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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 -
Open Medicine (Warsaw, Poland) 2024The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in...
OBJECTIVE
The aim of this study was to observe the remission of primary membranous nephropathy (PMN) and evaluate the efficacy of tacrolimus (TAC) monotherapy for PMN in comparison with TAC combined with a low-dose glucocorticoid (GC) protocol (TAC + GC).
METHODS
This was tested in a prospective monocentric observational trial of 70 patients with PMN, of whom 34 received TAC (0.05-0.075 mg/kg/day) or 36 received TAC (0.05-0.075 mg/kg/day) and GC (0.3-0.5 mg/kg/day of prednisone).
RESULTS
At 3, 6, 9, and 12 months of treatment, the effective rates in the TAC group and the TAC + GC group were similar ( > 0.05). The urinary protein quantification was reduced in patients under both therapeutic protocols, and the differences in the proteinuria quantification at 3, 6, 9, and 12 months of treatment were not statistically significant between the two groups ( > 0.05). The overall incidence of adverse reactions in the TAC group was lower than that in the TAC + GC group (23.5% < 36.1%), and the difference was statistically significant ( < 0.05).
CONCLUSION
TAC monotherapy for PMN could effectively reduce urinary protein quantification and increase serum albumin levels. Compared with TAC + GC, TAC monotherapy for PMN had no difference in efficacy and fewer incidences of adverse reactions.
PubMed: 38841175
DOI: 10.1515/med-2024-0957 -
Translational Pediatrics May 2024Alport syndrome (AS) is a rare progressive hereditary kidney disease that is clinically principally associated with hematuria, proteinuria, and progressive renal...
BACKGROUND
Alport syndrome (AS) is a rare progressive hereditary kidney disease that is clinically principally associated with hematuria, proteinuria, and progressive renal dysfunction. This condition not only impairs renal function but also potentially affects auditory and ocular health, significantly impacting the patient's quality of life.
CASE DESCRIPTION
This article reports a young girl with AS, combined with dwarfism attributable to growth hormone (GH) deficiency, diagnosed at Wenzhou People's Hospital in 2019. The clinical data and diagnostic steps were retrospectively analyzed. Genetic testing showed that she carried a new mutation in the gene, c.2317_2318delAG (p.R773Gfs*14), classified as "pathogenic" under the criteria of the American College of Medical Genetics and Genomics (ACMG), confirming her AS diagnosis. Significantly, the patient's height was more than two standard deviations (SDs) below the average for children of her race, sex, and age. The peak GH level post-stimulation was below 5 ng/mL, coupled with a growth rate of less than 5 cm/year, leading to the diagnosis of GH deficiency. Consequently, recombinant human GH (rhGH) therapy was initiated.
CONCLUSIONS
After a year of rhGH treatment, we observed a notable increase in her height, without any adverse effects like elevated intracranial pressure, hypothyroidism, or worsening kidney function.
PubMed: 38840691
DOI: 10.21037/tp-23-569 -
Journal of Primary Care & Community... 2024To assess the prevalence and risk factors for chronic kidney disease (CKD) among adults with type 2 diabetes within primary care.
AIMS
To assess the prevalence and risk factors for chronic kidney disease (CKD) among adults with type 2 diabetes within primary care.
METHODS
This cross-sectional study evaluated 1319 individuals receiving standard care across 26 primary units from July 2017 to January 2023. The estimated glomerular filtration rate (eGFR) and albuminuria were used for the diagnosis of CKD. CKD was defined by eGFR values of <60 mL/min/1.73 m and/or albumin-to-creatine ratio ≥30 mg/g. Logistic regression was applied to identify factors associated with CKD and study variables.
RESULTS
The median age of participants (60.6% females) was 55 years and the median diabetes duration was 10 years. The overall CKD prevalence in the study population was 39.2%. Within the CKD group, the prevalence rates of albuminuria, albuminuria coupled with low eGFR and isolated low eGFR were 72.1%, 19%, and 8.9%, respectively. The prevalence of CKD was 30.6% among participants under 40 years old and a higher value was observed in middle-aged adults with early-onset diabetes (at age <40 years) compared with the later-onset group. Multivariable analyses identified associations between CKD and factors such as age, the male sex, diabetes duration, hypertension, retinopathy, and metformin use.
CONCLUSION
A relatively high prevalence of CKD, especially in non-elderly adults, was revealed in this primary care study. Early recognition strategies for CKD are crucial for timely prevention within primary care.
Topics: Humans; Male; Female; Middle Aged; Cross-Sectional Studies; Diabetes Mellitus, Type 2; Renal Insufficiency, Chronic; Primary Health Care; Prevalence; Adult; Glomerular Filtration Rate; Risk Factors; Albuminuria; Aged
PubMed: 38840565
DOI: 10.1177/21501319241259325