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ObjectiveTo construct and validate a clinical prediction model for diabetic kidney disease （DKD） based on optical coherence tomography angiography （OCTA）. MethodsThis study enrolled 567 diabetes patients. The random forest algorithm as well as logistic regression analysis were applied to construct the prediction model. The model discrimination and clinical usefulness were evaluated by receiver operating characteristic curve （ROC） and decision curve analysis （DCA）， respectively. ResultsThe clinical prediction model for DKD based on OCTA was constructed with area under the curve （AUC） of 0.878 and Brier score of 0.11. ConclusionsThrough multidimensional verification， the clinical prediction nomogram model based on OCTA allowed for early warning and advanced intervention of DKD.
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Diabetic kidney disease （DKD） is a common microvascular complication of diabetics mellitus （DM） and the leading cause of end-stage renal disease （ESRD）. Renal interstitial fibrosis （RIF） is the primary pathological basis for DKD progression to ESRD， which significantly increases the mortality rate of DKD patients and burdens patients and society， and it is thus a clinical problem that needs to be solved urgently. The pathogenesis of RIF is complex and mainly associated with excessive deposition of extracellular matrix （ECM）， epithelial-mesenchymal transition （EMT）， oxidative stress， inflammation， and autophagy. Multiple signaling pathways such as transforming growth factor-β1/Smad （TGF-β1/Smad）， nuclear transcription factor-κB （NF-κB）， p38 mitogen-activated protein kinase （p38 MAPK）， secretory glycoprotein/β-catenin （Wnt/β-catenin）， mammalian target of rapamycin （mTOR）， Janus kinase/signal transducer and activator of transcription （JAK/STAT）， neurogenic site-gap homologous protein （Notch）， and nuclear factor E2-associated factor 2 （Nrf2） mediate the development of RIF， which are currently novel targets for DKD therapy. Due to the complexity of its pathogenesis， the current Western medical treatment mainly focuses on essential treatment to improve metabolism， which has poor efficacy and is difficult to prevent the progression of DKD， so it is significant to find new treatment methods clinically. In recent years， many studies have proved that traditional Chinese medicine can alleviate oxidative stress， inhibit inflammatory response， and regulate cellular autophagy by modulating relevant signaling pathways， so as to treat RIF in DKD， which has the advantages of multi-pathway， multi-targeting， multi-linking， and significant therapeutic efficacy. However， there is still a lack of relevant summary. By reviewing the latest research reports in China and abroad， this article examines the roles of the signaling pathways mentioned above in the occurrence and development of RIF in DKD and the recent research progress in the intervention of RIF in DKD by traditional Chinese medicine via these pathways， aiming to provide new ideas and references for further scientific research and clinical practice.
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Diabetic kidney disease （DKD） is the main cause of end-stage renal disease. Its high prevalence， mortality rate， and medical cost bring a heavy economic burden to society and families， and DKD has become one of the most important public health problems. Intestinal microecology is the most important and complex micro-ecosystem in the human body， which is involved in important life activities such as material and energy metabolism， immune system regulation， and signal transduction， thereby maintaining the dynamic balance of the human internal environment. The dynamic balance between the intestinal microecology and the body is essentially a Yin-Yang balance. Once this balance is broken， intestinal microbiota imbalance， intestinal mucosal barrier damage， immune dysfunction， and reduction of metabolite short-chain fatty acids （SCFAs） will occur， which play an important role in the progression of DKD. From the perspective of the Yin-Yang theory of traditional Chinese medicine （TCM）， the imbalance of intestinal microecology in DKD is equivalent to the excessive or insufficient constraint of Yin and Yang， or Yin deficiency affecting Yang， or Yang deficiency affecting Yin， or waning and waxing of Yin and Yang. For different pathogenesis changes， "Yin disease treated through Yang"， "treating Yin for Yang"， or "treating Yang for Yin" methods are adopted to regulate intestinal microbiota， inhibit immune inflammation， protect intestinal mucosal barrier， and increase SCFAs through TCM， thereby reconciling Yin and Yang to achieve the condition where "Yin is at peace and Yang is compact". Based on the Yin-Yang theory， this paper intended to interpret the scientific connotation of TCM in the treatment of DKD with intestinal microecology as the target and TCM in the treatment of DKD by regulating intestinal microecology as the breakthrough point to provide a novel insight for the occurrence and development of DKD and the mechanism of TCM.
