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

ABSTRACT: 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.

SUBMITTER: Sen U

PROVIDER: S-EPMC4719040 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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

Sen Utpal U Pushpakumar Sathnur S

American journal of physiology. Renal physiology 20151104 2

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 ...[more]

PMID: 26538437

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Project description:Pyroptosis is a recently identified type of lytic programmed cell death, in which pores form in the plasma membrane, and cells swell, rupture, and then release their contents, including inflammatory cytokines. Molecular studies indicated that pyroptosis may occur via a gasdermin D (GSDMD) and caspase-1 (Casp1) -dependent classical pathway, a GSDMD and Casp11/4/5-dependent non-classical pathway, or a gasdermin E (GSDME) and Casp3-dependent pathway. Studies of animal models and humans indicated that pyroptosis can exacerbate several complications of diabetes, including diabetic nephropathy (DN), a serious microvascular complication of diabetes. Many studies investigated the mechanism mediating the renoprotective effect of GSDMD regulation in the kidneys of patients and animal models with diabetes. As a newly discovered regulatory mechanism, GSDME and Casp3-dependent pyroptotic pathway in the progression of DN has also attracted people's attention. Z-DEVD-FMK, an inhibitor of Casp3, ameliorates albuminuria, improves renal function, and reduces tubulointerstitial fibrosis in diabetic mice, and these effects are associated with the inhibition of GSDME. Studies of HK-2 cells indicated that the molecular and histological features of secondary necrosis were present following glucose stimulation due to GSDME cleavage, such as cell swelling, and release of cellular contents. Therefore, therapies targeting Casp3/GSDME-dependent pyroptosis have potential for treatment of DN. A novel nephroprotective strategy that employs GSDME-derived peptides which are directed against Casp3-induced cell death may be a key breakthrough. This mini-review describes the discovery and history of research in this pyroptosis pathway and reviews the function of proteins in the gasdermin family, with a focus on the role of GSDME-mediated pyroptosis in DN. Many studies have investigated the impact of GSDME-mediated pyroptosis in kidney diseases, and these studies used multiple interventions, in vitro models, and in vivo models. We expect that further research on the function of GDSME in DN may provide valuable insights that may help to improve treatments for this disease.

Project description:PurposeEmerging data suggest that coronavirus disease 2019 (COVID-19) has extrapulmonary manifestations but its renal manifestations are not clearly defined. We aimed to evaluate renal complications of COVID-19 and their incidence using a systematic meta-analysis.DesignObservational studies reporting renal complications in COVID-19 patients were sought from MEDLINE, Embase and the Cochrane Library from 2019 to June 2020. The nine-star Newcastle-Ottawa Scale was used to evaluate methodological quality. Incidence with 95% confidence intervals (CIs) were pooled using random-effects models.ResultsWe included 22 observational cohort studies comprising of 17,391 COVID-19 patients. Quality scores of studies ranged from 4 to 6. The pooled prevalence of pre-existing chronic kidney disease (CKD) and end-stage kidney disease was 5.2% (2.8-8.1) and 2.3% (1.8-2.8), respectively. The pooled incidence over follow-up of 2-28 days was 12.5% (10.1-15.0) for electrolyte disturbance (e.g. hyperkalaemia), 11.0% (7.4-15.1) for acute kidney injury (AKI) and 6.8% (1.0-17.0) for renal replacement therapy (RRT). In subgroup analyses, there was a higher incidence of AKI in US populations and groups with higher prevalence of pre-existing CKD.ConclusionsFrequent renal complications reported among hospitalized COVID-19 patients are electrolyte disturbance, AKI and RRT. Aggressive monitoring and management of these renal complications may help in the prediction of favourable outcomes. Systematic review registration: PROSPERO 2020: CRD42020186873 KEY MESSAGES COVID-19 affects multiple organs apart from the respiratory system; however, its renal manifestations are not clearly defined. In this systematic meta-analysis of 22 observational cohort studies, the prevalence of pre-existing chronic kidney disease (CKD) in COVID-19 patients was 5.2%. The most frequent renal complication was electrolyte disturbance (particularly hyperkalaemia) with an incidence of 12.5% followed by acute kidney injury (AKI) with an incidence of 11.0%; US populations and groups with higher prevalence of CKD had higher incidence of AKI.

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

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

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