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Clinical Kidney Journal Jun 2024Phospholipase A2 receptor (PLA2R) is a major target antigen in idiopathic membranous nephropathy (MN). Anti-PLA2R antibodies are mainly of the immunoglobulin G (IgG)...
BACKGROUND
Phospholipase A2 receptor (PLA2R) is a major target antigen in idiopathic membranous nephropathy (MN). Anti-PLA2R antibodies are mainly of the immunoglobulin G (IgG) subclass IgG4, although other IgG subclass depositions in glomeruli may also be detected. However, the importance of the subclass of the IgG deposit has not been proven. Thus we investigated clinical findings from patients with idiopathic MN in relation to glomerular PLA2R deposition and IgG subclass.
METHODS
We enrolled 132 Japanese patients with biopsy-proven idiopathic MN in a multicentre retrospective observational study. We investigated the complete remission rate as the primary outcome and the development of end-stage kidney disease (ESKD) as the secondary outcome in relation to glomerular PLA2R deposition. Moreover, we evaluated prognostic factors, including glomerular IgG subclass, in the PLA2R-positive group.
RESULTS
The percentage of cases with glomerular PLA2R deposition was 76.5% ( = 101). The first complete remission rate of the PLA2R-positive group was worse than that of the PLA2R-negative group (logrank test < .001). ESKD incidence did not significantly differ between the glomerular PLA2R-negative and PLA2R-positive MN groups (logrank test = .608). In the PLA2R-positive group, higher PLA2R intensities and IgG2 staining were associated with a poorer first complete remission rate (logrank test < .001 and = .032, respectively). Cox proportional hazards analysis also showed that strong PLA2R deposition and positive IgG2 staining were significantly associated with a failure to reach complete remission [hazard ratio 2.09 ( = .004) and 1.78 ( = .030), respectively].
CONCLUSIONS
Our results suggest that intense glomerular PLA2R and IgG2 positivity predict a poor proteinuria remission rate in idiopathic MN.
PubMed: 38854426
DOI: 10.1093/ckj/sfae104 -
Cureus May 2024Introduction Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical and laboratory features. The incidence increases markedly in...
Introduction Systemic lupus erythematosus (SLE) is a complex autoimmune disease with heterogeneous clinical and laboratory features. The incidence increases markedly in women. The reason for the predominance of the female gender is still under study. The ethnicity could influence the clinical and serological features of SLE. Material and methods This is a retrospective, descriptive, and longitudinal study. We studied 89 patients diagnosed with childhood-onset systemic lupus erythematosus (cSLE) in our center in 2000-2020 for men and 2010-2020 for women. We investigated disease manifestations, ranging from clinical symptoms to renal involvement, at the time of diagnosis and compared them by gender. Results We studied 89 patients, comprising 23 males and 66 females. The mean age for both groups was 12 years. Concerning clinical manifestations, serositis exhibited a higher prevalence among males, while hair loss was more prominent among females. In the paraclinical evaluation, noteworthy differences were observed regarding average hemoglobin levels and the prevalence of positive anti-DNA antibodies. Males demonstrated an average hemoglobin level of 11.47 g/dL, whereas females displayed 9.84 g/dL (p=0.017). The prevalence of anti-DNA antibodies exhibited marked elevation in males, at 88.9%, compared to females' 42.9% (p=0.024). On a contrary note, our male cohort displayed heightened prevalence in using hydroxychloroquine, cyclophosphamide, and mycophenolate. Similarly, renal involvement presented a higher prevalence in males (100% against 83.3%), albeit lacking statistical significance. Nevertheless, significant disparities emerged in the occurrence of granular casts, proteinuria, and the average glomerular filtration rate, with males experiencing greater impact in each instance. Finally, it is noteworthy that the application of mycophenolate and azathioprine was more frequently observed among patients with renal involvement. Conclusion cSLE patients in our inception cohort showed statistical significance in dermatological and vascular manifestations, serositis, granular casts, low kidney glomerular filtration, and high proteinuria, which are predominant in male patients. Immunological features were predominantly positive in ds-DNA antibodies for male patients. Separation by gender for future studies might identify a better treatment strategy.
PubMed: 38854180
DOI: 10.7759/cureus.59851 -
Kidney & Blood Pressure Research Jun 2024Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome and diabetes mellitus. However, it remains...
Skipping Breakfast and Progression of Chronic Kidney Disease in the General Japanese Population: the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD).
