rss_2.0Diabetic Nephropathy FeedSciendo RSS Feed for Diabetic Nephropathy Nephropathy 's Cover biopsy in patients with diabetes: Yesterday, today, and tomorrow therapy in diabetic kidney disease<abstract><title style='display:none'>Abstract</title><p>Diabetic kidney disease (DKD) is the main cause of end-stage renal disease (ESRD). The use of insulin represents a challenge in patients with DKD due to the patient and medication issues. Insulin regimens, insulin dosing, and titration need to be individualized based on the patient's age, renal function, and comorbidities to improve glycemic control and reduce the risk of hypoglycemia. Insulin is the primary treatment in all patients with type 1 diabetes mellitus (T1DM) and DKD. For patients with type 2 diabetes mellitus (T2DM) and early stage of DKD, basal insulin combined with oral antidiabetic drugs (OADs) is recommended. In patients with middle and advanced DKD, it is necessary to adjust the dose of insulin according to stages of DKD, and the use of insulin analogs is recommended. In particular, elderly patients with DKD can simplify their insulin regimen to reduce the risk of hypoglycemia. In pregnant women with DKD, insulin requirements also vary based on parity and the stage of pregnancy.</p></abstract>ARTICLE2022-06-16T00:00:00.000+00:00Analysis of dapagliflozin-induced expression profile of long noncoding RNAs in proximal tubular epithelial cells of diabetic kidney disease<abstract><title style='display:none'>Abstract</title><sec><title style='display:none'>Background</title><p>Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play an important role in diabetic kidney disease (DKD). Dapagliflozin (DAPA), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, exerts protective effects against DKD, but the underlying mechanism remains unclear.</p></sec><sec><title style='display:none'>Methods</title><p>In this study, we performed RNA microarray analysis to investigate differentially expressed lncRNAs and mRNAs in human proximal tubular epithelial cells (HK-2 cells) cultured with normal glucose (Ng), high glucose (Hg), and Hg plus DAPA, and conducted bioinformatic analyses to investigate their functions.</p></sec><sec><title style='display:none'>Results</title><p>Compared with the Ng group, 6761 lncRNAs and 3162 mRNAs were differentially expressed in the Hg group. Expression levels of 714 and 259 lncRNAs were up- and down-regulated, respectively, whereas those of 138 and 127 mRNAs were up- and down-regulated, respectively, after DAPA treatment (fold change ≥2, <italic>P</italic> &lt; 0.05). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to assess the biological functions of lncRNAs and potential target genes. According to GO analysis, dysregulated mRNAs were primarily enriched in the cell cycle, whereas DAPA-induced mRNAs were enriched in collagen biosynthesis and regulation of programmed cell death. Type I diabetes mellitus and cell cycle signaling were the main KEGG pathways in the Hg group. However, cancer and signal transduction pathways were related to DAPA treatment.</p></sec><sec><title style='display:none'>Conclusions</title><p>Finally, we established protein–protein interaction (PPI) networks, as well as lncRNA–mRNA and lncRNA–miRNA–mRNA networks, and identified five potentially important lncRNAs whose expression levels were altered by DAPA treatment. Our findings suggest that lncRNAs are potential targets for DKD treatment.</p></sec></abstract>ARTICLE2022-06-16T00:00:00.000+00:00Renoprotective mechanisms of SGLT2 inhibitor in diabetic kidney disease<abstract> <title style='display:none'>Abstract</title> <p>Diabetic kidney disease (DKD), as the primary cause of end-stage renal disease (ESRD), is becoming a growing public health challenge worldwide. Early intervention in conditions involving high glucose levels will prevent the progression of DKD. Sodium-glucose cotransporter 2 inhibitors (SGLT2is) comprise a new class of medications used to reduce hyperglycemia in patients with diabetes by inhibiting renal reabsorption of filtered glucose. Interestingly, SGLT2i is not only capable of controlling the blood glucose level but also has other benefits in terms of blood pressure control, body weight decrease, and albuminuria reduction. It is assumed that various events, such as energy metabolism disorder, insulin resistance, glomerular hyperfiltration, oxidative stress, inflammation, and fibrosis, attributable to the pathogenesis of DKD, can be improved by SGLT2i. Clinical trials have demonstrated that SGLT2i can exert renoprotective effects and reduce the morbidity and mortality due to ESRD. In this review, we focus on the most recent findings from clinical trials and the underlying mechanisms by which SGLT2 inhibitors afford renal protection.