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La enfermedad renal diabética (ERD) es una comorbilidad con alta prevalencia a nivel mundial, siendo una de las complicaciones más frecuentes de la diabetes mellitus (DM). La ERD se relaciona con complicaciones cardiovasculares y progresión de la enfermedad renal crónica (ERC), por ello la identificación de factores modificables, como el control de la presión arterial, es uno de los pilares más importantes en el manejo integral. En esta revisión hacemos un recorrido sobre el papel de la hipertensión y el bloqueo del eje renina angiotensina aldosterona (RAAS) en el curso de la ERD y las estrategias terapéuticas orientadas a la reducción de la presión arterial (PA), el bloqueo RAAS y el impacto en resultados renales y cardiovasculares. El objetivo de este artículo es hacer una revisión de las intervenciones más importantes que actúan bloqueando el eje renina angiotensina aldosterona (RAAS) y determinar si estas medidas en los pacientes con ERD, solo tienen impacto en el control de la presión arterial o si también son estrategias de nefro y cardio-protección. Conclusión: La ERD es una de las complicaciones más frecuentes de la diabetes mellitus (DM). El control de la PA sigue siendo un pilar fundamental para lograr estos objetivos. Los bloqueadores del RAAS (iECAS y BRAs) son los antihipertensivos de elección con efecto terapéutico por el bloqueo RAAS y esto les permite tener además del control de la PA, efectos nefroprotectores y cardioprotectores importantes en pacientes con ERD, sobre todo cuando hay la presencia de albuminuria. Evaluamos que además de los inhibidores de la enzima convertidora de angiotensina (iECAs) y los bloqueadores del receptor de angiotensina (BRAs), vienen tomando importancia los antagonistas selectivos del receptor mineralocorticoide (ARM) como Finerenona.
Diabetic kidney disease (DKD) is a comorbidity with a high worldwide prevalence, and one of the most frequent complications of diabetes mellitus (DM). CKD is related to cardiovascular complications and the progression of chronic kidney disease (CKD), therefore the identification of modifiable factors, such as blood pressure control, is one of the most important pillars in comprehensive management. In this review, we will analyze the role of hypertension and the renin-angiotensin-aldosterone system (RAAS) and its suppression in the course of CKD, and therapeutic strategies aimed at reducing blood pressure (BP), RAAS blockade, and the impact on renal and cardiovascular outcomes. The objective of this article is to review the most important interventions that act by blocking the renin-angiotensin-aldosterone system (RAAS) and to determine if these measures in patients with CKD only have an impact on blood pressure control or if they are also nephron and cardio-protective strategies. Conclusion: DKD is one of the most frequent complications of diabetes mellitus (DM). BP control continues to be a fundamental pillar to achieve these objectives. RAAS blockers (iECAS and ARBs) are the first-line antihypertensive with a therapeutic effect due to RAAS blockade and this allows them to have, in addition to BP control, important nephroprotective and cardioprotective effects in patients with CKD, especially when there is albuminuria. We evaluated that in addition to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), selective mineralocorticoid receptor antagonists (MRA) such as Finerenone are gaining importance.
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Diabetes Mellitus , Renal Insufficiency, Chronic , Hypertension , Angiotensins , Receptors, Angiotensin , Renin , Angiotensin Receptor Antagonists , Kidney DiseasesABSTRACT
Introducción: La diabetes mellitus (DM) es una enfermedad crónica inflamatoria muy frecuente y por ende una de las emergencias sanitarias mundiales de más rápido crecimiento en las últimas décadas. Hay tres ejes que impactan en la progresión del compromiso renal del paciente diabético. El eje hemodinámico, metabólico e inflamatorio. Resaltamos la importancia del componente inflamatorio como actor protagónico en el desarrollo de la Enfermedad renal diabética (ERD). El manejo del paciente con ERD debe ser holístico, con tres objetivos claros: buen control metabólico, disminuir progresión de la enfermedad renal y disminuir los desenlaces cardiovasculares adversos. Actualmente además de las intervenciones no farmacológicas, el control de los factores de riesgo, el uso de los IECAS/ARA II hay nuevos pilares en el tratamiento de la ERD. Objetivos: El objetivo de esta comunicación es revisar los nuevos pilares en el manejo de la ERD. En la revisión bibliográfica que se hizo, encontramos que hay tres nuevos pilares en el tratamiento. Los inhibidores SGLT-2, los agonistas del receptor GLP-1 y por último finerenona, que es un antagonista selectivo no esteroideo del receptor mineralocorticoide (ARM), no es un antidiabético. Con estas nuevas terapias el manejo actual de estos pacientes ha cambiado considerablemente. Conclusión: Hay nuevos pilares en el tratamiento de la ERD. Los inhibidores SGLT-2, los Agonistas del receptor GLP-1 y el uso de ARM como finerenona, que nos brindan beneficios cardiorenales y que hacen que hoy en día el tratamiento de la ERD tenga un mejor panorama.
