二肽基肽酶-4抑制剂在糖尿病肾病治疗中的研究进展

糖尿病肾病(DKD)是糖尿病的严重并发症之一,亦是世界范围内导致终末期肾病的最常见原因。二肽基肽酶-4(DPP-4)抑制剂是以降低血糖为初衷而研发,由于DPP-4多样化的生物学特征,DPP-4抑制剂(DPP-4is)超越降低血糖以外的多效性肾脏保护的机制也不断被挖掘。越来越多的动物及临床研究证实DPP-4is可以改善DKD临床表现与组织病理,在DKD治疗中发挥重要的作用。但与安慰剂相比,DPP-4is在大规模临床研究中证实了非劣效性,而不是真正的肾保护功效。本文就DPP-4is在糖尿病肾病治疗中的研究进展进行综述。     

Neutrophil Extracellular Traps Promote NLRP3 Inflammasome Activation and Glomerular Endothelial Dysfunction in Diabetic Kidney Disease

Diabetes mellitus is a metabolic disease largely due to lifestyle and nutritional imbalance, resulting in insulin resistance, hyperglycemia and vascular complications. Diabetic kidney disease (DKD) is a major cause of end-stage renal failure contributing to morbidity and mortality worldwide. Therapeutic options to prevent or reverse DKD progression are limited. Endothelial and glomerular filtration barrier (GFB) dysfunction and sterile inflammation are associated with DKD. Neutrophil extracellular traps (NETs), originally identified as an innate immune mechanism to combat infection, have been implicated in sterile inflammatory responses in non-communicable diseases. However, the contribution of NETs in DKD remains unknown. Here, we show that biomarkers of NETs are increased in diabetic mice and diabetic patients and that these changes correlate with DKD severity. Mechanistically, NETs promote NLRP3 inflammasome activation and glomerular endothelial dysfunction under high glucose stress in vitro and in vivo. Inhibition of NETs (PAD4 inhibitor) ameliorate endothelial dysfunction and renal injury in DKD. Taken together, NET-induced sterile inflammation promotes diabetes-associated endothelial dysfunction, identifying a new pathomechanism contributing to DKD. Inhibition of NETs may be a promising therapeutic strategy in DKD.     

Dietary Phosphorus as a Marker of Mineral Metabolism and Progression of Diabetic Kidney Disease

Phosphorus is an essential nutrient that is critically important in the control of cell and tissue function and body homeostasis. Phosphorus excess may result in severe adverse medical consequences. The most apparent is an impact on cardiovascular (CV) disease, mainly through the ability of phosphate to change the phenotype of vascular smooth muscle cells and its contribution to pathologic vascular, valvular and other soft tissue calcification. Chronic kidney disease (CKD) is the most prevalent chronic disease manifesting with the persistent derangement of phosphate homeostasis. Diabetes and resulting diabetic kidney disease (DKD) remain the leading causes of CKD and end-stage kidney disease (ESRD) worldwide. Mineral and bone disorders of CKD (CKD-MBD), profound derangement of mineral metabolism, develop in the course of the disease and adversely impact on bone health and the CV system. In this review we aimed to discuss the data concerning CKD-MBD in patients with diabetes and to analyze the possible link between hyperphosphatemia, certain biomarkers of CKD-MBD and high dietary phosphate intake on prognosis in patients with diabetes and DKD. We also attempted to clarify if hyperphosphatemia and high phosphorus intake may impact the onset and progression of DKD. Careful analysis of the available literature brings us to the conclusion that, as for today, no clear recommendations based on the firm clinical data can be provided in terms of phosphorus intake aiming to prevent the incidence or progression of diabetic kidney disease.     

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD): A Korean Chronic Kidney Disease Cohort

The KoreaN Cohort Study for Outcomes in Patients With Chronic Kidney Disease (KNOW-CKD) was launched in 2011 with the support of the Korea Disease Control and Prevention Agency. The study was designed with the aim of exploring the various clinical features and characteristics of chronic kidney disease (CKD) in Koreans, and elucidating the risk factors for CKD progression and adverse outcomes of CKD. For the cohort study, nephrologists at 9 tertiary university-affiliated hospitals participated in patient recruitment and follow-up. Biostatisticians and epidemiologists also participated in the basic design and structuring of the study. From 2011 until 2016, the KNOW-CKD Phase I recruited 2238 adult patients with CKD from stages G1 to G5, who were not receiving renal replacement therapy. The KNOW-CKD Phase II recruitment was started in 2019, with an enrollment target of 1500 subjects, focused on diabetic nephropathy and hypertensive kidney diseases in patients with reduced kidney function who are presumed to be at a higher risk of adverse outcomes. As of 2021, the KNOW-CKD investigators have published articles in the fields of socioeconomics, quality of life, nutrition, physical activity, renal progression, cardiovascular disease and outcomes, anemia, mineral bone disease, serum and urine biomarkers, and international and inter-ethnic comparisons. The KNOW-CKD researchers will elaborate a prediction model for various outcomes of CKD such as the development of end-stage kidney disease, major adverse cardiovascular events, and death.     

