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Clinical characteristics and treatment compounds of obesity-related kidney injury

World Journal of Diabetes 2024年第6期15卷 1091-1110页

作者： Tuo-Hua Mao Han-Qi Huang Chuan-Hai Zhang Department of Endocrinology Renmin Hospital of Wuhan UniversityWuhan 430060Hubei ProvinceChina Department of Endocrinology Hubei No.3 People’s Hospital of Jianghan UniversityWuhan 430033Hubei ProvinceChina Department of Physiology UT Southwestern Medical CenterDallasTX 75390United States

Disorders in energy homeostasis can lead to various metabolic diseases,particularly obesity.The obesity epidemic has led to an increased incidence of obesityrelated nephropathy(ORN),a distinct entity characterized by proteinuria,glomerulomegaly,progressive glomerulosclerosis,and renal function decline.Obesity and its associated renal damage are common in clinical practice,and their incidence is increasing and attracting great attention.There is a great need to identify safe and effective therapeutic modalities,and therapeutics using chemical compounds and natural products are receiving increasing attention.However,the summary is lacking about the specific effects and mechanisms of action of compounds in the treatment of ORN.In this review,we summarize the important clinical features and compound treatment strategies for obesity and obesityinduced kidney injury.We also summarize the pathologic and clinical features of ORN as well as its pathogenesis and potential therapeutics targeting renal inflammation,oxidative stress,insulin resistance,fibrosis,kidney lipid accumulation,and dysregulated autophagy.In addition,detailed information on natural and synthetic compounds used for the treatment of obesity-related kidney disease is summarized.The synthesis of detailed information aims to contribute to a deeper understanding of the clinical treatment modalities for obesity-related kidney diseases,fostering the anticipation of novel insights in this domain.

关键词： Compounds Obesity kidney injury Obesity-related nephropathy Clinical features and treatment

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Imaging and spatial omics of kidney injury:significance,challenges,advances and perspectives

Medical Review

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Medical Review 2023年第6期3卷 514-520页

作者： Zehua Li Yao Lu Li Yang Renal Division Peking University Institute of NephrologyPeking University First HospitalBeijingChina Key Laboratory of Renal Disease-Ministry of Health of China Key Laboratory of CKD Prevention and Treatment(Peking University)-Ministry of Education of ChinaPeking University First HospitalBeijingChina Research Units of Diagnosis and Treatment of Immune-mediated kidney Diseases-Chinese Academy of Medical Sciences Peking University First HospitalBeijingChina Renal Division Peking University Institute of NephrologyPeking University First HospitalBeijing 100034China Key Laboratory of Renal Disease-Ministry of Health of China Key Laboratory of CKD Prevention and Treatment(Peking University)-Ministry of Education of ChinaPeking University First HospitalBeijing 100034China Research Units of Diagnosis and Treatment of Immunemediated kidney Diseases-Chinese Academy of Medical Sciences Peking University First HospitalXishiku Street#8Beijing 100034China

The kidneys are susceptible to a range of insults that can cause damage to them.Early diagnosis,timely prevention,and proper treatment are crucial for improving the outcome of kidney injury.However,the complexity of renal structure and function makes it difficult to reach the demand of early detection and comprehensive evaluation of kidney injury.No successful drug therapy caused by the elaborate pathogenesis mechanism network of kidney injury calls for a systematical interpretation in mechanism researches.Recent advances in renal imaging and omics studies have provided novel views and deeper insights into kidney injury,but also raise challenges in reaching a comprehensive cellular and molecular atlas of kidney injury.Progresses in imaging and omics of kidney injury are being made in various directions,with the initiative of construction a high-resolution structural atlas of kidney,dynamic and non-invasive evaluation of renal function,and systematic establishment of spatially resolved molecular atlas by transcriptomics and metabolomics.With the limitations of a single modality,novel multimodal integration technologies of imaging and omics are being attempted to achieve a systematic description of nephropathy mechanisms.Further extensive efforts in renal multimodal imaging and omics studies are extremely required to deepen our understanding on kidney injury in the context of diagnostic,mechanistic and therapeutic perspectives.

