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.

Targeted delivery of celastrol to glomerular endothelium and podocytes for chronic kidney disease treatment

The etiology of chronic kidney disease(CKD)is complex and diverse,which could be briefly categorized to glomerular-or tubularoriginated.However,the final outcomes of CKD are mainly glomerular sclerosis,endothelial dysfunction and injury,and chronic inflammation.Thus,targeted delivery of drugs to the glomeruli in order to ameliorate glomerular endothelial damage may help alleviate CKD and help enrich our knowledge.The herb tripterygium wilfordii shows therapeutic effect on kidney disease,and celastrol(CLT)is one of its active ingredients but with strong toxicity.Therefore,based on the unique structure and pathological characteristics of the glomerulus,we designed a targeted delivery system named peptides coupled CLT-phospholipid lipid nanoparticles(PC-PLNs)to efficiently deliver CLT to damaged endothelial cells and podocytes in the glomerulus for CKD treatment and research.PC-PLNs could effectively inhibit inflammation,reduce endothelial damage,alleviate CKD severity,and reduce the toxicity of CLT.We also studied the mechanism of CLT in the treatment of nephropathy and found that CLT can increase the level of NO by increasing eNOS while inhibiting the expression of VCAM-1,thus provides an anti-inflammatory effect.Therefore,our study not only offered an efficient CKD drug formulation for further development,but also provided new medical knowledge about CKD.

Focal Segmental Glomerulosclerosis in Côte d’Ivoire: Epidemiological, Clinical and Pathological Aspects

Focal segmental glomerulosclerosis (FSGS) is characterized histologically by hyalinosis and sclerosis of glomeruli associated or not with podocyte involvement. The objective of our work was to clarify the epidemiological aspects and histological variants of FSGS in Côte d’Ivoire. Materials and Methods: This was a descriptive retrospective study, conducted from January 2015 to December 2019 using the renal biopsy registers (RB) of the Pathological Anatomy and Cytology departments of the Teaching Hospital of Cocody and Bouake in collaboration with the Nephrology Services of Côte d'Ivoire and the sub-region. The biopsies underwent conventional histopathology and/or immunofluorescence techniques. The parameters analyzed were: frequency, age, gender, proteinuria, biopsy indications and histological aspects and the different correlations between histological aspects and socio-demographic characteristics. Results: FSGS represented 58.1% (n = 104) of glomerular nephropathies. The average age of patients was 32.1 ± 13.3 years, with extremes of 13 and 70 years. The sex ratio was equal to 1. Nephrotic syndrome (68.9%), chronic renal failure (14.3%) and acute renal failure (10.1%) were the main indications for renal biopsy (RB). The mean proteinuria at the time of diagnosis was 4 ± 3.7 g/24 h. It was massive (3.5 g/24 h) in 42.3% of patients. FSGS was primary in 29.8% (n = 31) and secondary in 70.2% (n = 73) of patients, of which 27.9% (n = 35) was due to HIV. According to the Columbia classification, 62.5% NOS type was found;23.1% collapsing type;7.7% tip lesion type;4.8% cell type and 1.9% perihilary type. Conclusion: FSGS is a complex heterogeneous entity. It affects young people in our context with a homogeneous gender distribution. Understanding its histogenesis is essential for optimal patient management.

Glomerular chemokine expression and the effect of steroid and cyclophosphamide pulse therapy in human crescentic glomerulonephritis