Blood DNA Methylation Predicts Diabetic Kidney Disease Progression in High Fat Diet-Fed Mice

Diabetic kidney disease (DKD) progresses at different rates among patients with type 2 diabetes mellitus (T2D). Early identification of patients with a higher risk of DKD progression is essential to improve prognosis. Epigenetic modifications, particularly DNA methylation, have been independently implicated in T2D and chronic kidney disease. The current study aimed to determine changes in blood DNA methylation that reflects and predicts DKD progression. C57BL/6 mice were fed a high-fat diet (HFD) from weaning and subclassified into two groups, HFD-1 and HFD-2, according to urinary kidney injury marker KIM-1/creatinine ratios (low vs. high) and histological abnormalities (mild–moderate vs. advanced). DNA methylation profiles were determined by reduced representative bisulfide sequencing (RRBS). Our results confirmed early and established DKD at week 9 and week 32, respectively. At week 32, advanced kidney injury was associated with dysregulation of methylation and demethylation enzymes in the kidney. Blood RRBS revealed 579 and 203 differentially methylated sites (DMS) between HFD-1 and HFD-2 animals at week 32 and week 9, respectively, among which 11 were common. The DMS in blood and kidney at week 32 were both related to organ development, neurogenesis, cell junction, and Wnt signalling, while the DMS in blood at week 9 suggested a specific enrichment of kidney development processes. In conclusion, our data strongly support the implication of early blood DNA methylation modifications and DKD progression in T2D that could be used to improve the disease’s prognostication.     

Medical Nutrition Therapy in Adults with Chronic Kidney Disease: Integrating Evidence and Consensus into Practice for the Generalist Registered Dietitian Nutritionist

Chronic kidney disease is classified in stages 1 to 5 by the National Kidney Foundation's Kidney Disease Outcomes Quality Initiative depending on the level of renal function by glomerular filtration rate and, more recently, using further categorization depending on the level of glomerular filtration rate and albuminuria by the Kidney Disease Improving Global Outcomes initiative. Registered dietitian nutritionists can be reimbursed for medical nutrition therapy in chronic kidney disease stages 3 to 4 for specific clients under Center for Medicare and Medicaid Services coverage. This predialysis medical nutrition therapy counseling has been shown to both potentially delay progression to stage 5 (renal replacement therapy) and decrease first-year mortality after initiation of hemodialysis. The Joint Standards Task Force of the American Dietetic Association (now the Academy of Nutrition and Dietetics), the Renal Nutrition Dietetic Practice Group, and the National Kidney Foundation Council on Renal Nutrition collaboratively published 2009 Standards of Practice and Standards of Professional Performance for generalist, specialty, and advanced practice registered dietitian nutritionists in nephrology care. The purpose of this article is to provide an update on current recommendations for screening, diagnosis, and treatment of adults with chronic kidney disease for application in clinical practice for the generalist registered dietitian nutritionist using the evidence-based library of the Academy of Nutrition and Dietetics, published clinical practice guidelines (ie, National Kidney Foundation Council on Renal Nutrition, Renal Nutrition Dietetic Practice Group, Kidney Disease Outcomes Quality Initiative, and Kidney Disease Improving Global Outcomes), the Nutrition Care Process model, and peer-reviewed literature.     

