Risk factors for developing osteoporosis in diabetic kidney disease and its correlation with calcium-phosphorus metabolism,FGF23,and Klotho

BACKGROUND The progression of diabetic kidney disease(DKD)affects the patient’s kidney glomeruli and tubules,whose normal functioning is essential for maintaining normal calcium(Ca)and phosphorus(P)metabolism in the body.The risk of developing osteoporosis(OP)in patients with DKD increases with the aggravation of the disease,including a higher risk of fractures,which not only affects the quality of life of patients but also increases the risk of death.AIM To analyze the risk factors for the development of OP in patients with DKD and their correlation with Ca-P metabolic indices,fibroblast growth factor 23(FGF23),and Klotho.METHODS One hundred and fifty-eight patients with DKD who were admitted into the Wuhu Second People’s Hospital from September 2019 to May 2021 were selected and divided into an OP group(n=103)and a normal bone mass group(n=55)according to their X-ray bone densitometry results.Baseline data and differences in Ca-P biochemical indices,FGF23,and Klotho were compared.The correlation of Ca-P metabolic indices with FGF23 and Klotho was discussed,and the related factors affecting OP in patients with DKD were examined by multivariate logistic regression analysis.RESULTS The OP group had a higher proportion of females,an older age,and a longer diabetes mellitus duration than the normal group(all P<0.05).Patients in the OP group exhibited significantly higher levels of intact parathyroid hormone(iPTH),blood P,Ca-P product(Ca×P),fractional excretion of phosphate(FeP),and FGF23,as well as lower estimated glomerular filtration rate,blood Ca,24-hour urinary phosphate excretion(24-hour UPE),and Klotho levels(all P<0.05).In the OP group,25-(OH)-D3,blood Ca,and 24-hour UPE were negatively correlated with FGF23 and positively correlated with Klotho.In contrast,iPTH,blood Ca,Ca×P,and FeP exhibited a positive correlation with FGF23 and an inverse association with Klotho(all P<0.05).Moreover,25-(OH)-D3,iPTH,blood Ca,FePO4,FGF23,Klotho,age,and female gender were key factors that affected the lumbar and left femoral neck bone mineral density.CONCLUSION The Ca-P metabolism metabolic indexes,FGF23,and Klotho in patients with DKD are closely related to the occurrence and development of OP.

Mechanistic study of lipid metabolism disorders in diabetic kidney disease treated with GLQMP based on network pharmacology,molecular docking and in vitro experiments

Background:In this study,we used network pharmacology and molecular docking combined with vitro experiments to explore the potential mechanism of action of Gualou Qumai pill(GLQMP)against DKD.Methods:We screened effective compounds and drug targets using Chinese medicine systemic pharmacology database and analysis platform and Chinese medicine molecular mechanism bioinformatics analysis tools;and searched for DKD targets using human online Mendelian genetics and gene cards.The potential targets of GLQMP for DKD were obtained through the intersection of drug targets and disease targets.Cytoscape software was applied to build herbal medicine-active compound-target-disease networks and analyze them;protein-protein interaction networks were analyzed using the STRING database platform;gene ontology and Kyoto Encyclopedia of Genes and Genomes were used for gene ontology and gene and genome encyclopedia to enrich potential targets using the DAVID database;and the AutoDock Vina 1.1.2 software for molecular docking of key targets with corresponding key components.In vitro experiments were validated by CCK8,oil red O staining,TC,TG,RT-qPCR,and Western blot.Results:Through network pharmacology analysis,a total of 99 potential therapeutic targets of GLQMP for DKD and the corresponding 38 active compounds were obtained,and 5 core compounds were identified.By constructing the protein-protein interaction network and performing network topology analysis,we found that PPARA and PPARG were the key targets,and then we molecularly docked these two key targets with the 38 active compounds,especially the 5 core compounds,and found that PPARA and PPARG had good binding ability with a variety of compounds.In vitro experiments showed that GLQMP was able to ameliorate HK-2 cell injury under high glucose stress,improve cell viability,reduce TC and TG levels as well as decrease the accumulation of lipid droplets,and RT-qPCR and Western blot confirmed that GLQMP was able to promote the expression levels of PPARA and PPARG.Conclusion:Overall,this study revealed the active compounds,important targets and possible mechanisms of GLQMP treatment for DKD,and conducted preliminary verification experiments on its correctness,provided novel insights into the treatment of DKD by GLQMP.

