n light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related giomerulopathy （ORG） is characterized by glomeru...n light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related giomerulopathy （ORG） is characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 （C3） nonspeciflcally deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria （ 〈 3.5 g/d） is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin-angiotensin-aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.展开更多
Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk ...Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-α plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.展开更多
Background Lipoprotein glomerulopathy (LPG) is a renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and its abnormal lipoprotein profiles with marked elevation of apolipoprotein E ...Background Lipoprotein glomerulopathy (LPG) is a renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and its abnormal lipoprotein profiles with marked elevation of apolipoprotein E (apoE). In this study, 15 Chinese patients with LPG were involed in exploring the association of the genetic variation and its plasma level in the pathogenesis of LPG.Methods A retrospective analysis of the clinical and pathological features was made in 15 patients with LPG. Plasma concentrations of apoE were measured with radial immunodiffusion assay. Genetic variations of apoE gene were detected using polymerase chain reaction and restriction fragment length polymorphism. Glomerular deposition of apoA, apoB and apoE in these patients were detected by immunofluorescence staining using monoclonal antibodies. Results Biochemical profiles of lipids and lipoproteins revealed markedly elevated levels of triglyceride, apoB and apoE, but approximately normal levels of total cholesterol, apoA1 and lipoprotein(a) [Lp(a)], which resembled familial hypertriglyceridemia. Genetic analysis demonstrated that the genotype distribution of apoE were 7 cases with (ε3/ε 4,)4 cases with ε3/ε 3 and 2 cases with ε2/ε 3. The other 2 cases (a mother and her son) showed a same distinct band. The band pattern of later 2 cases was quite similar to the apoE variant of Tokyo type. The calculated allele frequency of ε 4 was relatively high in cases with LPG in comparison with that in the normal controls. We further divided the 13 patients into three groups according to their genotypes of apoE. Patients with the genotype of apoE ε2/ε3 showed a lower level of plasma apoE as compared to those with apoE ε3/ε4 (P<0.05). The serum level of high-density lipoprotein (HDL) was the lowest in patients with the genotype of apoE ε3/ε4. No difference was found among the patients with different apoE genotype in the other clinical and pathological characteristics. Conclusions The genotype of apoE ε3/ε4 is the predominant one in Ch展开更多
Introduction: Vaccination against COVID-19 has proven highly effective in preventing severe forms of the disease. However, the literature reports several cases associating renal damage and the anti-COVID vaccine. The ...Introduction: Vaccination against COVID-19 has proven highly effective in preventing severe forms of the disease. However, the literature reports several cases associating renal damage and the anti-COVID vaccine. The aim of our work was to report a case series of patients who developed glomerulopathy after anti-COVID-19 vaccine. We evaluated the type of vaccine, the clinico-biological profile, and the anatomopathological, therapeutic and evolutionary aspects. Material and Methods: Prospective descriptive study conducted at the Nephrology Department of CHU IbnSina in Rabat between December 2021 and June 2022 including 9 patients who presented with glomerulopathy after the 1st dose of anti-COVID-19 vaccine. We excluded patients followed for nephropathy. Results: The mean age of our patients was 33 ± 16 years with a sex ratio of 0.8. Six patients received an inactivated vaccine, 2 patients received a mRNA vaccine and 1 patient received a viral vector vaccine. The mean delay between the onset of signs and the date of the first vaccine dose was 3.1 +/? 0.65 months (1 - 6 months). All patients had a nephrotic syndrome, 2 pure and 7 impure: 3 patients had acute renal failure and microscopic hematuria, 2 patients had microscopic hematuria and 2 patients had acute renal failure. Histologically, focal segmental glomerulosclerosis (FSGS) was noted in 4 patients, lupus nephropathy in 3, and membranous nephropathy (MN) in 2. Specific treatment was administered to each patient, depending on the histological type of renal involvement and the context. After 6 months, complete remission was achieved in 5 patients, with no improvement in 2, and one patient was placed on hemodialysis. One patient died of another cause. Conclusion: The causal link between anti-COVID 19 vaccination and renal disease is highly probable, but remains to be confirmed.展开更多