关键词： kidney injury imaging omics multi-modalities Introduction

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Timely renal replacement therapy linked to better outcome in patients with sepsis-associated acute kidney injury

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Journal of Intensive Medicine 2022年第3期2卷 173-182页

作者： Yiwen Fan Liang Chen Shaowei Jiang Yingying Huang Yuxin Leng Chengjin Gao Department of Emergency Shanghai Jiao Tong University School of MedicineShanghai 200092China Department of Pathology and Medical Biology University of GroningenUniversity Medical Center GroningenGronigen 9713GZthe Netherlands Department of Intensive Care Unit Peking University Third HospitalBeijing 100191China

Background:Recent studies suggest that acute kidney injury(AKI)can be treated with renal replacement therapy(RRT).However,its benefits to patients with sepsis-associated AKI(SA-AKI),which is linked to high mortality and morbidity rates,remain under debate.The aim of this study was to compare the outcomes of different RRT strategies for patients with SA-AKI.Methods:This retrospective study evaluated patients who were admitted to the hospital with sepsis and devel-oped SA-AKI during hospitalization from 1st January 2014 to 31st January 2019.Mortality,renal recovery,and systemic organ function at 90 days following admission were compared between the RRT group(RG)and non-RRT group(NRG),as well as the early-RRT group(EG)and delayed-RRT group(DG).The groups were defined according to the time from admission to RRT initiation(criterion 1,EG1 and DG1)and kidney Disease Improving Global Outcomes(KDIGO)classification(criterion 2,EG2 and DG2).Categorical and continuous variables were compared using the chi-squared test or Fisher’s exact test and Student’s t-test or Wilcoxon test.Kaplan-Meier curves were constructed to determine the unadjusted survival rates for the different subgroups.Results:A total of 116 patients were included in this study;of those,38 received RRT and 46 expired within 90 days.Among different strategies of RRT,there were no significant differences found in 90-day mortality(RG vs.NRG:𝜒2=0.610,P=0.435;EG1 vs.DG1:𝜒2=0.835,P=0.360;EG2 vs.DG2:𝜒2=0.022,P=0.899)and renal recovery.However,the values of change in sequential organ failure assessment(ΔSOFA)max-min of patients in the EG and RG were significantly higher than those recorded in the NRG(ΔSOFA RG=7.0,ΔSOFA NRG=3.60,ΔSOFA EG1=9.00,ΔSOFA EG2=6.30;P<0.050).Also,the 90-day renal recovery in the EG was better than that noted in the DG with criterion 1(87.5%vs.38.5%,respectively,𝜒2=10.425,P=0.032),suggesting that RRT(especially timely RRT)may be beneficial to the restoration of systemic organ function in patients with SA-AKI.Conclusion:RRT did not reduce the 9

关键词： Dialysis Sepsis Renal failure kidney injury Creatinine Shock

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T cell infiltration is associated with kidney injury in patients with anti-glomerular basement membrane disease

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Science China(Life Sciences) 2016年第12期59卷 1282-1289页

作者： Shui-Yi Hu Xiao-Yu Jia Jian-Nan Li Xin Zheng Jie Ao Gang Liu Zhao Cui Ming-Hui Zhao Renal Division Department of Medicine Peking University First HospitalInstitute of Nephrology Peking UniversityKey Laboratory of Renal Disease Ministry of Health of China Key Laboratory of CKD Prevention and Treatment Ministry of Education of China Beijing 100034 China Peking-Tsinghua Center for Life Sciences Beijing 100871 China Department of Nephrology Tianjin Medical University General Hospital Tianjin 300052 China

Cell-mediated autoimmunity, particularly that involving autoreactive T cells, participates in mediating anti-glomerular basement membrane(GBM) disease. However, direct kidney injury mediated by renal infiltrated T cells has not been clearly elucidated in humans. The T cell profile(CD3, CD4, CD8, IL-17, and foxp3) and macrophage(CD68) were examined by immunohistochemistry on renal biopsy tissues from 13 patients with anti-GBM disease. The correlation between cell infiltration and clinical data was also analyzed. We found that the distribution of T cell infiltration was predominant in the peri-glomerular and interstitial areas. CD3^+ T cell infiltratrion around the glomeruli with cellular crescent formations was significantly higher than that around the glomeruli with mild mesangial proliferation. CD8^+ T cells significantly accumulated around the glomeruli with cellular crescents without Ig G deposits compared to those with Ig G deposits. The prevalence of infiltrating CD8^+ T cells was correlated with the percentage of ruptured Bowman's capsules. In conclusion, cellular immunity may play a crucial role in the inflammatory kidney injury in anti-GBM patients. The periglomerular infiltration of T cells, especially CD8^+ T cells, may participate in the pathogenic mechanism of glomerular damage.

