Therapy Of Glomerulonephritis Research Articles

Immunoglobulin A-dominant membranoproliferative glomerulonephritis-like pattern of injury as a possible paraneoplastic nephropathy in a breast cancer patient.

A middle-aged woman was found to have proteinuria during a health check-up. About sixteen months later, she was diagnosed with stage IIA invasive ductal carcinoma of the right breast. Her proteinuria progressed to nephrotic syndrome with significant hematuria. Hormone therapy was initiated for her estrogen and progesterone receptor-positive breast cancer. A kidney biopsy performed 47days after starting the therapy revealed an IgA-dominant membranoproliferative glomerulonephritis-like pattern of injury. Electron microscopy showed subendothelial-dominant electron-dense deposits (EDD), with small amounts of mesangial EDD and a single occurrence of subepithelial hump-like EDD, along with occasional mesangial interpositions. Similar pathology can be caused by IgA vasculitis with nephritis, IgA-dominant infection-associated glomerulonephritis, and liver disease-associated glomerulopathy, but all of these were ruled out. The deposited IgA was found to be galactose-deficient IgA1. Thus, IgA nephropathy with glomerular capillary IgA deposition was considered. She underwent a right partial mastectomy and sentinel lymph node biopsy in the right axilla 75days after starting hormone therapy, followed by adjuvant radiation. Proteinuria and hematuria tended to decrease after the treatment, and this trend continued even after corticosteroid therapy for glomerulonephritis, which was administered 156days after starting hormone therapy. Approximately 15months after starting hormone therapy, her proteinuria had reduced to around 1.0g/g of creatinine, and her hematuria was negative. IgA nephropathy with glomerular capillary IgA deposition is known to be resistant to corticosteroid therapy. The favorable clinical course of the rare glomerulopathy following breast cancer treatment suggested a diagnosis of paraneoplastic glomerulopathy secondary to breast cancer in our patient.

A case of ANCA-negative pauci-immune crescentic glomerulonephritis with lung adenocarcinoma with mediastinal involvement successfully treated by corticosteroid and radiation therapy.

Pauci-immune crescentic glomerulonephritis (PICGN) is one of the pathologies causing rapidly progressive glomerulonephritis, often associated with anti-neutrophil cytoplasmic antibody (ANCA); however, in 10-30% of cases, ANCAs are negative. While a relatively large number of cases of ANCA-positive PICGN complicated with malignancy have been previously reported, the number of cases of ANCA-negative PICGN with malignancy is limited. The prognosis for such cases was poor, and many patients died within a relatively short period. Here, we report the case of ANCA-negative PICGN complicated with malignancy successfully treated by corticosteroid and radiation therapy. A 63-year-old Japanese man was admitted to our hospital due to spiking fevers in the previous 3months. Based on the findings of imaging and pathological tests, he was diagnosed with locally advanced lung adenocarcinoma with mediastinal involvement. After admission, his renal function rapidly deteriorated, and urinalysis showed heavy proteinuria. In serological tests, serology for autoantibodies, including ANCAs, was negative. The kidney biopsy revealed PICGN with prominent endocapillary proliferation. We administered corticosteroid therapy for glomerulonephritis and subsequent radiation therapy for lung carcinoma, both of which were effective. He has been alive without progression of malignancy or kidney disease for 5 years after discharge. In patients with malignancy presenting with acute deterioration of kidney function, although infrequent, one of the conceivable pathological conditions to consider is ANCA-negative PICGN associated with malignancy. In such cases, even with negative antibodies such as ANCA, pathological examination is warranted, and a combination of anti-tumor therapy and immunosuppressive therapy is expected to be effective.

