一次性膜性増殖性糸球体腎炎

BACKGROUND: Pathological renal injuries after liver transplantation are multifactorial, yet the clinicopathological characteristics of glomerulonephritis presenting as nephrotic syndrome remain unclear. This study aimed to investigate its clinicopathological features, treatment, and outcomes. METHODS: We retrospectively identified 12 patients with NS who underwent kidney biopsy after liver transplantation and investigated their clinicopathological findings, treatment, and clinical course. RESULTS: At the time of biopsy, the mean time after liver transplantation was 3.4 years, and mean age was 58.9 years. Mean estimated glomerular filtration rate (eGFR) and urinary protein-to-creatinine ratio (UP/UCr) were 40.1 ± 15.6 mL/min/1.73 m2 and 6.74 ± 3.01 g/gCr, respectively. The pathological diagnoses were: IgA nephropathy (IgA-N) in 5 patients (42%), membranoproliferative glomerulonephritis (MPGN) in 2 patients, diabetic nephropathy in 2 patients, thrombotic microangiopathy in 1 patient, pauci-immune crescentic glomerulonephritis (CrGN) in 1 patient, and membranous nephropathy in 1 patient. All patients were treated with induction or dose escalation of angiotensin II receptor blockers, and patients with IgA-N or CrGN received steroid pulse therapy; In patients with IgA-N, mean UP/UCr significantly decreased from 9.01 ± 3.32 g/gCr to 1.45 ± 1.40 g/gCr after 2 years. During the 5.8-year follow-up period, 8 patients (67%) achieved incomplete remission (< 3.5 g/gCr), but 3 patients (one each with IgA-N, MPGN and CrGN) progressed to end-stage kidney disease. CONCLUSIONS: The pathological findings of NS after liver transplantation in this selected cohort are heterogeneous, therefore kidney biopsy might be valuable for evaluating the condition and guiding the selection of appropriate therapeutic strategies.

The complement cascade is part of the innate immune system, and it provides an important line of defense against infections. Inappropriate or excessive activation of this system, however, is also a driver of kidney inflammation in many diseases. Complement inhibitory drugs have now been approved by the US Food and Drug Administration for the treatment of 5 renal diseases: atypical hemolytic uremic syndrome, C3 glomerulopathy, immune-complex membranoproliferative glomerulonephritis, antineutrophil cytoplasmic antibody-associated vasculitis, and IgA nephropathy. Ongoing clinical trials are testing new anticomplement drugs and additional renal indications for complement inhibitors. Most immunosuppressive drugs do not directly block complement activation, and the use of complement inhibitors for renal indications is likely to expand in the coming years. Complement activation in renal diseases also generates plasma, urine, and tissue biomarkers, and laboratory evaluation of the complement system is an important part of the clinical work-up of patients with these inflammatory and autoimmune conditions. It is essential, therefore, that nephrologists are familiar with the available anticomplement drugs and with complement diagnostics.

Immunotactoid glomerulopathy (ITG) is diagnosed by identifying organized microtubules on electron microscopy and it can therefore be missed when they are not demonstrated. A 48-year-old woman with hematuria, nephrotic-range proteinuria, and a faint IgG-κ monoclonal protein underwent an initial kidney biopsy, which showed endocapillary proliferative glomerulonephritis with membranoproliferative features and scant subendothelial deposits, but no diagnostic microtubules. With worsening renal dysfunction and a limited corticosteroid response, a repeat biopsy revealed IgG3-κ-restricted deposits and non-branching, hollow-core microtubules, confirming ITG associated with monoclonal gammopathy of renal significance. Rituximab-based B cell-directed therapy was followed by sustained remission with prednisolone tapered to 2.5 mg every other day.

PURPOSE OF REVIEW: Complement is a central effector of cell and tissue injury in hematological and autoimmune diseases, and recent intensive research brought new inhibitors to the clinic. This review summarizes complement-mediated mechanisms across hematological, systemic, and kidney-specific autoimmune diseases, appraises emerging biomarker strategies, and evaluates these therapies. RECENT FINDINGS: For years, clinical complement inhibition was possible only at C5, first in paroxysmal nocturnal hemoglobinuria. The arsenal has now expanded to the initiation pathways: sutimlimab (anti-C1s) is effective in the hematological autoimmune condition cold agglutinin disease, pegcetacoplan (C3-inhibitor) in C3 glomerulopathy and immune-complex membranoproliferative glomerulonephritis, and oral iptacopan (Factor B-inhibitor) reduces proteinuria in immunoglobulin A nephropathy and C3 glomerulopathy. Nevertheless, challenges remain. Avacopan (C5aR1-inhibitor) faces proposed withdrawal after trial manipulation and hepatotoxicity, and although complement is central to systemic lupus erythematosus and contributes to membranous nephropathy, no effective strategy has yet emerged. SUMMARY: Recognizing complement's role in the pathophysiology of hematological and autoimmune diseases has driven effective new therapies. Comprehensive profiling complement biomarkers, now feasible through complementomics in fluids and tissues, may reveal responsive endotypes and optimal cascade steps to target in diseases where complement is implicated but trials have not yet matched the right drug to the right patients.

BACKGROUND: Chronic Q fever, caused by Coxiella burnetii, presents significant diagnostic and management challenges due to its variable presentation and high morbidity, especially among patients with underlying cardiac or vascular disease. In the United States, cases are rising, often without identifiable exposures, and diagnostic delays remain common. METHODS: We conducted a retrospective cohort study of chronic Q fever cases at the Mayo Clinic from 2007 to 2023. Patients with clinical evidence and a phase I IgG titer ≥1:1024 and/or positive polymerase chain reaction for C burnetii were included. Data were abstracted from electronic health records, including demographics, exposures, clinical manifestations, diagnostics, treatments, and outcomes. Statistical analyses assessed factors influencing diagnostic delay and treatment response. RESULTS: We identified 33 patients with chronic Q fever (median age 56; 88% male). Median time to diagnosis was 99 days, with 11.4 days between infectious diseases evaluation and diagnosis. Animal exposure was reported in 17 patients (52%), while 8 (24%) had no identifiable exposure. Patients primarily presented with prosthetic valve endocarditis (n = 14, 42%) or vascular graft infection (n = 9, 27%). The majority were treated with doxycycline and hydroxychloroquine (n = 25, 75%), and 14 patients (42%) required surgical intervention. Mortality attributable to chronic Q fever was 6% (n = 2). CONCLUSIONS: Chronic Q fever remains under-recognized, with substantial diagnostic delays prior to treatment. Cardiovascular infection predominates, and surgical intervention is often required despite prolonged antimicrobial therapy. Early specialist evaluation and standardized diagnostic pathways may improve outcomes.