关键词： anti-GBM disease T cell IL-17 CD8 kidney injury

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Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication

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World Journal of Emergency Medicine 2017年第1期8卷 61-64页

作者： Jia-jun Xu Jian-tao Zhen Li Tang Qing-ming Lin Department of Emergency Medicine Quanzhou First Hospital Affiiated Fujian Medical University Department of Emergency Medicine Fujian Provincial Hospital Shengli Clinical Medical College of Fujian Medical University

BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury(AKI) in rats with paraquat intoxication.METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group(n=8), paraquat group(n=8) and Xuebijing-treated group(n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing(8 mL /kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-in? ammatory cytokines mR NA levels in kidney were assayed using real-time RT-PCR.RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group(P<0.05, respectively). Moreover, interleukin(IL)-1β, IL-6 and TNF-α m RNA levels were signi? cantly higher in the paraquat group(P<0.01, respectively). However, intravenous Xuebijing signi? cantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α m RNA levels, compared with the paraquat group(P<0.05, respectively).CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing in? ammatory response.

关键词： Paraquat Xuebijing kidney injury Inflammation

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Low-molecular-weight dextran for optical coherence tomography may not be protective against kidney injury in patients with renal insufficiency

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World Journal of Nephrology 2021年第2期10卷 8-20页

作者： Toru Misawa Tomoyo Sugiyama Yoshihisa Kanaji Masahiro Hoshino Masao Yamaguchi Masahiro Hada Tatsuhiro Nagamine Kai Nogami Yumi Yasui Eisuke Usui Tetsumin Lee Taishi Yonetsu Tetsuo Sasano Tsunekazu Kakuta Department of Cardiovascular Medicine Tsuchiura Kyodo General HospitalIbaraki 300-0028Japan Department of Interventional Cardiology Tokyo Medical and Dental UniversityTokyo 113-8519Japan Department of Cardiovascular Medicine Tokyo Medical and Dental UniversityTokyo 113-8519Japan

BACKGROUND Low-molecular-weight dextran(LMWD)is considered a safe alternative to contrast media for blood displacement during optical coherence tomography(OCT)imaging.AIM To investigate whether the use of LMWD for OCT is protective against kidney injury in patients with advanced renal insufficiency.METHODS In this retrospective cohort study,we identified 421 patients with advanced renal insufficiency(estimated glomerular filtration rate<45 mL/min/1.73 m2)who underwent coronary angiography or percutaneous coronary intervention;79 patients who used additional LMWD for OCT imaging(LMWD group)and 342 patients who used contrast medium exclusively(control group).We evaluated the differences between these two groups and performed a propensity score-matched subgroup comparison.RESULTS The median total volume of contrast medium was 133.0 mL in the control group vs 140.0 mL in the LMWD group.Although baseline renal function was not statistically different between these two groups,the LMWD group demonstrated a strong trend toward the progression of renal insufficiency as indicated by the greater change in serum creatinine level during the 1-year follow-up compared with the control group.Patients in the LMWD group experienced worsening renal function more frequently than patients in the control group.Propensity score matching adjusted for total contrast media volume consistently indicated a trend toward worsening renal function in the LMWD group at the 1-year follow-up.Delta serum creatinine at 1-year follow-up was significantly greater in the LMWD group than that in the control group[0.06(-0.06,0.29)vs-0.04(-0.23,0.08)mg/dL,P=0.001],despite using similar contrast volume.CONCLUSION OCT using LMWD may not be protective against worsening renal function in patients with advanced renal insufficiency.

关键词： Coronary artery disease kidney injury Contrast media Dextran Optical coherence tomography Renal insufficiency

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Hypobaric Hypoxia Aggravates Renal injury by Inducing the Formation of Neutrophil Extracellular Traps through the NF-κB Signaling Pathway

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当代医学科学(英文) 2023年第3期43卷 469-477页

作者： Jun-yu WEI Miao-yue HU Xiu-qi CHEN Jin-shuang WEI Jie CHEN Xuan-kai QIN Feng-ying LEI Jia-sen ZOU Shi-qun ZHU Yuan-han QIN Department of Pediatrics the First Affiliated HospitalGuangxi Medical UniversityNanning 530021China Children's Hospital of Chongqing Medical University Chongqing 400015China Shenzhen Children's Hospital Shenzhen 518034China