Targeted therapy of glomerulonephritis via salvianolic acid b-loaded biomimetic hybrid nanovesicles driven by homing

BackgroundMesangial cell (MC)-mediated immune inflammatory injury is a basic pathological process in glomerulonephritis. However, due to the limited drug accumulation and serious adverse effects, it remains challenging to explore a rational delivery system integrating high efficiency and low toxicity to deliver anti-inflammatory drugs to the glomerular MC region. ResultsSalvianolic acid B (SAB)-loaded hybrid membrane biomimetic nanovesicles (SAB@HMVs) were developed by fusing erythrocyte membrane nanovesicles with mesenchymal stem cells biomimetic membrane nanovesicles. SAB@HMVs had a spheroidal structure, low cytotoxicity, particle size of 143.83 ± 1.33 nm and exhibited a high drug loading capacity (7.02 %±0.30 %) along with a good sustained release function. The in vitro anti-inflammatory results revealed that HMVs were effectively taken up by MCs and showed significant anti-inflammatory activity. Furthermore, in vivo pharmacodynamic studies revealed that SAB@HMVs could deliver SAB to kidney tissue and elicit an effective anti-inflammatory response to improve the pathological changes in the glomerular mesangial region, significantly reducing the levels of cytokines and alleviating kidney inflammation. Especially, noteworthy was the observation that SAB@HMVs augmented the renal delivery of SAB, downregulated the gene expression of p38 MAPK and NF-κB, inhibited the levels of MMP9 and TNF-α proteins as well as elevated the level of iκB protein, indicating that the anti-inflammatory mechanism of SAB@HMVs should be based on regulating MAPK and NF-κB signaling pathways. ConclusionWe provided a novel strategy to increase nanovesicles accumulation in MCs with the potential to exert anti-inflammatory regulatory effects in glomerulonephritis. Furthermore, this biomimetic hybrid membrane loaded with pure drugs may offer a functional platform to address multiple clinical needs.

Analysis of gene expression and use of connectivity mapping to identify drugs for treatment of human glomerulopathies.

Human glomerulonephritis (GN)-membranous nephropathy (MN), focal segmental glomerulosclerosis (FSGS) and IgA nephropathy (IgAN), as well as diabetic nephropathy (DN) are leading causes of chronic kidney disease. In these glomerulopathies, distinct stimuli disrupt metabolic pathways in glomerular cells. Other pathways, including the endoplasmic reticulum (ER) unfolded protein response (UPR) and autophagy, are activated in parallel to attenuate cell injury or promote repair. We used publicly available datasets to examine gene transcriptional pathways in glomeruli of human GN and DN and to identify drugs. We demonstrate that there are many common genes upregulated in MN, FSGS, IgAN, and DN. Furthermore, these glomerulopathies were associated with increased expression of ER/UPR and autophagy genes, a significant number of which were shared. Several candidate drugs for treatment of glomerulopathies were identified by relating gene expression signatures of distinct drugs in cell culture with the ER/UPR and autophagy genes upregulated in the glomerulopathies ("connectivity mapping"). Using a glomerular cell culture assay that correlates with glomerular damage in vivo, we showed that one candidate drug - neratinib (an epidermal growth factor receptor inhibitor) is cytoprotective. The UPR and autophagy are activated in multiple types of glomerular injury. Connectivity mapping identified candidate drugs that shared common signatures with ER/UPR and autophagy genes upregulated in glomerulopathies, and one of these drugs attenuated injury of glomerular cells. The present study opens the possibility for modulating the UPR or autophagy pharmacologically as therapy for GN.

Targeted Therapy for Glomerulonephritis Using Arterial Delivery of Encapsulated Etanercept.

Complex immunosuppressive therapy is prescribed in medical practice to patients with glomerulonephritis to help them overcome symptoms and prevent chronic renal failure. Such an approach requires long-term systemic administration of strong medications, which causes severe side effects. This work shows the efficiency of polymer capsule accumulation (2.8 ± 0.4 µm) containing labeled etanercept (100 μg per dose) in the kidneys of mice. The comparison of injection into the renal artery and tail vein shows the significant superiority of the intra-arterial administration strategy. The etanercept retention rate of 18% and 8% ID in kidneys was found 1 min and 1 h after injection, respectively. The capsules were predominantly localized in the glomeruli after injection in mice using a model of acute glomerulonephritis. Histological analysis confirmed a significant therapeutic effect only in animals with intra-arterial administration of microcapsules with etanercept. The proposed strategy combines endovascular surgery and the use of polymer microcapsules containing a high molecular weight drug that can be successfully applied to treat a wide range of kidney diseases associated with glomerular pathology.

Glomerulonephritides associated with infections.