Peri-renal fat thickness is positively associated with the urine albumin excretion rate in patients with type 2 diabetes

BackgroundsAlbuminuria, the earliest clinical manifestation of diabetic kidney disease (DKD), is a major prognostic indicator of renal progression. Obesity itself is associated with the development of DKD and accelerates its progression. Accumulation of peri-renal fat on the kidneys can damage kidney function. Measuring the perirenal fat thickness (PFT) by ultrasound is a non-invasive method to measure ectopic fat deposition on the kidney. In this study, we aim to obtain the association between albuminuria and PFT.MethodsEighty-nine subjects with type 2 diabetes mellitus (T2DM) were enrolled. Albuminuria was defined as a urine albumin-to-creatinine ratio (UACR) ≧30 mg/g. Measurement of the PFT was performed by B-mode ultrasound (Toshiba SSA-680A) and determined from the surface of the abdominal musculature to the surface of kidney. Pearson correlation coefficients were determined to test the significant independent relationship between the PFT and demographic, anthropometric and laboratory parameters.ResultsPatients were divided into those with (n = 66) and without (n = 23) albuminuria. PFT (odds ratio [OR], 19.3; 95% CI, 2.25–165.00; p = 0.01) was significantly correlated with albuminuria based on multiple logistic regression analysis. Additionally, linear regression confirmed that degree of albuminuria has a positive association with the PFT (r = 0.233; p = 0.03).ConclusionsOur study showed that an increased PFT is positively associated with the albuminuria among patients with T2DM. Our findings suggest that measurement of the PFT may represent a helpful tool to assess the risk of developing albuminuria in patients with T2DM.     

Ketoanalogue Supplementation in Patients with Non-Dialysis Diabetic Kidney Disease: A Systematic Review and Meta-Analysis

The effects of supplemental ketoanalogues (KA) in patients with diabetic kidney disease (DKD) are not well characterized. Several databases for peer-reviewed articles were systematically searched to identify studies reporting outcomes associated with the effects of a low-protein diet (LPD) or very-low protein diet (VLPD) in combination with supplemental KA in adults with DKD. Meta-analyses were conducted when feasible. Of 213 identified articles, 11 could be included in the systematic review. Meta-analyses for renal outcomes (4 studies examining glomerular filtration rate; 5 studies examining 24-h urinary protein excretion), metabolic outcomes (5 studies examining serum urea; 7 studies examining blood glucose), clinical outcomes (6 studies examining blood pressure; 4 studies examining hemoglobin), and nutritional outcomes (3 studies examining serum albumin; 4 studies examining body weight) were all in favor of KA use in DKD patients. Data from individual studies that examined other related parameters also tended to show favorable effects from KA-supplemented LPD/VLPD. The regimens were safe and well tolerated, with no evidence of adverse effects on nutritional status. In conclusion, LPD/VLPD supplemented with KA could be considered effective and safe for patients with non-dialysis dependent DKD. Larger studies are warranted to confirm these observations.     

Failure of ICD-9-CM codes to identify patients with comorbid chronic kidney disease in diabetes

OBJECTIVE: To determine prevalence of chronic kidney disease (CKD) in patients with diabetes, and accuracy of International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes to identify such patients. DATA SOURCES/STUDY SETTING: Secondary data from 1999 to 2000. We linked all inpatient and outpatient administrative and clinical records of U.S. veterans with diabetes dually enrolled in Medicare and the Veterans Administration (VA) health care systems. STUDY DESIGN: We used a cross-sectional, observational design to determine the sensitivity and specificity of renal-related ICD-9-CM diagnosis codes in identifying individuals with chronic kidney disease. DATA COLLECTION/EXTRACTION METHODS: We estimated glomerular filtration rate (eGFR) from serum creatinine and defined CKD as Stage 3, 4, or 5 CKD by eGFR criterion according to the Kidney Disease Outcomes Quality Initiative guidelines. Renal-related ICD-9-CM codes were grouped by algorithm. PRINCIPAL FINDINGS: Prevalence of CKD was 31.6 percent in the veteran sample with diabetes. Depending on the detail of the algorithm, only 20.2 to 42.4 percent of individuals with CKD received a renal-related diagnosis code in either VA or Medicare records over 1 year. Specificity of renal codes for CKD ranged from 93.2 to 99.4 percent. Patients hospitalized in VA facilities were slightly more likely to be correctly coded for CKD than patients hospitalized in facilities reimbursed by Medicare (OR 5.4 versus 4.1, p=.0330) CONCLUSIONS: CKD is a common comorbidity for patients with diabetes in the VA system. Diagnosis codes in administrative records from Medicare and VA systems are insensitive, but specific markers for patients with CKD.     

