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

2016 ◽  
Vol 310 (2) ◽  
pp. F119-F122 ◽  
Author(s):  
Utpal Sen ◽  
Sathnur Pushpakumar

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.

2020 ◽  
Vol 27 (11) ◽  
pp. 1744-1763 ◽  
Author(s):  
Stefano Menini ◽  
Carla Iacobini ◽  
Claudia Blasetti Fantauzzi ◽  
Giuseppe Pugliese

Vascular complications are among the most serious manifestations of diabetes. Atherosclerosis is the main cause of reduced life quality and expectancy in diabetics, whereas diabetic nephropathy and retinopathy are the most common causes of end-stage renal disease and blindness. An effective therapeutic approach to prevent vascular complications should counteract the mechanisms of injury. Among them, the toxic effects of Advanced Glycation (AGEs) and Lipoxidation (ALEs) end-products are well-recognized contributors to these sequelae. L-carnosine (β-alanyl-Lhistidine) acts as a quencher of the AGE/ALE precursors Reactive Carbonyl Species (RCS), which are highly reactive aldehydes derived from oxidative and non-oxidative modifications of sugars and lipids. Consistently, L-carnosine was found to be effective in several disease models in which glyco/lipoxidation plays a central pathogenic role. Unfortunately, in humans, L-carnosine is rapidly inactivated by serum carnosinase. Therefore, the search for carnosinase-resistant derivatives of Lcarnosine represents a suitable strategy against carbonyl stress-dependent disorders, particularly diabetic vascular complications. In this review, we present and discuss available data on the efficacy of L-carnosine and its derivatives in preventing vascular complications in rodent models of diabetes and metabolic syndrome. We also discuss genetic findings providing evidence for the involvement of the carnosinase/L-carnosine system in the risk of developing diabetic nephropathy and for preferring the use of carnosinase-resistant compounds in human disease. The availability of therapeutic strategies capable to prevent both long-term glucose toxicity, resulting from insufficient glucoselowering therapy, and lipotoxicity may help reduce the clinical and economic burden of vascular complications of diabetes and related metabolic disorders.


1980 ◽  
Vol 1 (5) ◽  
pp. 54-58 ◽  
Author(s):  
Norbert H. Lameire ◽  
Marc De Paepe ◽  
Raymond Vanholder ◽  
Johan Verbanck ◽  
Severin Ringoir

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.


Antioxidants ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 321
Author(s):  
Mako Yasuda-Yamahara ◽  
Shinji Kume ◽  
Hiroshi Maegawa

Diabetic kidney disease (DKD) is the leading cause of end-stage renal disease and the number of patients affected is increasing worldwide. Thus, there is a need to establish a new treatment for DKD to improve the renal prognosis of diabetic patients. Recently, it has shown that intracellular metabolic abnormalities are involved in the pathogenesis of DKD. In particular, the activity of mechanistic target of rapamycin complex 1 (mTORC1), a nutrient-sensing signaling molecule, is hyperactivated in various organs of diabetic patients, which suggests the involvement of excessive mTORC1 activation in the pathogenesis of diabetes. In DKD, hyperactivated mTORC1 may be involved in the pathogenesis of podocyte damage, which causes proteinuria, and tubular cell injury that decreases renal function. Therefore, elucidating the role of mTORC1 in DKD and developing new therapeutic agents that suppress mTORC1 hyperactivity may shed new light on DKD treatments in the future.


2020 ◽  
Vol 21 (11) ◽  
pp. 3798 ◽  
Author(s):  
Sandra Rayego-Mateos ◽  
José Luis Morgado-Pascual ◽  
Lucas Opazo-Ríos ◽  
Melania Guerrero-Hue ◽  
Cristina García-Caballero ◽  
...  

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.


Renal Failure ◽  
2001 ◽  
Vol 23 (5) ◽  
pp. 669-677 ◽  
Author(s):  
Kiron Varghese ◽  
George Cherian ◽  
Mullaseril Thomas Abraham ◽  
Nasser J. Hayat ◽  
Kaivilayil Varghese Johny

2018 ◽  
Vol 69 (8) ◽  
pp. 2064-2066
Author(s):  
Mircea Munteanu ◽  
Adrian Apostol ◽  
Viviana Ivan

The aim of the present study is to investigate the prevalance of chronic kidney disease (CKD), of cardiovascular disease (CVD) and dyslipidemia in patients with diabetes mellitus (DM). We conducted a prospective, controlled study involving 420 diabetic patients (120 T1DM, 300 T2DM) and investigate the following aspects: the presence of vascular complications (stroke, coronary artery disease, peripheral artery disease), lipid profile (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides), kidney function (glomerular filtration rate, albuminuria), blood pressure, HbA1C. The results that in diabetic patients with CKD there is an increased prevalence of CVD and of dislipidemia. Also we noticed a negative correlation between total cholesterol level and decease in eGFR in all patients, with or without CKD.


Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  

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.


2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Cristina Mega ◽  
Edite Teixeira-de-Lemos ◽  
Rosa Fernandes ◽  
Flávio Reis

Diabetic nephropathy (DN) is now the single commonest cause of end-stage renal disease (ESRD) worldwide and one of the main causes of death in diabetic patients. It is also acknowledged as an independent risk factor for cardiovascular disease (CVD). Since sitagliptin was approved, many studies have been carried out revealing its ability to not only improve metabolic control but also ameliorate dysfunction in various diabetes-targeted organs, especially the kidney, due to putative underlying cytoprotective properties, namely, its antiapoptotic, antioxidant, anti-inflammatory, and antifibrotic properties. Despite overall recommendations, many patients spend a long time well outside the recommended glycaemic range and, therefore, have an increased risk for developing micro- and macrovascular complications. Currently, it is becoming clearer that type 2 diabetes mellitus (T2DM) management must envision not only the improvement in glycaemic control but also, and particularly, the prevention of pancreatic deterioration and the evolution of complications, such as DN. This review aims to provide an overview of the current knowledge in the field of renoprotective actions of sitagliptin, namely, improvement in diabetic dysmetabolism, hemodynamic factors, renal function, diabetic kidney lesions, and cytoprotective properties.


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