BACKGROUND The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure wi...BACKGROUND The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy.AIM To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications.METHODS In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy.RESULTS We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy(IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy(TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR(40%),TG(17%), and IFTA(13%). Most grafts failed within two years of post-transplant(36%). Subsequently, approximately 10%-15% of grafts failed every two years: >2-4 years(16%), > 4-6 years(13%), > 6-8 years(11%), > 8-10 years(9%) and > 10 years(16%). AR was the most common cause of graft failure in the first six years(48%), whereas TG was the most prevalent cause of graft failure after 6 years(32%) of transplant.CONCLUSION In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.展开更多
A 43-year-old female was admitted to the Department of Nephrology at Jinling Hospital （Nanjing,China） in January 2017 complaining of edema for 3 months with urine abnormalities.Her father had renal disease （with no...A 43-year-old female was admitted to the Department of Nephrology at Jinling Hospital （Nanjing,China） in January 2017 complaining of edema for 3 months with urine abnormalities.Her father had renal disease （with no biopsy performed） when he was 40 years old and died of uremia at 56 years old.Her mother and brother were healthy;however,her daughter and nephew （her brother＇s son） had slightly high microalbumin levels in routine urine screenings.Her daughter＇s urinary protein level was weakly positive,whereas her nephew＇s urinary protein level was negative.展开更多
Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the deve...Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene expression.To define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing.We report for the first time that immune cells,including T cells and B cells,are decreased in ORG patients.Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells.This gene is related to inflammation and cell proliferation.Analysis of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway.Moreover,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and podocytes.Altogether,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.展开更多
Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the...Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.展开更多
文摘n light of the rapid increase in the number of obesity incidences worldwide, obesity has become an independent risk factor for chronic kidney disease. Obesity-related giomerulopathy （ORG） is characterized by glomerulomegaly in the presence or absence of focal and segmental glomerulosclerosis lesions. IgM and complement 3 （C3） nonspeciflcally deposit in lesions without immune-complex-type deposits during ORG immunofluorescence. ORG-associated glomerulomegaly and focal and segmental glomerulosclerosis can superimpose on other renal pathologies. The mechanisms under ORG are complex, especially hemodynamic changes, inflammation, oxidative stress, apoptosis, and reduced functioning nephrons. These mechanisms synergize with obesity to induce end-stage renal disease. A slow increase of subnephrotic proteinuria （ 〈 3.5 g/d） is the most common clinical manifestation of ORG. Several treatment methods for ORG have been developed. Of these methods, renin-angiotensin-aldosterone system blockade and weight loss are proven effective. Targeting mitochondria may offer a novel strategy for ORG therapy. Nevertheless, more research is needed to further understand ORG.
文摘Hepatitis C virus (HCV) infection is a systemic disorder which is often associated with a number of extrahepatic manifestations including glomerulopathies. Patients with HCV infection were found to have a higher risk of end-stage renal disease. HCV positivity has also been linked to lower graft and patient survivals after kidney transplantation. Various histological types of renal diseases are reported in association with HCV infection including membranoproliferative glomerulonephritis (MPGN), membranous nephropathy, focal segmental glomerulosclerosis, fibrillary glomerulonephritis, immunotactoid glomerulopathy, IgA nephropathy, renal thrombotic microangiopathy, vasculitic renal involvement and interstitial nephritis. The most common type of HCV associated glomerulopathy is type I MPGN associated with type II mixed cryoglobulinemia. Clinically, typical renal manifestations in HCV-infected patients include proteinuria, microscopic hematuria, hypertension, acute nephritis and nephrotic syndrome. Three approaches may be suggested for the treatment of HCV-associated glomerulopathies and cryoglobulinemic renal disease: (1) antiviral therapy to prevent the further direct damage of HCV on kidneys and synthesis of immune-complexes; (2) B-cell depletion therapy to prevent formation of immune-complexes and cryoglobulins; and (3) nonspecific immunosuppressive therapy targeting inflammatory cells to prevent the synthesis of immune-complexes and to treat cryoglobulin associated vasculitis. In patients with moderate proteinuria and stable renal functions, anti-HCV therapy is advised to be started as pegylated interferon-α plus ribavirin. However in patients with nephrotic-range proteinuria and/or progressive kidney injury and other serious extra-renal manifestations, immunosuppressive therapy with cyclophosphamide, rituximab, steroid pulses and plasmapheresis should be administrated.