Objective The hypersensitivity of the kidney makes it susceptible to hypoxia injury.The involvement of neutrophil extracellular traps(NETs)in renal injury resulting from hypobaric hypoxia(HH)has not been reported.In this study,we aimed to investigate the expression of NETs in renal injury induced by HH and the possible underlying mechanism.Methods A total of 24 SD male rats were divided into three groups(n=8 each):normal control group,hypoxia group and hypoxia+pyrrolidine dithiocarbamate(PDTC)group.Rats in hypoxia group and hypoxia+PDTC group were placed in animal chambers with HH which was caused by simulating the altitude at 7000 meters(oxygen partial pressure about 6.9 kPa)for 7 days.PDTC was administered at a dose of 100 mg/kg intraperitoneally once daily for 7 days.Pathological changes of the rat renal tissues were observed under a light microscope;the levels of serum creatinine(SCr),blood urea nitrogen(BUN),cell-free DNA(cf-DNA)and reactive oxygen species(ROS)were measured;the expression levels of myeloperoxidase(MPO),citrullinated histone H3(cit-H3),B-cell lymphoma 2(Bcl-2),Bax,nuclear factor kappa B(NF-κB)p65 and phospho-NF-κB p65(p-NF-κB p65)in rat renal tissues were detected by qRT-qPCR and Western blotting;the localization of NF-κB p65 expression in rat renal tissues was observed by immunofluorescence staining and the expression changes of NETs in rat renal tissues were detected by multiplex fluorescence immunohistochemical staining.Results After hypoxia,the expression of NF-κB protein in renal tissues was significantly increased,the levels of SCr,BUN,cf-DNA and ROS in serum were significantly increased,the formation of NETs in renal tissues was significantly increased,and a large number of tubular dilatation and lymphocyte infiltration were observed in renal tissues.When PDTC was used to inhibit NF-κB activation,NETs formation in renal tissue was significantly decreased,the expression level of Bcl-2 in renal tissues was significantly increased,the expression level of Bax was significantly decreased,an

关键词： hypobaric hypoxia neutrophil extracellular traps hypoxia kidney injury NF-κB apoptosis

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Comparison of transient changes in renal function between off-pump and on-pump coronary artery bypass grafting

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Chinese Medical Journal 2008年第16期121卷 1537-1542页

作者： ZHANG Wen-feng GU Tian-xiang DIAO Cheng ZHANG Yu-hai WANG Chun FANG Qin WANG Hai-long Department of Cardiac Surgery First Affiliated Hospital of China Medical University Shenyang Liaoning 110001 China Department of Immunology Shenyang Medical College Shenyang Liaoning 110034 China Epidemiology Department China Medical University Shenyang Liaoning 110001 China

Background Acute renal failure following coronary artery bypass grafting （CABG） surgery is associated with high morbidity and mortality. Approximately half of all patients who develop acute kidney injury （AKI） subsequently develop acute renal failure （ARF）. The purpose of the study was to compare early transient changes in renal function within the first post-operative week following CABG in patients that were either off-pump or on-pump. Methods Eight hundred and forty-nine consecutive patients with isolated CABG in a single institution between January 1990 and August 2006 were retrospectively analyzed, including 518 off-pump and 331 on-pump patients. A multivariate Logistic regression model was constructed to identify risk factors for the development of AKI. Results Sixty-one off-pump patients and 63 on-pump patients developed AKI. Risk factors for the development of post-operative AKI included an ejection fraction ≥50% or ≤30%, a pulse pressure ≥60 mmHg, peripheral vascular disease diabetes, emergent procedure, triple-vessel disease, body mass index, peri-operative and post-operative intra-aortic balloon pumping, NYHA class III and IV, and cardiopulmonary bypass. An ejection fraction ≥50% and peri-operative and post-operative intra-aortic balloon pumping were protective （OR 〈1）. Peak serum creatinine for post-operative AKI was noted 12 hours and 24 hours in the off-pump and on-pump patients, respectively. Serum creatinine kinetics revealed rapid recovery in the 24th to 48th hour （off-pump） and the 48th to 72nd hour （on-pump）. Conclusion Renal protection strategies are indicated from general anesthesia induction until 48 and 72 hours post-operatively in off-pump and on-pump patients, respectively.

关键词： coronary artery bypass grafts kidney injury risk analysis

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Improvement in renal functions with transcatheter aortic valve implantation

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Journal of Geriatric Cardiology 2013年第4期10卷 317-322页

作者： Telat Keleş Huseyin Ayhan Durmaz Sarı Aslan AN Erdoğan KE Kasapkara Bilen Bayram Akçay Bozkurt Department of Cardiology Yıldırım Beyazıt University Bilkent 06800 Ankara Turkey Department of Cardiology Ankara Ataturk Education and Research Hospital Bilkent 06800 Ankara Turkey Department of Cardiovascular Surgery Ankara Ataturk Education and Research Hospital Bilkent 06800 Ankara Turkey.