Introduction: Diabetes mellitus (DM) is a very common chronic inflammatory disease and finally one of the fastest-growing global health emergencies in recent decades. Three axes impact the progression of renal compromise in diabetic patients. The hemodynamic, metabolic, and inflammatory axis. We highlight the importance of the inflammatory component as a leading actor in developing Diabetic Kidney Disease (DKD). The management of the patient with CKD must be holistic, with three clear objectives: reasonable metabolic control, slowing the progression of kidney disease, and reducing adverse cardiovascular outcomes. Currently, in addition to non-pharmacological interventions, the control of risk factors, and the use of ACE inhibitors/ARA II, there are new pillars in the treatment of CKD. Objectives: The objective of this communication is to review the new pillars in the management of DKD. In the bibliographic review that was carried out, we found that there are three new pillars in the treatment. SGLT-2 inhibitors, GLP-1 receptor agonists, and finally finerenone, which is a selective non-steroidal antagonist of the mineralocorticoid receptor (MRA), not an antidiabetic. With these new therapies, the current management of these patients has changed considerably. Conclusion: There are new pillars in the treatment of DKD. The SGLT-2 inhibitors, the GLP-1 receptor agonists, and the use of MRAs such as finerenone provide us with cardio-renal benefits and which today make the treatment of CKD have a better outlook.
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Diabetes Mellitus , Therapeutics , Kidney DiseasesABSTRACT
OBJECTIVE To systematically reevaluate （umbrella review） the systematic review/meta-analysis of Tripterygium glycosides （TG） in the treatment of diabetic kidney disease （DKD）， in order to provide a higher quality evidence-based reference for TG in the treatment of DKD. METHODS The systematic reviews/meta-analysis of TG in the treatment of DKD were searched from CNKI， Wanfang， VIP， CBM， PubMed， Cochrane Library and Embase. The PRISMA 2020 statement， the AMSTAR 2 scale and the GRADE tool were used to evaluate the quality of the report， the quality of the methodology， and the quality of the evidence， respectively. The quantitative results of the included systematic review/meta-analysis were analyzed comprehensively. RESULTS A total of 18 systematic reviews/meta-analyses were included. PRISMA 2020 stated that 3 reports were complete， 13 reports had partial information defects， and 2 reports had serious information defects. The results of the AMSTAR 2 scale evaluation showed that 4 literature had low methodological quality， and 14 literature had very low methodological quality. GRADE tool evaluation results showed that there were 106 outcome indicators， including 34 intermediate-quality evidence accounted for 32.1%， 51 poor-quality evidence accounted for 48.1%， 21 very poor-quality evidence accounted for 19.8%， and there was no high- quality evidence. Comprehensive analysis of quantitative results of various outcome indicators showed that TG had definite improvement effects on the total effective rate of DKD， 24-hour urinary protein quantity and serum albumin， and the adverse drug reactions were different in every study. CONCLUSIONS The efficacy of TG in the treatment of DKD is relatively accurate， safety still needs to be paid attention to， and future studies with larger sample size need to be verified.
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ObjectiveTo observe the effectiveness and safety of Qihuang Yishen Granules （芪黄益肾颗粒） combined with traditional Chinese medicine （TCM） chronic disease management on patients with diabetic kidney disease with deficiency qi and yin. MethodsTotally 140 patients diagnosed as diabetic kidney diseases with deficiency of both qi and yin were randomly divided into control group and trial group，with 70 cases in each group. Patients in the control group were treated with symptomatic treatment and routine chronic disease management. Patients in the trial group added Qihuang Yishen Granules and chronic disease management with TCM characteristics on the basis of symptomatic treatment. The course of treatment in both groups lasted for 6 months. The changes of laboratory indexes and chronic disease management level scores of the two groups of patients before treatment and after 3 and 6 months of treatment were compared， and their correlation were analyzed.The laboratory indexes of urinary protein and renal function related indicators such as 24-hour urinary protein quantification （24 hUTP）， serum creatinine （Scr）， blood urea nitrogen （BUN）， and estimated glomerular filtration rate （eGFR）， and control compliance rate， as well as blood glucose and lipid related indicators such as glycosylated hemoglobin （HbA1c）， low-density lipoprotein cholesterol （LDL-C）， triglyceride （TG） and control compliance rate were observed. The chronic disease management level scores included exercise，cognitive symptom management practice，communication with doctors， self-efficacy of symptom management，self-efficacy of disease commonness management. ResultsFinally，67 cases in the control group and 68 cases in the trial group completed the study. Compared with the group before treatment， the trial group had lower 24 hUTP and Scr， higher exercise score， total self-management score and all self-efficacy scale scores， higher TG at 3 months of treatment； at 6 months of treatment， the trial group had lower 24 hUTP， higher eGFR， and higher self-management scores and self-efficacy scale scores of all chronic diseases （P＜0.05）， and the control group had higher self-management total score （P＜0.05）. After 6 months of treatment， the trial group had lower 24 hUTP， Scr， LDL-C， and TG， higher eGFR， higher compliance rate of 24 