文摘Background Lipoprotein glomerulopathy (LPG) is a renal disease characterized by thrombus-like lipoproteins in the glomerular capillaries and its abnormal lipoprotein profiles with marked elevation of apolipoprotein E (apoE). In this study, 15 Chinese patients with LPG were involed in exploring the association of the genetic variation and its plasma level in the pathogenesis of LPG.Methods A retrospective analysis of the clinical and pathological features was made in 15 patients with LPG. Plasma concentrations of apoE were measured with radial immunodiffusion assay. Genetic variations of apoE gene were detected using polymerase chain reaction and restriction fragment length polymorphism. Glomerular deposition of apoA, apoB and apoE in these patients were detected by immunofluorescence staining using monoclonal antibodies. Results Biochemical profiles of lipids and lipoproteins revealed markedly elevated levels of triglyceride, apoB and apoE, but approximately normal levels of total cholesterol, apoA1 and lipoprotein(a) [Lp(a)], which resembled familial hypertriglyceridemia. Genetic analysis demonstrated that the genotype distribution of apoE were 7 cases with (ε3/ε 4,)4 cases with ε3/ε 3 and 2 cases with ε2/ε 3. The other 2 cases (a mother and her son) showed a same distinct band. The band pattern of later 2 cases was quite similar to the apoE variant of Tokyo type. The calculated allele frequency of ε 4 was relatively high in cases with LPG in comparison with that in the normal controls. We further divided the 13 patients into three groups according to their genotypes of apoE. Patients with the genotype of apoE ε2/ε3 showed a lower level of plasma apoE as compared to those with apoE ε3/ε4 (P<0.05). The serum level of high-density lipoprotein (HDL) was the lowest in patients with the genotype of apoE ε3/ε4. No difference was found among the patients with different apoE genotype in the other clinical and pathological characteristics. Conclusions The genotype of apoE ε3/ε4 is the predominant one in Ch
文摘Introduction: Vaccination against COVID-19 has proven highly effective in preventing severe forms of the disease. However, the literature reports several cases associating renal damage and the anti-COVID vaccine. The aim of our work was to report a case series of patients who developed glomerulopathy after anti-COVID-19 vaccine. We evaluated the type of vaccine, the clinico-biological profile, and the anatomopathological, therapeutic and evolutionary aspects. Material and Methods: Prospective descriptive study conducted at the Nephrology Department of CHU IbnSina in Rabat between December 2021 and June 2022 including 9 patients who presented with glomerulopathy after the 1st dose of anti-COVID-19 vaccine. We excluded patients followed for nephropathy. Results: The mean age of our patients was 33 ± 16 years with a sex ratio of 0.8. Six patients received an inactivated vaccine, 2 patients received a mRNA vaccine and 1 patient received a viral vector vaccine. The mean delay between the onset of signs and the date of the first vaccine dose was 3.1 +/? 0.65 months (1 - 6 months). All patients had a nephrotic syndrome, 2 pure and 7 impure: 3 patients had acute renal failure and microscopic hematuria, 2 patients had microscopic hematuria and 2 patients had acute renal failure. Histologically, focal segmental glomerulosclerosis (FSGS) was noted in 4 patients, lupus nephropathy in 3, and membranous nephropathy (MN) in 2. Specific treatment was administered to each patient, depending on the histological type of renal involvement and the context. After 6 months, complete remission was achieved in 5 patients, with no improvement in 2, and one patient was placed on hemodialysis. One patient died of another cause. Conclusion: The causal link between anti-COVID 19 vaccination and renal disease is highly probable, but remains to be confirmed.
文摘BACKGROUND The histopathological findings on the failing kidney allograft in the modern era is not well studied. In this study, we present our experience working with kidney transplant recipients with graft failure within one year of the biopsy.AIM To report the histopathological characteristics of failed kidney allografts in the current era of immunosuppression based on the time after transplant, cause of the end-stage renal disease and induction immunosuppressive medications.METHODS In a single-center observational study, we characterized the histopathological findings of allograft biopsies in kidney transplant recipients with graft failure within one year after the biopsy.RESULTS We identified 329 patients with graft failure that met the selection criteria between January 1, 2006 and December 31, 2016. The three most common biopsy findings were interstitial fibrosis and tubular atrophy(IFTA, 53%), acute rejection (AR, 43%) and transplant glomerulopathy(TG, 33%). Similarly, the three most common causes of graft failure based on the primary diagnosis were AR(40%),TG(17%), and IFTA(13%). Most grafts failed within two years of post-transplant(36%). Subsequently, approximately 10%-15% of grafts failed every two years: >2-4 years(16%), > 4-6 years(13%), > 6-8 years(11%), > 8-10 years(9%) and > 10 years(16%). AR was the most common cause of graft failure in the first six years(48%), whereas TG was the most prevalent cause of graft failure after 6 years(32%) of transplant.CONCLUSION In the current era of immunosuppression, AR is still the most common cause of early graft failure, while TG is the most prevalent cause of late graft failure.