</p> </abstract>ARTICLE2022-06-10T00:00:00.000+00:00Emerging role of macrophages in diabetic nephropathy<abstract> <title style='display:none'>Abstract</title> <p>Increasing evidence shows that diabetic nephropathy is associated with immune disorder. Macrophages are a key immune cell infiltrating the kidney in both patients and experimental animal models of diabetes, and correlate with progressive renal injury under diabetic conditions. Blockade of renal macrophage infiltration by either genetic deletion or pharmacological inhibition has been shown to improve diabetic renal injury, revealing a pathogenic role of macrophages in diabetic nephropathy. Further, studies identify that M1 macrophages are a key player responsible for diabetic renal injury by triggering renal inflammation, while M2 macrophages are highly heterogenous, and may play diverse roles in either initiating the renal repairing process if renal inflammation is resolved, or promoting progressive renal fibrosis via a macrophage-to-myofibroblast transition (MMT) process if renal inflammation is ongoing. Macrophages may also interact with intrinsic kidney cells to mediate renal inflammation or fibrosis directly or indirectly by producing a variety of proinflammatory cytokines/chemokines and growth factors, or by macrophage-derived exosomes. In summary, macrophages are immunologically important in the pathogenesis of diabetic kidney disease and may play a driving role in the progression of diabetic nephropathy. Targeting macrophages may thus be considered as a novel therapy for combatting diabetic nephropathy.</p> </abstract>ARTICLE2022-05-16T00:00:00.000+00:00Pyridoxamine alleviates high glucose induced fibrosis in renal tubular epithelial cell by inhibiting the activity of TGF-β1/Smad3 signaling pathway<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Background</title> <p>Renal fibrosis is one of the main characteristics of diabetic nephropathy. TGF-β1/Smad3 pathway is expected to reveal the pathogenesis of renal fibrosis in diabetic nephropathy (DN). Pyridoxamine (PM), a natural form of vitamin B6, is a powerful inhibitor of advanced glycation end products (AGEs). PM plays an anti-apoptotic, anti-oxidative stress, and fibrosis role in DN. The purpose of this study was to assess whether PM has a protective effect in renal tubular epithelial and to investigate its possible mechanism.</p> </sec> <sec><title style='display:none'>Methods</title> <p>The effects of PM were investigated in HK-2 cells induced by high glucose. HK-2 cells were administered with PM at a dose of 1 mmol/L. Western blot and Realtime PCR were used to detect the expression levels of renal fibrosis related proteins. The possible mechanism of PM was examined by expression of transforming growth factor-β1 (TGF-β1)/Smad3 pathway.</p> </sec> <sec><title style='display:none'>Results</title> <p>PM could reduce the expression of Fibronectin (FN) and α-smooth muscle actin (α-SMA) induced by high glucose. PM could also affect the activity of TGF-β1/Smad3 pathway in HK-2 cells. FN and α-SMA were up-regulated by overexpression of Smad3 for 48 h. After adding PM, the levels of FN and α-SMA are significantly decreased.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>Our findings indicate that PM showed a protective effect in HK-2 cells through the inhibition of TGF-β1/Smad3 pathway.</p> </sec> </abstract>ARTICLE2022-04-30T00:00:00.000+00:00Diabetic nephropathy with crescent: A case report<abstract> <title style='display:none'>Abstract</title> <p>Diabetic nephropathy is one of the main complications of diabetes, and is also one of the important causes of end-stage renal disease. It is characterized by pathological changes such as thickening of the glomerular basement membrane, expansion of the mesangial matrix, glomerular sclerosis, and hyalinosis of small arteries. However, diabetic nephropathy is rarely accompanied by the formation of a large number of crescents. At this time, renal puncture is required to search for the cause in diabetic nephropathy with worsening renal function. We report a case of diabetic nephropathy with the formation of a large number of crescents.</p> </abstract>ARTICLE2022-04-26T00:00:00.000+00:00Diabetic kidney disease, a potentially serious issue resulting from collision of the coronavirus disease 2019 and diabetes global pandemics nephropathy patient with heavy proteinuria: A case report<abstract><title style='display:none'>Abstract</title><p>We herein report a case of advanced stage rapidly progressive diabetic nephropathy that finally received long-term renal replacement therapy. A 53-year-old man with hypertension and heavy proteinuria suffered rapid progression of DKD [estimated glomerular filtration rate (eGFR): 18 mL/min/1.73m<sup>2</sup>; proteinuria: 12.21 g/d]. Renal biopsy revealed diabetic nephropathy (Class III) with severe interstitial lesion and tubular atrophy. Despite aggressive treatment, the proteinuria and blood pressure were poorly controlled. The patient finally became dialysis dependent. We hold the position that this is related to his proteinuria and hypertension.