INTRODUCTION
Breakfast-skipping habits are associated with adverse health outcomes including coronary heart disease, metabolic syndrome and diabetes mellitus. However, it remains uncertain whether skipping breakfast affects chronic kidney disease (CKD) risk. This study aimed to examine the association between skipping breakfast and progression of CKD.
METHODS
We retrospectively conducted a population-based cohort study using the data from the Iki City Epidemiological Study of Atherosclerosis and Chronic Kidney Disease (ISSA-CKD). Between 2008 and 2019, we included 922 participants aged 30 years or older who had CKD (estimated glomerular filtration rate <60 mL/min/1.73m2 and/or proteinuria) at baseline. Breakfast-skippers were defined as participants who skipped breakfast more than 3 times per week. The outcome was CKD progression defined as a decline of at least 30% in the eGFR from the baseline status. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CKD progression, adjusted for other CKD risk factors.
RESULTS
During a follow-up period with a mean of 5.5 years, CKD progression occurred in 60 (6.5%) participants. The incidence rate (per 1,000 person-years) of CKD progression was 21.5 in the breakfast-skipping group and 10.7 in the breakfast-eating group (p=0.029), respectively. The multivariable-adjusted HR (95% CI) for CKD progression was 2.60 (95% CI 1.29‒5.26) for the breakfast-skipping group (p=0.028) compared with the group eating breakfast. There were no clear differences in the association of skipping breakfast with CKD progression in subgroup analyses by sex, age, obesity, hypertension, diabetes mellitus, baseline eGFR and baseline proteinuria.
CONCLUSION
Skipping breakfast was significantly associated with higher risk of CKD progression in the general Japanese population.
PubMed: 38852587
DOI: 10.1159/000539653 -
Indian Journal of Pathology &... Jun 2024Myeloma cast nephropathy in renal allograft recipients without pre-transplant diagnosis of multiple myeloma is rare. A 32-year-old hypertensive male presented to our...
Myeloma cast nephropathy in renal allograft recipients without pre-transplant diagnosis of multiple myeloma is rare. A 32-year-old hypertensive male presented to our institute as a prospective renal allograft recipient. Hemoglobin was 10.1 mg/dl. He did not have hypercalcemia, and the albumin/globulin ratio was 1.33. Urinalysis did not show any proteinuria or active sediments. Ultrasonography of the abdomen showed bilateral contracted kidneys. He underwent an uneventful renal transplant surgery and had immediate graft function. After 1 month, he tested positive for severe acute respiratory syndrome coronavirus 2 and developed graft dysfunction. Graft biopsy showed features of myeloma cast nephropathy. He had elevated lambda chains with an involved-to-uninvolved free light chain ratio of >100. Serum immunofixation electrophoresis showed a monoclonal band in the lambda region. Bone marrow biopsy showed plasmacytosis with 18.6% immature plasma cells. He improved on cyclophosphamide, bortezomib, and dexamethasone regimens.
PubMed: 38847201
DOI: 10.4103/ijpm.ijpm_948_23 -
Frontiers in Genetics 2024Pre-eclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, severely affecting the health and quality of life of patients. However, the...
BACKGROUND
Pre-eclampsia is a pregnancy-related disorder characterized by hypertension and proteinuria, severely affecting the health and quality of life of patients. However, the molecular mechanism of macrophages in pre-eclampsia is not well understood.
METHODS
In this study, the key biomarkers during the development of pre-eclampsia were identified using bioinformatics analysis. The GSE75010 and GSE74341 datasets from the GEO database were obtained and merged for differential analysis. A weighted gene co-expression network analysis (WGCNA) was constructed based on macrophage content, and machine learning methods were employed to identify key genes. Immunoinfiltration analysis completed by the CIBERSORT method, R package "ClusterProfiler" to explore functional enrichment of these intersection genes, and potential drug predictions were conducted using the CMap database. Lastly, independent analysis of protein levels, localization, and quantitative analysis was performed on placental tissues collected from both preeclampsia patients and healthy control groups.
RESULTS
We identified 70 differentially expressed NETs genes and found 367 macrophage-related genes through WGCNA analysis. Machine learning identified three key genes: FNBP1L, NMUR1, and PP14571. These three key genes were significantly associated with immune cell content and enriched in multiple signaling pathways. Specifically, these genes were upregulated in PE patients. These findings establish the expression patterns of three key genes associated with M2 macrophage infiltration, providing potential targets for understanding the pathogenesis and treatment of PE. Additionally, CMap results suggested four potential drugs, including Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin, which may have the potential to reverse pre-eclampsia.
