Telitacicept Treatment Refractory Lupus Nephritis: A Case Report.

Introduction: Refractory lupus nephritis (LN) causes kidney disease progression and increases the risk of loss of renal function. Due to the high specificity and few side effects of biological agents, they are recommended for the treatment of systemic lupus erythematosus. There are few data on telitacicept for the treatment of refractory LN. Case Presentation: Here, we report the efficacy and safety of telitacicept in the treatment of refractory LN in a 25-year-old female patient. This patient with refractory lupus developed Pneumocystis jirovecii pneumonia while using multitargeted therapy, and the patient's urine protein was rapidly relieved after telitacicept combination with low-dose mycophenolate mofetil (MMF). Conclusion: This result suggests that telitacicept has a positive effect on refractory LN with no significant side effects. Further reports and a registry are necessary to confirm that telitacicept with low-dose MMF should be preferred in refractory LN.

Validation of metagenomic next-generation sequencing of bronchoalveolar lavage fluid for diagnosis of suspected pulmonary infections in patients with systemic autoimmune rheumatic diseases receiving immunosuppressant therapy.

Background: The accuracy and sensitivity of conventional microbiological tests (CMTs) are insufficient to identify opportunistic pathogens in patients with systemic autoimmune rheumatic diseases (SARDs). The study aimed to assess the usefulness of metagenomic next-generation sequencing (mNGS) vs. CMTs for the diagnosis of pulmonary infections in patients with SARDs receiving immunosuppressant therapy. Methods: The medical records of 40 patients with pulmonary infections and SARDs treated with immunosuppressants or corticosteroids were reviewed retrospectively. Bronchoalveolar lavage fluid (BALF) samples were collected from all patients and examined by mNGS and CMTs. Diagnostic values of the CMTs and mNGS were compared with the clinical composite diagnosis as the reference standard. Results: Of the 40 patients included for analysis, 37 (92.5%) were diagnosed with pulmonary infections and 3 (7.5%) with non-infectious diseases, of which two were considered primary diseases and one an asthma attack. In total, 15 pathogens (7 bacteria, 5 fungi, and 3 viruses) were detected by CMTs as compared to 58 (36 bacteria, 12 fungi, and 10 viruses) by mNGS. Diagnostic accuracy of mNGS was superior to that of the CMTs for the detection of co-infections with bacteria and fungi (95 vs. 53%, respectively, p < 0.01), and for the detection of single infections with fungi (97.5 vs. 55%, respectively, p < 0.01). Of the 31 patients diagnosed with co-infections, 4 (12.9%) were positive for two pathogens and 27 (87.1%) for three or more. The detection rate of co-infection was significantly higher for mNGS than CMTs (95 vs. 16%, respectively, p < 0.01). Conclusion: The accuracy of mNGS was superior to that of the CMTs for the diagnosis of pulmonary infections in patients with SARDs treated with immunosuppressants. The rapid diagnosis by mNGS can ensure timely adjustment of treatment regimens to improve diagnosis and outcomes.

A Case of Lupus Nephritis Preceded by Minimal Change Disease and Membranous Glomerulonephritis.

BACKGROUND Lupus nephritis (LN) is the most common and serious complication of systemic lupus erythematosus (SLE). Minimal change disease (MCD) and primary membranous nephropathy (PMN) are the 2 most common causes of primary nephrotic syndrome. Our purpose in publishing this case report is to introduce an unusual clinical course and initial renal biopsy revealed MCD and then PMN in second renal biopsy. Subsequently, a third renal biopsy resulted in a final diagnosis of LN. To the best of our knowledge, this is the first such report. CASE REPORT The 31-year-old male patient was initially diagnosed with MCD after the first renal biopsy in 2004. He improved with initial management and had a complete remission for 9 years. After 9 years, the patient again presented with heavy proteinuria without systemic lupus erythematous finding and he was diagnosed with MN following the second renal biopsy. Seven years later, he again developed proteinuria alone with concurrent systemic symptoms of systemic lupus erythematosus, and a third biopsy was performed, leading to final diagnosis as LN. He was well managed with the methylprednisolone and cyclophosphamide (CTX) regimen, which improved renal function and spared the patient from continuous hemodialysis. CONCLUSIONS In rare case, MCD may represent an early phase of lupus nephritis, which may subsequently develop into severe lupus nephritis.