hUTP， eGFR， LDL-C， and TG， and higher scores for all chronic disease management indexes compared with the control group （P＜0.05）. In terms of the correlation between laboratory indicators and chronic disease management level scores：there was a statistically significant difference in the correlation between 24hUTP and exercise，symptom management self-efficacy，and self-efficacy of disease commonness management （P＜0.05 or P＜0.01），all of which were negatively correlated. There was a statistically significant difference in the correlation between Scr and symptom management self-efficacy and self-efficacy of disease commonness management （P＜0.01），both of which were negatively correlated. There was a statistically significant difference in the correlation between eGFR and symptom management self-efficacy and self-efficacy of disease commonness management （P＜0.01），both of which were positively correlated. ConclusionQihuang Yishen Granules combined with chronic disease management of TCM can improve the level of proteinuria，renal function and lipid metabolism in patients with diabetic kidney disease with deficiency of both qi and yin，thus delaying the progress of diabetic kidney disease and also improve the level of chronic disease management of patients.
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Diabetic kidney disease (DKD) is the primary cause of mortality among diabetic patients. With the increasing prevalence of diabetes, it has become a major concern around the world. The therapeutic effect of clinical use of drugs is far from expected, and therapy choices to slow the progression of DKD remain restricted. Therefore, research on new drugs and treatments for DKD has been a hot topic in the medical field. It has been found that rhein has the potential to target the pathogenesis of DKD and has a wide range of pharmacological effects on DKD, such as anti-nephritis, decreasing blood glucose, controlling blood lipids and renal protection. In recent years, the medical value of rhein in the treatment of diabetes, DKD and renal disease has gradually attracted worldwide attention, especially its potential in the treatment of DKD. Currently, DKD can only be treated with medications from a single symptom and are accompanied by adverse effects, while rhein improves DKD with a multi-pathway and multi-target approach. Therefore, this paper reviews the therapeutic effects of rhein on DKD, and proposes solutions to the limitations of rhein itself, in order to provide valuable references for the clinical application of rhein in DKD and the development of new drugs.
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Humans , Diabetic Nephropathies/drug therapy , Kidney/pathology , Anthraquinones/therapeutic use , Diabetes MellitusABSTRACT
Previous studies have shown that high blood glucose-induced chronic microinflammation can cause inflammatory podocyte injury in patients with diabetic kidney disease(DKD). Therein, necroptosis is a new form of podocyte death that is closely associated with renal fibrosis(RF). To explore the effects and mechanisms in vivo of total flavones of Abelmoschus manihot(TFA), an extract from traditional Chinese herbal medicine Abelmoschus manihot for treating kidney diseases, on podocyte necroptosis and RF in DKD, and to further reveal its scientific connotation with multi-pathway and multi-target, the authors randomly divided all rats into four groups: a namely normal group, a model group, a TFA group and a rapamycin(RAP) group. After the modified DKD rat models were successfully established, four group rats were given double-distilled water, TFA suspension and RAP suspension, respectively by gavage every day. At the end of the 4th week of drug treatment, all rats were sacrificed, and the samples of their urine, blood and kidneys were collected. And then, the various indicators related to podocyte necroptosis and RF in the DKD model rats were observed, detected and analyzed, respectively. The results indicated that, general condition, body weight(BW), serum creatinine(Scr), urinary albumin(UAlb), and kidney hypertrophy index(KHI) in these modified DKD model rats were both improved by TFA and RAP. Indicators of RF, including glomerular histomorphological characteristics, fibronectin(FN) and collagen type Ⅰ(collagen Ⅰ) staining extent in glomeruli, as well as the protein expression levels of FN, collagen Ⅰ, transforming growth factor-β1(TGF-β1) and Smad2/3 in the kidneys were improved respectively by TFA and RAP. Podocyte damage, including foot process form and the protein expression levels of podocin and CD2AP in the kidneys was improved by TFA and RAP. In addition, tumor necrosis factor-α(TNF-α)-mediated podocyte necroptosis in the kidneys, including the morphological characteristics of podocyte necroptosis, the extent and levels of the protein expression of TNF-α and phosphorylated mixed lineage kinase domain like pseudokinase(p-MLKL) was improved respectively by TFA and RAP. Among them, RAP had the better effect on p-MLKL. More importantly, the activation of the receptor interacting serine/threonine protein kinase 1(RIPK1)/RIPK3/MLKL signaling axis in the kidneys, including the expression levels of its key signaling molecules, such as phosphorylated receptor interacting serine/threonine protein kinase 1(p-RIPK1), p-RIPK3, p-MLKL and cysteinyl aspartate specific proteinase-8(caspase-8) was improved respectively by TFA and RAP. Among them, the effect of TFA on p-RIPK1 was superior. On the whole, in this study, the authors demonstrated that TFA alleviates podocyte necroptosis and RF in DKD through inhibiting the activation of the TNF-α-mediated RIPK1/RIPK3/MLKL signaling axis in diabetic kidneys. The authors' findings provide new pharmacological evidence to reveal the scientific connotation of TFA in treating RF in DKD in more depth.
