scholarly journals Pathogenic Pathways and Therapeutic Approaches Targeting Inflammation in Diabetic Nephropathy

2020 ◽  
Vol 21 (11) ◽  
pp. 3798 ◽  
Author(s):  
Sandra Rayego-Mateos ◽  
José Luis Morgado-Pascual ◽  
Lucas Opazo-Ríos ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Intracellular Signaling ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Number Of Patients ◽  
Close Relationship ◽  
Stage Renal Disease ◽  
End Stage ◽  
Inflammatory Molecules

Diabetic nephropathy (DN) is associated with an increased morbidity and mortality, resulting in elevated cost for public health systems. DN is the main cause of chronic kidney disease (CKD) and its incidence increases the number of patients that develop the end-stage renal disease (ESRD). There are growing epidemiological and preclinical evidence about the close relationship between inflammatory response and the occurrence and progression of DN. Several anti-inflammatory strategies targeting specific inflammatory mediators (cell adhesion molecules, chemokines and cytokines) and intracellular signaling pathways have shown beneficial effects in experimental models of DN, decreasing proteinuria and renal lesions. A number of inflammatory molecules have been shown useful to identify diabetic patients at high risk of developing renal complications. In this review, we focus on the key role of inflammation in the genesis and progression of DN, with a special interest in effector molecules and activated intracellular pathways leading to renal damage, as well as a comprehensive update of new therapeutic strategies targeting inflammation to prevent and/or retard renal injury.

scholarly journals Revisiting Experimental Models of Diabetic Nephropathy

2020 ◽  
Vol 21 (10) ◽  
pp. 3587
Author(s):  
Anna Giralt-López ◽  
Mireia Molina-Van den Bosch ◽  
Ander Vergara ◽  
Clara García-Carro ◽  
Daniel Seron ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Kidney Disease ◽  
Experimental Models ◽  
Diabetic Patients ◽  
Rodent Models ◽  
Basement Membrane Thickening ◽  
Matrix Expansion ◽  
Risk Biomarkers ◽  
Stage Renal Disease ◽  
End Stage

Diabetes prevalence is constantly increasing and, nowadays, it affects more than 350 million people worldwide. Therefore, the prevalence of diabetic nephropathy (DN) has also increased, becoming the main cause of end-stage renal disease (ESRD) in the developed world. DN is characterized by albuminuria, a decline in glomerular filtration rate (GFR), hypertension, mesangial matrix expansion, glomerular basement membrane thickening, and tubulointerstitial fibrosis. The therapeutic advances in the last years have been able to modify and delay the natural course of diabetic kidney disease (DKD). Nevertheless, there is still an urgent need to characterize the pathways that are involved in DN, identify risk biomarkers and prevent kidney failure in diabetic patients. Rodent models provide valuable information regarding how DN is set and its progression through time. Despite the utility of these models, kidney disease progression depends on the diabetes induction method and susceptibility to diabetes of each experimental strain. The classical DN murine models (Streptozotocin-induced, Akita, or obese type 2 models) do not develop all of the typical DN features. For this reason, many models have been crossed to a susceptible genetic background. Knockout and transgenic strains have also been created to generate more robust models. In this review, we will focus on the description of the new DN rodent models and, additionally, we will provide an overview of the available methods for renal phenotyping.

scholarly journals Development of Biomarkers and Molecular Therapy Based on Inflammatory Genes in Diabetic Nephropathy

2021 ◽  
Vol 22 (18) ◽  
pp. 9985
Author(s):  
Amit K. Maiti
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Therapy ◽  
Renal Physiology ◽  
Complex Nature ◽  
Diabetic Patients ◽  
Renal Tubules ◽  
Stage Renal Disease ◽  
End Stage ◽  
Inflammatory Molecules