</p></abstract>ARTICLE2022-03-21T00:00:00.000+00:00 Foreword of diabetic kidney disease<abstract> <title style='display:none'>Abstract</title> <p>Diabetic kidney disease (DKD) is characterized by an accumulation of extracellular matrix proteins such as collagen and fibronectin in the kidney, resulting in tubulointerstitial fibrosis, glomerular mesangial hypertrophy and expansion, thickening of the glomerular basement membrane, podocyte foot process effacement, and inflammation due to the infiltration of monocytes and macrophages. All of these factors contribute to kidney function loss and can ultimately lead to progressive chronic kidney disease and kidney failure. In the review, we summarize the current state of knowledge in the pathogenesis of diabetic kidney disease to include the impact of genetic and environmental factors, hemodynamic changes, glycemic control, inflammation, proteinuria and novel mechanisms such as non-coding RNAs and lipotoxicity.</p> </abstract>ARTICLE2021-08-25T00:00:00.000+00:00The expression of POMC and AgRP in brain and kidney tissues at different stages of diabetic nephropathy rats<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Objective</title> <p>To explore the changes of proopiomelanocortin (POMC) and Agouti-Related Peptide (AgRP) expression in brain and kidney tissues under insulin intervention at different stages of diabetic nephropathy (DN) rats.</p> </sec> <sec><title style='display:none'>Methods</title> <p>The male Sprague-Dawley (SD) rats of DN were treated with high-fat diet for 8 weeks and induced by intraperitoneally injection of streptozotocin (30 mg/kg) for one time. Then DN rats were also injected insulin subcutaneously at 2–5 U/(kg·24 h) from initiation of the streptozotocin. Kidney tissue, blood sample, and 24 h-urine were collected to detect the ratio of kidney/body weight, blood glucose and 24-h urinary albumin excretion rate at different stages (4, 8, 12, and 16 weeks). Immunohistochemistry assay was used to measure the expression of POMC and AgRP at different stages of DN rats.</p> </sec> <sec><title style='display:none'>Results</title> <p>The DN rats were established successfully. With the progression of DN, blood glucose, 24-h urinary albumin excretion rate and kidney body weight ratio increased significantly, while decreased when insulin was injected. Immunohistochemistry showed that the expression levels of POMC were decreased gradually in brain and kidney tissues. Conversely, the expression of AgRP in kidney was highest at week 8 and then decreased gradually. The effect of insulin on normalizing POMC and AgRP expression in brain and renal tissues was also observed in DKD rats.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>With the progression of DN, the expression of POMC and AgRP in kidney tissues was observed at different stages of disease, and their expressions were significantly normalized by insulin. The mechanism of <italic>in situ</italic> expression of POMC and AGRP in kidney to the progression of DN needs further investigations.</p> </sec> </abstract>ARTICLE2021-08-25T00:00:00.000+00:00Sitagliptin ameliorates ER stress in diabetic kidney disease through upregulation of SIRT1<abstract> <title style='display:none'>Abstract</title> <sec><title style='display:none'>Objectives</title> <p>Endoplasmic reticulum (ER) stress plays a significant role in the progression of diabetic kidney disease (DKD), and dipeptidyl peptidase-4 (DPP4) inhibitors are widely used antihyperglycemic agents, exerting renal beneficial effects in DKD. Here, we investigated the role of DPP4 inhibitor Sitagliptin (Sita) in ER homeostasis in the kidneys of diabetic DBA2/J (D2) mice and in albumin-stimulated HK-2 cells.</p> </sec> <sec><title style='display:none'>Methods and Results</title> <p>ER stress was observed both <italic>in vivo</italic> and <italic>in vitro</italic>, as reflected by notably increased glucose-regulated protein of 78 kDa (GRP78), CHOP, high phosphorylation of PERK (p-PERK), and cleaved caspase3 (c-CASP3), whereas Sita effectively attenuated these disorders. Meanwhile, Sita increased the expression of SIRT1 both <italic>in vivo</italic> and <italic>in vitro</italic>. To further validate the potential effects of SIRT1 in regulating ER stress, we regulated SIRT1 by siRNA and overexpressed plasmids in albumin-overloaded HK-2 cells. Elevated SIRT1 alleviated albumin-induced ER stress, while decreased SIRT1 further aggravated ER stress in albumin-treated HK-2 cells.</p> </sec> <sec><title style='display:none'>Conclusion</title> <p>The results suggest that a novel mechanism links the DPP4 enzyme to ER stress during tubular injury in DKD and highlight that SIRT1 may be a potential target for managing DKD.