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Humans , Rats , Animals , Diabetic Nephropathies/drug therapy , Abelmoschus , Flavones/pharmacology , Podocytes , Tumor Necrosis Factor-alpha/metabolism , Necroptosis , Receptor-Interacting Protein Serine-Threonine Kinases/metabolism , Fibrosis , Threonine/pharmacology , Collagen/metabolism , Serine/pharmacology , Diabetes Mellitus/drug therapyABSTRACT
Diabetic kidney disease （DKD）， a chronic kidney disease with unique pathological structural and functional alterations in the kidney， is a common complication of diabetes mellitus （DM）. The majority of researchers believe that the occurrence of this disease is associated with glucose metabolism disorders， oxidative stress， inflammation， endoplasmic reticulum stress， autophagy， and disorders of lipid metabolism and exosome release. The mammalian target of rapamycin （mTOR） signaling pathway， which can maintain glomerular podocyte homeostasis and participate in autophagy， renal fibrosis， oxidative stress， lipid metabolism disorders， and inflammatory response in DKD， has been discovered to play a key role in DKD. Therefore， it has emerged as a novel target for the treatment of DKD. Studies have demonstrated that traditional Chinese medicine can prevent the renal damage in DKD by regulating the mTOR signaling pathway to delay the disease progression and improve the prognosis and the quality of life of the patients. This article summarizes the structure and role of the mTOR signaling pathway in DKD and briefs the research progress in the prevention and treatment of DKD via this signaling pathway by the active components， extracts， and compound prescriptions of Chinese medicines， aiming to present new ideas and approaches for the clinical treatment of DKD with traditional Chinese medicine.
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ObjectiveTo systematically evaluate the efficacy and safety of Jiedu Tongluo therapy in the treatment of diabetic kidney disease （DKD）. MethodDatabases including CNKI， Wanfang Data， PubMed， and Web of Science were systematically searched from January 2003 to December 2022 for clinical randomized controlled trials （RCTs） on the application of Jiedu Tongluo therapy for DKD treatment over the past 20 years. In these trials， the control group received conventional treatment （including diabetes and kidney health education， glycemic and blood pressure control， and lifestyle interventions）， along with western medicine or Chinese patent medicine treatment. The experimental group received primarily Jiedu Tongluo therapy via oral administration of Chinese medicine or in combination with western medicine. The Cochrane risk of bias assessment tool was used for the quality evaluation of the trials， and R 4.1.0 statistical software was used for analysis. ResultForty-one RCTs with 3 478 participants were included. The Meta-analysis results demonstrated that the experimental group， compared with the control group， showed significant improvement in overall clinical efficacy ［odds ratio （OR）=2.46， 95% confidence interval （CI） （2.08， 2.92）， I2=0%］， effective reduction of serum creatinine （Scr） levels ［mean difference （MD）=-15.83， 95% CI （-21.5， -10.37）， P< 0.01］， 24-hour urinary protein excretion rate （24 h-Up） ［MD=-350.88， 95% CI （-419.49， -282.28）， P< 0.01］， TCM syndrome score ［MD=-6.08， 95% CI （-7.81， -4.36）， P<0.01］， and effective regulation of fasting blood glucose （FBG） ［MD=-0.57， 95% CI （-0.75， -0.38）， P<0.01］. The treatment also demonstrated certain safety ［OR=0.99， 95% CI （0.35， 2.76）］. ConclusionJiedu Tongluo therapy in DKD treatment exhibits favorable clinical efficacy and safety. However， due to limitations in the quality and quantity of the included literature， these conclusions should be further validated through larger-scale， high-quality RCTs.