BACKGROUND & OBJECTIVES:In recent years, emerging transcatheter aortic valve implantation (TAVI) has become an alternative for surgery。 However, with advanced age, several co-morbid factors together with contrast agent usage can cause deterioration in renal function and increase in the risk of acute kidney injury (AKI) with poor prognosis in patients with AKI。 Therefore, many patients cannot benefit from this treatment。 In this study, we aim to examine the effects of TAVI on renal functions。 METHODS AND RESULTS: Seventy patients, mean age of 77.6 years, underwent TAVI between July 2011 and December 2012。 Estimated glomerular filtration rate (eGFR) was calculated by using the Cockcroft and Gault Formula。 Patients were monitored for 48 h for urine output。 Stage 1 AKI, according to the VARC-2 AKIN system, developed in only five (7.1%) of the patients after the procedure。 There was a statistically significant increase between the mean 1(st) month eGFRs before (68。2 vs。 61.0, P kidney disease before the procedure showed a statistically significant increase in renal functions。 The hospital mortality rate was higher in the group which developed AKI (P < 0.01)。 First month eGFR showed a more statistically significant increase than pre-TAVI eGFR (62.8 and 69.8, P < 0.05, respectively) in AKI developing patients and this difference - though statistically not significant - continued into the sixth month。 CONCLUSIONS: In this study, we showed that the treatment of aortic stenosis through TAVI allows improvement of renal functions, and that AKI rates will be lower with careful patient selection, proper pre-procedural hydration, and careful use of contrast agent。

关键词： Improvement kidney injury Transcatheter aortic valve implantation

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Urine Cystatin C Determination in the Establishment of Reference Interval in the Diagnosis and Treatment of Renal injury

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Natural Science 2022年第1期14卷 13-17页

作者： Xiaoyu Jiang Lihua Qin Jing Wei Guosheng Su Xiaoye Su Aihua Lu Jiansheng Huang Feng Lu Taixin Lu Pinchun Huang Buqing Su Department of Laboratory Medicine Third People’s Hospital of Nanning Nanning China Guangxi-ASEAN Economic and Technological Development Zone People’s Hospital Nanning China The Department of Nephrology & Laboratory Medicine of Tenth People’s Hospital of Nanning Nanning China Department of Nursing Graduate School of Everlasting University of the Philippines Fuzhou China Department of Critical Care Medicine Fuzhou Second People’s Hospital Fuzhou China Department of Nursing Liaoning Vocational College of Medicine Shenyang China

Objective: To establish the diagnostic concentration range of urine cystatin C and the control level of urine cystatin C for patients with renal injury, and to help promote the establishment of standardization of urine cystatin C detection. Methods: 150 urine specimens and blood specimens from kidney injury patients and healthy people were collected, and stored in the refrigerator at -80°C for later use. After the specimens were collected, they were uniformly tested. Comparing the difference of blood and urine cystatin C between the kidney injury group and the healthy control group, the application value of urine cystatin C in the diagnosis and treatment of kidney injury was put forward. Results: The concentrations of cystatin C in urine and blood of renal injury group were 1.04 ± 2.14 mg/L and 1.94 ± 2.36 mg/L respectively;the concentrations of cystatin C in urine and blood of healthy control group were 0.11 ± 0.05 mg/L and 0.83 ± 0.20 mg/L respectively. The urine and blood cystatin C of the kidney injury group were significantly higher than those of the healthy control group. Compared the results of the two groups, the t values were 5.3210 and 5.7399, respectively. The P value is 0.0000;the difference is statistically significant;in comparison of urine and blood cystatin C in the kidney injury group, the value is that t = 3.4600, P = 0.0003;in comparison of urine and blood cystatin C in the healthy control group, the value is that t = 42.7744, P = 0.0000. By investigating the urine cystatin C concentration of patients with kidney injury, whether it is kidney injury or healthy controls, urine cystatin C is significantly lower than blood cystatin C. Conclusion: According to the results of this study, the concentration of urinary cystatin C in the healthy control group is 0.11 ± 0.05 mg/L. The reference interval of urinary cystatin C proposed in this study is 0.06 - 0.16 mg/L, which can be established by comprehensive multi center research. Through a multi-center study of the baseline level of urinary cystatin C i

关键词： Urine Cystatin C kidney injury Concentration Interval Standardization

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