Hantavirus infection is a rodent-borne zoonotic disease that can present as Hemorrhagic Fever with Renal Syndrome (HFRS) or Hantavirus Cardiopulmonary Syndrome (HCPS). Both diseases are associated with substantial morbidity and mortality. The rise of new Hantavirus species and recurrent outbreaks worldwide has renewed interest in the epidemiology, pathogenesis, diagnosis, and management of this viral infection. A narrative literature review was conducted using published articles, review papers, epidemiological reports, and clinical studies on Hantavirus up to 2026. Relevant evidence regarding epidemiology, pathogenesis, clinical manifestations, diagnostic approaches, treatment, complications, and prevention was analyzed and synthesized. Hantaviruses primarily infect endothelial cells, leading to increased vascular permeability, thrombocytopenia, and capillary leakage through immune-mediated mechanisms. HFRS affects the kidneys, and HCPS is characterized by severe cardiopulmonary symptoms, although overlap between the two syndromes has increasingly been observed. Diagnosis is based on clinical suspicion supported by epidemiological exposure history, serological testing, and virological confirmation from reverse transcription polymerase chain reaction (RT-PCR). Current management remains largely supportive, including hemodynamic stabilization, respiratory support, and renal replacement therapy when indicated. Ribavirin may provide benefit in selected HFRS cases when given early, but evidence remains inconclusive, especially for HCPS. Favipiravir has demonstrated promising antiviral activity in vitro and in animal studies, yet clinical data in humans are still lacking. Preventive measures focus primarily on minimizing exposure to infected rodents and contaminated environments, while vaccine development remains ongoing. Hantavirus infection continues to represent an important global public health concern due to its potential for severe disease and high mortality. Improved understanding of disease pathogenesis, advances in diagnostic methods, and ongoing research into antiviral therapies and vaccines are essential to improve patient outcomes and strengthen future prevention strategies.

Renal coloboma syndrome (RCS) is an autosomal dominant disorder caused by pathogenic variants in the PAX2 gene, primarily affecting renal and optic nerve development. However, the presentation of RCS is highly heterogeneous, ranging from mild renal anomalies to severe multi-organ involvement. This phenotypic variability often poses significant challenges for accurate clinical diagnosis.

Alport syndrome (AS) is characterised by progressive chronic kidney disease (CKD) leading to kidney failure, sensorineural hearing loss and eye abnormalities. AS patients have reduced or no expression of the α3α4α5 triple helix, a major component of the kidney glomerular basement membrane (GBM), due to pathogenic variants in COL4A3, COL4A4 and COL4A5. Post-transplant anti-GBM nephritis continues to be seen in AS patients and is immunological distinct from 'traditional' anti-GBM (Goodpasture's) disease. Post-transplant anti-GBM nephritis is reported to affect 5% of AS patients. There is also an isolated immunological anti-GBM disease counterpart, where despite the production of anti-GBM antibodies, the AS patient does not ever develop clinical nephritis post-transplant. The pathophysiology of anti-GBM nephritis post-transplant relates to the presentation of non-tolerised antigen to the immune system. The intact donor GBM is immunogenic, specifically the α3α4α5(IV) triple helix, which leads to the production of anti-GBM antibodies that can initiate a crescentic glomerulonephritis in the allograft. The target alloantigen most often implicated in X-linked dominant AS patients with post-transplant anti-GBM nephritis is α5(IV), whereas for autosomal recessive AS patients it is α3(IV). There is no agreed protocol for the treatment or prophylaxis of post-transplant anti-GBM nephritis in AS patients. Immunosuppressive strategies vary including steroids in combination with tacrolimus, azathioprine and ciclosporin. Plasmapheresis can be used to remove pathogenic anti-GBM antibodies. On initial transplantation, allograft failure due to anti-GBM nephritis may occur within weeks-to-months, and not usually beyond the first year post-renal transplant. Progression to graft loss secondary to diagnosed anti-GBM nephritis is often rapid. The recurrence of anti-GBM nephritis and accelerated allograft rejection (occurring within days-to-weeks) is reported in multiple AS patients who underwent retransplantation, having lost their first renal transplant to the same immune phenomenon. Improved diagnostics and disease registries are needed to document these immune phenomena and optimise personalised patient management.

Immunoglobulin A vasculitis (IgAV), formerly known as Henoch-Schönlein purpura, is a small‑vessel vasculitis characterized by immunoglobulin A-predominant immune complex deposition in vessel walls and the glomerular mesangium. Although most commonly observed in children, adult‑onset disease is less frequent and is associated with a higher risk of significant renal involvement and poorer clinical outcomes. We report the case of a 56‑year‑old man with alcoholic cirrhosis and chronic methicillin‑sensitive Staphylococcus aureus prosthetic joint infection who presented with progressive anasarca and a diffuse non‑blanching petechial rash. Laboratory evaluation demonstrated elevated inflammatory markers and acute kidney injury with a serum creatinine of 1.9 mg/dL (baseline approximately 1.0 mg/dL one month prior). Urinalysis revealed 3+ proteinuria and microscopic hematuria. Serologic testing, including antinuclear antibodies, antineutrophil cytoplasmic antibodies, anti‑glomerular basement membrane antibodies, complement levels, cryoglobulins, hepatitis panel, human immunodeficiency virus testing, and rheumatoid factor, was negative or non‑reactive. Renal biopsy demonstrated immunoglobulin A-dominant glomerulonephritis with mesangial hypercellularity and crescent formation. Skin biopsy demonstrated leukocytoclastic vasculitis. Culture obtained from the prosthetic hip abscess grew methicillin‑sensitive Staphylococcus aureus. These findings support a diagnosis of suspected infection‑associated IgAV occurring in the setting of chronic prosthetic joint infection. This case highlights the importance of recognizing chronic infections as potential triggers of immunoglobulin A-mediated vasculitic disease in adults and emphasizes the need to differentiate systemic IgAV from infection‑associated immunoglobulin A-dominant glomerulonephritis.