Dietary Advanced Glycation End Products in an Elderly Population with Diabetic Nephropathy: An Exploratory Investigation

Advanced glycation end products (AGEs) are important in pathophysiology of type 2 diabetes mellitus (T2DM) and diabetic kidney disease (DKD). Dietary AGEs (dAGEs) contribute to the overall AGE pool in the body. Forty elderly T2DM patients with DKD were randomly allocated to a low-AGE (n = 20) or regular diabetic (n = 20) diet group. A three-day meal questionnaire was used to estimate average quantity of dAGEs. AGE accumulation was measured using skin autofluorescence and urine spectroscopy. sRAGE (soluble receptor AGE) was quantified using ELISA. After 8 weeks, the mean consumption of dAGEs was considerably reduced, both in the low-AGE diet (p = 0.004) and the control (p = 0.019) group. The expected urinary emission peak at 490 nm was shifted to 520 nm in some spectra. dAGEs did not correspond with urine AGE output. An AGE-limited diet for two months did not affect AGE content in skin and urine, or sRAGE concentration in the blood. The role of glycemia is likely to be greater than the impact of dAGE consumption. The unique observation of a fluorescence pattern at 520 nm warrants further examination, since it might point to genetic differences in AGE regulation, which could have clinical consequences, as AGE content depends on its formation and elimination.     

壮族2型糖尿病患者空腹甘油三酯变异性与糖尿病肾病的关系及影响因素分析

目的 探讨壮族2型糖尿病患者甘油三酯(triglycerides, TG)变异性对糖尿病肾病(diabetic kidney disease, DKD)发生风险的影响及分析影响因素。方法 选取2014年1—12月医院收治的276例基线无糖尿病肾病的广西壮族2型糖尿病患者作为研究对象,随访时间为2～5年。收集患者的一般资料和生理指标,根据随访时的TG测量值计算TG的均值和标准差,TG变异性采用TG标准差进行表示,根据TG标准差的中位数进行分组,分为低TG变异性组(标准差<1.14)和高TG变异性组(标准差≥1.14),比较两组基线时各类指标的差异,采用Cox比例风险模型分析TG变异性与DKD发生风险的关系,分析TG变异性及DKD发病的影响因素。结果 相较于低TG变异性组,高TG变异性组的女性、发生糖尿病肾病比例、体质指数、空腹血糖、总胆固醇、甘油三酯、低密度胆固醇水平较高、年龄较低,差异均有统计学意义(P<0.05)。多元线性回归显示,年龄、病程、收缩压、舒张压、总胆固醇是TG变异性的影响因素(P<0.05)。多因素Cox回归分析结果显示,TG变异性是DKD的独立影响因...     

2型糖尿病慢性并发症影响因素的病例对照研究

目的 研究影响2型糖尿病(T2DM)患者慢性并发症发生的主要因素.方法 运用以医院为基础的频数匹配的病例对照研究方法,以性别、年龄和民族进行频数匹配,运用单因素和多因素方法分析总慢性并发症及糖尿病心血管并发症、糖尿病眼病、糖尿病神经病变发生的影响因素.结果 (1)T2DM总慢性并发症的危险因素及其OR值:高C反应蛋白(CRP)(OR=5.568)、血脂异常(OR=4.400)、高尿素氮(BUN)(OR=4.399)、高LDL-C(OR=3,594)、住院总时间(OR=2.612)、病前喜食油腻(OR=2.300)、高糖化血红蛋白(HbA1c%)(OR=1.747)、病后缺乏锻炼(OR=1.672)、糖尿病病程(OR=1.509)、精神压力大(OR=1.427);保护因素及其OR值:睡眠质量高(OR=0.606)、血糖控制佳(OR=O.517)、血脂控制佳(OR=0.299)、使用胰岛素(OR=0.155).糖尿病心血管并发症的主要危险因素为高BUN、高血压、高CRP、高LDL-C.糖尿病眼病的主要危险因素为高BUN、高CRP、病前喜食油腻.糖尿病神经病变的主要危险因素为喜食甜食.结论 (1)高CRP、血脂异常、高BUN、高LDL-C是导致T2DM慢性并发症发生的主要危险因素;使用胰岛素、血脂控制佳是T2DM慢性并发症的主要保护因素.(2)心血管并发症独有的危险因素为高LDL-C、精神压力大,神经病变独有的危险因素为病后缺乏锻炼、喜食甜食,眼病并无其独有的危险因素;心血管疾病、神经病变、眼病共同的危险因素为糖尿病病程,共同的保护因素为使用胰岛素.     