CONCLUSION
Studying the expression levels of three key genes in pre-eclampsia provides valuable insights into the prevention and treatment of this condition. We propose that these genes play a crucial role in regulating the maternal-fetal immune microenvironment in PE patients, and the pathways associated with these genes offer potential avenues for exploring the molecular mechanisms underlying preeclampsia and identifying therapeutic targets. Additionally, by utilizing the Connectivity Map database, we identified drug targets like Ttnpb, Doxorubicin, Tyrphostin AG 825, and Tanespimycin as potential clinical treatments for preeclampsia.
PubMed: 38846957
DOI: 10.3389/fgene.2024.1376971 -
Frontiers in Immunology 2024Macrophages are a rich source of macrophage migration inhibitory factor (MIF). It is well established that macrophages and MIF play a pathogenic role in anti-glomerular...
Macrophages are a rich source of macrophage migration inhibitory factor (MIF). It is well established that macrophages and MIF play a pathogenic role in anti-glomerular basement membrane crescentic glomerulonephritis (anti-GBM CGN). However, whether macrophages mediate anti-GBM CGN via MIF-dependent mechanism remains unexplored, which was investigated in this study by specifically deleting MIF from macrophages in MIF mice. We found that compared to anti-GBM CGN induced in MIF control mice, conditional ablation of MIF in macrophages significantly suppressed anti-GBM CGN by inhibiting glomerular crescent formation and reducing serum creatinine and proteinuria while improving creatine clearance. Mechanistically, selective MIF depletion in macrophages largely inhibited renal macrophage and T cell recruitment, promoted the polarization of macrophage from M1 towards M2 via the CD74/NF-κB/p38MAPK-dependent mechanism. Unexpectedly, selective depletion of macrophage MIF also significantly promoted Treg while inhibiting Th1 and Th17 immune responses. In summary, MIF produced by macrophages plays a pathogenic role in anti-GBM CGN. Targeting macrophage-derived MIF may represent a novel and promising therapeutic approach for the treatment of immune-mediated kidney diseases.
Topics: Macrophage Migration-Inhibitory Factors; Animals; Macrophages; Mice; Anti-Glomerular Basement Membrane Disease; Intramolecular Oxidoreductases; Histocompatibility Antigens Class II; Antigens, Differentiation, B-Lymphocyte; Disease Models, Animal; NF-kappa B; Mice, Knockout; p38 Mitogen-Activated Protein Kinases; T-Lymphocytes, Regulatory; Mice, Inbred C57BL; Th17 Cells; Proteinuria; Signal Transduction
PubMed: 38846956
DOI: 10.3389/fimmu.2024.1361343 -
European Journal of Case Reports in... 2024Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, characterised by multi-organ affections. Haematological involvement is a common manifestation of...
BACKGROUND
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, characterised by multi-organ affections. Haematological involvement is a common manifestation of SLE, consisting of autoimmune peripheral cytopenia. Autoimmune myelofibrosis (AIMF) is a rare cause of cytopenia in SLE; it could precede or be concurrent with the diagnosis of SLE. There are few studies that describe this association.
CASE DESCRIPTION
We report a case of AIMF revealing the diagnosis of SLE in 34-year-old female, presented with episodes of gingival bleeding associated with peripheral inflammatory polyarthralgia, photosensitivity and deterioration of general condition. Clinical examination revealed a soft pitting oedema in the lower limbs. Laboratory investigations showed a pancytopenia, inflammatory biological syndrome, with positive 24-hour proteinuria and anti-native DNA antibodies. A bone marrow biopsy showed diffuse myelofibrosis associated with maturation disorders and no tumour infiltrate. Renal biopsy revealed proliferative glomerulonephritis class III with immune deposits.
CONCLUSION
The association of AIMF with SLE has been rarely reported, and it could be another cause for cytopenia in SLE.
LEARNING POINTS
Autoimmune myelofibrosis can be associated with systemic lupus erythematosus (SLE), even though it is rare.This association should be considered when pancytopenia is not well controlled during SLE, prompting a bone marrow biopsy to confirm the diagnosis.The therapeutic management of this association is the same as that used in SLE.