文摘A 43-year-old female was admitted to the Department of Nephrology at Jinling Hospital （Nanjing,China） in January 2017 complaining of edema for 3 months with urine abnormalities.Her father had renal disease （with no biopsy performed） when he was 40 years old and died of uremia at 56 years old.Her mother and brother were healthy;however,her daughter and nephew （her brother＇s son） had slightly high microalbumin levels in routine urine screenings.Her daughter＇s urinary protein level was weakly positive,whereas her nephew＇s urinary protein level was negative.
基金supported by the Hunan Provincial Natural Science Foundation for Outstanding Youth(China)(No.2022JJ10093,2020JJ2020)the Scientific Research Fund of Hunan Provincial Health Commission(China)(No.B202303056777)+1 种基金the Major Research and Development Program of Hunan Province,China(No.2020SK2116)the Key Program of Hunan Provincial Health Commission(China)(No.202203052969).
文摘Obesity-related glomerulopathy(ORG)is an independent risk factor for chronic kid-ney disease and even progression to end-stage renal disease.Efforts have been undertaken to elucidate the mechanisms underlying the development of ORG and substantial advances have been made in the treatment of ORG,but relatively little is known about cell-specific changes in gene expression.To define the transcriptomic landscape at single-cell resolution,we analyzed kidney samples from four patients with ORG and three obese control subjects without kidney disease using single-cell RNA sequencing.We report for the first time that immune cells,including T cells and B cells,are decreased in ORG patients.Further analysis indicated that SPP1 was significantly up-regulated in T cells and B cells.This gene is related to inflammation and cell proliferation.Analysis of differential gene expression in glomerular cells(endothelial cells,mesangial cells,and podocytes)showed that these cell types were mainly enriched in genes related to oxidative phosphorylation,cell adhesion,thermogenesis,and inflammatory pathways(PI3K-Akt signaling,MAPK signaling).Furthermore,we found that the podocytes of ORG patients were enriched in genes related to the fluid shear stress pathway.Moreover,an evaluation of cell-cell communications revealed that there were interactions between glomerular parietal epithelial cells and other cells in ORG patients,with major interactions between parietal epithelial cells and podocytes.Altogether,our identification of molecular events,cell types,and differentially expressed genes may facilitate the development of new preventive or therapeutic approaches for ORG.
基金grants from the National Natural Science Foundation of China (No.81573745and No.8160140274)Beijing Municipal Natural Science Foundation (No.7172066) Beijing Development Foundation of Traditional Chinese Medicine (QN2016-23).
文摘Background:The nucleotide-binding and oligomerization domain-like receptor protein 3 (NLRP3) inflammasome composed of NLRP3,apoptosis-associated speck-like protein containing CARD (ASC),and caspase-1 is engaged in the inflammatory response of many kidney diseases and can be activated by purinergic 2X7 receptor (P2X7R).This study was conducted to explore whether P2X7R plays a pathogenic role in the podocyte damage of obesity-related glomerulopathy (ORG) and whether this role is mediated by the activation ofNLRP3 inflammasome.Methods:A mouse model of ORG was established by high-fat diet feeding.The conditionally immortalized mouse podocytes were cultured with leptin or with leptin and P2X7R antagonist (KN-62 or A438079).The mRNA and protein expression of the P2X7R and NLRP3 inflammasome components including NLRP3,ASC,and caspase-1,as well as the podocyte-associated molecules including nephrin,podocin,and desmin in mouse renal cortex or cultured mouse podocytes were tested by real-time-polymerase chain reaction and Westem blot analysis,respectively.Results:The significantly upregulated expression of P2X7R and NLRP3 inflammasome components and the NLRP3 inflammasome activation were observed in the renal cortex (in fact their location in podocytes was proved by confocal microscopy) of ORG mice in vivo,which were accompanied with the morphological changes of podocyte damage and the expression changes of podocyte-associated molecules.Similar changes in the expression of P2X7R and NLRP3 inflammasome components as well as in the expression ofpodocyte-associated molecules were also observed in the cultured podocyte studies treated by leptin in vitro,and all of the above changes were significantly attenuated by the P2X7R antagonist KN-62 or A438079.Conclusions:P2X7R could trigger the activation ofNLRP3 inflammasome,and the activated P2X7R/NLRP3 inflammasome in podocytes might be involved in the podocyte damage of ORG.