OBJECTIVE: To study glomerular expression of C-C chemokines, monocyte chemoattractant protein-1 (MCP-1), macrophage inflammatory protein-1alpha and beta (MIP-1alpha, MIP-1beta) and the effect of steroid and cyclophosphamide (CTX) intermittent intravenous pulse therapy on expression in patients with crescentic glomerulonephritis (CGN) to further investigate the underlying mechanism of the treatment. METHODS: Twelve patients with initial biopsy-proven CGN(2), 6 with lupus nephritis (lupus-CGN, LN-CGN) and 6 with vasculitis, (vasculitis-CGN, V-CGN) were enrolled in this study. They underwent an initial biopsy before steroid and CTX intermittent intravenous pulse therapy and were biopsied again one to three months later. Expression of MCP-1, MIP-1alpha, MIP-1beta, and CD68 in glomeruli with cellular and fibrocellular crescents were examined by immunohistochemical analysis in serial sections of renal biopsies. The effect of the pulse therapy on histopathological changes was also observed. RESULTS: Although steroid and CTX intermittent intravenous pulse therapy markedly reduced the degree of glomerular crescent formation both in LN-CGN and V-CGN, the effect of the therapy on glomerular chemokine expression was significantly different between LN-CGN and V-CGN. It was found that steroid and CTX intermittent intravenous pulse therapy reduced the expression of CD68, MCP-1, and MIP-1alpha, but had no effect on MIP-1beta in glomeruli with cellular crescents of patients with LN-CGN. In patients with V-CGN, the therapy also reduced the expression of CD68, but had no effect on MCP-1, MIP-1alpha, and MIP-1beta in glomeruli with cellular crescents. It was noted that the degree of glomerulosclerosis and tubular interstitial fibrosis increased more significantly at the second biopsy in V-CGN as compared to LN-CGN. CONCLUSIONS: The efficacy of steroid and CTX intermittent intravenous pulse therapy in CGN might be affected by reduction of glomerular chemokine expression. The different changes in glomerular expression of MCP-1 and MIP-1alpha in patients with LN-CGN and V-CGN after pulse therapy may correlate to different responses to treatment and prognosis.

Establishment and functional characterization of the reversibly immortalized mouse glomerular podocytes(imPODs)

Glomerular podocytes are highly specialized epithelial cells and play an essential role in establishing the selective permeability of the glomerular filtration barrier of kidney.Maintaining the viability and structural integrity of podocytes is critical to the clinical management of glomerular diseases,which requires a thorough understanding of podocyte cell biology.As mature podocytes lose proliferative capacity,a conditionally SV40 mutant tsA58-immortalized mouse podocyte line(designated as tsPC)was established from the Immortomouse over 20 years ago.However,the utility of the tsPC cells is hampered by the practical inconvenience of culturing these cells.In this study,we establish a user-friendly and reversibly-immortalized mouse podocyte line(designated as imPOD),on the basis of the tsPC cells by stably expressing the wildtype SV40 T-antigen,which is flanked with FRT sites.We show the imPOD cells exhibit long-term high proliferative activity,which can be effectively reversed by FLP recombinase.The imPOD cells express most podocyte-related markers,including WT-1,Nephrin,Tubulin and Vinculin,but not differentiation marker Synaptopodin.The imPOD cells do not form tumor-like masses in vivo.We further demonstrate that TGFb1 induces a podocyte injury-like response in the FLP-reverted imPOD cells by suppressing the expression of slit diaphragm-associated proteins P-Cadherin and ZO-1 and upregulating the expression of mesenchymal markers,a-SMA,Vimentin and Nestin,as well as fibrogenic factors CTGF and Col1a1.Collectively,our results strongly demonstrate that the newly engineered im-POD cells should be a valuable tool to study podocyte biology both under normal and under pathological conditions.

Genetic variation of mannose-binding protein associated with glomerular immune deposition in IgA nephropathy

OBJECTIVE: To investigate the relationship between codon 54 gene polymorphism of the host defense molecule, mannose-binding protein (MBP), and the patterns of glomerular immune deposition in IgA nephropathy (IgAN). METHODS: IgAN patients with different patterns of glomerular immune deposition were selected and divided into two groups. Group A consisted of 77 patients with glomerular IgA and C3 deposits, and Group AGM consisted of 70 patients with glomerular IgA, IgG, IgM, C3 and Clq deposits. Clinical features and laboratory relevant data of all patients were collected. One-hundred and forty healthy adults were recruited as normal controls. The MBP gene codon 54 GGC/GAC polymorphism was investigated by using polymerase chain reaction and restriction fragment length polymorphism. RESULTS: The genotype frequency of GGC/GAC heterozygotes was significantly higher in Group AGM as compared with that of Group A (41.4% vs 19.5%, P

Prenatal prednisone exposure disturbs fetal kidney development and its characteristics