COMMD5 is involved in the mechanisms of hypotension after parathyroidectomy in patients receiving hemodialysis.

BACKGROUND: Secondary hyperparathyroidism (SHPT) is a common complication of end-stage renal disease. Parathyroidectomy (PTx) is often employed for treatment of severe SHPT. However, PTx may cause hypotension via unknown mechanisms. COMM domain-containing protein 5 (COMMD5) in the parathyroid glands has been linked to blood pressure regulation of spontaneously hypertensive rats. OBJECTIVE: To explore the relationship between COMMD5 levels and reduced BP after PTx in patients receiving hemodialysis (HD). METHODS AND RESULTS: (1) The study cohort included 31 patients receiving HD who underwent PTx. Serum COMMD5 levels were higher post-PTx vs. pre-PTx. (2) Sprague-Dawley rats (n = 22) were assigned to a 5/6 nephrectomy group or sham surgery group, vascular rings of the thoracic aorta from rats with CKD were incubated with COMMD5, and changes in vascular tension were compared. COMMD5 inhibited vasoconstriction of vascular rings with intact endothelium, but had no effect on vascular rings without the endothelium. (3) Human umbilical vein endothelial cells were stimulated with COMMD5 or small interfering RNA (siRNA). The expression levels of atrial natriuretic peptide (ANP) and endothelial nitric oxide synthase (eNOS) were up-regulated and down-regulated, respectively. CONCLUSIONS: Serum COMMD5 levels were increased after PTx in SHPT patients. COMMD5 promoted high expression of ANP and eNOS in endothelial cells, leading to vasodilation and resulting in hypotension.

Hydroxyapatite nanoparticles promote mitochondrial-based pyroptosis via activating calcium homeostasis and redox imbalance in vascular smooth muscle cells.

Hydroxyapatite nanoparticles (HAP) have been widely used in various fields because of their natural biological origin and functional properties. The emerging evidence on their toxicities has attracted research interest. HAP-induced vascular smooth muscle cell (VSMC) damage is a key step in vascular calcification (VC), particularly in patients with chronic kidney disease. However, the injury effects and mechanism of action of HAP on VSMCs have not been extensively investigated. This study comprehensively characterized commercially available HAP and investigated its adverse biological effects in cultured A7R5 cells.In vitroexperiments revealed that internalized HAP was localized in lysosomes, followed by the release of Ca2+owing to the low pH microenvironment. Upon Ca2+homeostasis, Ca2+enters the mitochondria, leading to the simultaneous generation of reactive oxygen species (ROS). ROS subsequently attack mitochondrial transmembrane potentials, promote mitochondrial ROS production, and oxidize mitochondrial DNA (Ox-mtDNA). Mitochondrial permeability-transition pores open, followed by the release of more Ox-mtDNA from the mitochondria into the cytosol due to the redox imbalance. This activates NLRP3/caspase-1/gasdermin D-dependent pyroptosis and finally excretes inflammatory factors to induce VC; an antioxidant could rescue this process. It has been suggested that HAP could induce an imbalance in intracellular Ca2+homeostasis in A7R5 cells, followed by the promotion of mitochondrial dysfunction and cell pyroptosis, finally enhancing VC. To detect thein vivotoxicity of HAP, mice were treated with Cy7-labelled HAP NPs for 24 h.In vivoresults also demonstrated that HAP accumulated in the kidneys, accompined with increased Ca concentration, upregulated oxidative stress-related factor and kidney damage. Overall, our research elucidates the mechanism of calcium homeostasis and redox imbalance, providing insights into the prevention of HAP-induced cell death.