Publications by authors named "Guangyan Cai"

131 Publications

LncRNA-HOTAIR promotes endothelial cell pyroptosis by regulating the miR-22/NLRP3 axis in hyperuricaemia.

J Cell Mol Med 2021 Jul 22. Epub 2021 Jul 22.

Department of Nephrology, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China.

Long non-coding RNA (lncRNA) plays an important role in the renal inflammatory response caused by hyperuricaemia. However, the underlying molecular mechanisms through which lncRNA is involved in endothelial injury induced by hyperuricaemia remain unclear. In this study, we investigated the regulatory role of lncRNA-HOTAIR in high concentration of uric acid (HUA)-induced renal injury. We established hyperuricaemia mouse model and an in vitro uric acid (UA)-induced human umbilical vein endothelial cell (HUVEC) injury model. In HUA-treated HUVECs and hyperuricaemia mice, we observed increased HOTAIR and decreased miR-22 expression. The expression of pyroptosis-associated protein (NLRP3, Caspase-1, GSDMD-N, GSDMD-FL) was increased. The release of LDH, IL-1β and IL-18 in cell supernatants and the sera of model mice was also increased. The proliferation of HUVECs stimulated by HUA was significantly inhibited, and the number of TUNEL-positive cells in hyperuricaemia mouse kidney was increased. Bioinformatics analysis and luciferase reporter and RIP assays confirmed that HOTAIR promoted NLRP3 inflammasome activation by competitively binding miR-22. In gain- or loss-of-function experiments, we found that HOTAIR and NLRP3 overexpression or miR-22 knock down activated the NLRP3 inflammasome and promoted pyroptosis in HUA-treated HUVECs, while NLRP3 and HOTAIR knockdown or a miR-22 mimic exerted the opposite effects. Furthermore, in vivo experiments validated that HOTAIR knockdown alleviated renal inflammation in hyperuricaemia mice. In conclusion, we demonstrated that in hyperuricaemia, lncRNA-HOTAIR promotes endothelial cell pyroptosis by competitively binding miR-22 to regulate NLRP3 expression.
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http://dx.doi.org/10.1111/jcmm.16812DOI Listing
July 2021

Expression characteristics of interferon-stimulated genes and possible regulatory mechanisms in lupus patients using transcriptomics analyses.

EBioMedicine 2021 Jul 17;70:103477. Epub 2021 Jul 17.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, 28 Fuxing Road, Haidian District, Beijing 100853, China. Electronic address:

Background: Type I interferon signature is one of the most important features of systemic lupus erythematosus (SLE), which indicates an active immune response to antigen invasion. Characteristics of type I interferon-stimulated genes (ISGs) in SLE patients have not been well described thus far.

Methods: We analyzed 35,842 cells of PBMC single-cell RNA sequencing data of five SLE patients and three healthy controls. Thereafter, 178 type I ISGs among DEGs of all cell clusters were screened based on the Interferome Database and AUCell package was used for ISGs activity calculation. To determine whether common ISG features exist in PBMCs and kidneys of patients with SLE, we analyzed kidney transcriptomic data from patients with lupus nephritis (LN) from the GEO database. MRL/lpr mice model were used to verify our findings.

Findings: We found that monocytes, B cells, dendritic cells, and granulocytes were significantly increased in SLE patients, while subsets of T cells were significantly decreased. Neutrophils and low-density granulocytes (LDGs) exhibited the highest ISG activity. GO and pathway enrichment analyses showed that DEGs focused on leukocyte activation, cell secretion, and pathogen infection. Thirty-one common ISGs were found expressed in both PBMCs and kidneys; these ISGs were also most active in neutrophils and LDGs. Transcription factors including PLSCR1, TCF4, IRF9 and STAT1 were found to be associated to ISGs expression. Consistently, we found granulocyte infiltration in the kidneys of MRL/lpr mice. Granulocyte inhibitor Avacopan reduced granulocyte infiltration and reversed renal conditions in MRL/lpr mice.

Interpretation: This study shows for the first time, the use of the AUCell method to describe ISG activity of granulocytes in SLE patients. Moreover, Avacopan may serve as a granulocyte inhibitor for treatment of lupus patients in the future.
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http://dx.doi.org/10.1016/j.ebiom.2021.103477DOI Listing
July 2021

Urinary sediment microRNAs can be used as potential noninvasive biomarkers for diagnosis, reflecting the severity and prognosis of diabetic nephropathy.

Nutr Diabetes 2021 06 30;11(1):24. Epub 2021 Jun 30.

Department of Nephrology, First Medical Center of Chinese People's Liberation Army General Hospital, Nephrology Institute of the Chinese People's Liberation Army, Beijing Key Laboratory of Kidney Disease Research, Beijing, China.

Background: Patients with both diabetes mellitus (DM) and kidney disease could have diabetic nephropathy (DN) or non-diabetic renal disease (NDRD). IgA nephropathy (IgAN) and membranous nephropathy (MN) are the major types of NDRD. No ideal noninvasive diagnostic model exists for differentiating them. Our study sought to construct diagnostic models for these diseases and to identify noninvasive biomarkers that can reflect the severity and prognosis of DN.

Methods: The diagnostic models were constructed using logistic regression analysis and were validated in an external cohort by receiver operating characteristic curve analysis method. The associations between these microRNAs and disease severity and prognosis were explored using Pearson correlation analysis, Cox regression, Kaplan-Meier survival curves, and log-rank tests.

Results: Our diagnostic models showed that miR-95-3p, miR-185-5p, miR-1246, and miR-631 could serve as simple and noninvasive tools to distinguish patients with DM, DN, DM with IgAN, and DM with MN. The areas under the curve of the diagnostic models for the four diseases were 0.995, 0.863, 0.859, and 0.792, respectively. The miR-95-3p level was positively correlated with the estimated glomerular filtration rate (p < 0.001) but was negatively correlated with serum creatinine (p < 0.01), classes of glomerular lesions (p < 0.05), and scores of interstitial and vascular lesions (p < 0.05). However, the miR-631 level was positively correlated with proteinuria (p < 0.001). A low miR-95-3p level and a high miR-631 level increased the risk of progression to end-stage renal disease (p = 0.002, p = 0.011).