Diabetic Nephropathy (DN) is a debilitating consequence of both Type 1 and Type 2 diabetes affecting the kidney and renal tubules leading to End Stage Renal Disease (ESRD). As diabetes is a world epidemic and almost half of diabetic patients develop DN in their lifetime, a large group of people is affected. Due to the complex nature of the disease, current diagnosis and treatment are not adequate to halt disease progression or provide an effective cure. DN is now considered a manifestation of inflammation where inflammatory molecules regulate most of the renal physiology. Recent advances in genetics and genomic technology have identified numerous susceptibility genes that are associated with DN, many of which have inflammatory functions. Based on their role in DN, we will discuss the current aspects of developing biomarkers and molecular therapy for advancing precision medicine.

scholarly journals Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Kidney Injury ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Zucker Diabetic Fatty Rats ◽  
Kidney Injury Molecule 1 ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

Podocalyxin as an early marker predicting diabetic nephropathy and its correlation with stages of diabetic nephropathy in type two diabetic patients

QJM ◽  
2021 ◽  
Vol 114 (Supplement_1) ◽  
Author(s):  
Salah El-Din A Shelbaya ◽  
Hanan M Ali ◽  
Rana H Ibrahim ◽  
Nourhan Safwat Sawirs
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Control Group ◽  
Diabetic Patients ◽  
Type 2 Dm ◽  
Stage Renal Disease ◽  
End Stage ◽  
Positive Significant Correlation

Abstract Background Nephropathy, a major complication of diabetes, is the leading cause of end-stage renal disease. Early identification of nephropathy in diabetes patients is crucial because it creates opportunity for preventing the incidence of DN and/or even slows down the process of end-stage renal disease attributed to diabetes. Human podocytes (Pods) have been demonstrated to be functionally and structurally injured in the natural history of diabetic nephropathy. Aim of the Work To evaluate the possible association between the urinary podocalyxin levels and severity and grade of diabetic nephropathy and to use urinary podocalyxin as a non-invasive marker for early stage of diabetic nephropathy in type 2 DM. Patients and Methods We collected 60 known clinically and biochemically type 2 diabetic patients.20 diabetic patients with no evidence of diabetic nephropathy, 20 patients diagnosed as diabetic nephropathy in microalbuminuria stages and 20 patients diagnosed as diabetic nephropathy in macroalbuminuria stages from Ain Shams University hospitals between April and December 2018 and 20 apparently healthy volunteers will included as a control group. Results Urinary PCX was significantly higher in patients group compared to control group. Urinary PCX was significantly higher in microalbuminuric group than in normoalbuminuric group and higher in macroalbuminuric group than in microalbuminuric group. There was a positive significant correlation between FBS, 2HrPP, HBA1C and urinary PCX. There was a positive significant correlation between s.create and urinary PCX. There was a positive significant correlation between ACR and urinary PCX. Conclusion Urinary podocalyxin seems to be beneficial as an early marker for early stages of diabetic nephropathy in type 2 DM patients.

Experience with Continuous Ambulatory Peritoneal Dialysis in Belgium

1980 ◽  
Vol 1 (5) ◽  
pp. 54-58 ◽  
Author(s):  
Norbert H. Lameire ◽  
Marc De Paepe ◽  
Raymond Vanholder ◽  
Johan Verbanck ◽  
Severin Ringoir
Keyword(s):  
Peritoneal Dialysis ◽  
Continuous Ambulatory Peritoneal Dialysis ◽  
Average Rate ◽  
Sodium Concentration ◽  
Risk Category ◽  
Diabetic Patients ◽  
Serum Triglycerides ◽  
Number Of Patients ◽  
Stage Renal Disease ◽  
End Stage