Effects of Yue-Bi-Tang on water metabolism in severe acute pancreatitis rats with acute lung-kidney injury

BACKGROUND The complications acute lung injury and acute kidney injury caused by severe inflammation are the main reasons of high mortality of severe acute pancreatitis(SAP).These two complications can both lead to water metabolism and acid-base balance disorders,which could act as additional critical factors affecting the disease trend.Aquaporins(AQPs),which can regulate the transmembrane water transport,have been proved to participate in the pathophysiological process of SAP and the associated complications,such as acute lung injury and acute kidney injury.Thus,exploring herbs that can effectively regulate the expression of AQP in SAP could benefit the prognosis of this disease.AIM To determine whether Yue-Bi-Tang(YBT)can regulate the water metabolism in rats with severe acute pancreatitis via regulating the expression of aquaporins.METHODS Sprague-Dawley rats were randomly divided into three groups,sham operation group(SOG),model group(MG),and treatment group(TG).SAP was induced with 3.5%sodium taurocholate in the MG and TG.Rats in the TG were administered with YBT while SOG and MG rats were given the same volume of saline.Blood and tissue samples were harvested to detect serum inflammatory cytokines,histopathological changes,malondialdehyde and superoxide dismutase in the lung,and protein and mRNA expression of kidney injury molecule-1,α-smooth muscle actin,and vimentin in the kidney,and AQP1 and 4 in the lung,pancreas,and kidney.RESULTS The serum interleukin-10,tumor necrosis factorα,and creatinine levels were higher in the MG than in the SOG.Tumor necrosis factorαlevel in the TG was lower than that in the MG.Malondialdehyde level in lung tissues was higher than in the SOG.The pathological scores and edema scores of the pancreas,lung,and kidney tissues in the MG were all higher than those in the SOG and TG.The protein expression of AQP4 in lung tissues and AQP1 in kidney tissues in the MG were higher than those in the SOG and TG.The expression of vimentin was significantly higher in the MG than in the SOG.The expression of AQP1 mRNA in the lung and kidney,and AQP4 mRNA in the kidney was up-regulated in the MG compared to the SOG.CONCLUSION YBT might regulate water metabolism to reduce lung and kidney edema of SAP rats via decreasing AQP expression,and alleviate the tissue inflammatory injury.

Effects of hypoxia on bone metabolism and anemia in patients with chronic kidney disease