Conclusions: These four microRNAs could be noninvasive tools for distinguishing patients with DN and NDRD. The levels of miR-95-3p and miR-631 could reflect the severity and prognosis of DN.
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http://dx.doi.org/10.1038/s41387-021-00166-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8245546PMC
June 2021

Immunomodulatory Effects of Mesenchymal Stem Cells on Drug-Induced Acute Kidney Injury.

Front Immunol 2021 4;12:683003. Epub 2021 Jun 4.

Department of Nephrology, First Medical Center of Chinese People's Liberation Army (PLA) General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China.

Drug-induced nephrotoxicity is an important and increasing cause of acute kidney injury (AKI), which accounts for approximately 20% of hospitalized patients. Previous reviews studies on immunity and AKI focused mainly on ischemia-reperfusion (IR), whereas no systematic review addressing drug-induced AKI and its related immune mechanisms is available. Recent studies have provided a deeper understanding on the mechanisms of drug-induced AKI, among which acute tubular interstitial injury induced by the breakdown of innate immunity was reported to play an important role. Emerging research on mesenchymal stem cell (MSC) therapy has revealed its potential as treatment for drug-induced AKI. MSCs can inhibit kidney damage by regulating the innate immune balance, promoting kidney repair, and preventing kidney fibrosis. However, it is important to note that there are various sources of MSCs, which impacts on the immunomodulatory ability of the cells. This review aims to address the immune pathogenesis of drug-induced AKI versus that of IR-induced AKI, and to explore the immunomodulatory effects and therapeutic potential of MSCs for drug-induced AKI.
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http://dx.doi.org/10.3389/fimmu.2021.683003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213363PMC
June 2021

Exogenous Biological Renal Support Improves Kidney Function in Mice With Rhabdomyolysis-Induced Acute Kidney Injury.

Front Med (Lausanne) 2021 28;8:655787. Epub 2021 May 28.

State Key Laboratory of Kidney Diseases, Department of Nephrology, National Clinical Research Center for Kidney Diseases, Chinese People's Liberation Army (PLA) Institute of Nephrology, Chinese People's Liberation Army (PLA) General Hospital, Beijing, China.

Rhabdomyolysis (RM) is a clinical syndrome characterized by breakdown of skeletal muscle fibers and release of their contents into the circulation. Myoglobin-induced acute kidney injury (AKI) is one of the most severe complications of RM. Based on our previous research, exogenous biological renal support alleviates renal ischemia-reperfusion injury in elderly mice. This study aimed to determine whether exogenous biological renal support promotes renal recovery from RM-induced AKI and to preliminarily explore the mechanisms involved. A parabiosis animal model was established to investigate the effects of exogenous biological renal support on RM-induced AKI. Mice were divided into three groups: the control group (in which mice were injected with sterile saline), the RM group (in which mice were injected with 8 mL/kg glycerol), and the parabiosis + RM group (in which recipient mice were injected with glycerol 3 weeks after parabiosis model establishment). Blood samples and kidney tissue were collected for further processing 48 h after RM induction. Bioinformatics analysis was conducted via Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes pathway analysis, functional enrichment analysis, and clustering analysis. No mice died within 48 h after the procedure. Exogenous biological renal support attenuated the histological and functional deterioration in mice with RM-induced AKI. Bioinformatics analysis identified key pathways and proteins involved in this process. We further demonstrated that exogenous biological renal support ameliorated AKI through multiple mechanisms, including by suppressing the complement system; attenuating oxidative stress, inflammation, and cell death; and increasing proliferation. Exogenous biological renal support provided by parabiosis can improve renal function in RM-induced AKI by suppressing the complement system; decreasing oxidative stress, inflammation, and cell death; and promoting tubular cell proliferation. Our study provides basic research evidence for the use of bioartificial kidneys to treat RM-induced AKI.
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http://dx.doi.org/10.3389/fmed.2021.655787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193099PMC
May 2021

Genetic analysis of gene and diagnostic process in patients with Gitelman syndrome.

Clin Nephrol 2021 May 17. Epub 2021 May 17.

As the most frequent inherited tubulopathy, Gitelman syndrome (GS), has an incidence that has increased worldwide. The distribution of gene mutation hotspots deserves exploration. In addition, GS is not a benign syndrome; however, the diagnostic process of GS has not yet been completely detailed.

Materials And Methods: We report two cases of GS pedigrees involving two previously unreported mutations, c. 676G>A, p. A226T and c. 421G>A, p. G141R, in the gene and reviewed relevant literature. We searched the literature for nucleotide of in PubMed and other databases as of April 20, 2020.

Results: A total of 1,794 detected mutated alleles in 939 patients worldwide were included in this study. Splicing mutations and p. Gly741Arg were mutation hotspots in a European population. P. Leu858His and p. Thr60Met were mutation hotspots in an Asian population. P. Leu858His and p. Thr180Lys were considered mutation hotspots in the Japanese population, while p. Thr60Met and p. Asp486Asn were considered mutation hotspots in the Chinese population.

Conclusion: Our results identified two novel mutation sites (c. 676G>A, p. A226T and c. 421G>A, p. G141R), if their pathogenicity was determined this could contribute to the enrichment of database resources on GS. Our study has compiled the most comprehensive gene mutation database in the world thus far to reveal that different regions have different mutation hotspots in SLC12A3. Moreover, the establishment of a diagnostic process for GS has important implications for confirmed cases.
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http://dx.doi.org/10.5414/CN110425DOI Listing
May 2021

Activated mesangial cells induce glomerular endothelial cells proliferation in rat anti-Thy-1 nephritis through VEGFA/VEGFR2 and Angpt2/Tie2 pathway.

Cell Prolif 2021 Jun 13;54(6):e13055. Epub 2021 May 13.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, China.

Objectives: We aimed to investigate the underlying mechanism of endothelial cells (ECs) proliferation in anti-Thy-1 nephritis.

Materials And Methods: We established anti-Thy-1 nephritis and co-culture system to explore the underlying mechanism of ECs proliferation in vivo and in vitro. EdU assay kit was used for measuring cell proliferation. Immunohistochemical staining and immunofluorescence staining were used to detect protein expression. ELISA was used to measure the concentration of protein in serum and medium. RT-qPCR and Western blot were used to qualify the mRNA and protein expression. siRNA was used to knock down specific protein expression.