Glomerulonephritides associated with infections constitute an important group of diseases. Their occurrence is shifting from children and young people to elderly people. The rates of acute post-streptococcal glomerulonephritis, a condition with a good prognosis, are decreasing, and the rates of glomerulonephritides associated with various bacterial, viral, or parasitic infections, often with a poor prognosis, are increasing. Renal biopsy plays an important role in the diagnostic process. Manifestations of glomerulonephritis can be the initial sign of an occult infection. When evaluating renal biopsy specimens, certain signs may suggest this option, but it cannot be relied on completely. The search for an active infection is warranted in every patient with newly diagnosed glomerulonephritis. Hepatitis B and C serology is always performed, with other investigations depending on individual risk factors, clinical manifestations, and laboratory and histological findings. Failure to follow this rule may have serious consequences, in part because immunosuppressive therapy for glomerulonephritis can worsen the underlying infection and also because the progressive nature of parainfective glomerulonephritis cannot be reversed without eliminating the causative infection. Distinguishing between parainfective and autoimmune glomerulonephritis can be difficult, as there are no major differences in clinical manifestations, laboratory, and sometimes even histological findings. In the setting of the Czech Republic, important diseases include, in particular, staphylococcus infection-associated glomerulonephritis (SAGN) and, in general, infective endocarditis-associated glomerulonephritis, shunt nephritis, and other cases associated with foreign-material infection, such as catheters or electrodes. Among viral diseases, glomerulonephritides associated with the hepatitis B virus, hepatitis C virus, and the SARS CoV-2 virus are of major significance. The treatment of parainfectious glomerulonephritides involves elimination of the causative infection; only in rare cases, a combination of anti-infective treatment and mild immunosuppression can be indicated.

Co-Delivery of Dexamethasone and Captopril by α8 Integrin Antibodies Modified Liposome-PLGA Nanoparticle Hybrids for Targeted Anti-Inflammatory/Anti-Fibrosis Therapy of Glomerulonephritis.

PurposeMesangial cells-mediated glomerulonephritis refers to a category of immunologically mediated glomerular injuries characterized by infiltration of circulating inflammatory cells, proliferation of mesangial cells, and the common pathological manifestation to the later stage is renal fibrosis, accompanied by excessive accumulation of extracellular matrix (ECM). Treatment regimens include glucocorticoids and immunosuppressive agents, but their off-target distribution causes severe systemic toxicity. Hence, specific co-delivery of “anti-inflammatory/anti-fibrosis” drugs to the glomerular mesangial cell (MC) region is expected to produce better therapeutic effects.MethodsA novel kidney-targeted nanocarrier drug delivery system targeting MCs was constructed using passive targeting resulting from the difference in pore size between the glomerular endothelial layer and the basement membrane, and active targeting based on the specific binding of antibodies and antigens. Specifically, a liposome-nanoparticle hybrid (PLGA-LNHy) was formed by coating the surface of PLGA nanoparticles (NPs) with a phospholipid bilayer, and then PLGA-LNHy was co-modified with PEG and α8 integrin antibodies to obtain PLGA immunoliposomes (PLGA-ILs).ResultsThe results showed that the obtained NPs had a core-shell structure, uniform and suitable particle size (119.1 ± 2.31 nm), low cytotoxicity, and good mesangial cell-entry ability, which can successfully accumulate in the glomerular MC region. Both dexamethasone (DXMS) and captopril (CAP) were loaded onto PLGA-ILs with a drug loading of 10.22 ± 1.00% for DXMS and 6.37 ± 0.25% for CAP (DXMS/CAP@PLGA-ILs). In vivo pharmacodynamics showed that DXMS/CAP@PLGA-ILs can effectively improve the pathological changes in the mesangial area and positive expression of proliferating cell nuclear antigen (PCNA) in glomeruli as well as reduce the expression of inflammatory factors, fibrotic factors and reactive oxygen species (ROS). Thus, renal inflammation and fibrosis were relieved.ConclusionWe have provided a strategy to increase nanoparticle accumulation in MCs with the potential to implement regulatory effects of anti-inflammatory and anti-fibrosis in glomerulonephritis (GN).

Dual-Regulated Functionalized Liposome-Nanoparticle Hybrids Loaded with Dexamethasone/TGFβ1-siRNA for Targeted Therapy of Glomerulonephritis.