PubMed: 38846662
DOI: 10.12890/2024_004511 -
Frontiers in Endocrinology 2024According to previous studies, triglyceride-glucose (TyG) is related to chronic kidney disease (CKD), but no studies have explored the correlation between TyG and CKD... (Observational Study)
Observational Study
BACKGROUND AND AIMS
According to previous studies, triglyceride-glucose (TyG) is related to chronic kidney disease (CKD), but no studies have explored the correlation between TyG and CKD among adults with metabolic dysfunction-associated fatty liver disease (MAFLD). We aimed to explore the associations of the TyG index with CKD among adults with MAFLD.
METHODS
In this retrospective observational cohort study, data from 11,860 participants who underwent a minimum of three health assessments between 2008 and 2015 were retrospectively collected. Participants were followed up until the final medical visit or health examination. CKD refers to an eGFR < 60 mL/min per 1·73 m or the occurrence of two or more incidents of proteinuria.
RESULTS
Within a median 10·02-year follow-up period, 2005 (16·9%) participants reported developing CKD. Multivariate Cox regression models indicated a noticeable correlation between the TyG index and CKD incidence (HR per unit increase, 1.19; 95% CI: 1.09-1.29) and between the TyG index and CKD incidence (HR per SD increase, 1.12; 95% CI: 1.06-1.18). The CKD incidence increased by 1.8 times in participants in the highest TyG index quartile relative to patients in the lowest quartile of the TyG index quartile (HR 1·18, 95% CI: 1.01-1.38, P = 0.007). According to subgroup analysis, an elevated TyG index is likely to become more harmful to participants younger than 60 years (P for interaction = 0.035).
CONCLUSION
An elevated TyG index may increase CKD incidence among MAFLD adults, particularly among younger people. Early intervention may help reduce the incidence of CKD.
Topics: Humans; Renal Insufficiency, Chronic; Male; Female; Middle Aged; Triglycerides; Retrospective Studies; Follow-Up Studies; Adult; Blood Glucose; Incidence; Non-alcoholic Fatty Liver Disease; Aged; Risk Factors
PubMed: 38846493
DOI: 10.3389/fendo.2024.1400448 -
PloS One 2024High concentration of Angiotensin converting enzyme receptors in the proximal tubules make kidneys an early target in COVID-19. Proximal tubular dysfunction (PTD) may... (Observational Study)
Observational Study
BACKGROUND
High concentration of Angiotensin converting enzyme receptors in the proximal tubules make kidneys an early target in COVID-19. Proximal tubular dysfunction (PTD) may act as an early predictor of acute kidney injury (AKI) and more severe disease.
METHODS
This prospective observational study was conducted in the COVID unit, Bangabandhu Sheikh Mujib Medical University. 87 COVID-19 patients without known kidney disease were screened for 6 markers of PTD on admission-hyperuricosuria, normoglycemic glycosuria, proteinuria, renal phosphate leak, sodium leak and potassium leak. Positivity of 2 of the first 4 markers was considered as PTD. 35 patients with PTD and 35 without PTD were followed up throughout their hospital stay.
RESULTS
52.9% had PTD on admission. The most prevalent markers were renal sodium leak (67%), followed by proteinuria (66.7%), hyperuricosuria (42.5%), potassium leak (32.2%), phosphate leak (28.7%) and normoglycemic glycosuria (20.7%). Mean age was 55.7 years. 32.9% patients developed AKI. PTD group had higher odds of developing AKI (odds ratio 17.5 for stage 1, 24.8 for stage 2 and 25.5 for stage 3; p<0.0001). The mean duration of hospital stay was 9 days higher in the PTD group (p<0.001). PTD group also had higher odds of transferring to ICU (OR = 9.4, p = 0.002), need for mechanical ventilation (OR = 10.1, p = 0.002) and death (OR = 10.3, p = 0.001). 32.6% had complete PTD recovery during follow-up.
CONCLUSION
Proximal tubular dysfunction is highly prevalent in COVID-19 patients very early in the disease and may act as a predictor of AKI, ICU transfer, need for mechanical ventilation and death.
Topics: Humans; COVID-19; Acute Kidney Injury; Middle Aged; Male; Female; Prospective Studies; Kidney Tubules, Proximal; Aged; Adult; Hospitalization; SARS-CoV-2; Biomarkers
PubMed: 38843279
DOI: 10.1371/journal.pone.0298408