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Objective:To study the changes in long non-coding RNA C2dat1 expression in kidney tissues of rats at different stages of diabetic kidney disease (DKD) and its relationship with renal interstitial fibrosis.Methods:Forty-eight male SD rats were randomly divided into two groups with 24 rats in each group: control group and DKD group. The rats in the control group were fed with ordinary diet, while those in the DKD group were fed with high-fat diet and drank water freely. After eight weeks of feeding, the rats were fasted for 12 h with free access to water. Then, the DKD group was given a one-time intrabitoneal injection of streptozotocin and the control group was given an equal dose of sodium citrate buffer. After 72 h, the random peripheral blood glucose concentration (≥ 16.7 mmol/L for three consecutive days) and urine sugar (positive) were tested to assess the establishment of the diabetes model. Urine, blood and kidney samples were collected at 3, 6, 9 and 12 weeks. The urinary protein excretion rate within 24 h, urinary creatinine and serum total cholesterol were measured by automatic biochemical apparatus. Pathological changes in kidney tissues were observed by HE staining. The expression of calcium/calmodulin-dependent protein kinase Ⅱ delta (CaMK2D), p65, p50, α-SMA and E-cardherin was detected by immunohistochemistry. Quantitative real-time PCR (qPCR) was used to detect the expression of lncRNA C2dat1 and CaMK2D. The relationship of lncRNA C2dat1 with α-SMA, E-cardherin and CaMK2D was analyzed by correlation analysis. In in vitro experiment, renal tubular epithelial cells HK-2 were induced by high glucose. The expression of lncRNA C2dat1 and CaMK2D in HK-2 cells was detected by qPCR after 24, 48 and 72 h of intervention. Results:The rats in the DKD group showed typical symptoms such as polydipsia, polyphagia, significant weight loss and increased blood glucose as compared with the rats in the control group. Results of the biochemical tests revealed that compared with the control group, the DKD group had increased 24 h excretion rate of urinary protein, decreased urinary creatinine and up-regulated total cholesterol. HE staining showed that the rats in the control group had intact glomeruli, normal basement membrane and no mesangial hyperplasia or inflammatory cell infiltration. However, enlarged glomeruli and evenly thickened basement membrane were observed in the DKD group. Immunohistochemistry indicated that the expression of CaMK2D, p50 and α-SMA was higher in the DKD group than in the control group, while the expression of E-cardherin was lower in the DKD group. qPCR results showed that the expression of lncRNA C2dat1 and CaMK2D at mRNA level was higher in the DKD group than in the control group. In in vitro experiment, the expression of lncRNA C2dat1 and CaMK2D at mRNA level was also higher in HK-2 cells induced by high glucose than in the control group. Correlation analysis indicated that lncRNA C2dat1 was positively correlated with α-SMA and CaMK2D, but negatively correlated with E-cardherin. Conclusions:During the progression of DKD, the high expression of lncRNA C2dat1 might promote diabetic renal interstitial fibrosis by regulating the expression of CaMK2D to activate the NF-κB signaling pathway.
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It was a retrospective study. The patients with type 2 diabetes mellitus (T2DM) who underwent renal biopsy in the Department of Nephrology, the First Affiliated Hospital of Xi'an Jiaotong University from 2015 to 2021 were enrolled to analyze the pathological and clinical manifestations of kidney. There were 483 patients enrolled, including 136 patients who had no history of diabetes mellitus, newly diagnosed as T2DM according to an oral glucose tolerance test. The age was (52.80±13.13) years old. There were 337 males (69.77%). Based on the renal biopsy, the patients were classified as diabetic kidney disease (DKD, 22.15%, 107/483), DKD+non-diabetic kidney disease (NDKD)(6.63%, 32/483), and NDKD (71.22%, 344/483). Membranous nephropathy was the most common pathology in patients with NDKD (40.41%, 139/344) and DKD+NDKD (34.38%, 11/32). In the 136 newly diagnosed T2DM patients, there were 3 patients (2.21%) with DKD, 2 patients (1.47%) with DKD+NDKD, and 131 patients with NDKD (96.32%). The proportions of DKD in patients with diabetes history ≤3 months, 3-12 months, 1-5 years, 5-10 years and ≥10 years were 10.53% (6/57), 25.00% (16/64), 26.53% (26/98), 41.56% (32/77) and 47.06% (24/51), respectively. The proportions of DKD+NDKD in patients with diabetes history ≤3 months, 3-12 months, 1-5 years, 5-10 years and ≥10 years were 3.51% (2/57), 3.13% (2/64), 10.20% (10/98), 9.09% (7/77) and 17.65% (9/51), respectively. Multivariate logistic regression analysis results showed that, the duration of diabetes history ( OR=1.130, 95% CI 1.057-1.208, P<0.001), diabetes retinopathy ( OR=12.185, 95% CI 5.331-27.849, P<0.001), urinary red blood cell count ( OR=0.987, 95% CI 0.974-0.999, P=0.039), glycosylated hemoglobin ( OR=1.482, 95% CI 1.119-1.961, P=0.006) as well as hemoglobin ( OR=0.973, 95% CI 0.957-0.990, P=0.001) were independently correlated with DKD. The proportions of DKD and DKD+NDKD increase with the prolongation of diabetes history. Membranous nephropathy is the most common pathology in NDKD and DKD+NDKD patients. Even in patients newly diagnosed with T2DM, it is necessary to screen for DKD. The duration of diabetes history, diabetes retinopathy, urinary red blood cell count, glycosylated hemoglobin and hemoglobin may be used to identify DKD from NDKD.