Prednisone is a synthetic glucocorticoid that is commonly used in both human and veterinary medication.Now,it is also recognized as an emerging environmental contaminant.Pregnantwomenmay be exposed to prednisone actively or passively throughmultiple pathways and cause developmental toxicity to the fetus.However,the impact of prenatal prednisone exposure(PPE)on fetal kidney development remains unclear.In this study,pregnant mice were administered prednisone intragastrically during full-term pregnancy with different doses(0.25,0.5,or 1 mg/(kg·day)),or at the dose of 1 mg/(kg·day)in different gestational days(GD)(GD0-9,GD10-18,or GD0-18).The pregnant mice were euthanized on GD18.HE staining revealed fetal kidney dysplasia,with an enlarged glomerular Bowman’s capsule space and a reduced capillary network in the PPE groups.The expression of the podocyte and the mesangial cell marker genes was significantly reduced in the PPE groups.However,overall gene expression in renal tubules and collecting ducts were markedly increased.All of the above effects were more pronounced in high-dose,full-term pregnancy,and female fetuses.Studies on the mechanism of the female fetal kidney have revealed that PPE reduced the expression of Six2,increased the expression of Hnf1β,Hnf4α,and Wnt9b,and inhibited the expression of glial cell line-derived neurotrophic factor(GDNF)and Notch signaling pathways.In conclusion,this study demonstrated that there is a sex difference in the developmental toxicity of PPE to the fetal kidney,and the time effect is manifested as full-term pregnancy>early pregnancy>mid-late pregnancy.

核因子-κB对阿霉素肾病大鼠肾小球细胞凋亡的影响

目的探讨核转录因子κB（NF-κB）对阿霉素肾病大鼠肾小球细胞凋亡的影响。方法SD雄性大鼠分成两大组，A组（假手术组）6只，B组（硬化组）6只。采用右肾切除加尾静脉注射阿霉素制成肾小球硬化动物模型。分别在8周、9周两个不同时上间点，应用免疫组化检测肾组织Caspase-3、NF—κBp65的表达，TUNEL检测肾小球细胞凋亡指数。结果在不同的时间点，B组NF-κB阳性表达指数比A组明显增高（P〈0.05）；肾小球系膜细胞（MC）凋亡指数、Caspase-3的表达与NF-κB呈正相关关系。结论NF-κB参与肾小球系膜细胞凋亡的调控，促进肾小球硬化的进程。

氧化应激及足细胞损伤在甲状腺功能亢进大鼠肾损害中的作用

目的观察氧化应激、转化生长因子-β1和巢蛋白表达变化在甲状腺功能亢进大鼠肾损害中的作用。方法优甲乐灌胃法制作甲亢大鼠模型，测定25，45，60d大鼠肾组织中抗氧化酶：超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH—Px）、过氧化氢酶（CAT）活性，丙二醛（MDA）含量及TGF—β1、Nestin表达变化。结果随甲亢病程延长，CAT、GSH—Px、SOD活性逐渐降低，MDA含量逐渐增加；TGF—β1表达逐渐增多，而Nestin表达逐渐减少；且TGF—β1及Nestin表达均与氧化应激有相关性。结论氧化应激、TGF-β1表达增加及足细胞损伤相互作用共同参与甲亢肾脏损伤过程。

Epidemiology of biopsy-proven glomerular diseases in Chinese children: A scoping review

Background: Glomerular disease is the leading cause of chronic kidney disease globally. No scoping review reports have focused on China’’s spectrum of glomerular diseases in children. This study aimed to systematically identify and describe retrospective studies on pediatric glomerular disease based on available data on sex, age, study period, and region.Methods: Six databases were systematically searched for relevant studies from initiation to December 2021 in PubMed, Embase, Web of Science, Global Health Library, Wangfang Database, and CNKI.Results: Thirty-four studies were identified in the scoping review, including 40,430 patients with biopsy-proven diagnoses. The proportion of boys was significantly higher than that of girls. In this study, 28,280 (70%) cases were primary glomerular disease, 10,547 (26.1%) cases were diagnosed as secondary glomerular disease, and 1146 (2.8%) cases were hereditary glomerular disease. Minimal change disease is the most common glomerular disease among children in China, followed by mesangial proliferative glomerulonephritis, IgA nephropathy, and purpura nephritis. We observed increments in glomerular diseases in periods 2 (2001–2010) and 3 (2011–2021). The proportion of major glomerular diseases varies significantly in the different regions of China.Conclusion: The spectrum of pediatric glomerular diseases varied across sex, age groups, study periods, and regions, and has changed considerably over the past 30 years.