scholarly journals Could IL-17A Be a Novel Therapeutic Target in Diabetic Nephropathy?

2020 ◽  
Vol 9 (1) ◽  
pp. 272 ◽  
Author(s):  
Carolina Lavoz ◽  
Sandra Rayego-Mateos ◽  
Macarena Orejudo ◽  
Lucas Opazo-Ríos ◽  
Vanessa Marchant ◽  
...  

Chronic kidney disease has become a major medical issue in recent years due to its high prevalence worldwide, its association with premature mortality, and its social and economic implications. A number of patients gradually progress to end-stage renal disease (ESRD), requiring then dialysis and kidney transplantation. Currently, approximately 40% of patients with diabetes develop kidney disease, making it the most prevalent cause of ESRD. Thus, more effective therapies for diabetic nephropathy are needed. In preclinical studies of diabetes, anti-inflammatory therapeutic strategies have been used to protect the kidneys. Recent evidence supports that immune cells play an active role in the pathogenesis of diabetic nephropathy. Th17 immune cells and their effector cytokine IL-17A have recently emerged as promising targets in several clinical conditions, including renal diseases. Here, we review current knowledge regarding the involvement of Th17/IL-17A in the genesis of diabetic renal injury, as well as the rationale behind targeting IL-17A as an additional therapy in patients with diabetic nephropathy.

2021 ◽  
Vol 10 (10) ◽  
pp. 2046
Author(s):  
Goren Saenz-Pipaon ◽  
Saioa Echeverria ◽  
Josune Orbe ◽  
Carmen Roncal

Diabetic kidney disease (DKD) is the leading cause of end stage renal disease (ESRD) in developed countries, affecting more than 40% of diabetes mellitus (DM) patients. DKD pathogenesis is multifactorial leading to a clinical presentation characterized by proteinuria, hypertension, and a gradual reduction in kidney function, accompanied by a high incidence of cardiovascular (CV) events and mortality. Unlike other diabetes-related complications, DKD prevalence has failed to decline over the past 30 years, becoming a growing socioeconomic burden. Treatments controlling glucose levels, albuminuria and blood pressure may slow down DKD evolution and reduce CV events, but are not able to completely halt its progression. Moreover, one in five patients with diabetes develop DKD in the absence of albuminuria, and in others nephropathy goes unrecognized at the time of diagnosis, urging to find novel noninvasive and more precise early diagnosis and prognosis biomarkers and therapeutic targets for these patient subgroups. Extracellular vesicles (EVs), especially urinary (u)EVs, have emerged as an alternative for this purpose, as changes in their numbers and composition have been reported in clinical conditions involving DM and renal diseases. In this review, we will summarize the current knowledge on the role of (u)EVs in DKD.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Mostafa Abdelsalam ◽  
A. M. Wahab ◽  
Maysaa El Sayed Zaki ◽  
Mohamad Motawea

Background. Diabetes mellitus is the leading cause of end-stage renal disease worldwide. Microalbuminuria is the cornerstone for the diagnosis of diabetic nephropathy. However, it is an inadequate marker for early diagnosis. MicroRNAs are not only new and promising markers for early diagnosis but also, but they may also play a role in the prevention of disease progression. Methods. This study included ninety patients with type 2 DM in addition to 30 control subjects. MicroRNA-451 expression in blood and plasma using real-time PCR was evaluated in addition to the classic diabetic nephropathy markers (serum creatinine, urinary albumin, and eGFR). Results. There was a significant difference between the studied groups versus control regarding serum creatinine, eGFR, urinary, and plasma microRNA-451 with p=0.0001. Patients with eGFR 60 ml/min/1.73 m2 showed a significantly higher plasma microRNA-451 (29.6 ± 1.6) and significantly lower urinary microRNA-451 (21 ± 0.9) in comparison to patients with eGFR >60 ml/min/1.73 m2 and p=0.0001. eGFR showed a positive correlation with urinary microRNA-451 and negative correlation with both plasma microRNA-451 and urinary albumin. Both plasma and urinary microRNA-451 are highly sensitive and specific markers for chronicity in diabetic nephropathy patients with sensitivity of 90.9% and 95.5% and specificity of 67.6% and 95.6%, respectively. Conclusion. MicroRNA-451 is a promising early biomarker for chronic kidney disease in diabetic nephropathy with high sensitivity and specificity.