Results: In anti-Thy-1 nephritis, ECs proliferation was associated with mesangial cells (MCs)-derived vascular endothelial growth factor A (VEGFA) and ECs-derived angiopoietin2 (Angpt2). In vitro co-culture system activated MCs-expressed VEGFA to promote vascular endothelial growth factor receptor2 (VEGFR2) activation, Angpt2 expression and ECs proliferation, but inhibit TEK tyrosine kinase (Tie2) phosphorylation. MCs-derived VEGFA stimulated Angpt2 expression in ECs, which inhibited Tie2 phosphorylation and promoted ECs proliferation. And decline of Tie2 phosphorylation induced ECs proliferation. In anti-Thy-1 nephritis, promoting Tie2 phosphorylation could alleviate ECs proliferation.

Conclusions: Our study showed that activated MCs promoted ECs proliferation through VEGFA/VEGFR2 and Angpt2/Tie2 pathway in experimental mesangial proliferative glomerulonephritis (MPGN) and in vitro co-culture system. And enhancing Tie2 phosphorylation could alleviate ECs proliferation, which will provide a new idea for MPGN treatment.
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http://dx.doi.org/10.1111/cpr.13055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168418PMC
June 2021

Krϋppel-like factor 15 suppresses renal glomerular mesangial cell proliferation via enhancing P53 SUMO1 conjugation.

J Cell Mol Med 2021 Jun 4;25(12):5691-5706. Epub 2021 May 4.

Department of Nephrology, First Medical Center of Chinese PLA General Hospital, Nephrology Institute of the Chinese People's Liberation Army, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Chinese PLA Institute of Nephrology, Chinese PLA General Hospital, Beijing, China.

Mesangial cell (MC) proliferation is a key pathological feature in a number of common human renal diseases, including mesangial proliferative nephritis and diabetic nephropathies. Knowledge of MC responses to pathological stimuli is crucial to the understanding of these disease processes. We previously determined that Krϋppel-like factor 15 (KLF15), a kidney-enriched zinc-finger transcription factor, was required for inhibition of MC proliferation. In the present study, we investigated the direct target gene and the underlying mechanism by which KLF15 regulated mesangial proliferation. First, we screened small ubiquitin-related modifier 1 (SUMO1) as the direct transcriptional target of KLF15 and validated this finding with ChIP-PCR and luciferase assays. Furthermore, we demonstrated that overexpressing KLF15 or SUMO1 enhanced the stability of P53, which blocked the cell cycle of human renal MCs (HRMCs) and therefore abolished cell proliferation. Conversely, knockdown of SUMO1 in HRMCs, even those overexpressed with KLF15, could not inhibit HRMC proliferation rates and increase SUMOylation of P53. Finally, the results showed that the levels of SUMOylated P53 in the kidney cortices of anti-Thy 1 model rats were decreased during proliferation periods. These findings reveal the critical mechanism by which KLF15 targets SUMO1 to mediate the proliferation of MCs.
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http://dx.doi.org/10.1111/jcmm.16583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184688PMC
June 2021

Ultrasound enhances the therapeutic potential of mesenchymal stem cells wrapped in greater omentum for aristolochic acid nephropathy.

Stem Cell Res Ther 2021 05 3;12(1):261. Epub 2021 May 3.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing, 100853, China.

Background: Mesenchymal stem cells (MSCs) have been reported to promote regeneration in both subjects with acute kidney injury (AKI) and chronic kidney disease (CKD), but their efficacy remains limited, probably because most of the cells accumulate in the lungs, liver, and spleen after an intravenous infusion. Therefore, ultrasound-guided administration of MSCs represents a possible approach to solve this problem. The greater omentum is used to promote cell survival due to its rich vasculature. We hypothesized that ultrasound-guided administration of MSCs combined with greater omentum might be more curative than currently available approaches.

Methods: In this study, we established an aristolochic acid nephropathy (AAN) model by intraperitoneally administering aristolochic acid I sodium salt (AA-I) at a dose of 5 mg/kg body weight on alternate days for 4 weeks. Subsequently, a laparotomy was performed, and the left kidney from which the capsule had been removed was wrapped with the greater omentum. A dose of 2 × 10 MSCs was injected into the space between the greater omentum and the left kidney. Equal amounts of MSCs were administered under ultrasound guidance every second week for a total of 4 treatments. Mice were sacrificed 4 weeks after surgery. Serum creatinine and blood urea levels were measured to assess renal function. qPCR, Western blot, and histological analyses were conducted to further investigate the therapeutic mechanism of MSCs.

Results: Ultrasound-guided injection of MSCs into the greater omentum that surrounds the kidney enriched cells in the kidney region for up to 5 days. Renal function tests indicated that MSCs improved renal function to a great extent, as reflected by decreased blood urea nitrogen and serum creatinine levels. In addition, histological analyses showed that MSCs noticeably attenuated kidney injury, as evidenced by the amelioration of tubular necrosis and peritubular interstitial fibrosis. Mitigation of renal interstitial fibrosis was further confirmed by immunohistochemistry, qPCR, and western blotting after MSC treatment. Moreover, immunofluorescence staining revealed that MSCs alleviated inflammatory responses by increasing the counts of CD206+ cells and decreasing the counts of CD68+ cells. MSC migration was initiated in response to AA-I-treated renal epithelial cells in an in vitro migration assay.

Conclusions: These findings suggested that administration of MSCs into the cavity formed by the injured kidney and the greater omentum under ultrasound guidance improved renal function, attenuated kidney injury, and mitigated renal interstitial fibrosis and inflammatory responses. Thus, this approach might be a safe and effective therapy for CKD.
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http://dx.doi.org/10.1186/s13287-021-02243-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091698PMC
May 2021

Establishment of PLAFMCi004-A induced pluripotent stem cells derived from PBMCs from a healthy individual.

Stem Cell Res 2021 05 5;53:102316. Epub 2021 Apr 5.

Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China. Electronic address:

Peripheral blood mononuclear cells (PBMCs) were isolated from a healthy male individual. PBMCs were reprogrammed into human induced pluripotent stem cells (iPSCs) using plasmids carrying the following reprogramming factors: NANOG, LIN28, OCT4, SOX2, c-MYC, and KLF4. This cell line expressed pluripotency markers, exhibited the normal male karyotype (46, XY), and had the potential to differentiate into 3 germ layers, as confirmed by techniques such as flow cytometry. The iPSC obtained from a healthy individual can be used for organoids to reveal developmental mechanism of tissue and organ regeneration, stem cell therapy and drug screening.
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http://dx.doi.org/10.1016/j.scr.2021.102316DOI Listing
May 2021

Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway.

