Immunosuppressant-resistant nephrotic syndrome and primary amenorrhea: A case report of adult Frasier syndrome and literature review.

We present a case of a 19-year-old who developed nephrotic syndrome with preserved renal function. Renal biopsy confirmed focal segmental glomerular sclerosis (FSGS). No remission was achieved despite 2 years of treatment with glucocorticoids, mycophenolate mofetil, tacrolimus, and cyclophosphamide. After transfer to our center, we performed re-examination of renal pathology by electron microscope (EM), chromosomal karyotype, and gene analysis. EM revealed uneven thickness of the glomerular basement membrane without obvious stratification or fracture. Gene analysis revealed a splice mutation (1447+1G>A) in IVS9 and chromosomal karyotype was (46, XY), confirming the diagnosis of Frasier syndrome, which was consistent with primary amenorrhea overlooked by local nephrologists. Cyclosporin A was prescribed to reduce the proteinuria, but serum creatinine increased to 152 µmol/L.

Disparity of serum uric acid threshold for CKD among hypertensive and non-hypertensive individuals.

INTRODUCTION: Hypertension and rising serum uric acid (sUA) played a pivotal role in the development of Chronic Kidney Disease (CKD). This study investigates the interactive effect of sUA and hypertension on CKD and identifies the optimal threshold of sUA among individuals with and without hypertension in the Chinese community population. MATERIALS AND METHODS: The study included 4180 individuals aged 45-85 years, derived from the China Health and Retirement Longitudinal Study (CHARLS) between 2011 and 2015. Additionally, a hospital-based study enrolled subjects in the Department of Nephrology at Zhongshan Hospital, China from January 1, 2019, to December 31, 2021. The interaction effect analysis were used to assess the impact of sUA and hypertension on CKD. We also compared the distribution of sUA and the CKD risk in community populations, distinguishing between those with and without hypertension. For the hospital-based population, kidney injury was marked by a KIM-1 positive area. RESULTS: Our results indicate a higher prevalence of CKD in the community population with hypertension (10.2% vs. 3.9%, p < .001). A significant additive synergistic effects of the sUA and hypertension on the CKD risk were found. When the sUA level was < 4.55 mg/dL in the hypertensive population and < 5.58 mg/dL in the non-hypertensive population, the risk of CKD was comparable (p = .809). In the propensity score matched (PSM) population, the result remained roughly constant. CONCLUSION: Therefore, even moderate levels of sUA was associated with a higher risk of CKD in middle-aged hypertensive patients, who warrant stricter sUA control.

Ordered mesoporous carbon with binary CoFe atomic species for highly efficient oxygen reduction electrocatalysis.

The exploration of powerful, efficient and precious metal-free electrocatalysts for facilitating the sluggish kinetics of the oxygen reduction reaction (ORR) is a crucial endeavor in the development and application of energy conversion and storage devices. Herein, we have rationally designed and synthesized bimetallic CoFe species consisting of CoFe nanoparticles and atomically dispersed dual atoms anchored on an ordered mesoporous carbon matrix (CoFe/NC) as highly efficient ORR electrocatalysts. The pyrolyzation temperature for CoFe/NC plays a vital role in regulating the morphology and composition of both the carbon matrix and CoFe species. The optimized CoFe/NC-750 exhibits a favorable ORR performance in 0.1 M KOH with a high half-wave potential (E1/2) of 0.87 V vs. RHE, excellent tolerance to methanol and remarkable durability (no obvious decrease in E1/2 value after 3000 cycles), all of which are superior to the performance of commercial Pt/C. Experimental measurements and density functional theory (DFT) calculations reveal that the improved ORR performance of CoFe/NC-750 is mainly attributed to the electronic structure of atomically dispersed Fe active sites modulated by the surrounding CoFe alloys and Co single atoms, which accelerates the dissociation and reduction of intermediate OH* species and promotes the ORR process.

Multimodal imaging of bilateral retinal pigment epithelial immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition.

