scholarly journals Impact of Diabetic Stress Conditions on Renal Cell Metabolome

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1141 ◽  
Author(s):  
Lagies ◽  
Bork ◽  
Kaminski ◽  
Troendle ◽  
Zimmermann ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Cell Lines ◽  
Diabetic Kidney Disease ◽  
Collecting Duct ◽  
Stress Conditions ◽  
Proximal Tubular Cells ◽  
Diabetic Kidney ◽  
Tubular Cells ◽  
Proximal Tubular

Diabetic kidney disease is a major complication in diabetes mellitus, and the most common reason for end-stage renal disease. Patients suffering from diabetes mellitus encounter glomerular damage by basement membrane thickening, and develop albuminuria. Subsequently, albuminuria can deteriorate the tubular function and impair the renal outcome. The impact of diabetic stress conditions on the metabolome was investigated by untargeted gas chromatography–mass spectrometry (GC-MS) analyses. The results were validated by qPCR analyses. In total, four cell lines were tested, representing the glomerulus, proximal nephron tubule, and collecting duct. Both murine and human cell lines were used. In podocytes, proximal tubular and collecting duct cells, high glucose concentrations led to global metabolic alterations in amino acid metabolism and the polyol pathway. Albumin overload led to the further activation of the latter pathway in human proximal tubular cells. In the proximal tubular cells, aldo-keto reductase was concordantly increased by glucose, and partially increased by albumin overload. Here, the combinatorial impact of two stressful agents in diabetes on the metabolome of kidney cells was investigated, revealing effects of glucose and albumin on polyol metabolism in human proximal tubular cells. This study shows the importance of including highly concentrated albumin in in vitro studies for mimicking diabetic kidney disease.

scholarly journals A Vaspin–HSPA1L complex protects proximal tubular cells from organelle stress in diabetic kidney disease

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Atsuko Nakatsuka ◽  
Satoshi Yamaguchi ◽  
Jun Eguchi ◽  
Shigeru Kakuta ◽  
Yoichiro Iwakura ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Obese Mice ◽  
Proximal Tubular Cells ◽  
Diabetic Kidney ◽  
Tubular Cells ◽  
Extracellular Release ◽  
Proximal Tubular ◽  
Visceral Adipose ◽  
Glucose Regulated Protein

AbstractProximal tubular cells (PTCs) are crucial for maintaining renal homeostasis, and tubular injuries contribute to progression of diabetic kidney disease (DKD). However, the roles of visceral adipose tissue-derived serine protease inhibitor (vaspin) in the development of DKD is not known. We found vaspin maintains PTCs through ameliorating ER stress, autophagy impairment, and lysosome dysfunction in DKD. Vaspin−/− obese mice showed enlarged and leaky lysosomes in PTCs associated with increased apoptosis, and these abnormalities were also observed in the patients with DKD. During internalization into PTCs, vaspin formed a complex with heat shock protein family A (Hsp70) member 1 like (HSPA1L) as well as 78 kDa glucose-regulated protein (GRP78). Both vaspin-partners bind to clathrin heavy chain and involve in the endocytosis. Notably, albumin-overload enhanced extracellular release of HSPA1L and overexpression of HSPA1L dissolved organelle stresses, especially autophagy impairment. Thus, vapsin/HSPA1L-mediated pathways play critical roles in maintaining organellar function of PTCs in DKD.

scholarly journals (−)-Epicatechin and the colonic metabolite 2,3-dihydroxybenzoic acid protect against high glucose and lipopolysaccharide-induced inflammation in renal proximal tubular cells through NOX-4/p38 signalling

2020 ◽  
Vol 11 (10) ◽  
pp. 8811-8824
Author(s):  
David Álvarez Cilleros ◽  
María Elvira López-Oliva ◽  
María Ángeles Martín ◽  
Sonia Ramos
Keyword(s):  
Kidney Disease ◽  
High Glucose ◽  
Diabetic Kidney Disease ◽  
Dihydroxybenzoic Acid ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Chronic Hyperglycaemia

Chronic hyperglycaemia and inflammation are present in diabetes and both processes have been related to the pathogenesis of diabetic kidney disease.