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Objective:To systematically evaluate the clinical efficacy of compound α-ketoacid tablets in the treatment of diabetic kidney disease (DKD).Methods:CNKI, Wanfang database, EMBASE, PubMed and Cochrane Library database were searched for eligible records published from the establishment of individual database to November 13 th, 2022. The quality of the included studies were assessed, data were extracted, and meta-analysis was conducted using RevMan5.3. Results:A total of 26 randomized controlled trials were included, with a total of 2 790 DKD patients (1 465 in the experimental group and 1 325 in the control group). Multiple parameters were significantly improved in the experimental group compared with the control group, including 24-hour urinary protein, blood creatinine, urea nitrogen, nutritional index, oxidative stress level, fasting blood glucose, glycated hemoglobin, homocysteine, HGF, VEGF, TGF-β1, and systolic blood pressure.Conclusions:Limited low-quality evidence showed that compound α-ketoacid tablets combined with low-protein diet may be related to the improved 24-hour urinary protein, renal function, and glucose metabolism in patients with DKD. Due to the lack of randomized controlled trials designed for respective stages of DKD, the inclusion criteria of our study were relatively general, possibly leading to the lack of pertinence of the results. Some indicators showed apparent heterogeneity among different groups, and more high-quality multi-center studies with large sample sizes are still needed to verify our findings.
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Diabetic kidney disease （DKD） is characterized by the hyperfiltration and albuminuria in the early phase which are followed by progressive renal function decline， renal tubular epithelial cell hypertrophy， and tubulointerstitial fibrosis. Thus， it is one of the leading causes of chronic kidney diseases. The currently available therapies mainly aim to control the primary diseases and reduce the risk of kidney injury. Based on syndrome differentiation， traditional Chinese medicine （TCM） relieves the symptoms by excreting water and alleviating edema and eliminates the root cause by tonifying deficiency and supplementing the original Qi， thereby showing therapeutic effect and delaying the progression of DKD. It excels in comprehensively regulating the constitution of patients with little side effects. Among the Zang-fu organs， kidney takes the second place in the content of mitochondria which participate in the metabolism of water and fluid and are the foundation of kidney Yin and kidney Yang. Mitochondria are energy producers within a cell， which carry out cellular respiration， produce reactive oxygen species， and generate adenosine triphosphate by oxidative phosphorylation. Mitochondrial quality control （MQC） is an effective way to maintain mitochondrial dynamic balance， whose imbalances， such as mitochondrial oxidative stress， mitophagy， mitochondrial dynamic changes， and abnormal calcium regulation， are related to the occurrence and development of DKD. It is generally believed that the destruction of mitochondrial structure in the case of metabolic disorder is the main cause of the disease. In recent years， TCM has attracted the attention of both Chinese and foreign researchers for the unique advantages of treating both symptoms and root cause at the same time and multi-target synergy in the treatment of DKD. However， the specific mechanism is still unclear. It has been frequently verified that mitochondria may be one of the targets of TCM in the treatment of DKD. At the moment， no review on the treatment of DKD by TCM through the intervention of MQC is available. Therefore， this paper aims to summarize the research on TCM treatment of DKD by regulating MQC in the past 10 years， which is expected to provide a new direction for the treatment of DKD by TCM.