Front Cell Dev Biol 2021 22;9:630412. Epub 2021 Mar 22.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China.

Cardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis to figure out the primary mediator of cardiac dysfunction. Herein proteomic analysis was operated in CRS-3 and growth factor receptor-bound protein 2 (Grb2) was identified as a regulator involving AKI-related myocardial damage. Increased Grb2 was associated with cardiac diastolic dysfunction and mitochondrial bioenergetics impairment; these pathological changes could be reversed through the administration of a Grb2-specific inhibitor during AKI. Molecular investigation illustrated that augmented Grb2 promoted cardiomyocyte mitochondrial metabolism disorder through inhibiting the Akt/mTOR signaling pathway. Besides that, Mouse Inflammation Array Q1 further identified IL-6 as the upstream stimulator of Grb2 upregulation after AKI. Exogenous administration of IL-6 induced cardiomyocyte damage and mitochondrial bioenergetics impairment, whereas these effects were nullified in cardiomyocytes pretreated with Grb2 inhibitor. Our results altogether identify CRS-3 to be caused by the upregulations of IL-6/Grb2 which contribute to cardiac dysfunction through inhibiting the Akt/mTOR signaling pathway and inducing cardiomyocyte mitochondrial bioenergetics impairment. This finding provides a potential target for the clinical treatment of patients with CRS-3.
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http://dx.doi.org/10.3389/fcell.2021.630412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019825PMC
March 2021

Interpretable Machine Learning Model for Early Prediction of Mortality in ICU Patients with Rhabdomyolysis.

Med Sci Sports Exerc 2021 Mar 31. Epub 2021 Mar 31.

Medical School of Chinese PLA, Beijing, China Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China School of Biological Science and Medical Engineering, Beihang University, Beijing, China Department of Critical Care Medicine, Chinese PLA General Hospital, Beijing, China Department of Anesthesiology, The 920 Hospital of Joint Logistic Support Force of Chinese PLA, Kunming Yunnan, China.

Purpose: Rhabdomyolysis (RM) is a complex set of clinical syndromes that involves the rapid dissolution of skeletal muscles. Mortality from rhabdomyolysis is approximately 10%. This study aimed to develop an interpretable and generalizable model for early mortality prediction in RM patients.

Method: Retrospective analyses were performed on two electronic medical record databases: the eICU Collaborative Research Database (eICU-CRD) and the Medical Information Mart for Intensive Care III (MIMIC- III) database. We extracted data from the first 24h after patient ICU admission. Data from the two datasets were merged for further analysis. The merged datasets were randomly divided, with 70% used for training and 30% for validation. We used the machine learning model XGBoost (extreme gradient boosting (XGBoost) with the Shapley additive explanation method to conduct early and interpretable predictions of patient mortality. Five typical evaluation indexes were adopted to develop a generalizable model.

Results: In total, 938 patients with RM were eligible for this analysis. The AUC of the XGBoost model in predicting hospital mortality was 0.871, the sensitivity was 0.885, the specificity was 0.816, the accuracy was 0.915 and the F1 score was 0.624. The XGBoost model performance was superior to that of other models (logistic regression (AUC = 0.862), support vector machine (AUC = 0.843), random forest (AUC = 0.825) and naive Bayesian (AUC = 0.805) and clinical scores (SOFA (AUC = 0.747) and APS III (AUC = 0.721)).

Conclusions: Although the XGBoost model is still not great from an absolute performance perspective, it provides better predictive performance than other models for estimating the mortality of patients with RM based on patient characteristics in the first 24h of admission to the ICU.
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http://dx.doi.org/10.1249/MSS.0000000000002674DOI Listing
March 2021

Lowest nocturnal systolic blood pressure is related to heavy proteinuria and outcomes in elderly patients with chronic kidney disease.

Sci Rep 2021 Mar 12;11(1):5846. Epub 2021 Mar 12.

Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, 28 Fuxing Road, Haidian District, Beijing, China.

Ambulatory blood pressure monitoring (ABPM) can produce many variables, of which the lowest nocturnal systolic blood pressure (LNSBP) currently used in calculating morning surge is occasionally overlooked in recent kidney studies compared with other ABPM parameters. We explored the clinical effects of LNSBP in elderly patients with chronic kidney disease (CKD) in a multicenter, observational cohort study. A total of 356 elderly patients with CKD from 19 clinics were included in this analysis. We used multiple logistic regression and survival analyses to assess the associations between the lowest nocturnal systolic blood pressure and heavy proteinuria and kidney disease outcomes, respectively. The median age was 66 years, and 66.6% were men. The median eGFR was 49.2 ml/min/1.73 m. Multivariate logistic regression analysis demonstrated that LNSBP (OR 1.24; 95% CI 1.10-1.39; P < 0.001; per 10 mmHg) was associated with heavy proteinuria. During the median follow-up of 23 months, 70 patients (19.7%) had a composite outcome; of these, 25 initiated dialysis, 25 had 40% eGFR loss, and 20 died. Cox analysis showed that the renal risk of LNSBP for CKD outcomes remained significant even after adjusting for background factors, including age, sex, medical history of hypertension and diabetes, smoking status, eGFR, 24-h proteinuria, and etiology of CKD (HR 1.18; 95% CI 1.06-1.32; P = 0.002; per 10 mmHg). Concentrating on LNSBP could be valuable in guiding antihypertensive treatment to control heavy proteinuria and improve renal prognosis in elderly CKD patients.
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http://dx.doi.org/10.1038/s41598-021-85071-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7955052PMC
March 2021

Regulation of connective tissue growth factor expression by miR-133b for the treatment of renal interstitial fibrosis in aged mice with unilateral ureteral obstruction.

Stem Cell Res Ther 2021 03 10;12(1):171. Epub 2021 Mar 10.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, 28 Fuxing Road, Beijing, China.

Introduction: Renal interstitial fibrosis, an important pathological feature of kidney aging and chronic renal failure, is regulated by mesenchymal stem cells (MSCs). We have previously demonstrated low expression of miR-133b in MSC-derived extracellular vesicles (MSC-EVs) in aged rats. However, miR-133b can mediate the inhibition of epithelial-mesenchymal transition (EMT) of renal tubules induced by transforming growth factor-β1 (TGF-β1). We investigated the effect of miR-133b for the treatment of geriatric renal interstitial fibrosis and evaluated its target genes.

