Proliferative glomerulonephritis with monoclonal immunoglobulin G deposits in a young woman: A case report

BACKGROUND Proliferative glomerulonephritis with monoclonal immunoglobulin G(IgG)deposits(PGNMID)is a newly recognized rare disease.The renal pathology is characterized by prominent manifestations of membranous hyperplasia,which are easy to misdiagnose.The clinical symptoms are severe.Massive proteinuria and hypoproteinemia are conspicuous,and most patients are accompanied by renal insufficiency and microscopic hematuria.CASE SUMMARY A 27-year-old woman was admitted to a hospital for macroscopic hematuria and proteinuria 4 years prior,and renal biopsy in the hospital suggested moderate-tosevere mesangial proliferating glomerulonephritis(MsPGN).She had taken a glucocorticoid,cyclophosphamide,mycophenolate mofetil,and other treatments and achieved brief partial remission.Recently,the patient visited our hospital due to massive proteinuria.Repeated renal biopsy and re-evaluation of the first biopsy obtained 4 years previously revealed monoclonal immunoglobulin deposition in the glomeruli.A bone marrow examination was performed to exclude hematologic malignancy,and a diagnosis of PGNMID was established.The patient showed remission after four cycles of a bortezomib+cyclophosphamide+dexamethasone scheme.CONCLUSION PGNMID is usually misdiagnosed as MsPGN or membranoproliferative glomerulonephritis.Although it often occurs in middle-aged and elderly individuals,it cannot be readily excluded in young people,even when serum immunofixation electrophoresis is negative.IgG subtype and light chain staining are necessary when this disease is highly suspected.An accurate diagnosis at the earliest stage may avoid the overuse of glucocorticoids and immunosuppressants.

Changes in renal function and morphological variations of kidney diseases in rheumatoid arthritis patients

Objective:Rheumatoid nephropathy is one of the most severe extra-articular manifestations of rheumatoid arthritis(RA)associated with a very unfavorable prognosis.This study aimed to identify changes in renal function and morphological variations of kidney diseases in RA patients.Methods:The study enrolled patients(126 patients)between 18 and 55 years of age with a confirmed active RA of more than 12 months.Each patient underwent the following range of laboratory and instrumental research methods:general clinical analysis of blood and urine,performing urinalysis according to Nechiporenko method;determining daily proteinuria;determining the blood content of glucose,urea,creatinine,uric acid,total bilirubin,liver transaminase level,ionogram,lipidogram,and coagulogram;determining the blood content of rheumatoid factor,anti-streptolysin O,and C-reactive protein;and X-ray of the joints of hands and feet.Renal function was examined by estimating glomerular filtration rate,tubular reabsorption index,and renal functional reserve.For studying the morphological changes in the kidneys under ultrasound examination,renal biopsy was performed in 31 patients with RA with urinary syndrome(proteinuria more than 0.3 g per day and hematuria).Results:Nephropathy in RA is characterized by impaired renal function and manifested by an increased blood creatinine and a decrease in glomerular filtration rate and renal functional reserve.Among morphological variations of nephropathy at RA,mesangial proliferative glomerulonephritis prevails,accounting for 48.4%of patients.Other disorders include the secondary amyloidosis(29.0%of patients),tubulointerstitial nephritis(16.1%),membranous glomerulonephritis(3.2%),and focal-segmental glomerulosclerosis(3.2%).Conclusion:Kidney damage is a common systemic manifestation of RA with a long and active course,a major nephropathy trigger.

The role of transcriptional factor D-site-binding protein in circadian CCL2 gene expression in anti-Thy1 nephritis

Mesangial proliferative glomerulonephritis(MsPGN)is an inflammatory disease,but both the nature of disease progression and its regulation remain unclear.In the present study,we monitored the course of anti-Thy1 nephritis from days 1 to 5 and established gene expression profiles at each time point using microarrays to explore the development of inflammation.According to the gene expression profiles,macrophage infiltration(triggered by CCL2 activation)was evident on day 1 and enhanced inflammation over the next few days.We screened for genes with expression levels similar to CCL2 and found that the upregulation of the circadian gene albumin D-site-binding protein(DBP)was involved in CCL2 activation in mesangial cells.More importantly,CCL2 expression showed oscillatory changes similar to DBP,and DBP induced peak CCL2 expression at 16:00 a clock on day 1 in the anti-Thy1 nephritis model.We knocked down DBP through transfection with a small interfering RNA(siRNA)and used RNA sequencing to identify the DBP-regulated TNF-α-CCL2 pathway.We performed chromatin immunoprecipitation sequencing(ChIP-Seq)and the dual luciferase assay to show that DBP bound to the TRIM55 promoter,regulating gene expression and in turn controlling the TNF-α-CCL2 pathway.In conclusion,DBP-regulated circadian CCL2 expression by the TRIM55-TNF pathway in injured mesangial cells at an early stage,which promoted macrophage recruitment and in turn triggered infiltration and inflammation in a model of anti-Thy1 nephritis.