Mesangial cell (MC)-mediated glomerulonephritis is a frequent cause of end-stage renal disease, with immune inflammatory damage and fibrosis as its basic pathological processes. However, the treatment of glomerulonephritis remains challenging owing to limited drug accumulation and serious side effects. Hence, the specific codelivery of "anti-inflammatory/antifibrosis" drugs to the glomerular MC region is expected to yield better therapeutic effects. In this study, liposome-nanoparticle hybrids (Au-LNHy) were formed by coating the surface of gold nanoparticles with a phospholipid bilayer; the Au-LNHys formed were comodified with PEG and α8 integrin antibodies to obtain gold nanoparticle immunoliposomes (Au-ILs). Next, the Au-ILs were loaded with dexamethasone and TGFβ1 siRNA to obtain DXMS/siRNA@Au-ILs. Our results showed that the functionalized nanoparticles had a core-shell structure, a uniform and suitable particle size, low cytotoxicity, and good MC entry, and lysosomal escape abilities. The nanoparticles were found to exhibit enhanced retention in glomerular MCs due to anti-α8 integrin antibody mediation. In vivo and in vitro pharmacodynamic studies showed the enhanced efficacy of DXMS/siRNA@Au-ILs modified with α8 integrin antibodies in the treatment of glomerulonephritis. In addition, DXMS/siRNA@Au-ILs were capable of effectively reducing the expression levels of TNF-α, TGF-β1, and other cytokines, thereby improving pathological inflammatory and fibrotic conditions in the kidney, and significantly mediating the dual regulation of inflammation and fibrosis. In summary, our results demonstrated that effectively targeting the MCs of the glomerulus for drug delivery can inhibit local inflammation and fibrosis and produce better therapeutic effects, providing a new strategy and promising therapeutic approach for the development of targeted therapies for glomerular diseases.

Crescentic Glomerulonephritis: Pathogenesis and Therapeutic Potential of Human Amniotic Stem Cells.

Chronic kidney disease (CKD) leads to significant morbidity and mortality worldwide. Glomerulonephritis (GN) is the second leading cause of CKD resulting in end stage renal failure. The most severe and rapidly progressive type of GN is characterized by glomerular crescent formation. The current therapies for crescentic GN, which consist of broad immunosuppressive drugs, are partially effective, non-specific, toxic and cause many serious side effects including infections, cancer, and cardiovascular problems. Therefore, new and safer therapies are needed. Human amniotic epithelial cells (hAECs) are a type of stem cell which are isolated from the placenta after birth. They represent an attractive and novel therapeutic option for the treatment of various inflammatory conditions owing to their unique and selective immunosuppressive ability, as well as their excellent safety profile and clinical applicability. In this review, we will discuss the immunopathogenesis of crescentic GN, issues with currently available treatments and how hAECs offer potential to become a new and harmless treatment option for this condition.

The effect of blood levels of heparan sulfate, VCAM-1 and ICAM-1 in combination with clinical and morphological features of the course of glomerulonephritis on the probability of achieving remission

Objective: to analyze the effect of adhesion molecules (ICAM-1, VCAM-1) and blood heparan sulfate in combination with clinical and morphological signs on the likelihood of remission in glomerulonephritis. Material and methods: 80 patients with glomerulonephritis aged 35.7±10.9 years were included. Serum levels of ICAM-1, VCAM-1 and heparan sulfate were determined in all patients by quantitative enzyme immunoassay. Puncture nephrobiopsy was performed with verification of the form of nephritis and determination of signs of TIC, TIV, glomerulosclerosis. Results: It was shown that high values of heparan sulfate and uric acid in the blood reduce the likelihood of achieving remission in glomerulonephritis. Also, high values of heparan sulfate in the blood against the background of pronounced TIC or TIV were accompanied by a decrease in the probability of remission. An increase in the level of ICAM-1 in the blood, combined with an increase in age, the level of fibrinogen in the blood, as well as an increase in the phenomena of TIC, TIV and glomerulosclerosis, reduce the likelihood of achieving remission in glomerulonephritis. It was also shown that an increase in the level of VCAM-1 in the blood against the background of an increase in the patient’s age, hyperuricemia, an increase in the phenomena of TIV, TIC and glomerulosclerosis is accompanied by a decrease in the probability of achieving remission. We have compiled nomograms for assessing the prognosis of remission development. Conclusion: the assessment of the levels of heparan sulfate, ICAM-1 and VCAM-1 in the blood, together with a number of clinical and morphological signs, is an important tool for predicting the effectiveness of glomerulonephritis therapy.