糖尿病患者尿蛋白及踝肱指数异常的相关性分析

目的了解糖尿病肾病（DKD）与下肢动脉病变（PAD）的关系及相关因素。方法分析了4031例2型糖尿病患者的临床资料,将患者分为正常蛋白尿、微量蛋白尿和临床蛋白尿组,并根据踝肱动脉压指数（ABI）分为正常组与异常组,统计各组中尿蛋白和ABI的异常率,采用Logistic回归方法分析PAD与DKD相关性及其影响因素。结果全组患者中尿蛋白异常率26．35％,ABI异常率17．73％;异常组与正常组相比,年龄大,病程长,糖化血红蛋白（HbAIC）高,血压高,脉压差大。正常蛋白尿、微量蛋白尿和临床蛋白尿组的ABI异常率分别为14．55％,21．92％和28．42％;ABI正常和ABI≤0．9、ABI〉1．3的患者DKD患病率分别为23．79％,41．43％,30．60％;多因素分析发现,年龄、性别、尿蛋白异常、体质指数（BMI）、立位收缩压、立位舒张压、空腹血糖、总蛋白（TP）、血清白蛋白（AIB）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）、肌酐（Cr）是PAD的独立危险因素;年龄、病程、ABI异常、BMI、卧位收缩压、卧位舒张压、餐后血糖、HbA。白蛋白、白蛋白／球蛋白（MG）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL—C）,Cr、尿素氮（BUN）是DKD的主要危险因素。结论糖尿病肾病与下肢动脉病变密切相关,可相互促进病情发展。     

Saccharin and Sucralose Protect the Glomerular Microvasculature In Vitro against VEGF-Induced Permeability

Diabetic kidney disease (DKD) has become a global health concern, with about 40% of people living with type 1 and type 2 diabetes mellitus developing DKD. Upregulation of vascular endothelial growth factor (VEGF) in the kidney is a significant pathology of DKD associated with increased glomerular vascular permeability. To date, however, current anti-VEGF therapies have demonstrated limited success in treating DKD. Recent studies have shown that artificial sweeteners exhibit anti-VEGF potential. The aim of this study was therefore to assess the effects of aspartame, saccharin, and sucralose on VEGF-induced leak using an in vitro model of the glomerular endothelium. Saccharin and sucralose but not aspartame protected against VEGF-induced permeability. Whilst the sweeteners had no effect on traditional VEGF signalling, GC-MS analysis demonstrated that the sweetener sucralose was not able to enter the glomerular endothelial cell to exert the protective effect. Chemical and molecular inhibition studies demonstrated that sweetener-mediated protection of the glomerular endothelium against VEGF is dependent on the sweet taste receptor, T1R3. These studies demonstrate the potential for sweeteners to exert a protective effect against VEGF-induced increased permeability to maintain a healthy endothelium and protect against vascular leak in the glomerulus in settings of DKD.     

慢性肾脏病患者糖皮质激素治疗中的

糖皮质激素作为一种抗炎介质在慢性肾脏病的治疗中有重要地位,而糖皮质激素的使用可使患者发生胰岛素抵抗或使原有胰岛素抵抗加重。胰岛素抵抗与肾脏病变关系密切,可作为慢性肾脏病发生发展的独立危险因素,并加重肾脏病变。慢性肾脏病患者亦可有胰岛素抵抗表现,这给慢性肾脏病患者的糖皮质激素治疗造成了困难,本文就这一问题进行综述。     

2型糖尿病慢性并发症影响因素的病例对照研究

目的 研究影响2型糖尿病(T2DM)患者慢性并发症发生的主要因素.方法 运用以医院为基础的频数匹配的病例对照研究方法,以性别、年龄和民族进行频数匹配,运用单因素和多因素方法分析总慢性并发症及糖尿病心血管并发症、糖尿病眼病、糖尿病神经病变发生的影响因素.结果 (1)T2DM总慢性并发症的危险因素及其OR值:高C反应蛋白(CRP)(OR=5.568)、血脂异常(OR=4.400)、高尿素氮(BUN)(OR=4.399)、高LDL-C(OR=3,594)、住院总时间(OR=2.612)、病前喜食油腻(OR=2.300)、高糖化血红蛋白(HbA1c%)(OR=1.747)、病后缺乏锻炼(OR=1.672)、糖尿病病程(OR=1.509)、精神压力大(OR=1.427);保护因素及其OR值:睡眠质量高(OR=0.606)、血糖控制佳(OR=O.517)、血脂控制佳(OR=0.299)、使用胰岛素(OR=0.155).糖尿病心血管并发症的主要危险因素为高BUN、高血压、高CRP、高LDL-C.糖尿病眼病的主要危险因素为高BUN、高CRP、病前喜食油腻.糖尿病神经病变的主要危险因素为喜食甜食.结论 (1)高CRP、血脂异常、高BUN、高LDL-C是导致T2DM慢性并发症发生的主要危险因素;使用胰岛素、血脂控制佳是T2DM慢性并发症的主要保护因素.(2)心血管并发症独有的危险因素为高LDL-C、精神压力大,神经病变独有的危险因素为病后缺乏锻炼、喜食甜食,眼病并无其独有的危险因素;心血管疾病、神经病变、眼病共同的危险因素为糖尿病病程,共同的保护因素为使用胰岛素.     

