Diabetic Kidney
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2021 ◽  
pp. cd210078
Andrew A. Swanner ◽  
Chelsea E. Hawley ◽  
Kay Li ◽  
Laura K. Triantafylidis ◽  
Jiahua Li ◽  

Sarah Gleeson ◽  
Shuli Svetitsky ◽  
Charlotte Frise

Introduction: We systematically reviewed all relevant literature on diabetic kidney disease (DKD) and pregnancy published in the last 20 years to provide accurate and up-to-date information to inform family planning and maternal care. Methods: A systematic review was completed in PubMed and Embase. Papers reporting maternal, fetal or renal outcomes of pregnant women with DKD published between 2001 and 2020 were included. Results: 799 potentially relevant articles were identified, 731 of which were excluded on abstract alone. 68 full-text articles were reviewed and 15 papers were included as they met the selection criteria but were heterogeneous for size, study setting and years studied. The definition of DKD varied between papers and changed over time. 843 women with 873 pregnancies were included. There were high rates of pre-eclampsia and caesarean section, up to 64% and 100% respectively. Prematurity and neonatal intensive care admission were common, reported in up to 100% and 75%, respectively. Maternal and fetal complications were more common with more severe proteinuria and renal impairment. Pregnancy did not hasten progression of DKD. Discussion: Adverse pregnancy outcomes are frequently encountered and correlate with degree of proteinuria and renal impairment. This information enables individualised risk stratification when a woman is considering pregnancy.

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Zhenhong Guo ◽  
Xiaoyue Sun ◽  
Juhong Yang ◽  
Jinlan Xie ◽  
Feifei Zhong ◽  

Aims. We investigated the changes of retinal structure in normal glucose tolerance (NGT), impaired glucose tolerance (IGT), diabetes mellitus (DM), and diabetic kidney disease (DKD) stages in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods. We assigned OLETF rats to four groups based on their OGTT results and 24 h urinary microalbumin (24 h UMA) levels: NGT, IGT, DM, and DKD groups. We observed the structural and the corresponding pathological changes and quantified the expression of HIF-1α, iNOS, NF-κB, VEGF, ICAM-1, and occludin in the retina. Results. Significant damage to the retinal structure, especially in retinal ganglion cells (RGCs), was observed in the IGT stage. The expression of HIF-1α, iNOS, NF-κB, VEGF, and ICAM-1 was significantly upregulated, while that of occludin was downregulated. Conclusion. Significant retinal neuropathy occurs in the IGT stage. Inflammation and hypoxia may damage the blood retina barrier (BRB), leading to diabetic retinopathy.

2021 ◽  
Vol 11 (1) ◽  
Kenneth R. Laurita ◽  
Shenaz Khan ◽  
Tracy McMahon ◽  
Adrienne T. Dennis ◽  
Vincent Li ◽  

AbstractChronic kidney disease (CKD) affects more than 20 million people in the US, and it is associated with a significantly increased risk of sudden cardiac death (SCD). Despite the significance, the mechanistic relationship between SCD and CKD is not clear and there are few effective therapies. Using optical mapping techniques, we tested the hypothesis that mouse models of progressive diabetic kidney disease (DKD) exhibit enhanced ventricular arrhythmia incidence and underlying arrhythmia substrates. Compared to wild-type mice, both Leprdb/db eNOS−/− (2KO) and high fat diet plus low dose streptozotocin (HFD + STZ) mouse models of DKD experienced sudden death and greater arrhythmia inducibility, which was more common with isoproterenol than programmed electrical stimulation. 2KO mice demonstrated slowed conduction velocity, prolonged action potential duration (APD), and myocardial fibrosis; both 2KO and HFD + STZ mice exhibited arrhythmias and calcium dysregulation with isoproterenol challenge. Finally, circulating concentrations of the uremic toxin asymmetric dimethylarginine (ADMA) were elevated in 2KO mice. Incubation of human cardiac myocytes with ADMA prolonged APD, as also observed in 2KO mice hearts ex vivo. The present study elucidates an arrhythmia-associated mechanism of sudden death associated with DKD, which may lead to more effective treatments in the vulnerable DKD patient population.

2021 ◽  
Vol 12 (11) ◽  
Man Wu ◽  
Minjie Zhang ◽  
Yaozhi Zhang ◽  
Zixian Li ◽  
Xingyu Li ◽  

AbstractLysosomes are organelles involved in cell metabolism, waste degradation, and cellular material circulation. They play a key role in the maintenance of cellular physiological homeostasis. Compared with the lysosomal content of other organs, that of the kidney is abundant, and lysosomal abnormalities are associated with the occurrence and development of certain renal diseases. Lysosomal structure and function in intrinsic renal cells are impaired in diabetic kidney disease (DKD). Promoting lysosomal biosynthesis and/or restoring lysosomal function can repair damaged podocytes and proximal tubular epithelial cells, and delay the progression of DKD. Lysosomal homeostasis maintenance may be advantageous in alleviating DKD. Here, we systematically reviewed the latest advances in the relationship between lysosomal dyshomeostasis and progression of DKD based on recent literature to further elucidate the mechanism of renal injury in diabetes mellitus and to highlight the application potential of lysosomal homeostasis maintenance as a new prevention and treatment strategy for DKD. However, research on screening effective interventions for lysosomal dyshomeostasis is still in its infancy, and thus should be the focus of future research studies. The screening out of cell-specific lysosomal function regulation targets according to the different stages of DKD, so as to realize the controllable targeted regulation of cell lysosomal function during DKD, is the key to the successful clinical development of this therapeutic strategy.

2021 ◽  
Vol 22 (20) ◽  
pp. 11196
Christodoula Kourtidou ◽  
Maria Stangou ◽  
Smaragdi Marinaki ◽  
Konstantinos Tziomalos

Patients with diabetic kidney disease (DKD) are at very high risk for cardiovascular events. Only part of this increased risk can be attributed to the presence of diabetes mellitus (DM) and to other DM-related comorbidities, including hypertension and obesity. The identification of novel risk factors that underpin the association between DKD and cardiovascular disease (CVD) is essential for risk stratification, for individualization of treatment and for identification of novel treatment targets.In the present review, we summarize the current knowledge regarding the role of emerging cardiovascular risk markers in patients with DKD. Among these biomarkers, fibroblast growth factor-23 and copeptin were studied more extensively and consistently predicted cardiovascular events in this population. Therefore, it might be useful to incorporate them in risk stratification strategies in patients with DKD to identify those who would possibly benefit from more aggressive management of cardiovascular risk factors.

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