Modern principles of treatment of arterial hypertension in patients with chronic kidney disease and glomerulonephritis

The literature review presents current international data on the principles of choice of hypotensive therapy tactics in patients with chronic kidney disease and glomerulonephritis. safe levels of blood pressure reduction, reflected in the regulatory documents of European and American nephrological and cardiological associations, methods of their control are discussed. Data on the nephroprotective effects of the main classes of hypotensive drugs – angiotensin-converting enzyme inhibitors and angiotensin receptor blockers – are presented. The necessity of monitoring the safety of hypotensive therapy in glomerulonephritis with chronic kidney disease using methods of blood pressure monitoring is emphasized.

A new Cu(II)-based coordination polymer: treatment activity on the glomerulonephritis via inhibiting the mesangial cell proliferation

Through applying the mixed-ligand method, a new coordination polymer (CP) of Cu(II) with the chemical formula of {Cu5(L)2(1,4-bimb)(μ3-OH)2(H2O)8]·2H2O}n (1, 1,4-bimb = 1,4-bis(imidazol-1-ylmethyl)benzene and H4L = 1,2,4,5-cyclohexanetetracarboxylic acid) was synthesized under the solvothermal conditions. Furthermore, the biological effect of compound against glomerulonephritis therapy was detected, and the details mechanism was investigated. First of all, the mesangial cells proliferation was detected through using the Cell Counting Kit-8 (CCK-8) method. Then, the Annexin V-FITC/PI method was utilized to determine cell cycle arrest and the apoptosis rate. Next, the caspase-8 and caspase-3 expression level in mesangial cells was detected via applying the western blot method. Finally, the inflammatory cytokines released into the plasma was assessed by ELISA detection kit.

Acute Kidney Injury in Pregnancy.

Acute kidney injury in pregnancy is a public health problem and a significant cause of maternal and fetal morbidity and mortality. The incidence of pregnancy-related acute kidney injury has increased in the developed countries, theorized to be the result of an increase in pregnancies in advanced maternal age, and continues to remain higher in developing countries owing to inadequate antenatal care. While hyperemesis gravidarum is a common cause of pregnancy-related acute kidney injury during the first trimester, complications such as preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, acute fatty liver disease of pregnancy, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome are important causes of acute kidney injury later in the pregnancy. Diagnosis of pregnancy-related acute kidney injury can be difficult owing to lack of diagnostic criteria and overlapping clinical features between various causes. General measures to treat pregnancy-related acute kidney injury include identification of the underlying cause of kidney injury, intravenous fluid resuscitation, timely initiation of dialysis if needed, and prompt fetal delivery, if necessary. Specific treatment includes steroid and immunosuppressive therapy for glomerulonephritis; prompt delivery for severe preeclampsia, hemolysis, elevated liver enzymes, and low platelet count syndrome, and acute fatty liver of pregnancy; and plasmapheresis and eculizumab for thrombotic microangiopathies such as thrombotic thrombocytopenic purpura and atypical hemolytic uremic syndrome.

Treatment of idiopathic membranous nephropathy in adults: KDIGO 2012, cyclophosphamide and cyclosporine A are out, rituximab is the new normal.

The 2012 Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines for glomerulonephritis shed light on the complex world of glomerulonephritis therapy. However, they may no longer apply to idiopathic membranous nephropathy, as recently concluded by the KDIGO 2019 Working Group. This is due to the discovery of autoantibodies such as anti-phospholipase A2 receptor (anti-PLA2R) that allow disease monitoring as well as to results from recent clinical trials, comparative cohort studies and meta-analyses. Perhaps the most disruptive of them is the Membranous Nephropathy Trial of Rituximab (MENTOR) trial comparing rituximab with cyclosporine A, which supports the superiority of rituximab in efficacy and safety. Furthermore, rituximab results compared favourably with the short-term results of classical clinical trials that supported the KDIGO 2012 recommendation of immunosuppressive cyclophosphamide-based regimens as first choice for active treatment of idiopathic membranous nephropathy. Thus, the KDIGO recommendations for cyclophosphamide-based regimens or calcineurin inhibitors as the first line of active treatment regimens for idiopathic membranous nephropathy with nephrotic syndrome may no longer apply. By contrast, rituximab-based regimens or other B-cell-targeted therapies appear to represent the present and future of membranous nephropathy therapy.