This paper has reviewed experience in Belgium with 99 patients on CAPD. They represent 6-7% of all dialysis patients in this country. The principle reasons for selecting CAPD were old age, problems with vascular access and major cardiovas cular complications. Hemoglobin and hematrocrit values increased in all patients but preliminary measurements of red cell volume in some of them showed no change. Most patients showed moderate increases in serum triglycerides. In three non-diabetic patients with marked elevation in triglyceride levels, insulin, given intraperitoneally, prevented further increases. The frequency of peritonitis was still high; the average rate was one episode every 7.6 patient months. Other major complications included hypotension, which improved after the substitution of dialysate with a higher sodium concentration, severe respiratory disease and gangrene of the legs. After a mean follow-up of seven months, the death rate was 18% and the rate of technical success was 70%. The fact that most of our patients were in the high-risk category should be kept in mind when comparing these results with those obtained with other modes of treatment. At the end of 1978, a total of 1195 patients with end-stage renal disease (ESRD) were treated on either home or hospital dialysis in Belgium. There were 50 dialysis centers for a total population of 9.8 million. Of these 1195 patients, only seven were treated with either continuous ambulatory peritoneal dialysis (2-4) or intermittent peritoneal dialysis. Since then and until July 1, 1980 the number of patients treated with CAPD in Belgium has increased to 99 and this paper describes our experience with these patients.

scholarly journals Mini-review: diabetic renal complications, a potential stinky remedy

2016 ◽  
Vol 310 (2) ◽  
pp. F119-F122 ◽  
Author(s):  
Utpal Sen ◽  
Sathnur Pushpakumar
Keyword(s):  
Therapeutic Potential ◽  
Vascular Complications ◽  
Vital Role ◽  
Diabetic Patients ◽  
Diabetic Vascular Complications ◽  
Number Of Patients ◽  
Matrix Metabolism ◽  
Artery Disease ◽  
Stage Renal Disease ◽  
End Stage

Chronic kidney disease is associated with vasculitis and is also an independent risk factor for peripheral vascular and coronary artery disease in diabetic patients. Despite optimal management, a significant number of patients progress toward end-stage renal disease (ESRD), a suggestion that the disease mechanism is far from clear. A reduction in hydrogen sulfide (H2S) has been suggested to play a vital role in diabetic vascular complications including diabetic nephropathy (DN). This mini-review highlights the recent findings on the role of H2S in mitigating abnormal extracellular matrix metabolism in DN. A discussion on the development of the newer slow-releasing H2S compounds and its therapeutic potential is also included.

scholarly journals Diabetic nephropathy as a cause of end-stage renal disease in Egypt: a six-year study

2004 ◽  
Vol 10 (4-5) ◽  
pp. 620-626 ◽  
Author(s):  
A. Afifi ◽  
M. El Setouhy ◽  
M. El Sharkawy ◽  
M. Ali ◽  
H. Ahmed ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Large Scale ◽  
Cross Sectional Study ◽  
Diabetic Patients ◽  
Cross Sectional ◽  
Stage Renal Disease ◽  
End Stage ◽  
Esrd Patients

The prevalence of diabetic nephropathy as a cause of end-stage renal disease [ESRD] in Egypt has been examined in small cross-sectional studies, with conflicting results. The need for a large-scale study prompted us to perform this 6-year multiple cross-sectional study. A sample of ESRD patients enrolled in the Egyptian renal data system was evaluated during the period 1996-2001 for the prevalence of diabetic nephropathy. Prevalence gradually increased from 8.9% in 1996, to 14.5% in 2001. The mean age of patients with diabetic nephropathy was significantly higher than that of patients with ESRD from other causes. Mortality was also significantly higher in diabetic patients with ESRD

scholarly journals Endothelin Receptor Antagonists in Diabetic Nephropathy

2010 ◽  
Vol 8 (1) ◽  
pp. 32
Author(s):  
René R Wenzel ◽  
Eberhard Ritz ◽  
Maximilian Q Wenzel ◽  
◽  
◽  
...  
Keyword(s):  
Clinical Trials ◽  
Diabetic Nephropathy ◽  
Collecting Duct ◽  
Water Excretion ◽  
Beneficial Effects ◽  
Subtype B ◽  
Microvascular Architecture ◽  
High Doses ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease and affects an estimated 150 million people worldwide. Despite optimal treatment, including glycaemic control and antihypertensive therapy (e.g., renin–angiotensin–aldosterone system [RAS] blockade), the disease progresses. A ‘late escape’ phenomenon has been described, where proteinuria reappears despite continued RAS blockade. The endothelin (ET) system is strongly involved in the pathophysiology of the disease and contributes to vasoconstriction, inflammation and proliferation. ET antagonists are promising drugs that potently slow down disease progression in animal models and have beneficial effects on cardiac structure, mitochondrial damage and microvascular architecture. However, the available ET antagonists, at least in higher doses, may also inhibit tubular endothelin receptors subtype B, which promote sodium and water excretion. The three clinical trials with avosentan and atrasentan published so far show the unique nephroprotective effects of these drugs, with a reduction of up to 45 % in albuminuria. However, fluid retention, oedema and, in higher stages of chronic kidney disease, heart failure limit their use. The reason may be that we have been using too high doses of these ET antagonists so far and they are inhibiting tubular sodium and water excretion. Thus, we will need to learn more about the role of ET and its antagonists in the tubular and collecting duct system, and on how to use these potent drugs in DN. ET antagonists are among the most promising molecules for the treatment of nephropathies. We should definitely not abandon these drugs because of the initial drawbacks in the first clinical trials.