MO021ENHANCED MCP-1 RELEASE IN EARLY AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Peter Janssens ◽  
Jean-Paul Decuypere ◽  
Stéphanie De Rechter ◽  
Luc Breysem ◽  
Dorien Van Giel ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Autosomal Dominant ◽  
Collecting Duct ◽  
Polycystic Kidney ◽  
Proximal Tubular Cells ◽  
Early Disease ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Collecting Duct Cells ◽  
Autosomal Dominant Polycystic Kidney

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in either the PKD1 or PKD2 gene. While kidney failure typically occurs in adulthood, the disease starts in utero. The best change of preserving renal function long term might be the use of agents with few side effects as early as possible. For this approach, both better early prognostic stratification and novel treatment options are needed. The pediatric phase of ADPKD, while kidney function is still normal and before significant tissue destruction has occurred could be the best stage both to identify and study prognostic biomarkers as well as to identify novel targets for early treatment. Copeptin (a surrogate for vasopressin), epidermal growth factor (EGF) ( a measure for functional tubular mass) and monocyte chemoattractant protein-1 (MCP-1) ( a chemoattractant for macrophages) are associated with severity and hold prognostic value in adults but remain unstudied in the early disease stage. Kidneys from adults with ADPKD exhibit macrophage infiltration, and a prominent role of MCP-1 secretion by tubular epithelial cells is suggested from rodent models. Method A monocentric cross-sectional study in a tertiary referral center was performed. All consenting genotyped ADPKD patients attending the outpatient pediatric ADPKD clinic of the university hospital of Leuven and age, sex and BMI matched healthy controls were included between June and October 2017. Plasma copeptin, urinary EGF and urinary MCP-1 were evaluated. MCP-1 was studied in mouse collecting duct cells, human proximal tubular cells and fetal kidney tissue. Results 53 genotyped ADPKD patients and 53 controls were included. Mean (SD) age was 10.4 (5.9) vs 10.5 (6.1) years (P=0.543), and eGFR 122.7 (39.8) vs 114.5 (23.1) ml/min/1.73 m2 (P= 0.177) in patients vs controls respectively. Outcome parameters in table. Plasma copeptin and EGF secretion were comparable between both groups. Median (IQR) urinary MCP-1 (pg/mg creatinine) was significantly higher in ADPKD patients (185.4 (213.8)) compared to controls (154.7 (98.0)) (P= 0.010). Human proximal tubular cells with a heterozygous PKD1 mutation and mouse collecting duct cells with a PKD1 knockout exhibited increased MCP-1 secretion triggered by fetal bovine serum. Human fetal ADPKD kidneys displayed prominent MCP-1 immunoreactivity and M2 macrophage infiltration. Conclusion An increase in tubular MCP-1 secretion is an early event in ADPKD, long before kidney function decline and in children with few kidney cysts. MCP-1 is a promising early disease severity marker and a potential treatment target.

scholarly journals Early Renoprotective Effect of Ruxolitinib in a Rat Model of Diabetic Nephropathy

2021 ◽  
Vol 14 (7) ◽  
pp. 608
Author(s):  
Mohamed M. El-Kady ◽  
Reham A. Naggar ◽  
Maha Guimei ◽  
Iman M. Talaat ◽  
Olfat G. Shaker ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Rat Model ◽  
Diabetic Kidney Disease ◽  
Tubulointerstitial Fibrosis ◽  
Favorable Effect ◽  
Glomerular Sclerosis ◽  
Diabetic Kidney ◽  
Renoprotective Effect ◽  
Tgf Β1

Diabetic kidney disease (DKD) is still one of the unresolved major complications of diabetes mellitus, which leads ultimately to end-stage renal disease in both type 1 and type 2 diabetes patients. Available drugs that suppress the renin–angiotensin system have partially minimized the disease impact. Yet, there is an unmet need for new therapeutic interventions to protect the kidneys of diabetic patients. In DN, glomerular sclerosis and tubulointerstitial fibrosis are mediated through several pathways, of which JAK/STAT is a key one. The current study explored the potential renoprotective effect of the JAK1/JAK2 inhibitor ruxolitinib (at doses of 0.44, 2.2, and 4.4 mg·kg−1) compared to that of enalapril at a dose of 10 mg·kg−1, in a rat model of streptozotocin-induced diabetes mellitus over 8 weeks. The effect of ruxolitinib was assessed by determining urinary albumin/creatinine ratio, serum level of cystatin, and levels of TGF-β1, NF-κB, and TNF-α in renal tissue homogenates by biochemical assays, the glomerular sclerosis and tubulointerstitial fibrosis scores by histological analysis, and fibronectin, TGF-β1, and Vimentin levels by immunohistochemical staining with the respective antibodies. Our results revealed a significant early favorable effect of a two-week ruxolitinib treatment on the renal function, supported by a decline in the proinflammatory biomarkers of DKD. This pre-clinical study suggests that the renoprotective effect of ruxolitinib in the long term should be investigated in animals, as this drug may prove to be a potential option for the treatment of diabetic kidney disease.