The effectiveness of chitosan-mediated silencing of PDGF-B and PDGFR-β in the mesangial proliferative glomerulonephritis therapy

Platelet-derived growth factor-B (PDGF-B) is a growth factor that plays an important role in the progression of mesangial proliferative glomerulonephritis (MsPGN). PDGF-B may contribute to mesangioproliferative changes and is overexpressed in MsPGN. Recently, small interfering RNAs (siRNAs) have been widely used for gene silencing effects in experimental models of renal diseases. Nanoparticle-based therapeutics are preferred for reasons such as increasing therapeutic efficacy and reducing toxic effects caused by high doses. The distribution of nanoparticles to the kidney is a significant advantage in siRNA delivery. The aim of this study was to investigate the efficacy of chitosan/siRNA nanoplexes in silencing of PDGF-B and PDGFR-β genes in kidney and to decrease mesangial cell proliferation and matrix accumulation in MsPGN model induced by anti-Thy-1.1 antibody. The therapeutic effects of chitosan/siPDGF-B + siPDGFR-β nanoplexes in glomerulonephritic rats were studied by molecular, biochemical, and histopathologic evaluations. Chitosan/siPDGF-B + siPDGFR-β nanoplexes markedly reduced PDGF-B and PDGFR-β mRNA and protein expressions in experimental MsPGN model. Histopathologic examination results showed that the silencing of PDGF-B and its receptor PDGFR-β led to reduction in mesangial cell proliferation and matrix accumulation. The use of chitosan/siPDGF-B + siPDGFR-β nanoplexes for silencing the PDGF-B pathway in MsPGN can be considered as a new effective therapeutic strategy.

Prospects for Precision Medicine in Glomerulonephritis Treatment.

Background:Glomerulonephritis (GN) consists of a group of kidney diseases that are categorized based on shared histopathological features. The current classifications for GN make it difficult to distinguish the individual variability in presentation, disease progression, and response to treatment. GN is a significant cause of end-stage renal disease (ESRD), and improved therapies are desperately needed because current immunosuppressive therapies sometimes lack efficacy and can lead to significant toxicities. In recent years, the combination of high-throughput genetic approaches and technological advances has identified important regulators contributing to GN.Objectives:In this review, we summarize recent findings in podocyte biology and advances in experimental approaches that have opened the possibility of precision medicine in GN treatment. We provide an integrative basic science and clinical overview of new developments in GN research and the discovery of potential candidates for targeted therapies in GN.Findings:Advances in podocyte biology have identified many candidates for therapeutic targets and potential biomarkers of glomerular disease. The goal of precision medicine in GN is now being pursued with recent technological improvements in genetics, accessibility of biologic and clinical information with tissue biobanks, high-throughput analysis of large-scale data sets, and new human model systems such as kidney organoids.Conclusion:With advances in data collection, technologies, and experimental model systems, we now have vast tools available to pursue precision medicine in GN. We anticipate a growing number of studies integrating data from high-throughput analysis with the development of diagnostic tools and targeted therapies for GN in the near future.

Recurrence of primary glomerulonephritis: Review of the current evidence.

In view of the availability of new immunosuppression strategies, the recurrence of allograft glomerulonephritis (GN) are reported to be increasing with time post transplantation. Recent advances in understanding the pathogenesis of the GN recurrent disease provided a better chance to develop new strategies to deal with the GN recurrence. Recurrent GN diseases manifest with a variable course, stubborn behavior, and poor response to therapy. Some types of GN lead to rapid decline of kidney function resulting in a frustrating return to maintenance dialysis. This subgroup of aggressive diseases actually requires intensive efforts to ascertain their pathogenesis so that strategy could be implemented for better allograft survival. Epidemiology of native glomerulonephritis as the cause of end-stage renal failure and subsequent recurrence of individual glomerulonephritis after renal transplantation was evaluated using data from various registries, and pathogenesis of individual glomerulonephritis is discussed. The following review is aimed to define current protocols of the recurrent primary glomerulonephritis therapy.