Methods: We performed real-time polymerase chain reaction to detect miR-133b expression induced during EMT of HK2 cells by TGF-β1 at different concentrations (0, 6, 8, and 10 ng/mL) and at different time points (0, 24, 48, and 72 h). The target genes of miR-133b were validated using the dual-luciferase reporter assay. In vitro experiments were performed to evaluate mRNA and protein expression of miR-133b targets, E-cadherin, α-smooth muscle actin (SMA), fibronectin, and collagen 3A1 (Col3A1), in HK2 cells transfected with miR-133b under TGF-β1 stimulation. A 24-month-old unilateral ureteral obstruction (UUO) mouse model was established and injected with transfection reagent and miR-133b into the caudal vein. The target gene of miR-133b and other parameters mentioned above such as mRNA and protein expression levels and renal interstitial fibrosis were detected at 7 and 14 days.

Results: miR-133b expression gradually decreased with an increase in TGF-β1 concentration and treatment time, and the miR-133b mimic downregulated connective tissue growth factor (CTGF) expression. The dual-luciferase reporter assay confirmed CTGF as a direct target of miR-133b. Transfection of the miR-133b mimic inhibited TGF-β1-induced EMT of HK2 cells; this effect was reversed by CTGF overexpression. miRNA-133b expression significantly increased (approximately 70-100 times) in mouse kidney tissues after injection of the miRNA-133b overexpression complex, which significantly alleviated renal interstitial fibrosis in mice with UUO.

Conclusion: miR-133b exerted targeted inhibitory effects on CTGF expression, which consequently reduced TGF-β1-induced EMT of HK2 cells and renal interstitial fibrosis in aged mice with UUO.
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http://dx.doi.org/10.1186/s13287-021-02210-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7944614PMC
March 2021

Evaluating the safety and efficacy of argatroban locking solution in the prevention of the dysfunction of haemodialysis central venous catheters: a study protocol for a randomized controlled trial.

Ann Palliat Med 2021 Feb 25;10(2):2260-2270. Epub 2021 Jan 25.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Background: Use of anticoagulant as lock solutions is an important method to maintain the function of haemodialysis (HD) central venous catheters (CVCs), and the common anticoagulants heparin and citrate are not suitable for some patients. Argatroban can inhibit thrombin directly, has a definite anticoagulant effect, and is expected to be a new anticoagulant for CVC lock solutions.

Methods: A total of 60 HD patients with non-tunnelled or tunnelled CVCs will be randomly assigned to two groups: an argatroban group and a control group. The participants will be given argatroban 0.5 mg/mL or unfractionated heparin (UFH) 1,000 U/mL locked post-dialysis instilled into the CVC lumens and followed up for 2 weeks. Data on demographic and general clinical information, laboratory examination, adverse events, adverse reactions and serious adverse events in the two groups will be collected. The differences in coagulation indexes at 30 min following catheter lock will be compared. The thrombosis rate, infection rate and percentage of catheter-days in the two groups will be observed. The primary outcomes include: efficacy assessments of combined outcome events: (I) rates of cumulative catheter survival in the 2-week HD session (the standard of catheter survival was catheter mean blood flow ≥250 mL/min); (II) rates of cumulative survival free of catheter thrombosis in the 2-week HD session. The second outcomes include: catheter dysfunction, the variation value (seconds) in activated partial thromboplastin time (aPTT) at 30 min following catheter locking and aPTT before next dialysis, catheter-associated bleeding, and catheterassociated infections.

Discussion: At present, there is no clinical study of argatroban as a CVC lock solution. This study will explore the efficacy and safety of the argatroban as locking solution in the prevention of the dysfunction of HD CVCs to provide evidence for further research.

Trial Registration: Chinese Clinical Trial Registry, ChiCTR1800017105. Registered 12 July, 2018 (prospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=29054).
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http://dx.doi.org/10.21037/apm-20-1641DOI Listing
February 2021

Noninvasive markers of arterial stiffness and renal outcomes in patients with chronic kidney disease.

J Clin Hypertens (Greenwich) 2021 04 1;23(4):823-830. Epub 2021 Feb 1.

Department of Nephrology, Medical School of Chinese PLA, The First Medical Center, Chinese PLA General Hospital, Beijing, China.

Our study aimed to explore the intercorrelations of brachial-ankle pulse wave velocity (baPWV), ankle-brachial index (ABI), ambulatory arterial stiffness index (AASI), 24-hour mean pulse pressure (24-h   PP), and augmentation index (AIx, [email protected], the AIx standardized to a heart rate of 75) and compare the effectiveness of these markers for predicting renal outcomes. A total of 117 patients with chronic kidney disease (CKD) who received noninvasive arterial stiffness examinations were enrolled. We used correlation analysis and linear regression to explore the correlations between these five arterial stiffness markers and the Cox proportional hazards model and receiver operator characteristic (ROC) curve to assess the associations of markers with kidney disease outcomes. The median (interquartile range) of age and eGFR were 61 (49-65) years and 50.5 (35.5-84.1) ml/min/1.73 m , respectively. In Pearson correlation analysis, baPWV was significantly associated with 24-h  PP (r = .531, p < .001), [email protected] (r = .306, p < .001). Additionally, 24-h  PP was associated with AASI (r = .507, p < .001) and [email protected] (r = .217, p = .019). During follow-up for a median of 25 months, 26.5% (n = 31) of patients had a composite outcome; of these, 10 initiated dialysis, 17 had 40% eGFR loss, and 4 died. Increased AASI, 24-h  PP, and baPWV were associated with poor renal outcomes in a univariate Cox analysis. After adjusting for age, sex, MAP, eGFR, and 24 hours proteinuria, 1-SD increase in AASI and 24-h  PP was associated with renal outcomes. The ROC analysis yielded the largest area under the curve (AUC) of 0.727 (95% CI: 0.624 to 0.831; p < .001) for 24  -h PP. When the Youden's index was at its maximum, the 24-h PP value was 52 mmHg. In conclusion, 24-h  PP, baPWV, and [email protected] were linked well to one another. Arterial stiffness is a target for delaying the decline in kidney function. The use of 24-h  PP as an arterial stiffness marker should be valued in CKD clinical practice.
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http://dx.doi.org/10.1111/jch.14185DOI Listing
April 2021

Generation of iPSC from peripheral blood mononuclear cells obtained from a patient with TSC2-PKD1 contiguous gene deletion syndrome.