BACKGROUND Abnormal bone metabolism and renal anemia seriously affect the prognosis of patients with chronic kidney disease(CKD).Existing studies have mostly addressed the pathogenesis and treatment of bone metabolism abnormality and anemia in patients with CKD,but few have evaluated their mutual connection.Administration of exogenous erythropoietin to CKD patients with anemia used to be the mainstay of therapeutic approaches;however,with the availability of hypoxia-inducible factor(HIF)stabilizers such as roxadustat,more therapeutic choices for renal anemia are expected in the future.However,the effects posed by the hypoxic environment on both CKD complications remain incompletely understood.AIM To summarize the relationship between renal anemia and abnormal bone metabolism,and to discuss the influence of hypoxia on bone metabolism.METHODS CNKI and PubMed searches were performed using the key words“chronic kidney disease,”“abnormal bone metabolism,”“anemia,”“hypoxia,”and“HIF”to identify relevant articles published in multiple languages and fields.Reference lists from identified articles were reviewed to extract additional pertinent articles.Then we retrieved the Abstract and Introduction and searched the results from the literature,classified the extracted information,and summarized important information.Finally,we made our own conclusions.RESULTS There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Abnormal vitamin D metabolism and hyperparathyroidism can affect bone metabolism,blood cell production,and survival rates through multiple pathways.Anemia will further attenuate the normal bone growth.The hypoxic environment regulates bone morphogenetic protein,vascular endothelial growth factor,and neuropilin-1,and affects osteoblast/osteoclast maturation and differentiation through bone metabolic changes.Hypoxia preconditioning of mesenchymal stem cells(MSCs)can enhance their paracrine effects and promote fracture healing.Concurrently,hypoxia reduces the inhibitory effect on osteocyte differentiation by inhibiting the expression of fibroblast growth factor 23.Hypoxia potentially improves bone metabolism,but it still carries potential risks.The optimal concentration and duration of hypoxia remain unclear.CONCLUSION There is a bidirectional relationship between renal anemia and abnormal bone metabolism.Hypoxia may improve bone metabolism but the concentration and duration of hypoxia remain unclear and need further study.

Eff ects of continuous renal replacement therapy on infl ammation-related anemia, iron metabolism and prognosis in sepsis patients with acute kidney injury

BACKGROUND:This study aims to evaluate the eff ect of continuous renal replacement therapy(CRRT)on inflammation-related anemia,iron metabolism,and the prognosis in sepsis patients with acute kidney injury(AKI).METHODS:Sepsis patients with AKI were prospectively enrolled and randomized into the CRRT and control groups.The clinical and laboratory data on days 1,3 and 7 after intensive care unit(ICU)admission were collected.The serum interleukin(IL)-6,hepcidin,erythropoietin,ferritin,and soluble transferrin receptor(sTfR)were determined by enzyme-linked immunosorbent assay.The Sequential Organ Failure Assessment(SOFA)score and 28-day mortality were recorded.Data were analyzed using Pearson’s Chi-square test or Fisher’s exact test(categorical variables),and Mann-Whitney U-test or t-test(continuous variables).RESULTS:The hemoglobin and serum erythropoietin levels did not signifi cantly diff er between the CRRT and control groups though gradually decreased within the first week of ICU admission.On days 3 and 7,the serum IL-6,hepcidin,ferritin,and red blood cell distribution width significantly decreased in the CRRT group compared to the control group(all P<0.05).On day 7,the serum iron was significantly elevated in the CRRT group compared to the control group(P<0.05).However,the serum sTfR did not signifi cantly diff er between the groups over time.In addition,the SOFA scores were signifi cantly lower in the CRRT group compared to the control group on day 7.The 28-day mortality did not signifi cantly diff er between the control and CRRT groups(38.0%vs.28.2%,P=0.332).CONCLUSION:CRRT might have beneficial effects on the improvement in inflammationrelated iron metabolism and disease severity during the fi rst week of ICU admission but not anemia and 28-day mortality in sepsis patients with AKI.

The research progress of epigenetics and metabolic memory in diabetic kidney disease

Diabetic kidney disease(DKD)is a clinical syndrome that is one of the major causes of end-stage renal disease(ESRD).The pathogenesis of DKD is complex and multifaceted,with most studies indicating its association with genetics,advanced glycosylation end-product deposition,polyol pathway and protein C activation,lipid metabolism abnormalities,microcirculatory dysfunction,oxidative stress,inflammatory factors,and the kallikrein-kinin system.Epigenetics is the science studying gene expression regulation without changes in the DNA sequence.In recent years,increasing evidence has shown that epigenetic mechanisms play a crucial role in the initiation and progression of DKD.For instance,epigenetic modifications such as DNA methylation,histone modifications,and non-coding RNAs can influence the expression of DKD-related genes,thereby regulating the development and progression of DKD.On the other hand,metabolic memory is an important concept in DKD research.Metabolic memory refers to the phenomenon where cells maintain a certain metabolic state even after the disappearance of metabolic stress factors.This state can influence cell function and fate.In DKD,metabolic stress factors such as hyperglycemia can lead to metabolic memory in renal cells,affecting their function and fate,ultimately leading to the development and progression of DKD.Therefore,to further explore the pathogenesis of DKD,research on epigenetics should be strengthened,aiming to provide new ideas and methods for the prevention and treatment of DKD.