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Diabetes and its complications are major public health issues of worldwide concern. Diabetic microangiopathy is a vascular complication of diabetes caused by blood stasis and deficiency， characterized by impaired microcirculation with hyaline deposits. Diabetic nephropathy， diabetic retinopathy， and diabetic neuropathy are the most common types of diabetic microangiopathy， which can be traced back to the pre-diabetes period and is aggravated by the dynamic evolution of diabetes. Therefore， early intervention is required. Anti-oxidative， anti-inflammatory， and microcirculation-improving drugs should be chosen to treat diabetic microangiopathy based on hypoglycemic， lipid-lowering， and hypotensive treatment in clinical practice. Diabetic microangiopathy belongs to the theoretical concept of "collateral disease" in traditional Chinese medicine （TCM）. The core of the treatment of diabetic microangiopathy with Chinese medicine is to protect "tertiary collateral vessels-microvascular"， and Chinese medicines with Qi-replenishing， Yin-nourishing， heat-clearing， and blood-activating effect are used for compatibility in Chinese medicine prescriptions. Based on the understanding and treatment principles of TCM and western medicine for diabetic microangiopathy， this review briefly summarized the research progress of commonly used prescriptions such as Renshen Baihutang， Yuye Tang， Simiao Yongantang， Gegen Qiliantang， Liuwei Dihuangwan， and modern Chinese medicine preparations for the treatment of diabetic microangiopathy. Moreover， the research progress of Chinese medicines including Ginseng Radix et Rhizoma， Astragali Radix， Rehmannia Radix， Lycii Fructus， Notoginseng Radix et Rhizoma， Salviea Miltiorrhizae Radix et Rhizoma， Lonicera Japonica Flos， and Puerariae Lobatae Radix were outlined. This review is expected to provide the clinical basis and theoretical guidance for the treatment of diabetic microangiopathy with Chinese medicine.
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AIM: To observe the clinical efficacy of multi -glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ
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Aim To investigate the therapeutic effect of Jiangtang Wan (JTW) on mioe with diabetic kidney disease (DKD) and to explore its potential moiecuiar mechanism on ameliorating renal injury and fibrosis. Methods C57BL/6 mice were randomly divided into four groups: the control group, the model group, JTW group (1250 mg • kg
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Aim To investigate the effeots of empagliflozin on kidney tissue and autophagy-lysosome pathway in diabetio kidney disease (DKD) mice. Methods The db/m group as the control group, the db/db mice were randomly divided into the model group and empagliflozin group. After 8 weeks of administration, the levels of 24 h urine protein (24 h-UTP), fasting blood glucose (FBG), glycosylated hemoglobin (HBAlc), total cholestérol (TC), triglycéride (TG), blood urea nitrogen (BUN), serum creatinine (Scr), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β, and monocyte chemoattractant protein-1 (MCP-1) were detected. The expression of p62, LC3B, Beclinl, Agt7, LAMP1, Bcl-2, caspase-3 and Bax in kidney tissue was measured by Western blot. The pathological changes of kidney were observed under light microscope. Results Compared with the control group, the model group showed thickening of basement membrane, increased extracellular matrix, interstitial inflammatory cell infiltration and interstitial fibrosis (P < 0. 01). Moreover, the model group had higher content of FBG, HBAlc, 24h-UTP, TC, TG, BUN, Scr, TNF-α, IL-1β, and MCP-1 (P < 0. 01), higher expression of LC3B-/LC3B- I, Beclinl, LAMP1, Agt7 and Bcl-2 (P<0. 01), and lower expression of p62, caspase-3 and Bax in rénal tissue (P < 0. 01) than those in the control group. Compared with the model group, empagliflozin alleviated the pathological injury in kidney (P < 0. 01), and the changes in the above indicators were reversed. Conclusion By irepairing autophagy-lysosomal pathway in renal tissue, empagliflozin can promote the degradation of autophagy substrates, inhibit the production of inflammatory factors and apoptosis, thereby protecting the kidney.
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As the incidence of diabetes mellitus is rapidly increasing worldwide,that of related complications,such as diabetic kidney disease(DKD),also increases,conferring a heavy economic burden on the patients,families,society,and government.Diabetes mellitus complicated with chronic kidney disease(CKD)includes DKD and the CKD caused by other reasons.Because of the insufficient knowledge about CKD,the assessment of diabetes mellitus complicated with CKD remains to be improved.The therapies for diabetes mellitus complicated with CKD focus on reducing the risk factors.In clinical practice,DKD may not be the CKD caused by diabetes.According to clinical criteria,some non-diabetic kidney disease may be misdiagnosed as DKD and not be treated accurately.This review summarizes the status quo and research progress in the assessment,diagnosis,and treatment of diabetes mellitus complicated with CKD and predicts the directions of future research in this field.