Stem Cell Res 2021 03 18;51:102181. Epub 2021 Jan 18.

Department of Nephrology, The First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing 100853, China. Electronic address:

TSC2-PKD1 contiguous gene deletion syndrome is characterized by tuberous sclerosis complex and polycystic kidney disease. We obtained peripheral blood mononuclear cells from a patient with TSC2-PKD1 contiguous gene deletion syndrome. We performed reprogramming using non-integrative episomal vectors to obtain human induced pluripotent stem cells (iPSCs). The obtained iPSCs had a normal karyotype and expressed human ES cell-specific cell surface markers and genes; in teratomas, iPSCs differentiated into derivatives of all three germ layers. The iPSCs can be used to study pathogenesis of TSC2-PKD1 contiguous gene deletion syndrome and serve as a potential therapeutic target.
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http://dx.doi.org/10.1016/j.scr.2021.102181DOI Listing
March 2021

Analysis of the influencing factors on the quality of life of the elderly hemodialysis patients.

Int Urol Nephrol 2021 Apr 3;53(4):763-770. Epub 2021 Jan 3.

Department of Nephrology, Chinese People's Liberation Army General Hospital, Chinese People's Liberation Army Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Disease Research, Beijing, 100853, China.

Objective: The present study aims to identify factors affecting quality of life in elderly patients undergoing maintenance hemodialysis (MHD).

Methods: A total of 656 patients undergoing MHD in 10 hospitals in Beijing were enrolled. Patients aged ≥ 65 years were allocated to the elderly group; patients aged < 65 years were allocated to the non-elderly group. The patients' quality of life was described based on their general situation, physiological function, cognitive status (which was assessed using the Basic Montreal Cognitive Assessment), and answers to the Kidney Disease Quality of Life questionnaire.

Results: Statistically significant differences between the two groups (P < 0.05) were observed in gender ratio, marital status, medical type, and sleep duration. Patients who did not live alone, had a higher average annual income, and had a longer sleep duration also had a higher cognitive ability. Total protein concentration and a depressive state were positive predictors of renal disease burden.

Conclusion: Age, underlying disease, and complications can affect the quality of life of patients on MHD.
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http://dx.doi.org/10.1007/s11255-020-02714-5DOI Listing
April 2021

Single-Cell Transcriptomics Reveal Immune Mechanisms of the Onset and Progression of IgA Nephropathy.

Cell Rep 2020 12;33(12):108525

Beijing Advanced Innovation Center for Genomics (ICG), College of Life Science, Peking University, Beijing 100871, China; Biomedical Pioneering Innovation Center (BIOPIC), Peking University, Beijing 100871, China. Electronic address:

IgA nephropathy (IgAN) is the leading cause of kidney failure due to an incomplete understanding of its pathogenesis. We perform single-cell RNA sequencing (RNA-seq) on kidneys and CD14 peripheral blood mononuclear cells (PBMCs) collected from IgAN and normal samples. In IgAN, upregulation of JCHAIN in mesangial cells provides insight into the trigger mechanism for the dimerization and deposition of IgA1 in situ. The pathological mesangium also demonstrates a prominent inflammatory signature and increased cell-cell communication with other renal parenchymal cells and immune cells, suggesting disease progress from the mesangium to the entire kidney. Specific gene expression of kidney-resident macrophages and CD8 T cells further indicates abnormal regulation associated with proliferation and inflammation. A transitional cell type among intercalated cells with fibrosis signatures is identified, suggesting an adverse outcome of interstitial fibrosis. Altogether, we systematically analyze the molecular events in the onset and progression of IgAN, providing a promising landscape for disease treatment.
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http://dx.doi.org/10.1016/j.celrep.2020.108525DOI Listing
December 2020

Generation of induced pluripotent stem cell PLAFMCi002-A derived from peripheral blood mononuclear cells of polycystic kidney disease patient with PKD1 mutation.

Stem Cell Res 2020 12 9;49:102039. Epub 2020 Oct 9.

Department of Nephrology, the First Medical Center, Chinese PLA General Hospital, Medical School of Chinese PLA, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China. Electronic address:

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disease, which characterized by formation and expansion of cysts within the kidney, leading to kidney failure. Thus, Peripheral blood mononuclear cells (PBMCs) were isolated from a 32-year-old male patient carrying the PKD1 compound mutations p.M3091R and p.S843P, and were reprogrammed to human induced pluripotent stem cells (iPSCs) using non-integrative episomal vectors. The PLAFMCi002-A iPSC line expresses pluripotency markers, exhibits the capacity to differentiate into three germ layers in vivo. This iPSC line may be used for studying the molecular basis of the disease, screening potential therapeutic targets and drug testing.
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http://dx.doi.org/10.1016/j.scr.2020.102039DOI Listing
December 2020

SARS-CoV-2-Related Kidney Injury: Current Concern and Challenges.

SN Compr Clin Med 2020 Sep 23:1-10. Epub 2020 Sep 23.

Department of Geriatrics, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039 China.

Coronavirus disease 2019 (COVID-19) not only causes pulmonary inflammation but also causes multiple organ damages, including the kidney. ACE2, as one of the receptors for SARS-CoV-2 intrusion, is widely distributed in kidney tissues. Currently, the diagnosis and treatment of SARS-CoV-2 infection in patients with chronic kidney disease (CKD) are still unclear. Here, we review the recent findings of characteristics of COVID-19 in CKD patients and highlight the possible mechanisms of kidney injury caused by SARS-CoV-2 infection. We then discuss the emerging therapeutic approaches aimed at reducing kidney damage and protecting kidney function including virus removal, immunotherapy, supporting treatment, special blood purification therapy, etc. Problems unresolved and challenges ahead are also discussed.
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http://dx.doi.org/10.1007/s42399-020-00529-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509500PMC
September 2020

Factors Associated with Brachial-Ankle Pulse Wave Velocity in an Apparently Healthy Chinese Population.

Biomed Res Int 2020 23;2020:9795240. Epub 2020 Jul 23.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing Key Laboratory of Kidney Disease, Beijing, China.

Purpose: To investigate the factors influencing brachial-ankle pulse wave velocity (baPWV) in an apparently healthy Chinese population, especially the associations between baPWV and indices of blood pressure (BP).

Methods: A total of 1123 participants with no history of hypertension were enrolled in this study, and the baPWV and BP of all four limbs were measured along with other covariates. Correlation analyses and multivariate linear regression models were used to identify factors associated with baPWV.