A rare case of enteric and systemic Yersinia enterocolitica infection in a chronic, not iron-overloaded dialysis patient

We present herein a case of bacterial gastroenteritis due to <em>Yersinia</em> <em>enterocolitica</em>, occurred in a young woman undergoing haemodialysis with a previous history positive for prolonged (20 years) immunosuppressive therapy for glomerulonephritis before and for kidney transplant later. The patient’s outcome was favourable after a third-generation cephalosporin treatment without complications. The possible pathophysiological association between patient clinical condition and <em>Yersinia</em> bacteraemia is discussed, along with the review of literature.

Hepatitis B reactivation in HBsAg-negative/HBcAb-positive patients receiving immunosuppressive therapy for glomerulonephritis: a retrospective analysis.

The aim of this study is to investigate the prevalence and risk factors for hepatitis B virus (HBV) reactivation in HBsAg-negative/HBcAb-positive patients receiving immunosuppressive therapy for glomerulonephritis. We performed a retrospective study of 745 HBsAg-negative/HBcAb-positive patients undergoing immunosuppressive therapy for glomerulonephritis from years 2003 to 2012 at the department of nephrology, China-Japan Friendship Hospital, Beijing, China. The patients were divided into HBV reactivation group (n=27) and non-HBV reactivation group (n=718). The prevalence of HBV reactivation in patients receiving immunosuppressive therapy for glomerulonephritis was up to 3.62% in serological status of HBsAg-negative/HBcAb-positive. HBV reactivation was associated with several findings: greater proportion of lupus nephritis (25.93 vs. 9.61%, p=0.014), much higher percentage of HBsAb-negative (74.07 vs. 23.82%, p<0.001), longer duration of immunosuppressive treatment (100 vs. 70.06%, p<0.001), as well as more cases of combined immunosuppressant (92.59 vs. 61.56%, p=0.001). After univariate and multivariate analysis, three variables remained as independent risk factors for HBV reactivation: serological status of HBsAb-negative (OR 8.375, 95% CI 3.674-19.776, p=0.001), length of immunosuppressive treatment more than 1year (OR 1.308, 95% CI 1.121-1.358, p=0.024), and combined immunosuppressant (OR 6.342, 95% CI 1.675-30.166, p=0.003). HBV reactivation is not uncommon in HBsAg-negative/HBcAb-positive glomerulonephritis patients treated with immunosuppressant, and the prevalence was up to 3.62%. Patients with serological status of HBsAb-negative, more than 1year of immunosuppressive therapy, and combined immunosuppressant are independent risk factors for HBV reactivation.

Classifying murine glomerulonephritis using optical coherence tomography and optical coherence elastography.

Acute glomerulonephritis caused by antiglomerular basement membrane marked by high mortality. The primary reason for this is delayed diagnosis via blood examination, urine analysis, tissue biopsy, or ultrasound and X-ray computed tomography imaging. Blood, urine, and tissue-based diagnoses can be time consuming, while ultrasound and CT imaging have relatively low spatial resolution, with reduced sensitivity. Optical coherence tomography is a noninvasive and high-resolution imaging technique that provides superior spatial resolution (micrometer scale) as compared to ultrasound and CT. Changes in tissue properties can be detected based on the optical metrics analyzed from the OCT signals, such as optical attenuation and speckle variance. Furthermore, OCT does not rely on ionizing radiation as with CT imaging. In addition to structural changes, the elasticity of the kidney can significantly change due to nephritis. In this work, OCT has been utilized to quantify the difference in tissue properties between healthy and nephritic murine kidneys. Although OCT imaging could identify the diseased tissue, its classification accuracy is clinically inadequate. By combining optical metrics with elasticity, the classification accuracy improves from 76% to 95%. These results show that OCT combined with OCE can be a powerful tool for identifying and classifying nephritis. Therefore, the OCT/OCE method could potentially be used as a minimally invasive tool for longitudinal studies during the progression and therapy of glomerulonephritis as well as complement and, perhaps, substitute highly invasive tissue biopsies. Elastic-wave propagation in mouse healthy and nephritic kidneys.