Changes Of KLF9,KLF15,PGC-1? Expression In Patients With Kidney Disease Before And After Treatment With Glucocorticoid

Objective:As a commonly used treatment for glomerular disease,glucocorticoid(GC)is often used in a large dose and long-term therapeutic course,which may affect the glycometabolism in multiple ways and lead to steroid diabetes therefore.The purpose of this study was explore the role of KLF9?KLF15 and PGC-1? in the glycometabolism by detecting the expression level of the KLF9?KLF15 and PGC-1? m RNA of patients with kidney disease before and after they were treated with GC,and to provide a theoretical basis for the early prevention of GC-induced hyperglycemia and the treatment of steroid diabetes mellitus(SDM).Methods:The patients admitted to the Nephrology Department of the Second Affiliated Hospital of Dalian Medical University from 2016 October to 2017 January were enrolled.Inclusion criteria: Patients who were diagnosed as glomerular nephritis with indication for GC treatment.We ensure that they had never be treated with GC before or was not treated with GC in the last three months.We applied GC to them orally with full dose of GC during the initial stage of GC application(60mg prednison were taken at a draught at eight in the morning).Exclusion criteria:(1)Pregnant and lactating women;(2)Patients allergic to glucocorticoid;(3)Mental disorders;(4)Severe infection(viruses,bacteria,fungi and active tuberculosis,etc.);(5)Severe osteoporosis;(6)Diabetes mellitus,severe hypertension;(7)Glaucoma;(8)Gastric and duodenal ulcer active bleeding;(9)Family history of diabetes mellitus.Basic clinical information of all the research subjects,including gender,age,body mass index and so on were collected.Hemoglobin,albumin,triglyceride,cholesterol,low density lipoprotein-cholesterol,high density lipoprotein-cholesterol,serum creatinie,serum uric acid,urinary uric acid(24-hour)and urinary protein(24-hour)were assessed by autobiochemistry machine.Urine samples were evaluated by microscopy and urine analyzer techniques.Percutaneous renal biopsy was performed in each patient and slides were made from pathological sample specimens.Pathological observation by Light microscope and Immunofluorescence were then made by two senior pathologists in our department.The pathologists were unaware of the clinical information of the subjects and they carried out independent and unbiased examinations as far as possible.Electron microscope diagnosises were made by the Electron Microscope Room of XX Hospital.All statistical analyses were performed using SPSS 22.0.P values<0.05 were comsidered as statistically significant.Finally 7 patients met the criteria,the general clinical data of them were collected,including renal protopathy,age,gender,blood pressure,heart rate,BMI and so on.Blood glucose,blood lipids,urine protein,creatinine and other biochemical indexes were measured before the GC application.Blood samples were collected before the GC application and at hour 2,6 and 24 after the initial application of GC,from which a whole-blood RNA was extracted and reversely transcribed into c DNA,q PCR method was applied to detect the expression of KLF9?KLF15 and PGC-1? m RNA.These patients received a follow-up checkup to monitore the patient's condition and side effect of GC application,the level of fasting blood glucose and postprandial blood glucose of them were recorded two months after the GC application.Results : 1.This study included 7 patients,with their age ranging from 29 to 72years-old,54.00±15.07 years-old in average.6 of them are males(85.70%)while 1 of them is female(14.30%).There are 4 cases of membranous nephropathy(57.1%),2cases of minimal change disease(28.6%)and 1 case of mesangial proliferative glomerulonephritis(14.3%)among these patients.2.Observation of the KLF9 m RNA expression before and after GC application: compared with the pre-GC baseline level,the expression of the KLF9 m RNA elevated to some extent 2 hours after GC application,but the difference was not statistically significant(1.303±0.762 vs 1.000±0.000,P>0.05);while the expression level of KLF9 m RNA markedly elevated 6 hours after GC application,reaching the peak(1.887±0.956 vs 1.000±0.000,P<0.01),Since then,the expression level of KLF9 m RNA went down gradually,which came close to the baseline level 24 hours after GC application(1.070±0.579 vs 1.000±0.000,P>0.05)3.Observation of the KLF15 m RNA expression before and after GC application: compared with the pre-GC baseline level,the expression of the KLF15 m RNA elevated to some extent 2 hours after GC application,but the difference was not statistically significant(1.361±0.768 vs 1.000±0.000,P>0.05);while the expression level of the KLF15 m RNA markedly elevated 6 hours after GC application,reaching the peak(2.247±1.346 vs 1.000±0.000,P<0.01);Since then,the expression level of the KLF9 m RNA went gradually back to the level which was just slightly higher than the baseline(1.141±0.696 vs 1.000±0.000,P>0.05).4.Observation of the PGC-1? m RNA expression before and after GC application: similar to KLF9 and KLF15,the expression level of PGC-1? m RNA was elevated somewhat 2 hours after GC application as compared to the pre-GC baseline level,but the difference was not statistically significant(1.391±1.015 vs 1.000±0.000,P>0.05);The expression level of the PGC-1? m RNA markedly elevated 6 hours after GC application,reaching its peak(2.190±1.317 vs 1.000±0.000,P<0.01);Since then,its expression level went gradually back to the level which was just slightly higher than the baseline(1.139±0.676 vs 1.000±0.000,P>0.05).5.Follow-up checkup of Post-GC Blood glucose level: No abnormality in the patient's fasting and postprandial blood glucose level was found 2 months after GC application.Conclusion : The genetic expression levels of KLF9 ? KLF15 and PGC-1? can be up-regulated by glucocorticoid application,which reach their peaks 6 hours after the application and basically return to the normal level on hour 24.