Results: A total of 1123 participants (male 43.3%, mean age: 58.4 ± 13.9 years) were included. The average baPWV was 14.87 ± 3.21 m/s, and no difference was found between the sexes. Age was positively correlated with baPWV ( = 0.65, < 0.01), especially in females ( = 0.71 versus 0.56 in males). The correlation coefficient between age and baPWV increased markedly after the age of 65 years. In addition, the resting heart rate (RHR), waist-hip ratio, glomerular filtration rate, and plasma glucose level were significantly correlated with baPWV ( = 0.25, 0.22, -0.43, and 0.25, respectively; < 0.01). BP parameters were highly positively correlated with baPWV, especially systolic BP (SBP) and pulse pressure (PP). Multivariate regression revealed that age, BP parameters, and RHR were independently correlated with baPWV ( < 0.01) after adjusting for confounding factors. The standardized coefficients of SBP were greater than those of PP, followed by diastolic BP (DBP).

Conclusion: BaPWV increased with age, especially after 65 years. Age, BP, and RHR were independent factors associated with baPWV. The effect of SBP on baPWV was more prominent than that of PP.
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http://dx.doi.org/10.1155/2020/9795240DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396024PMC
April 2021

rs2241766 Gene Polymorphism and Predisposition to Diabetic Kidney Disease.

J Diabetes Res 2020 28;2020:5158497. Epub 2020 Jun 28.

Department of Nephrology, The First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Beijing Key Laboratory of Kidney Disease, China.

Background: This meta-analysis was performed to obtain a more comprehensive estimation of the role of the single nucleotide polymorphism (SNP) rs2241766 in the gene in the occurrence of diabetic kidney disease (DKD).

Methods: Relevant studies were identified from digital databases such as Embase, PubMed, Medline, Cochrane Library, Google Scholar, WanFang, and Chinese National Knowledge Infrastructure (CNKI). Odds ratios (ORs) with their corresponding 95% confidence intervals (95% CIs) were pooled by means of fixed- or random-effects models. Interstudy heterogeneity was examined using the Q test and statistic, and sensitivity analysis was implemented to test the statistical stability of the overall estimates. Begg's funnel plot and Egger's test were applied to inspect potential publication bias among the included studies.

Results: The overall ORs reflected a positive correlation between the rs2241766 polymorphism and susceptibility to DKD in the GG vs. TT and GG vs. TT+TG comparisons (OR = 1.51, 95%CI = 1.16 - 1.95; OR = 1.43, 95%CI = 1.11 - 1.85). After stratification analyses by ethnicity and disease type, a similar trend was also revealed in the Caucasian and African subgroups as well as in the type 2 diabetes mellitus (T2DM) subgroup.

Conclusion: The rs2241766 polymorphism may be associated with an increased risk of DKD, especially in Caucasian and African populations as well as in T2DM patients.
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http://dx.doi.org/10.1155/2020/5158497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7341419PMC
May 2021

High Concentrations of Uric Acid and Angiotensin II Act Additively to Produce Endothelial Injury.

Mediators Inflamm 2020 22;2020:8387654. Epub 2020 May 22.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center of Kidney Diseases, Chinese PLA General Hospital, Beijing 100853, China.

Renin angiotensin (Ang) system (RAS) activation in metabolic syndrome (MS) patients is associated with elevated uric acid (UA) levels, resulting in endothelial system dysfunction. Our previous study demonstrated that excessive UA could cause endothelial injury through the aldose reductase (AR) pathway. This study is the first to show that a high concentration of Ang II in human umbilical vein endothelial cells (HUVECs) increases reactive oxygen species (ROS) components, including O and HO, and further aggravates endothelial system injury induced by high UA (HUA). In a MS/hyperuricemia model, nitric oxide (NO) production was decreased, followed by a decrease in total antioxidant capacity (TAC), and the concentration of the endothelial injury marker von Willebrand factor (vWF) in the serum was increased. Treatment with catalase and polyethylene glycol covalently linked to superoxide dismutase (PEG-SOD) to individually remove HO and O or treatment with the AR inhibitor epalrestat decreased ROS and HO, increased NO levels and TAC, and reduced vWF release. Taken together, these data indicate that HUA and Ang II act additively to cause endothelial dysfunction via oxidative stress, and specific elimination of O and HO improves endothelial function. We provide theoretical evidence to prevent or delay endothelial injury caused by metabolic diseases.
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http://dx.doi.org/10.1155/2020/8387654DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261330PMC
July 2021

Haploinsufficiency Does Not Cause Polycystic Kidney Disease or Polycystic Liver Disease in Mice.

Biomed Res Int 2020 19;2020:7469428. Epub 2020 May 19.

Medical School of Chinese PLA, Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Background: Heterozygous mutations that can cause autosomal dominant polycystic kidney disease (ADPKD) and polycystic liver disease (PLD) have been described previously, but their roles in ADPKD and PLD are largely unknown. With the increase in polycystic kidney disease caused by gene mutations in recent years, a suitable animal model is still needed to further explore the pathogenic role of this gene.

Methods: To construct a mouse model of gene deletion, we analyzed gene structure and designed two CRISPR-/Cas9-based targeting strategies. The Cas9/sgRNA we constructed was microinjected into fertilized mouse eggs to obtain chimeric F0 mice. Mice with stable genotypes were selected from offspring born after mating F0 mice with wild-type mice.

Results: We found that homozygous mutation of the gene in C57BL/6 mice resulted in early embryonic lethality, and there were no cysts in the kidneys or livers of mice. Additionally, protein expression was reduced by at least 50%, while the expression of ADPKD proteins (PC1 and PC2) and acetylated tubulin was not affected in the kidney. However, the mice did not show any abnormal clinical phenotypes after birth and failed to reveal renal tubule dilatation or any abnormalities of the glomeruli in the kidney.

Conclusions: Homozygous mutations are lethal in the fetal stage, and haploinsufficiency does not cause kidney or liver cysts in mice, suggesting that it may not be the causative gene in polycystic kidney disease.
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http://dx.doi.org/10.1155/2020/7469428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7256702PMC
March 2021

Efficacy and safety of Abelmoschus manihot for IgA nephropathy: A multicenter randomized clinical trial.

Phytomedicine 2020 May 18;76:153231. Epub 2020 May 18.