Arterial stiffness, vascular calcification and bone metabolism in chronic kidney disease

Patients with chronic kidney disease （CKD） have an extremely poor cardiovascular outcome. Arterial stiff-ness, a strong independent predictor of survival in CKD, is connected to arterial media calcification. A huge number of different factors contribute to the increased arterial calcification and stiffening in CKD, a process which is in parallel with impaired bone metabolism. This coincidence was demonstrated to be part of the direct inhibition of calcifcation in the vessels, which is a counterbalancing effect but also leads to low bone turnover. Due to the growing evidence, the defnition of “CKD mineral bone disorder” was created recently, un-derlining the strong connection of the two phenomena. In this review, we aim to demonstrate the mechanisms leading to increased arterial stiffness and the up-to date data of the bone-vascular axis in CKD. We over-view a list of the different factors, including inhibitors of bone metabolism like osteoprotegerin, fetuin-A, pyro-phosphates, matrix Gla protein, osteopontin, fbroblast growth factor 23 and bone morphogenic protein, which seem to play role in the progression of vascular calcif-cation and we evaluate their connection to impaired ar-terial stiffness in the mirror of recent scientifc results.

Water metabolism from lung,spleen and kidney

Water and liquid are the material basis of human metabolism.Traditional Chinese medicine believes that water and liquid metabolism is a very complex process that requires the synergy of the internal organs,but mainly the physiological functions of the lungs,spleen and kidneys.If the function or structure of the spleen,lungs,kidneys,or triple-burner is abnormal,it is easy to cause abnormalities in the body's water metabolism,which in turn leads to the production of pathological products such as damp phlegm.

Influence of tacrolimus metabolism rate on renal function after solid organ transplantation

The calcineurin inhibitor(CNI) tacrolimus(TAC) is an integral part of the immunosuppressive regimen after solid organ transplantation. Although TAC is very effective in prevention of acute rejection episodes, its highly variable pharmacokinetic and narrow therapeutic window require frequent monitoring of drug levels and dose adjustments. TAC can cause CNI nephrotoxicity even at low blood trough levels(4-6 ng/m L). Thus, other factors besides the TAC trough level might contribute to CNI-related kidney injury. Unfortunately, TAC pharmacokinetic is determined by a whole bunch of parameters. However, for daily clinical routine a simple application strategy is needed. To address this problem, we and others have evaluated a simple calculation method in which the TAC blood trough concentration(C) is divided by the daily dose(D). Fast TAC metabolism(C/D ratio < 1.05) was identified as a potential risk factor for an inferior kidney function after transplantation. In this regard, we recently showed a strong association between fast TAC metabolism and CNI nephrotoxicity as well as BKV infection. Therefore, the TAC C/D ratio may assist transplant clinicians in a simple way to individualize the immunosuppressive regimen.

Metabolic Syndrome and Insulin Resistance Are Associated with Chronic Kidney Disease in Nondiabetic Adults with Abdominal Obesity