Renin inhibition in the treatment of diabetic kidney disease

2013 ◽  
Vol 124 (9) ◽  
pp. 553-566 ◽  
Author(s):  
Radko Komers
Keyword(s):  
Kidney Diseases ◽  
Diabetic Patients ◽  
Beneficial Effects ◽  
Rate Limiting Step ◽  
Renin Inhibition ◽  
Raas Inhibitors ◽  
Stage Renal Disease ◽  
End Stage ◽  
Activation Cascade

Inhibition of the RAAS (renin–angiotensin–aldosterone system) plays a pivotal role in the prevention and treatment of diabetic nephropathy and a spectrum of other proteinuric kidney diseases. Despite documented beneficial effects of RAAS inhibitors in diabetic patients with nephropathy, reversal of the progressive course of this disorder or at least long-term stabilization of renal function are often difficult to achieve, and many patients still progress to end-stage renal disease. Incomplete inhibition of the RAAS has been postulated as one of reasons for unsatisfactory therapeutic responses to RAAS inhibition in some patients. Inhibition of renin, a rate-limiting step in the RAAS activation cascade, could overcome at least some of the abovementioned problems associated with the treatment with traditional RAAS inhibitors. The present review focuses on experimental and clinical studies evaluating the two principal approaches to renin inhibition, namely direct renin inhibition with aliskiren and inhibition of the (pro)renin receptor. Moreover, the possibilities of renin inhibition and nephroprotection by interventions primarily aiming at non-RAAS targets, such as vitamin D, urocortins or inhibition of the succinate receptor GPR91 and cyclo-oxygenase-2, are also discussed.

scholarly journals Changes of MicroRNA-377 in Diabetic Nephropathy

QJM ◽  
2020 ◽  
Vol 113 (Supplement_1) ◽  
Author(s):  
H A Elshinnawy ◽  
C R Kamel ◽  
M H A Elkeleng
Keyword(s):  
Diabetic Nephropathy ◽  
Diabetic Patients ◽  
Ckd Stage ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Stage Renal Disease ◽  
End Stage ◽  
Stage 1

Abstract Background as one of the most important long term complications of diabetes, Diabetic nephropathy is the major cause of end stage renal disease and high mortality. Purpose to identify the pattern of microRNA-377 changes specific for diabetic nephropathy in diabetic patients and in patients with chronic kidney disease of different etiology. Patients and Methods the study was conducted from 2016 to 2018, included 50 patients for analysis of MicroRNA-377 and its control gene U18 at El Demrdash Hospital Ain shams university and Quessena Hospital El Monfia. The miRNA-U18 was analyzed for normalization of correction ratio. Results the results of our research found that the highest median IQR of miR-377 was significantly present in DN stage 1&2 and the lowest median IQR was significantly present in CKD stage 1&2, and there was significant difference between group 1 (DN stage 1&2) versus group 2 (DN stage 3&4), group 3 (Diabetics without nephropathy) and all stages of CKD. Conclusion in diabetic nephropathy stage 1&2, serum miR-377 was highly significant increased more than diabetics without nephropathy, diabetic nephropathy stage 3&4 and all satges of CKD.

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