2003 ◽  
Vol 284 (6) ◽  
pp. F1138-F1144 ◽  
Author(s):  
Kumar Sharma ◽  
Peter McCue ◽  
Stephen R. Dunn

Diabetic nephropathy is increasing in incidence and is now the number one cause of end-stage renal disease in the industrialized world. To gain insight into the genetic susceptibility and pathophysiology of diabetic nephropathy, an appropriate mouse model of diabetic nephropathy would be critical. A large number of mouse models of diabetes have been identified and their kidney disease characterized to various degrees. Perhaps the best characterized and most intensively investigated model is the db/ db mouse. Because this model appears to exhibit the most consistent and robust increase in albuminuria and mesangial matrix expansion, it has been used as a model of progressive diabetic renal disease. In this review, we present the findings from various studies on the renal pathology of the db/ db mouse model of diabetes in the context of human diabetic nephropathy. Furthermore, we discuss shortfalls of assessing functional renal disease in mouse models of diabetic kidney disease.


2021 ◽  
Vol 22 (4) ◽  
pp. 2009
Author(s):  
Anne Grunenwald ◽  
Lubka T. Roumenina ◽  
Marie Frimat

The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1’s functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.


PEDIATRICS ◽  
1983 ◽  
Vol 72 (6) ◽  
pp. 840-846
Author(s):  
Alan M. Krensky ◽  
Joseph M. Reddish ◽  
Rita Littlewood Teele

Review of 2,700 abdominal ultrasonic examinations revealed 56 patients whose kidneys showed increased echogenicity. Echogenic kidneys were associated with medical renal disease in 94% of cases (30% glomerular, 48% tubulointerstitial, 16% end-stage) and with no detectable renal disease in 6% (three patients). Patterns of increased echogenicity and renal size were evaluated. Specific patterns occurred in end-stage renal disease and polycystic kidney disease. Other medical renal diseases had overlapping ultrasonographic features. Some generalizations could be made although increased echogenicity was often nonspecific.


2021 ◽  
pp. 353-382
Author(s):  
Gopesh K. Modi ◽  
Vivekanand Jha

Assessing renal function, Urinalysis, Proteinuria, Hematuria, Chyluria, Imaging in renal disease, Kidney biopsy, Acute Kidney Injury (AKI), Chronic Kidney Disease (CKD), Diabetic Nephropathy, End Stage Renal Disease and Dialysis, Kidney Transplantation, Glomerular diseases, Acute glomerulonephritis, Urinary schistosomiasis (bilharzia), Infections and Kidney Disease, Rapidly Progressive glomerulonephritis, Tubulointerstitial Disease, Urinary Tract Infection, Vesico-ureteric reflux, Renal Stones, Renal Disease in Pregnancy, Renal Artery Stenosis, Renal Mass, Inherited Renal Diseases


BMJ Open ◽  
2020 ◽  
Vol 10 (9) ◽  
pp. e033923
Author(s):  
Kieran Mccafferty ◽  
Ben Caplin ◽  
Sinead Knight ◽  
Paul Hockings ◽  
David Wheeler ◽  
...  

IntroductionDiabetic kidney disease (DKD) is the leading cause of end-stage kidney disease worldwide and a major cause of premature mortality in diabetes mellitus (DM). While improvements in care have reduced the incidence of kidney disease among those with DM, the increasing prevalence of DM means that the number of patients worldwide with DKD is increasing. Improved understanding of the biology of DKD and identification of novel therapeutic targets may lead to new treatments. A major challenge to progress has been the heterogeneity of the DKD phenotype and renal progression. To investigate the heterogeneity of DKD we have set up The East and North London Diabetes Cohort (HEROIC) Study, a secondary care-based, multiethnic observational study of patients with biopsy-proven DKD. Our primary objective is to identify histological features of DKD associated with kidney endpoints in a cohort of patients diagnosed with type 1 and type 2 DM, proteinuria and kidney impairment.Methods and analysisHEROIC is a longitudinal observational study that aims to recruit 500 patients with DKD at high-risk of renal and cardiovascular events. Demographic, clinical and laboratory data will be collected and assessed annually for 5 years. Renal biopsy tissue will be collected and archived at recruitment. Blood and urine samples will be collected at baseline and during annual follow-up visits. Measured glomerular filtration rate (GFR), echocardiography, retinal optical coherence tomography angiography and kidney and cardiac MRI will be performed at baseline and twice more during follow-up. The study is 90% powered to detect an association between key histological and imaging parameters and a composite of death, renal replacement therapy or a 30% decline in estimated GFR.Ethics and disseminationEthical approval has been obtained from the Bloomsbury Research Ethics Committee (REC 18-LO-1921). Any patient identifiable data will be stored on a password-protected National Health Services N3 network with full audit trail. Anonymised imaging data will be stored in a ISO27001-certificated data warehouse.Results will be reported through peer-reviewed manuscripts and conferences and disseminated to participants, patients and the public using web-based and social media engagement tools as well as through public events.