Aims: we investigate whether insulin resistance is associated with an increased prevalence for chronic kidney disease irrespective of the concurrent presence of metabolic syndrome. Methods: 1638 patients with abdominal obesity were selected. Metabolic syndrome and abdominal obesity were defined according to the International Diabetes Federation criteria. Insulin resistance was defined by Homeostasis Model Assessment Index >P75. Chronic kidney disease was defined by the presence of a low estimated glomerular filtration rate (Results: metabolic syndrome was present in 1030 (62.9%) patients and insulin resistance in 787 (48%). Conversely 61% of those with metabolic syndrome were insulin resistant and 79% of those with insulin resistance had metabolic syndrome. Chronic kidney disease was present in 18%. In multivariate analysis, chronic kidney disease was increased in subjects with insulin resistance (odds ratio [OR] = 1.350;CI 95%: 1.021 - 1.785;p = 0.035) and in those with metabolic syndrome (OR = 1.417;CI 95%: 1.045 - 1.922;p = 0.025). Conclusions: Metabolic syndrome and insulin resistance were significant and independently associated with chronic kidney disease in nondiabetic adults with abdominal obesity.

Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?

Growing prevalence of diabetes(type 2 as well as type 1) and its related morbidity due to vascular complications creates a large burden on medical care worldwide. Understanding the molecular pathogenesis of chronic micro-, macro- and avascular complications mediated by hyperglycemia is of crucial importance since novel therapeutic targets can be identified and tested. Thiamine(vitamin B1) is an essential cofactor of several enzymes involved in carbohydrate metabolism and published data suggest that thiamine metabolism in diabetes is deficient. This review aims to point out the physiological role of thiamine in metabolism of glucose and amino acids, to present overview of thiamine metabolism and to describe the consequences of thiamine deficiency(either clinically manifest or latent). Furthermore, we want to explain why thiamine demands are increased in diabetes and to summarise data indicating thiamine mishandling in diabetics(by review of the studies mapping the prevalence and the degree ofthiamine deficiency in diabetics). Finally, we would like to summarise the evidence for the beneficial effect of thiamine supplementation in progression of hyperglycemia-related pathology and, therefore, to justify its importance in determining the harmful impact of hyperglycemia in diabetes. Based on the data presented it could be concluded that although experimental studies mostly resulted in beneficial effects, clinical studies of appropriate size and duration focusing on the effect of thiamine supplementation/therapy on hard endpoints are missing at present. Moreover, it is not currently clear which mechanisms contribute to the deficient action of thiamine in diabetes most. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given.

Impact of the adherence to medical treatment on the main urinary metabolic disorders in patients with kidney stones

Objective:To assess the effect of the adherence to medical treatment on urinary parameters in the 24-h metabolic study of patients with kidney stones.Methods:A retrospective,longitudinal,descriptive,and observational study was carried out by reviewing the hospital electronic medical record from 2014 to 2018.The adherence to drug treatment was measured 6 months after its initiation,and the numerical values of the metabolic studies were compared.Wilcoxon tests were performed to compare the difference before and after treatment.Results:Ninety patients were evaluated,with 73.3% of adherence.The 180-day overall adherence rate was 61.2% in patients treated with a single drug and 85.4% in patients treated with multiple drugs.There is a statistically significant increase in citrate levels in patients with good adherence in comparison with non-adherent patients(p=0.031 vs.p=0.528).Conclusions:Medical treatment and dietary measures in patients with kidney stones have an initial impact at 6 months on the values of the main urinary metabolic alterations that predispose to calculi formation;the most significant is seen in those patients with adherence to medical treatment for hypocitraturia.

Interplay between metabolic dysfunction-associated fatty liver disease and chronic kidney disease:Epidemiology,pathophysiologic mechanisms,and treatment considerations