Department of Nephrology, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Chinese PLA General Hospital, Chinese PLA Medical School, Beijing 100853, China. Electronic address:

Rationale And Objective: IgA nephropathy (IgAN) is an important cause for end-stage renal disease worldwide. The treatment for IgAN remains challenging, and few randomized and controlled clinical trials have been conducted to evaluate new therapies. The present study assesses the efficacy and safety of Abelmoschus manihot (AM) in IgAN patients.

Study Design: Randomized, non-inferiority, double-blind, double-dummy multicenter trial.

Setting And Participants: This trial was designed to recruit 1,600 biopsy-proven IgAN patients (proteinuria between 0.5-3.0 g/d and estimated glomerular filtration rate [eGFR] of ≥ 45 ml/min/1.73 m) across China.

Interventions: The participants were randomized at 1:1 to AM (2.5 g for three times per day) or losartan potassium (100 mg per day) for 48 weeks.

Outcomes: The primary outcome was the change in 24-hour proteinuria from baseline to week 48. The secondary outcomes were the change in eGFR from baseline to week 48, and the incidents of endpoint events (proteinuria ≥ 3.5 g/24 h, doubling of serum creatinine, or receiving renal replacement treatment).

Results: Among 1,470 randomized patients (mean age, 37.4 [SD, 10.6] years old; 777 [52.9%] were female; mean eGFR, 95.0 [SD, 24.3] mL/min/1.73 m; mean 24-hour proteinuria, 1.2 [SD, 0.7] g/d), the mean decline in 24-h proteinuria at week 48 was 230 mg and 253 mg in the AM and losartan potassium groups, respectively (P = 0.676). The mean difference in the change in 24-h proteinuria between these two groups was -23.32 mg (95% confident interval: -123.2 to 76.6, p = 0.647). The mean decline in eGFR was 0.41 ml/min/1.73 m and 0.76 ml/min/1.73 m in the AM and losartan potassium groups, respectively (p = 0.661). The mean difference in the change in eGFR between these two groups was -0.43 ml/min/1.73 m (95% confident interval: -1.99 to 1.13, p = 0.589). The incidence of endpoint events was 8.6% in the AM group and 8.2% in the losartan group (p = 0.851).

Limitations: The results of the trial may not be generalized to IgAN patients with a proteinuria of > 3.0 g/d and an eGFR of < 45 ml/min/1.73 m. The long-term benefits of AM in reducing the risk of progressive renal dysfunction remains unclear, based on this 48-week observation.

Conclusion: AM can be recommended as a promising treatment for IgAN patients.
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http://dx.doi.org/10.1016/j.phymed.2020.153231DOI Listing
May 2020

Cisplatin-induced renal toxicity in elderly people.

Ther Adv Med Oncol 2020 18;12:1758835920923430. Epub 2020 May 18.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing, China.

Despite available prevention and treatment measures, such as hydration, diuresis, magnesium supplementation, and amifostine, renal toxicity is still one of the major dose-limiting side effects of cisplatin. The aim of this review is to discuss the issue of cisplatin-induced nephrotoxicity in the elderly. Compared with young patients, the incidences of cisplatin-induced nephrotoxicity and acute kidney injury (AKI) in elderly patients are significantly increased, and survival time may be decreased. Following cisplatin treatment of elderly patients, tubulointerstitial injuries will be significantly aggravated based on their original age, both for acute injuries due to cell necrosis and exfoliation and chronic injuries due to interstitial fibrosis, tubular atrophy, and dilatation. The high incidence of cisplatin-induced nephrotoxicity in elderly patients may be associated with renal hypoperfusion; increased comorbidities, such as chronic kidney disease (CKD), cardiovascular disease, and diabetes mellitus; increased use of combined drugs [especially non-steroidal anti-inflammatory drugs, angiotensin-converting enzyme and angiotensin receptor blockers (ACEI/ARB), and antibiotics]; decreased clearance of cisplatin; and high plasma ultrafilterable cisplatin. Considering hemodynamic stability and water balance, short duration and low volume hydration may be more suitable for treating elderly people. With the increasing popularity of low-dose daily/weekly regimens, we do not recommend routine diuretic treatment for elderly patients. We recommend using a less nephrotoxic platinum if large doses of cisplatin (100mg/m) are needed.
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http://dx.doi.org/10.1177/1758835920923430DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238313PMC
May 2020

Percutaneous insertion of peritoneal dialysis catheter is a safe and effective technique irrespective of BMI.

BMC Nephrol 2020 05 25;21(1):199. Epub 2020 May 25.

Department of Nephrology, the First Medical Centre, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases (2011DAV00088), National Clinical Research Center for Kidney Diseases, Fuxing Road 28, Beijing, 100853, People's Republic of China.

Background: A large body mass index (BMI) has been considered as a relative contraindication for percutaneous catheter insertion, although this technique has many advantages. Up to now, there are few studies on peritoneal catheter placement and obesity. The aim of this study was to determine whether patients with large BMI can also choose the percutaneous technique for peritoneal dialysis catheter insertion.

Methods: One hundred eighty seven consecutive patients underwent peritoneal catheter insertions in the Chinese PLA General Hospital between January 1, 2015 and December 31, 2016, with 178 eligible cases being included in the analysis. Two groups were created based on the catheter insertion techniques, the percutaneous group (group P) and the surgical group (group S). Subgroups were created according to BMI > 28 or ≤ 28. The outcomes included catheter related complications and catheter survival.

Results: Total infectious complication rates were significantly lower in group P than in group S. There were no significant differences in peritonitis rate between group P and group S (1.20% vs. 3.16% with P = 0.71 in early stage, and 4.82% vs. 11.58% with P = 0.11 in late stage). All other measured complications were similar between the two groups. Though the one-year infection-free catheter survival in group P was 7.5% higher than group S, the difference was not significant. The one-year dysfunction-free catheter survival, one-year dysfunction-and-infection-free catheter survival, and overall catheter survival were similar between the two groups. Subgroup analyses showed a superior one-year infection-free catheter survival of percutaneous technique in patients with BMI > 28, which was confirmed by Kaplan-Meier analysis.

Conclusions: Despite the challenges that may be encountered with patients who have a large BMI, the percutaneous technique seems to be a safe and effective approach to placing a peritoneal dialysis catheter.
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http://dx.doi.org/10.1186/s12882-020-01850-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7249625PMC
May 2020
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