Glomerular CD68 macrophages infiltration at initial biopsy predicts response to standard immunosuppression in proliferative lupus nephritis: CD68 Mø predicts LN treatment response.

Objective: Predictive models of kidney response to standard immunosuppression are needed in proliferative lupus nephritis (LN). We tested the kidney macrophage infiltration at initial biopsy.

Methods: The prospective study was performed in 247 patients with newly diagnosed proliferative LN in 2 independent cohorts.

Epidemiological study of HPV infection in 24,588 rural women in Luonan, China.

Cervical cancer is a significant public health issue for women, with human papillomavirus (HPV) infection rates exhibiting regional variations throughout China. This study examined data from a cohort of 24,588 rural women who engaged in cervical cancer screening in Luonan County from 2021 to 2023, utilizing high-risk HPV (hrHPV) testing methodologies. The findings revealed an overall HPV positivity rate of 14.

Glycolysis in Peritubular Endothelial Cells and Microvascular Rarefaction in CKD.

Key Points: Peritubular endothelial cells have a hypoglycolytic metabolism in CKD. Restoration of glycolysis in CKD peritubular endothelial cells by overexpressing 6-phosphofructo-2-kinase/fructose-2, 6-bisphosphatase attenuates microvascular rarefaction and kidney fibrosis. Strategies targeting the metabolic defect in glycolysis in peritubular endothelial cells may be effective in the treatment of CKD.

Dynamically visualizing profibrotic maladaptive repair after acute kidney injury by fibroblast activation protein imaging.

A major challenge in prevention and early treatment of organ fibrosis is the lack of valuable tools to assess the evolving profibrotic maladaptive repair after injury in vivo in a non-invasive way. Here, using acute kidney injury (AKI) as an example, we tested the utility of fibroblast activation protein (FAP) imaging for dynamic assessment of maladaptive repair after injury. The temporospatial pattern of kidney FAP expression after injury was first characterized.

Hyperglycolysis in endothelial cells drives endothelial injury and microvascular alterations in peritoneal dialysis.

Background: Endothelial cell (EC) dysfunction leading to microvascular alterations is a hallmark of technique failure in peritoneal dialysis (PD). However, the mechanisms underlying EC dysfunction in PD are poorly defined.

Methods: We combined RNA sequencing with metabolite set analysis to characterize the metabolic profile of peritoneal ECs from a mouse model of PD.

Restoration of CPT1A-mediated fatty acid oxidation in mesothelial cells protects against peritoneal fibrosis.

Peritoneal dialysis (PD) is limited by gradual fibrotic remodeling in the peritoneum, a process involving profibrotic response of mesothelial cells. However, the role of fatty acid oxidation (FAO) and carnitine palmitoyltransferase 1A (CPT1A) in this process remains unexplored. FAO and CPT1A expression were characterized in mesothelial cells from patients on long-term PD and from a mouse model of PD using multiple experimental methods, including single-cell sequencing, seahorse assay, real-time quantitative PCR, Western blot, and immunofluorescence staining.

Neural and central mechanisms of kidney fibrosis after relief of ureteral obstruction.

Obstructive uropathy from nephrolithiasis remains a leading cause of end-stage kidney disease. Mechanisms of kidney fibrosis after relief of ureteral obstruction represent opportunities for therapeutic intervention. Here, in mouse models of ureteral obstruction, we have combined methods of virus tracing and optogenetic techniques to identify an overactive central pathway in the paraventricular nucleus (PVN)-rostral ventrolateral medulla (RVLM) that determines the fibrotic fate of kidney after relief of the obstruction.

Clinicopathological Characteristics and Outcomes of PLAR-Associated Membranous Nephropathy in Seropositive Patients Without PLAR Staining on Kidney Biopsy.

Rationale & Objective: Phospholipase A receptor (PLAR)-associated membranous nephropathy (MN) with circulating serum autoantibodies to PLAR (SAb) but no deposits of PLAR antigen in glomerular tissue by immunofluorescence (GAg) has been reported. However, little is known about the clinicopathological characteristics or prognosis of this subtype of MN.

Study Design: Retrospective cohort study.

Urinary Matrix Metalloproteinase 7 Activated by Oxidative Stress Predicts Kidney Prognosis in Myeloperoxidase-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

Effective and applicable predictors of end-stage kidney disease (ESKD) are needed for patients with myeloperoxidase-antineutrophil cytoplasmic antibody-associated vasculitis (MPO-AAV) and kidney involvement. We investigated whether urinary matrix metalloproteinase-7 (uMMP7) was associated with kidney injury severity and incident ESKD in MPO-AAV. A prospective two-stage study was conducted in 150 patients with newly diagnosed MPO-AAV in two independent cohorts.

Intensity of Macrophage Infiltration in Glomeruli Predicts Response to Immunosuppressive Therapy in Patients with IgA Nephropathy.

Background: The lack of a tool for predicting the response to immunosuppressive therapy in IgA nephropathy (IgAN) limits patient-specific risk stratification and early treatment decision making. Models for predicting response to immunosuppression in IgAN that can be applied at the time of kidney biopsy are needed.

Methods: This prospective cohort study involved 621 Chinese patients with IgAN who were at high risk for disease progression and had persistent proteinuria ≥1 g/d, despite 3 months of optimized supportive care with renin-angiotensin system inhibitors.

Seropositive PLA2R-associated membranous nephropathy but biopsy-negative PLA2R staining.

Background: Serum phospholipase A2 receptor (PLA2R) antibody (SAb) and glomerular deposits of PLA2R antigen (GAg) have been tested widely in idiopathic membranous nephropathy (MN). Recently, we noticed a special form of PLA2R-associated MN with positive circulating PLA2R antibody but negative PLA2R deposits in the glomeruli by immunofluorescence on frozen tissue (IF-F). The significance of this form of PLA2R-associated MN is yet to be elucidated.

Association of Urinary Matrix Metalloproteinase 7 Levels With Incident Renal Flare in Lupus Nephritis.

Objective: Flares of lupus nephritis (LN) are frequent and associated with impaired renal prognosis. One major management obstacle in LN flare is the lack of effective methods to identify at-risk patients earlier in their disease course. This study was undertaken to test the utility of measurement of urinary matrix metalloproteinase 7 (MMP-7) for the dynamic surveillance of renal disease activity and prediction of renal flares in LN.

Urinary Angiotensinogen Predicts Renal Disease Activity in Lupus Nephritis.

A noninvasive indicator of renal histological lesions and disease activity in lupus nephritis (LN) is needed for timely and targeted treatment before overt renal injury. Here, we tested the utility of urinary angiotensinogen (UAGT) to predict renal disease activity in LN. A prospective, three-stage study was performed in patients with LN.

Urinary angiotensinogen predicts progressive chronic kidney disease after an episode of experimental acute kidney injury.

One of the major obstacles to prevent AKI-CKD transition is the lack of effective methods to follow and predict the ongoing kidney injury after an AKI episode. In the present study, we test the utility of urinary angiotensinogen (UAGT) for dynamically evaluating renal structural changes and predicting AKI-CKD progression by using both mild and severe bilateral renal ischemia/reperfusion injury mice. UAGT returns to pre-ischemic levels 14 days after mild AKI followed by kidney architecture restoration, whereas sustained increase in UAGT accompanies by ongoing renal fibrosis after severe AKI.