Contemporary Monoclonal Antibody Utilization in Glomerular Diseases.

Therapeutic monoclonal antibodies (MAbs) have been one of the fastest growing drug classes in the past 2 decades and are indicated in the treatment of cancer, autoimmune disorders, solid organ transplantation, and glomerular diseases. The Food and Drug Administration has approved 100 MAbs between 1986 and 2021, and MAbs account for 20% of Food and Drug Administration's new drug approval every year. MAbs are preferred over traditional immunosuppressive agents because of their high specificity, reduced number of drug-drug interactions, and low toxicity, which make them a prime example of personalized medicine. In this review article, we provide an overview of the taxonomy, pharmacology, and therapeutic applications of MAbs in glomerular diseases. We searched the literature through PubMed using the following search terms: monoclonal antibodies, glomerular diseases, pharmacokinetics, pharmacodynamics, immunoglobulin, murine, chimeric,humanized, and fully human, and limited our search to years 2018-2023. We selected peer-reviewed journal articles with an evidence-based approach, prioritizing randomized control trials in specific glomerular diseases, if available. Advances in the MAb field have resulted in a significant paradigm shift in targeted treatment of immune-mediated glomerular diseases, and multiple randomized control trials are currently being conducted. Increased recognition is critical to expand their use in experimental research and personalized medicine.

The Impact of Nirmatrelvir-Ritonavir in Reducing Hospitalizations Among High-Risk Patients With SARS-CoV-2 During the Omicron Predominant Era.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality in high-risk populations. Several therapeutics have been developed to reduce the risk of complications related to COVID-19, hospitalizations, and death. In several studies, nirmatrelvir-ritonavir (NR) was reported to reduce the risk of hospitalizations and death. We aimed to evaluate the efficacy of NR in preventing hospitalizations and death during the Omicron predominant period. METHODS: We retrospectively evaluated patients from June 1, 2022, through September 24, 2022. There were a total of 25,939 documented COVID-19 cases. Using propensity matching, we matched 5754 patients treated with NR with untreated patients. RESULTS: Postmatching, the median age of the NR-treated group was 58 years (interquartile range, 43-70 years) and 42% were vaccinated. Postmatching composite outcome of the 30-day hospitalization and mortality in the NR-treated group were 0.9% (95% confidence interval [CI]: 0.7%-1.2%) versus 2.1% (95% CI: 1.8%-2.5%) in the matched control group, with a difference of -1.2 (-1.7, -0.8), P value <.01. The difference rates (NR vs. control) in 30-day all-cause hospitalizations and mortality were -1.2% (95% CI: -1.6% to -0.7%, P value <.01) and -0.1% (95% CI: -0.2% to 0.0%, P value = 0.29), respectively. We found similar finding across different age groups (≥65 vs. <65) and the vaccinated group. CONCLUSION: We report a significant benefit with the use of NR in reducing hospitalizations among various high-risk COVID-19 groups during the Omicron BA.5 predominant period.

Navigating the initial diagnosis and management of adult IgA vasculitis: A review.

Background: IgA vasculitis in adults has not been thoroughly studied. This has left a practice gap related to the management and follow-up of a population that is at an increased risk of comorbidities and potentially poor outcomes. For this reason, it is important to synthesize evidence from the current literature because this can help direct the movement for more robust studies to clarify best practice recommendations. Objective: We sought to create a narrative review for the practicing dermatologist when diagnosing and leading the care of IgA vasculitis in adult patients. Methods: A broad literature search was performed with a focus on articles that were published after the introduction of the most updated European Alliance of Associations for Rheumatology/Pediatric Rheumatology International Trials Organization/Pediatric Rheumatology European Society criteria. Results: The characteristics and management guidelines for IgA vasculitis in adults have been refined, although more rigorous studies are needed to develop best practice recommendations. Limitations: Because of the lack of sufficient randomized controlled trials on IgA vasculitis in adults, this narrative review is composed of mostly observational, descriptive studies. Conclusion: Adults with IgA vasculitis are at an increased risk of complicated disease course, necessitating formal diagnostic assessment and clear-cut follow-up recommendations to manage and prevent poor health outcomes related to various comorbidities.

Epidemiology of Glomerular Disease in Southern Arizona: Review of 10-Year Renal Biopsy Data.