Chronic Kidney Disease: Role of Diet for a Reduction in the Severity of the Disease

Chronic kidney disease affects ~37 million adults in the US, and it is often undiagnosed due to a lack of apparent symptoms in early stages. Chronic kidney disease (CKD) interferes with the body’s physiological and biological mechanisms, such as fluid electrolyte and pH balance, blood pressure regulation, excretion of toxins and waste, vitamin D metabolism, and hormonal regulation. Many CKD patients are at risk of hyperkalemia, hyperphosphatemia, chronic metabolic acidosis, bone deterioration, blood pressure abnormalities, and edema. These risks may be minimized, and the disease’s progression may be slowed through careful monitoring of protein, phosphorus, potassium, sodium, and calcium, relieving symptoms experienced by CKD patients. In this review, the current Kidney Disease Outcomes Quality Initiative (KDOQI) recommendations are highlighted, reflecting the 2020 update, including explanations for the pathophysiology behind the recommendations. The Dietary Approaches to Stop Hypertension, the Mediterranean diet, and the whole foods plant-based diet are currently being examined for their potential role in delaying CKD progression. Biological explanations for why the whole foods plant-based diet may benefit CKD patients compared to diets that include animal products are examined. Strong evidence continues to support the importance of diet meeting the daily requirement in the prevention and progression of kidney disease, and medical nutrition therapy with a registered dietitian is a critical aspect in medical intervention for CKD.     

Activated Protein C Ameliorates Tubular Mitochondrial Reactive Oxygen Species and Inflammation in Diabetic Kidney Disease

Diabetic kidney disease (DKD) is an emerging pandemic, paralleling the worldwide increase in obesity and diabetes mellitus. DKD is now the most frequent cause of end-stage renal disease and is associated with an excessive risk of cardiovascular morbidity and mortality. DKD is a consequence of systemic endothelial dysfunction. The endothelial-dependent cytoprotective coagulation protease activated protein C (aPC) ameliorates glomerular damage in DKD, in part by reducing mitochondrial ROS generation in glomerular cells. Whether aPC reduces mitochondrial ROS generation in the tubular compartment remains unknown. Here, we conducted expression profiling of kidneys in diabetic mice (wild-type and mice with increased plasma levels of aPC, APC^high mice). The top induced pathways were related to metabolism and in particular to oxidoreductase activity. In tubular cells, aPC maintained the expression of genes related to the electron transport chain, PGC1-α expression, and mitochondrial mass. These effects were associated with reduced mitochondrial ROS generation. Likewise, NLRP3 inflammasome activation and sterile inflammation, which are known to be linked to excess ROS generation in DKD, were reduced in diabetic APC^high mice. Thus, aPC reduces mitochondrial ROS generation in tubular cells and dampens the associated renal sterile inflammation. These studies support approaches harnessing the cytoprotective effects of aPC in DKD.     

Role and Treatment of Insulin Resistance in Patients with Chronic Kidney Disease: A Review

Patients with chronic kidney disease (CKD) and dialysis have higher mortality than those without, and cardiovascular disease (CVD) is the main cause of death. As CVD is caused by several mechanisms, insulin resistance plays an important role in CVD. This review summarizes the importance and mechanism of insulin resistance in CKD and discusses the current evidence regarding insulin resistance in patients with CKD and dialysis. Insulin resistance has been reported to influence endothelial dysfunction, plaque formation, hypertension, and dyslipidemia. A recent study also reported an association between insulin resistance and cognitive dysfunction, non-alcoholic fatty liver disease, polycystic ovary syndrome, and malignancy. Insulin resistance increases as renal function decrease in patients with CKD and dialysis. Several mechanisms increase insulin resistance in patients with CKD, such as chronic inflammation, oxidative stress, obesity, and mineral bone disorder. There is the possibility that insulin resistance is the potential future target of treatment in patients with CKD.