The recently proposed nomenclature change from non-alcoholic fatty liver disease to metabolic dysfunction-associated fatty liver disease(MAFLD)has resulted in the reappraisal of epidemiological trends and associations with other chronic diseases.In this context,MAFLD appears to be tightly linked to incident chronic kidney disease(CKD).This association may be attributed to multiple shared risk factors including type 2 diabetes mellitus,arterial hypertension,obesity,dyslipidemia,and insulin resistance.Moreover,similarities in their molecular pathophysiologic mechanisms can be detected,since inflammation,oxidative stress,fibrosis,and gut dysbiosis are highly prevalent in these pathologic states.At the same time,lines of evidence suggest a genetic predisposition to MAFLD due to gene polymorphisms,such as the PNPLA3 rs738409 G allele polymorphism,which may also propagate renal dysfunction.Concerning their management,available treatment considerations for obesity(bariatric surgery)and novel antidiabetic agents(glucagon-like peptide 1 receptor agonists,sodiumglucose co-transporter 2 inhibitors)appear beneficial in preclinical and clinical studies of MAFLD and CKD modeling.Moreover,alternative approaches such as melatonin supplementation,farnesoid X receptor agonists,and gut microbiota modulation may represent attractive options in the future.With a look to the future,additional adequately sized studies are required,focusing on preventing renal complications in patients with MAFLD and the appropriate management of individuals with concomitant MAFLD and CKD.

Oral alkali therapy and the management of metabolic acidosis of chronic kidney disease:A narrative literature review

Chronic metabolic acidosis is a common complication seen in advanced chronic kidney disease(CKD). There is currently no consensus on its management in the Republic of Ireland. Recent trials have suggested that appropriate active management of metabolic acidosis through oral alkali therapy and modified diet can have a deterring impact on CKD progression. The potential benefits of treatment include preservation of bone health and improvement in muscle function; however,present data is limited. This review highlights the current evidence,available primarily from randomised control trials(RCTs) over the last decade,in managing the metabolic acidosis of CKD and outlines ongoing RCTs that are promising. An economic perspective is also briefly discussed to support decision-making.

Association of Visit-to-Visit Variabilities in Metabolic Factors with Chronic Kidney Disease in Chinese Adults Living in Shanghai

Objective This study aimed to examine the association of visit-to-visit variabilities in metabolic factors with chronic kidney disease(CKD)in Shanghai community residents.Methods We used data from a cohort study of community residents who participated in three examinations in 2008,2009,and 2013,respectively.Fasting plasma glucose(FPG)level,blood pressure(BP),and lipid levels were determined in 2,109 participants at all three visits,and CKD was evaluated between the second and the third visits.Visit-to-visit variabilities in metabolic factors were described by coefficients of variation(CV)at three visits.A variability score was calculated by adding the numbers of metabolic factors with a high variability defined as the highest quartile of CV.CKD was defined as the estimated glomerular filtration rate<60 mL/min per 1.73 m2 or urinary albumin-to-creatinine ratio≥30 mg/g.Results A total of 200(9.5%)participants had CKD at the third visit.Compared with the lowest quartile of CV,the highest quartile was associated with a 70%increased risk of CKD for FPG[odds ratio,OR=1.70;95%confidence interval(CI)1.06–2.72],62%for systolic BP(OR=1.62,95%CI 1.04–2.50),and 85%for low-density lipoprotein cholesterol(OR=1.85,95%CI 1.23–2.80).Furthermore,the risk of CKD increased significantly with an increasing variability score.Compared with participants with score 0,participants with scores of 1,2,and 3 were associated with 58%(OR=1.58,95%CI 1.08–2.32),121%(OR=2.21,95%CI 1.40–3.49),and 548%(OR=6.48,95%CI 3.18–13.21)higher risks of CKD,respectively.Conclusion The visit-to-visit variabilities in metabolic factors were significantly associated with the risks of CKD in Shanghai community residents.

Association of Metabolic Syndrome with Inflammation in Chinese Adults with Different Kidney Function

Chronic kidney disease （CKD） has become a worldwide public health problem, and currently, it affects approximately 10% of adults in the United States[I]. Meanwhile, it also has emerged as an important social challenge in China[2]. CKD has been reported to be a major risk factor for cardiovascular diseases, premature death, and end-stage renal diseaseTM. Thus, it is necessary to determine the risk factors for CKD.