2019 ◽  
Vol 20 (14) ◽  
pp. 3567 ◽  
Author(s):  
Teresa Seccia ◽  
Brasilina Caroccia ◽  
Maria Piazza ◽  
Gian Paolo Rossi

Accumulating evidence indicates that epithelial-to-mesenchymal transition (EMT), originally described as a key process for organ development and metastasis budding in cancer, plays a key role in the development of renal fibrosis in several diseases, including hypertensive nephroangiosclerosis. We herein reviewed the concept of EMT and its role in renal diseases, with particular focus on hypertensive kidney disease, the second leading cause of end-stage renal disease after diabetes mellitus. After discussing the pathophysiology of hypertensive nephropathy, the ‘classic’ view of hypertensive nephrosclerosis entailing hyalinization, and sclerosis of interlobular and afferent arterioles, we examined the changes occurring in the glomerulus and tubulo-interstitium and the studies that investigated the role of EMT and its molecular mechanisms in hypertensive kidney disease. Finally, we examined the reasons why some studies failed to provide solid evidence for renal EMT in hypertension.


Author(s):  
Michiaki Abe ◽  
Tetsuya Akaishi ◽  
Koto Ishizawa ◽  
Hirohisa Shinano ◽  
Hiroshi Ohtomo ◽  
...  

Abstract Background Disaster-related stress can increase blood pressure and the incidence of cardiovascular diseases. However, the role of massive disasters in the development of end-stage kidney disease (ESKD) remains unknown. We investigated the incidence and different causes of dialysis initiation in patients with chronic kidney disease in a city affected by the Great East Japan Earthquake. Methods This was a single-center, retrospective observational study. All patients who initiated or were treated with dialysis at Kesennuma City Hospital between 2007 and 2020 were enrolled. The year of dialysis initiation was retrospectively determined based on the initiation date. The causative renal diseases that led to the need for dialysis initiation were divided into four groups: diabetic nephropathy, hypertensive renal disease, glomerulonephritis, and others. Results Age at dialysis initiation differed significantly among the four groups (p = 0.0262). There was a significant difference in the numbers of the four groups before and after the Great East Japan Earthquake (p = 0.0193). The age of hypertensive renal disease patients was significantly higher than those of patients with diabetic nephropathy (p = 0.0070) and glomerulonephritis (p = 0.0386) after the disaster. The increasing number of dialysis initiations after the Great East Japan Earthquake appeared to be associated with changes in hypertensive renal diseases; the number peaked after 10 years. Conclusions There was an increase in the number of dialysis initiations, especially caused by hypertensive renal diseases, for up to 10 years after the Great East Japan Earthquake. Graphic abstract


KYAMC Journal ◽  
2013 ◽  
Vol 2 (2) ◽  
pp. 182-186
Author(s):  
ST Ahmed ◽  
MA Rahim ◽  
Z Ali ◽  
MM Iqbal

Background: Chronic Kidney Disease (CKD) is the third most common non-communicable disease throughout the world. Studies have shown that kidney patients suffer much from hypertension, diabetes than glomerulonephritis. Many of these CKD patients ultimately terminate to End Stage Renal Disease (ESRD) when life is not sustainable unless hemodialysis is initiated. Aim: The aim of this study was to identify primary renal disease leading to ESRD requiring hemodialysis and associated co-morbidities. Material and methods: Data was collected purposively from selected six hemodialysis centers. Patients were selected purposively who were available at the time of interview. Data was collected on working days at three shifts After taking informed consent from patients the pre-tested questionnaire was filled up by taking general history, family history, socioeconomic condition, drug history and available records were reviewed for collecting previous biochemical parameters. All entered data were analyzed by using SPSS program version 13.0. Result: Among total 393 subjects, male was 247(63%) and female 146 (37%). Majority were middle aged. Glomerulonephritis were found to be the leading cause of End Stage Renal Disease (ESRD) (50.4%), followed by diabetes in 31.1%, Poly Cystic Kidney Disease (PKD) 5.3%, Renal Stone in 3.7% and rest other. Among the study population hypertension was the most common co morbidity disease (63%) followed by ischemic heart disease and Cerebrovascular accidents. Conclusion: Glomerulonephritis was found to be the leading cause of End Stage Renal Disease (ESRD) and diabetic nephropathy was the second common cause. Hypertension was the most common associated co morbid disease. To evaluate the actual disease pattern a large scale study is required to find the outcome of haemodialysis patients.DOI: http://dx.doi.org/10.3329/kyamcj.v2i2.13262KYAMC Journal Vol.2(2) January 2012, 182-186


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