Glomerulonephritis stands third in terms of the etiologies for end-stage kidney disease in the USA. The aim of this study was to look at the patterns of biopsy-proven glomerulonephritis based on data from a single center.Kidney biopsy specimens of all patients above the age of 18 years, over a 10-year period, who had diagnosis of nondiabetic glomerular disease, were selected for the study.The most common histopathological diagnosis was focal and segmental glomerulosclerosis (FSGS) (22.25%, 158/710) followed by membranous nephropathy (20.28%, 144/710) and immunoglobulin (Ig)A nephropathy (19.71%, 140/710). There was male preponderance in all histological variants except IgA nephropathy, lupus nephritis, and pauci-immune glomerulonephritis. The race distribution was uneven, and all histological variants, except minimal change disease and lupus nephritis, were more commonly seen in whites. In a separate analysis of the histological pattern in Hispanics, lupus nephritis was the most common pathology (28.70%, 62/216) followed by FSGS (18.05%, 39/216). In American Indian population, the most common pathology was IgA nephropathy (33.33%, 8/24) followed by FSGS (16.67%, 4/24).This study highlights the histopathological patterns of glomerular disease in southern Arizona. The data suggest regional and ethnic variations in glomerular disease that may point towards genetic or environmental influence in the pathogenesis of glomerular diseases.

Improvement in Gemcitabine-Induced Thrombotic Microangiopathy with Rituximab in a Patient with Ovarian Cancer: Mechanistic Considerations.

Gemcitabine is a potent and widely used anticancer drug. We report a case of gemcitabine-induced thrombotic microangiopathy (GCI-TMA), a known but not widely recognized complication of gemcitabine use, and our experience of treating GCI-TMA with rituximab. A 74-year-old woman was referred to our clinic for an evaluation of worsening renal function. She has recently been treated for ovarian cancer (diagnosed in 2011) with surgery (tumor debulking and bilateral salpingo-oophorectomy) along with cisplatin chemotherapy in 2012, followed by carboplatin/doxorubicin in 2013 and recent therapy for resistant disease with gemcitabine. Laboratory tests showed anemia, normal platelets and elevated lactate dehydrogenase. A peripheral smear revealed numerous schistocytes, and a kidney biopsy showed acute as well as chronic TMA. The patient continued on gemcitabine therapy, and treatment with plasma exchange was started. Since there was no response to treatment even after 5 sessions of plasma exchange, one dose of rituximab was given, which was associated with a drop in the creatinine level to 2 mg/dl. The pathogenesis of renal injury could be the effect of direct injury to the endothelium mediated by cytokines. Usual treatment includes withdrawing the drug and initiation of treatment with plasmapheresis with or without steroids. In cases resistant to plasmapheresis, treatment with rituximab can be tried. The mechanism of action of rituximab might be due to the reduced production of B-cell-dependent cytokines that drive endothelial dysfunction by depleting B cells. Patients receiving gemcitabine chemotherapy should be monitored for the development of TMA, and early treatment with plasma exchange along with rituximab might benefit these patients who already have a bad prognosis.

Obstructive Jaundice as Initial Presentation of Multiple Myeloma: Case Presentation and Literature Review.

Multiple myeloma is a malignant plasma-cell disorder that primarily involves the bone marrow, but extramedullary involvement is becoming increasingly common (Bladé et al., 2012) both at initial presentation and follow-up. Most common initial presentations for multiple myeloma include generalized fatigue, renal insufficiency, bone pain, and recurrent bacterial infections. We present a case of a healthy 55-year-old man that presented to the emergency department with a three-week history of anorexia and jaundice without any past medical history. Patient's initial labs were significant for hyperbilirubinemia and elevated liver function enzymes (AST, ALT, ALP, and GGT). Additional laboratory workup was significant for mild hypercalcemia and increased protein gap. MRI and ERCP suggested primary sclerosing cholangitis but were not diagnostic. Liver biopsy illustrated plasma-cell infiltration and bone marrow biopsy diagnosed multiple myeloma with extramedullary disease. Patient was started on dexamethasone, bortezomib, and cyclophosphamide, but, despite this aggressive regimen, the patient continued to decline. We take this opportunity to present this atypical presentation of a common hematological malignancy and review the associated literature.

Late onset ipilimumab-induced pericarditis and pericardial effusion: a rare but life threatening complication.

Metastatic cutaneous melanoma has poor prognosis with 2-year survival rate of 10-20%. Melanoma cells express various antigens including gp100, melanoma antigen recognized by T cells 1 (MART-1), and tyrosinase, which can induce immune-mediated anticancer response via T cell activation. Cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) is an immune check point molecule that negatively regulates T cell activation and proliferation. Accordingly, recent phase III clinical trials demonstrated significant survival benefit with ipilimumab, a human monoclonal antibody (IgG1) that blocks the interaction of CTLA-4 with its ligands. Since the efficacy of ipilimumab depends on T cell activation, it is associated with substantial risk of immune mediated adverse reactions such as colitis, hepatitis, thyroiditis, and hypophysitis. We report the first case of late onset pericarditis and cardiac tamponade associated with ipilimumab treatment in patient with metastatic cutaneous melanoma.