Disorders of potassium homeostasis after kidney transplantation

Disturbances of potassium balance are often encountered when managing kidney transplant recipients(KTR).Both hyperkalemia and hypokalemia may present either as medical emergencies or chronic outpatient abnormalities.Despite the high incidence of hyperkalemia and its potential life-threatening implications,consensus on its management in KTR is lacking.Hypokalemia in KTR is also well-described,although it is given less attention by clinicians compared to hyper-kalemia.This article discusses the etiology,pathophysiology and management of both types of potassium disorders in KTR.Once any emergent situation has been corrected,treatment approaches include correcting insulin deficiency if present,adjusting non-immunosuppressive and immunosuppressive medications,elimi-nating or supplementing potassium as needed,and dietary counselling.Although commonly of multifactorial etiology,ascertaining the specific cause in a particular patient will help guide successful management.Monitoring KTR through regular laboratory testing is essential to detect serious disturbances in potassium balance since patients are often asymptomatic.

The influence of metabolic syndrome and its components on the development of nephrolithiasis

The prevalence of kidney stone disease is increasing,afflicting 7%-11% of the United States population.Multiple systemic conditions,including obesity and diabetes,are also on the rise.Further,the literature has demonstrated a strong association between metabolic syndrome,its components,and kidney stone disease.In this article,we aim to review the associations of metabolic syndrome and nephrolithiasis,discussing the pathophysiology,urinary parameters,and clinical presentations.With this knowledge,urologists will have a more comprehensive understanding of this complex population of metabolic stone formers enabling improved patient management and treatment of stone disease.

Codonopsis tangshen Oliv.Amelioration Effect on Diabetic Kidney Disease Rats Induced by High Fat Diet Feeding Combined with Streptozotocin

Diabetic kidney disease(DKD)is the most serious microvascular complication during the development of diabetes with the characterizations of glomerular basement membrane thickening,mesangial expansion,and glomerular sclerosis,eventually leading to end-stage renal disease.This study aimed to investigate the melioration effect of Codonopisis tangshen Oliv.(COD)on the DKD model,which was established by unilateral nephrectomy(UN)-high fat diet feeding(HFD)combined with streptozotocin(STZ).After the DKD rats were oral treated with COD at a dose of 2.7 mg/kg for 4 consecutive weeks,the blood glucose,lipid metabolism,renal function,inflammatory mediators,and fibrosis-associated proteins were examined.In vivo,the COD administration obviously relieved the weight loss,water intake,and blood glucose;decreased the total cholesterol,triglyceride,and low-density lipoprotein cholesterol levels;and improved the renal function by reducing the expression of serum creatinine,uric acid,and urinary protein compared with the model group.The levels of pro-inflammatory cytokines of tumor necrosis factor-a,interleukin-1β,and IL-6 were significantly inhibited by COD.Meanwhile,the deposition of collagen fiber was markedly increased,and the protein and mRNA expressions of transforming growth factor-b1 and a-smooth muscle actin were markedly elevated in DKD rats,but they were decreased to some extent after the COD treatment.In conclusion,COD exhibited a protective effect on the UN-HFD feeding combined with STZ-induced DKD model by improving the blood glucose and lipid metabolism,relieving the inflammatory response,and mitigating the renal fibrosis,which provided scientific evidence for its applications in clinic.

Optical coherence tomography of the living human kidney

Acute tubular necrosis(ATN)induced by ischemia is the most common insult to donor kidneysdestined for trarsplantation.ATN results from sweling and subsequent damage to cells lining thelkidney tubules.In this study,we demonstrate the capability of optical coherence tomography(OcT)to image the renal microst ructures of living human donor kidneys and potentially providea measure to det ermine the extent of A TN.We also found that Doppler-based OCT(i.e.,DOCT)reveals renal blood flow dynamics that is another major factor which could relate to post-transplant renal finction.All OCT/DoCT oberva tions were performed in a noninvasive,sterileand timely manner on intact human kidneys both prior to(er vivo)and following(in vivo)theirtransplantation.Our results indicate that this imaging model provides transplant surgeons withan objective visualization of the transplant lidneys prior and immediately post transplantation.