OBJECTIVE: To describe multimodal imaging of peculiar bilateral globular subretinal deposits and acquired serous retinal detachment in patients with systemic immunoglobulin light chain deposition. DESIGN: A retrospective observational case series. PARTICIPANTS: We examined six eyes in three patients (one with multiple myeloma, one with membranous nephropathy, and one with immunoglobulin A nephropathy) at the Eye and ENT Hospital of Fudan University. The patients presented with peculiar globular subretinal deposits along the retinal pigment epithelium (RPE)‒Bruch's membrane complex and acquired serous retinal detachment. METHODS: Fundus appearance was documented with multimodal imaging, which included fundus photography, fundus autofluorescence, spectral domain optical coherence tomography (OCT), swept-source OCT (SS-OCT), en-face OCT, and SS-OCT angiography. Additional evaluations included serum protein electrophoreses, positron emission tomography computed tomography, and renal and bone biopsies to assess the primary diseases. MAIN OUTCOME MEASURES: Multimodal imaging, course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. RESULTS: Bilateral, multiple, speckled, or patchy RPE changes in the posterior fundus that corresponded to striking multifocal hyperautofluorescence on fundus autofluorescence and lumpy, globular hyperreflective deposits along the RPE‒Bruch's membrane complex were identified as characteristic features of bilateral RPE light chain deposition. These features may be accompanied by dense light chain deposits in the choriocapillaris and choroid vessels, diffuse choroidal thickening, and "angiographically silent" serous retinal detachment in patients with systemic immunoglobulin light chain deposition. CONCLUSIONS: We have documented the characteristic features, clinical course, and prognosis of bilateral RPE immunoglobulin light chain deposition in patients with systemic immunoglobulin light chain deposition. Appropriate evaluations, including serum protein electrophoresis and hematologic consultation, are recommended to manage patients with this fundus abnormality.

Clinicopathological features of kidney injury in patients receiving immune checkpoint inhibitors (ICPi) combined with anti-vascular endothelial growth factor (anti-VEGF) therapy.

BACKGROUND: Immune checkpoint inhibitor (ICPi) combined with anti-vascular endothelial growth factor (VEGF) therapy has increasingly become a promising strategy in various malignancies. However, the combination might be associated with increased risk of nephrotoxicity. METHODS: We retrospectively recruited patients who suffered kidney injury and received renal biopsy after anti-VEGF/ICPi mono- or combination therapy and divided them into three groups: anti-VEGF monotherapy, ICPi monotherapy and combination therapy. Clinical and histopathological features of three groups were analysed. All patients were followed-up for 3 months after biopsy, with or without glucocorticoid treatment, and renal outcome were compared. RESULTS: A total of 46 patients were enrolled. Eighteen patients received anti-VEGF monotherapy, 12 received ICPi monotherapy and 16 received combined treatment of anti-VEGF and ICPi. Proteinuria level of anti-VEGF group, ICPi group and combination group were 4.07±3.17 g/day, 0.60±0.61 g/day and 2.05±2.50 g/day, respectively (p=0.002). The peak serum creatinine level of combination group (1.75±0.77 mg/dL) was also in between ICPi group (2.79±0.90 mg/dL) and anti-VEGF group (1.34±0.60 mg/dL) (p<0.001). Multiple histopathological patterns involving glomerulus, tubulointerstitium and vessel existed in the majority of cases in combination group (68.8%). Renal complete and partial recovery rate of combination therapy were also in between monotherapy (57.1% vs 40.0% in anti-VEGF group, 100.0% in ICPi group, respectively). CONCLUSIONS: Kidney injury in patients treated with combination therapy of ICPi and anti-VEGF shows hybrid pathological patterns and intermediate clinical features compared with monotherapy. Cohorts with larger sample and better design, as well as basic research, are needed to elucidate the mechanism of 'protection' effect of combination anti-cancer therapy to renal function.

Crosstalk among proximal tubular cells, macrophages, and fibroblasts in acute kidney injury: single-cell profiling from the perspective of ferroptosis.

The link between ferroptosis, a form of cell death mediated by iron and acute kidney injury (AKI) is recently gaining widespread attention. However, the mechanism of the crosstalk between cells in the pathogenesis and progression of acute kidney injury remains unexplored. In our research, we performed a non-negative matrix decomposition (NMF) algorithm on acute kidney injury single-cell RNA sequencing data based specifically focusing in ferroptosis-associated genes. Through a combination with pseudo-time analysis, cell-cell interaction analysis and SCENIC analysis, we discovered that proximal tubular cells, macrophages, and fibroblasts all showed associations with ferroptosis in different pathways and at various time. This involvement influenced cellular functions, enhancing cellular communication and activating multiple transcription factors. In addition, analyzing bulk expression profiles and marker genes of newly defined ferroptosis subtypes of cells, we have identified crucial cell subtypes, including Egr1 + PTC-C1, Jun + PTC-C3, Cxcl2 + Mac-C1 and Egr1 + Fib-C1. All these subtypes which were found in AKI mice kidneys and played significantly distinct roles from those of normal mice. Moreover, we verified the differential expression of Egr1, Jun, and Cxcl2 in the IRI mouse model and acute kidney injury human samples. Finally, our research presented a novel analysis of the crosstalk of proximal tubular cells, macrophages and fibroblasts in acute kidney injury targeting ferroptosis, therefore, contributing to better understanding the acute kidney injury pathogenesis, self-repairment and acute kidney injury-chronic kidney disease (AKI-CKD) progression.