[ ABSTRACT] AIM:To investigate the effect of paricalcitol ( P) on renal tubulointerstitial fibrosis and the under-lying mechanisms in diabetic nephropathy ( DN) .METHODS:DN rat model was induced by a single intraperitoneal in-jection of streptozotocin after fasting.The animals were randomly divided into 2 groups: the DN rats in paricalcitol-inter-vened group ( group P) were injected intraperitoneally with paricalcitol dissolved in propylene glycol after the day when the model was induced successfully at a dose of 0.4μg/kg (3 times a week);the DN rats in DN group ( group D) were given isopyknic propylene glycol.Normal control group ( group C) was also set up.The samples of blood, urine and renal tissue were collected after intervention of paricalcitol for 12 weeks.The biochemical indexes were measured.The renal tissues were used for pathologic observation and determining the expression of transforming growth factor-β1 (TGF-β1), Wnt-4,β-catenin and Klotho by immunohistochemistry and Western blotting.In addition, the correlation among the above indexes was analyzed.RESULTS:(1) Scr, BUN and 24 h urine protein increased significantly in group D compared with group C, while decreased in group P compared with group D ( P<0.05 ) .( 2 ) The area of renal tubulointerstitial fibrosis in-creased in group D compared with group C, while decreased in group P compared with group D (P<0.05).(3) The ex-pression of Klotho decreased, while the expression of TGF-β1, Wnt-4 and β-catenin increased in group D compared with group C (P<0.05).Compared with group D, the expression of Klotho increased, while the expression of TGF-β1, Wnt-4 andβ-catenin decreased in group P (P<0.05).(4) The expression of Klotho was negatively correlated with the fibrosis area, TGF-β1, Wnt-4 andβ-catenin (P<0.05).CONCLUSION:Paricalcitol inhibits renal tubulointerstitial fibrosis in DN by promoting the expression of renal Klotho, and inhibiting Wnt/β-catenin signaling pathway activation and TGF-β1 synthesis.

ObjectiveTo study the effect of 1,25-(OH)2D3 analogs paricalcitol on proteinuriaindiabeticnephropathy (DN)rats, andtoinvestigateitspossiblemechanism.Methods DN model rats were established by intraperitoneal injection with streptozotocin.All the DN rats were randomly divided into the paricalcitol group(group P ) and DN group(group D).Healthy rats were chosen as healthy control group(group N).24-h urinary protein and serum biochemical indicators were examined after 12 weeks.ELISA was applied to detect the level of renin and Ang Ⅱ in the kidney.Immunohistochemistry and real-time PCR were used to detect the protein and mRNA expression of heparanases(HPA)and podoein.Results Compared with group N,24-h urinary protein,serum creatinine,renin and Ang Ⅱ in group D and group P were markedly increased,and they were significantly higher in group D as compared to group P (all P＜0.05).Compared with group N,the expression of HPA protein and mRNA in group D and group P increased markedly,and higher expression was found in group D(all P＜0.05).The expression of podocin protein and mRNA in group D and group P decreased markedly,and lower expression was found in group D(all P＜0.05).Renin level was positively correlated with HPA protein expression (r=0.78,P＜O.OS),negatively correlated with podocin protein expression(r=-0.63,P＜O.05),and not correlated with their mRNA expression.Conclusion Paricalcitol can significantly reduce the proteinuria,which may be associated with the inhibition of renin by down-regulating protein expression of HPAin glomerular basement membrane and up-regulating protein expression of podocin in podocyte.

Objective To build an antibody microarray based on direct labeling strategy for microalbnrninuria measurement, and evaluate it's technical potentiality for clinical application. Methods Urine samples of diabetic patients were collected. Antibody microarrays were constructed by preparation of array support, array fabrication, then protein assay and data analysis were performed. Procedure conditions for each step especially the labeling of samples were optimized. The set-ups were evaluated in terms of sensitivity, specificity and reproducibility. Urinary albumin excretion in the samples was detected by fabricated protein array, which was compared to that detected with immunoturbidimetry. Results The signal intensity was best when protein quality ratio of pure albumin or urine sample against NHS-biotin was 2:1. A calibration curve with a correlation coefficient of 0.9995 was established. The lower limit of detection was 0.0617 mg/L. Interehip and intrachip variation studies conducted on patient urine demonstrated CVs as 6.78%-9.22% and 3.35%-7.59%, respectively. Compared with the immunoturbidimetry, the antibody microarray was able to detect the extremely lower grade albumin in urine samples. The correlation coefficient of the results obtained by the two methods was 0.9199 (P <0.01). Conclusion An antibody microarray based on direct labeling strategy for microalbuminuria measurement is successfully established, which is comparable to immunoturbidimctry in its accuracy and will have great potential for clinical use with its high throughput, sensitivity, specifity and reproducibility.

Kidney disease affects a large number of people around the world, imposing a significant burden to people's health and life. If early prediction, rapid diagnosis and prognosis prediction of kidney disease can be carried out, the health of patients will be better protected. Machine learning belongs to the category of artificial intelligence, which can be divided into supervised learning, unsupervised learning and reinforcement learning. With the increasing requirements for the processing and analyzing large-scale and high-dimensional data, machine learning is playing an increasingly important role in the medical domain, and the field of kidney disease is no exception. This article presents a comprehensive overview of the application progress of machine learning in kidney disease, aiming to make medical staff's decision-making in kidney disease more early, accurate and rapid, and better escort the life and health of patients.
Humans ; Artificial Intelligence ; Machine Learning ; Kidney ; Kidney Diseases/diagnosis*

Objective: To evaluate the efficacy and safety of steroids-free immunosuppressive therapy including tacrolimus, cyclosporin A, tripterygium glycosides or intravenous cyclophosphamide in membranous nephropathy (MN) patients combined with type 2 diabetes mellitus (T2DM). Methods: This study was a retrospective analysis of patients with T2DM complicated with biopsy proved MN in the First Affiliated Hospital, College of Medicine, Zhejiang University from January 2009 to January 2017. The patients were divided into steroids-free group and control group. The patients in steroids-free group were treated with one or two immunosuppressive agents except glucocorticoids. The patients in control group were treated with glucocorticoid combining with immunosuppressive agents. Results: A total of 64 patients were enrolled in this study. There were 26 cases in steroids-free group and 38 cases in control group. The total remission rate was 69.24% in steroids-free group and 73.68% in control group at 12 months. In a median follow up of 33(12-106) months, two patients in control group entered hemodialysis and one of them died after 1 year of dialysis. One patient in steroids-free group died of accidental death and no patient entered dialysis. All patients in control group had elevated blood glucose level, whereas only 5 patients in steroids-free group had elevated blood glucose and all these 5 patients used tacrolimus. Conclusion Immunosuppressive regimen without glucocorticoid treatment can reduce side effects on blood glucose level in MN patients with type 2 diabetes, with a certain rate of treatment response.