Contribution to the Study of Diabetic Kidney Disease in a Sub-Saharan Environment: An Example of the Aristide Le Dantec University Hospital in Dakar

Introduction: Diabetic kidney disease (DKD) is a leading cause of chronic kidney disease and dialysis admission. Few studies are available in Sub-Saharan Africa. The objective of this work was to study the epidemiological, clinical, diagnostic and therapeutic characteristics of DKD in our context. Patients and Methods: We conducted an observational, exhaustive and retrospective study focusing on diabetic patients seen in consultation or hospitalized in the Nephrology Department of at the Aristide Le Dantec University Hospital in Dakar during a period of 5 years from January 1, 2017 to December 31, 2021. Results: Of 4735 patients seen during the study period, 491 had DKD, i.e. a hospital prevalence of 10.36%. The average age was 59.1 ± 11.4 years with a sex ratio of 0.95. Type 2 diabetes predominated with 93.4%. The average duration of diabetes was 11.5 ± 7.6 years. Diabetes was associated with high blood pressure in 78.81% of cases, dyslipidemia in 23.2% of cases, active smoking in 6.7% of cases and obesity in 1.6% of cases. Renal failure was the main reason for referral 72.3%. One hundred and forty-eight patients (30.1%) had uncontrolled diabetes. Macroalbuminuria was found in 64.8% and microalbuminuria in 18.7% of cases. One hundred and eighty-five patients (37.7%) were in Stage V of kidney disease and 137 patients were in Stage III (18.1% in Stage IIIb and 9.8% in Stage IIIa). Diabetic nephropathy was the main etiology at 61.30%. Nephropathy was mixed (diabetic and hypertensive) in 18.12 cases. Renin-angiotensin-aldosterone system (RAAS) blockers were prescribed in 83.5% of patients. Conclusion: The different etiologies encountered during the study show the diversity of diabetic kidney disease. Diabetic nephropathy is not the only kidney damage that can occur in diabetics in our context.

Identifying Biomarkers for Diabetic Kidney Disease Using GraphSAGE Neural Network

Diabetic Kidney Disease (DKD) is a common chronic complication of diabetes. Despite advancements in accurately identifying biomarkers for detecting and diagnosing this harmful disease, there remains an urgent need for new biomarkers to enable early detection of DKD. In this study, we modeled publicly available transcriptome datasets as a graph problem and used GraphSAGE Neural Networks (GNNs) to identify potential biomarkers. The GraphSAGE model effectively learned representations that captured the intricate interactions, dependencies among genes, and disease-specific gene expression patterns necessary to classify samples as DKD and Control. We finally extracted the features of importance;the identified set of genes exhibited an impressive ability to distinguish between healthy and unhealthy samples, even though these genes differ from previous research findings. The unexpected biomarker variations in this study suggest more exploration and validation studies for discovering biomarkers in DKD. In conclusion, our study showcases the effectiveness of modeling transcriptome data as a graph problem, demonstrates the use of GraphSAGE models for biomarker discovery in DKD, and advocates for integrating advanced machine-learning techniques in DKD biomarker research, emphasizing the need for a holistic approach to unravel the intricacies of biological systems.

加减猪苓汤治疗糖尿病肾病Ⅳ期的临床观察及对尿AQP2的影响

目的探讨加减猪苓汤治疗糖尿病肾病(diabetic kidney disease,DKD)Ⅳ期的临床疗效及对尿水通道蛋白2(Aquaporin2,AQP2)的影响。方法临床采用辨证属阴虚水肿型DKDⅣ期样本50例,随机分为治疗组25例和对照组25例,所有病例均进行常规降糖药控制血糖、低盐、优质低蛋白、低脂饮食、控制血压和运动指导等一般治疗。对照组口服厄贝沙坦片150 mg/d,治疗组在上述治疗基础上,加用加减猪苓汤,6周后比较治疗前后两组24尿蛋白定量、肝肾功能、糖化血红蛋白、血糖、中医症候积分情况等,同时分别在第1、3、6周末检测两组尿AQP2表达。结果治疗6周后,两组中医症候积分、24 h尿蛋白定量、血浆白蛋白、血肌酐及均较治疗前有所改善,差异有统计学意义(P<0.05),且治疗组优于对照组(P<0.05),治疗组尿AQP2在第3周及第6周均表达高于第1周(P<0.05),且高于对照组(P<0.05)。结论猪苓汤猪苓汤治疗DKDⅣ期的患者可减少尿蛋白、改善肾功能及减少中医症候积分,同时提高尿中AQP2表达,延缓DKD的进展。

Losartan Protects Podocytes against High Glucose-induced Injury by Inhibiting B7-1 Expression

The role of B7-1 in podocyte injury has received increasing attention.The aim of this study was to investigate whether losartan protects podocytes of patients with diabetic kidney disease(DKD)by regulating B7-1 and the underlying mechanisms.Rats with streptozotocin-induced DKD were treated with losartan for 8 weeks.Biochemical changes in blood and urine were analyzed.Kidneys were isolated for electron microscopy,immunofluorescence,real-time quantitative PCR(RT-PCR),and Western blot analysis.Immortalized mouse podocyte cells were cultured in normal or high glucose medium in the presence or absence of losartan for 48 h,and then the cells were collected for immunofluorescence,PCR,Western blotting and monolayer permeability detection.The phosphatidylinositol 3-kinase(PI3K)110a subunit and angiotensin II type 1 receptor(AT1R)plasmids were transfected into podocytes,respectively,and then Western blotting was performed to assess the expression of B7-1 protein.The results showed that losartan ameliorated podocyte structure and function in the rat model of DKD,and reduced the expression of B7-1 protein.Overexpression of PI3K 110a subunit in podocytes attenuated the inhibitory effect of losartan on B7-1 expression in high glucose-stimulated podocytes.The expression of B7-1 was significantly increased by overexpression of ATI R and significantly reduced by blocking PI3K 110a subunit.We conclude that losartan protects podocytes against high glucose-induced injury by inhibiting AT1R-mediated B7-1 expression.This effect is dependent on the AT1R-PI3K 110a subunit pathway.

Qianjin Wenwu decoction suppresses renal interstitial fibrosis by enhancing the degradation of extracellular matrix in mice with unilateral ureteral obstruction

Diabetic kidney disease(DKD)is the most common complication of diabetes mellitus(DM).Qianjin Wenwu decoction(QWD),a well-known traditional Korean medicine,has been used for the treatment of DKD,with satisfactory therapeutic effects.This study was designed to investigate the active components and mechanisms of action of QWD in the treatment of DKD.The results demonstrated that a total of 13 active components in five types were found in QwD,including flavonoids,flavonoid glycosides,phenylpropionic acids,saponins,coumarins,and lignins.Two key proteins,TGF-β1 and TIMP-1,were identified as the target proteins through molecular docking.Furthermore,QWD significantly suppressed Scr and BUN levels which increased after unilateral ureteral obstruction(UUO).Hematoxylin&eosin(H&E)and Masson staining results demonstrated that QWD significantly alleviated renal interstitial fibrosis in UUO mice.We also found that QWD promoted ECM degradation by regulating MMP-9/TIMP-1 homeostasis to improve renal tubulointerstitial fibrosis and interfere with the expression and activity of TGF-βl in DKD treatment.These findings explain the underlying mechanism of QWD for the treatment of DKD,and also provide methodological reference for investigating the mechanism of traditional medicine in the treatment of DKD.