scholarly journals Diabetic kidney disease in patients with type 2 diabetes mellitus: a cross-sectional study

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Randa I. Farah ◽  
Mohammed Q. Al-Sabbagh ◽  
Munther S. Momani ◽  
Asma Albtoosh ◽  
Majd Arabiat ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Laboratory Data ◽  
Cross Sectional Study ◽  
Sectional Study ◽  
Cross Sectional ◽  
Diabetic Kidney ◽  
Type 2 Dm

Abstract Aim Diabetic kidney disease (DKD) is a major long-term complication of diabetes mellitus (DM). Given the paucity of data on DKD in Jordan, we aimed to evaluate the prevalence, characteristics and correlates of DKD in Jordanian patients with type 2 DM. Methods This cross-sectional study included 1398 adult patients with type 2 DM who sought medical advice in the endocrinology clinic between March and September 2019. Demographic, clinical and laboratory data were reviewed. DKD was defined as reduced eGFR, and/or albuminuria. Three regression models were constructed to identify factors associated with CKD stages, albuminuria and DKD. Results Overall, 701 (50.14%) patients had DKD, with a median age of 59.71 ± 11.36  years. Older age, high triglycerides, and low high-density lipoprotein were associated with DKD (multivariable odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01–1.03, p < 0.01; OR: 1.1, 95% CI: 1.01–1.2; and OR: 0.98, 95% CI: 0.97–0.99, p < 0.01 respectively). Metformin and renin-angiotensin system blockers were negatively associated with albuminuria and chronic kidney disease stages (p < 0.01). Conclusion Our study demonstrated that approximately one half of patients with type 2 DM had DKD. Further studies are necessary to understand this high prevalence and the underlying factors. Future research are needed to assess implementing targeted community-based intervention.

scholarly journals Diabetic Kidney Disease in Childhood and Adolescence: Conventional and Novel Renoprotective Strategies

2020 ◽  
pp. 68-77
Author(s):  
Samuel N Uwaezuoke ◽  
Adaeze C Ayuk
Keyword(s):  
Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Microvascular Complications ◽  
Clinical Syndrome ◽  
Clinical Staging ◽  
Childhood And Adolescence ◽  
Diabetic Kidney ◽  
Haemodynamic Changes ◽  
End Stage

Diabetic kidney disease (DKD) is defined as a clinical syndrome consisting of persistent macroalbuminuria, progressive decline in glomerular filtration rate (GFR), hypertension, increased cardiovascular disease events, and the associated mortality of these conditions. The disease evolves from the microvascular complications of poorly controlled Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM). The pathogenic pathways comprise renal haemodynamic changes, ischaemia and inflammation, and overactive renin–angiotensin–aldosterone system (RAAS), through which several events cascade down from hyperglycaemia to renal fibrosis. Conventional and novel renoprotective strategies target modifiable DKD risk factors and specific stages of the pathogenic pathways, respectively. Although these strategies may slow DKD progression to end-stage kidney disease (ESKD), novel drugs are still undergoing trials for validation in human participants. This narrative review appraises these renoprotective strategies and highlights the current clinical staging and pathogenesis of the disease.

scholarly journals Association Between Classical and Emerging Risk Factors for Diabetic Kidney Disease and Albuminuria in a Cohort of Type 2 Diabetes Mellitus Patients

2021 ◽  
Vol 18 (3) ◽  
pp. 17-25
Author(s):  
Stoiţă Marcel ◽  
Popa Amorin Remus
Keyword(s):  
Diabetes Mellitus ◽  
Risk Factors ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Significant Positive Association ◽  
Diabetic Kidney

Abstract The presence of albuminuria in patients with type 2 diabetes mellitus is a marker of endothelial dysfunction and also one of the criteria for diagnosing diabetic kidney disease. The present study aimed to identify associations between cardiovascular risk factors and renal albumin excretion in a group of 218 patients with type 2 diabetes mellitus. HbA1c values, systolic blood pressure, diastolic blood pressure were statistically significantly higher in patients with microalbuinuria or macroalbuminuria compared to patients with normoalbuminuria (p <0.01). We identified a statistically significant positive association between uric acid values and albuminuria, respectively 25- (OH)2 vitamin D3 deficiency and microalbuminuria (p <0.01).

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