</p> </sec> </abstract>ARTICLE2021-08-25T00:00:00.000+00:00Inaugural Statement point mutation of mitochondrial genes in diabetes and deafness with focal segmental glomerular sclerosis<abstract> <title style='display:none'>Abstract</title> <p>Deafness, diabetes and proteinuria are typically understood to be an uncommon combination. Here, we reported a 26-year-old woman with a history of persistent deafness, diabetes mellitus, and proteinuria. The diagnosis mainly depends on clinical symptoms, but the cause of the disease should be examined. The histological finding in renal biopsy showed secondary focal segmental glomerular sclerosis (FSGS), but not classic diabetic nephropathy. Further pathogeny was found. Subsequently, a 3243A&gt;G mutation in the mitochondrial DNA was found. Thus, the diagnosis of maternally inherited deafness and diabetes (MIDD) was considered. Ineffective and unnecessary immunosuppression can be avoided through timely diagnosis. Long-term treatment of CoQ10 can be useful in MIDD patients.</p> </abstract>ARTICLE2021-08-25T00:00:00.000+00:00The multifaceted contributions of long noncoding RNAs on mitochondrial dysfunction in diabetic nephropathy A potential target for the treatment of diabetic nephropathy<abstract> <title style='display:none'>Abstract</title> <p>One of the major complications of diabetes mellitus is diabetic nephropathy (DN), the pathogenesis of which is primarily driven by oxidative stress. As a major regulator of antioxidant responses, the transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) has recently attracted much interest. NRF2 is a primary defense mechanism against the cytotoxic effects of oxidative stress, involving heterogeneous detoxification, the production of antioxidants and anti-inflammatory molecules, DNA repair, nuclear chaperones, and proteasome systems. A myriad of studies in pre-clinical models of DN have consistently demonstrated a beneficial effect of NRF2 activation, suggesting that NRF2 is likely a promising target for treating DN. This has been further supported by findings from clinical trials of bardoxolone methyl, an activator of NRF2, despite the unexpected adverse cardiovascular effects. This review summarizes the support for therapeutic targeting of NRF2 in DN and emphasizes the need for the optimization of NRF2-based treatment with the minimization of potential adverse effects.</p> </abstract>ARTICLE2021-08-25T00:00:00.000+00:00Key profibrotic and pro-inflammatory pathways in the pathogenesis of diabetic kidney disease<abstract> <title style='display:none'>Abstract</title> <p>Diabetes is a noncommunicable disease and arguably represents the greatest pandemic in human history. Diabetic kidney disease (DKD) is seen in both type 1 and type 2 diabetes and can be detected in up to 30–50% of diabetic subjects. DKD is a progressive chronic kidney disease (CKD) and is a leading cause of mortality and morbidity in patients with diabetes. Renal fibrosis and inflammation are the major pathological features of DKD. There are a large number of independent and overlapping profibrotic and pro-inflammatory pathways involved in the pathogenesis and progression of DKD. Among these pathways, the transforming growth factor-β (TGF-β) pathway plays a key pathological role by promoting fibrosis. Sirtuin-1 (SIRT1) is a protein deacetylase that has been shown to be renoprotective with an anti-inflammatory effect. It is postulated that a reduction in renal SIRT1 levels could play a key role in the pathogenesis of DKD and that restoration of SIRT1 will attenuate DKD. Cell division autoantigen 1 (CDA1) synergistically enhances the profibrotic effect of TGF-β in DKD by regulating the expression of the TGF-β type I receptor (TβRI). CDA1 has also been found to be an inhibitor of SIRT1 in the DNA damage response. Indeed, targeting CDA1 in experimental DKD not only attenuates diabetes-associated renal fibrosis but also attenuates the expression of key pro-inflammatory genes such as tumor necrosis factor-α (TNF-α) and Monocyte Che moattractant Protein-1 (MCP-1). In conclusion, there is a large body of experimental data to support the view that targeting CDA1 is a superior approach to directly targeting TGF-β in DKD since it is not only safe but also efficacious in retarding both fibrosis and inflammation.</p> </abstract>ARTICLE2021-08-25T00:00:00.000+00:00Simultaneous membranous nephropathy and diabetic nephropathy occurrence in a patient: A case report<abstract> <title style='display:none'>Abstract</title> <p>Membranous nephropathy (MN) is the most common glomerular disease in adults and is constantly associated with the occurrence of nephrotic syndrome. While diabetic kidney disease (DKD) and diabetic nephropathy (DN), which often occur in diabetic patients, are considered as the major causes of end-stage kidney disease. Actually, MN often occurs in patients with diabetes mellitus (DM), but to obtain a clear differential diagnosis without a renal biopsy has become difficult. Here we report the case of a female diabetic patient who developed both MN and DN simultaneously.</p> </abstract>ARTICLE2021-08-25T00:00:00.000+00:00en-us-1