1 day;UDCA treatment group,UDCA capsule(after),250mg/1 day.The levels of urinary microalbumin,urinary albumin/creatinine ratio,creatinine,and estimated glomerular filtration rate(eGFR),and the contents of inflammatory cytokines in blood were measured or calculated before and in 12 months after treatment,and the results were compared between the 2 groups.The study was approved by the Second Affiliated Hospital of the Army Military Medical University Ethics Committee(Approval no.yan di2018-056-01).Result:1.There was no difference in the age,duration of diabetes,protein creatinine ratio,eGFR between the two groups.After the treatment,the urinary albumin,serum creatinine,protein creatinine ratio decreased,eGFR increased in the irbesartan group,compared with before treatment,the differences were statistically significant(P<0.05);urinary albumin,protein creatinine ratio and serum creatinine decreased,eGFR increased in the UDCA group,compared with before treatment,the differences were statistically significant(p<0.05).However,there was no significant difference in the differences between the two groups(p> 0.05).2.In the Irbesartan group,the white blood cell(WBC)and blood potassium increased slightly,while the number of red blood cells(RBC)decreased slightly,but in the normal range.After the treatment of ursodeoxycholic acid(UDCA)group,the number of blood white blood cells(WBC)and blood potassium were slightly elevated,and the difference was statistically significant(p<0.05).Changes of ALT and AST were no significant in two groups after treatment.3.The patients in group UDCA had no palpitations,chest pain,dizziness and other obvious heart and brain discomfort during the treatment.Only in the initial stage of treatment,2 patients had mild diarrhea,but they all disappeared after treatment and continued to adhere to the treatment.4.Level of serum CRP,IL-6,TNF-? of group with therapy of aprovel were respectively decreased by 13.7% 、 8.7% 、 5.9%,significant difference was noted after treatment(p<0.05);level of serum CRP,IL-6,TNF-? of group with therapy of ursodeoxycholic acid were respectively decreased by 16.2%,14.1%,16.8%,significant difference was noted after treatment(p<0.05).But no significant difference was observed between two groups in the serum(P>0.05).Conclusions:Ursodeoxycholic acid can significantly reduce urinary albumin excretion in patients with diabetic nephropathy and protect the renal function,which is quite effective with angiotensin converting enzyme inhibitors.This protective effect may be associated with the inhibition of inflammatory reactions in the kidneys.