Immune-mediated glomerulonephritis represents a diverse group of kidney disorders caused by dysregulated immune responses and constitutes a major contributor to chronic kidney disease. Its pathogenesis can be conceptualized as a three-step cascade: aberrant activation of innate immunity through pattern-recognition receptors, inflammasome complexes, and complement pathways; adaptive immune dysregulation characterized by imbalanced B- and T-cell responses and the production of pathogenic autoantibodies; and terminal effector injury involving complement-mediated damage and progressive fibrosis. This narrative review summarizes current advances in anti-inflammatory biologics that intervene at these critical points across a broad spectrum of entities, including IgA nephropathy (IgAN), membranous nephropathy (MN), lupus nephritis (LN), focal segmental glomerulosclerosis (FSGS), minimal change nephropathy (MCN), anti-glomerular basement membrane (anti-GBM) disease, ANCA-associated vasculitis (AAV), and C3 glomerulopathy (C3G). Therapies including cytokine inhibitors targeting TNF-α or IL-6, B-cell-depleting antibodies such as anti-CD20, plasma cell-directed agents, and complement blockers against C5 or Factor B have demonstrated clinical benefits in IgAN, MN, and LN, where evidence from randomized controlled trials supports their efficacy in reducing proteinuria and preserving renal function. For other entities such as FSGS, MCN, anti-GBM disease, and C3G, the evidence remains preliminary, based largely on case reports, preclinical models, or early-phase trials. Despite therapeutic advances, challenges persist regarding efficacy variability, infection risks, and financial burden. Future research aims to achieve precision therapy through multi-omics-based stratification, next-generation biologics such as bispecific antibodies and gene therapies, and optimized drug delivery systems, steering immune-mediated glomerulonephritis management toward truly disease-modifying treatment.

Anti-glomerular basement membrane antibody (anti-GBM) disease is a rare yet aggressive autoimmune disorder that affects the kidneys and lungs. Patients with renal involvement often progressed to death or end-stage renal disease. Treatment with plasmapheresis, along with cyclophosphamide and corticosteroids, has been suggested to improve renal and patient survival; however, it showed little benefit in patients who presented with severe disease. We herein report a critically ill case with anuria, creatinine value of 752 μmol/L, anti-GBM antibody titer of 92.54 RU/mL, and 96.7% fibro-cellular crescent formation at renal biopsy. The patient was diagnosed with anti-GBM disease and treated with plasmapheresis and immunosuppressive therapy. Plasmapheresis was not ceased until the total clearance of pathogenic autoantibodies. The patient's renal function was successfully rescued and maintained normal during the 5-year follow-up. Our experience implicated that early and persistent plasmapheresis could rescue the kidney function of anti-GBM patients who have extremely poor prognosis.

We examined a kidney biopsy from an 83-year-old woman with rapidly progressive renal failure who tested positive for anti-GBM antibody, MPO-ANCA, and PR3-ANCA. Of the 50 obtained glomeruli, 40 showed acute-phase necrotizing glomerulitis with fibrin deposition. Five glomeruli showed fibrocellular crescent formation, and the remaining five showed chronic changes with global sclerosis. Very small necrotizing vasculitis was observed in the small arteries. Widespread tubulointerstitial nephritis was observed. The high incidence of acute-phase lesions in this case can be explained by anti-GBM glomerulonephritis. However, the coexistence of the latter chronic lesions suggests the involvement of MPO- and PR3-ANCA-associated vasculitis. After steroid pulse therapy followed by the tapering oral prednisolone, hemodialysis was initiated, and the serologic remission of anti-GBM antibodies and ANCAs was achieved without additional immunosuppression. However, febrile relapse with a re-elevation of anti-GBM antibody and myeloperoxidase-ANCA levels occurred 18 months after steroid discontinuation and she promptly responded to reintroduction of low-dose prednisolone, with no further recurrence. Together with the biopsy findings of acute anti-GBM-type necrotizing glomerulitis superimposed on lesions suggestive of ANCA-associated vasculitis, this course supports overlapping pathogenic mechanisms in triple-seropositive disease and underscores the need for long-term clinical and serologic follow-up even after apparent remission.

A therapeutic antibody, CSL305, has been developed, which combines inhibition of the complement classical and lectin pathways via complement C2 binding with an ability to act as an antagonist of the neonatal Fc receptor (FcRn). CSL305 binds to human C2 (huC2) but shows no binding or activity against mouse C2 precluding its use in mouse models of disease to fully assess in vivo efficacy. To circumvent this, a mouse strain was developed that replaced the expression of mouse C2 with huC2 by homologous recombination. These mice (huC2 "knock-in"; KI) were shown to express huC2 protein and to have complement activity. Interestingly, male huC2-KI mice showed much stronger complement activity compared to female mice and were also sensitive to inhibition by CSL305. Two models of disease using male huC2-KI mice were then used to assess the in vivo efficacy of CSL305. The first was an attenuated passive anti-glomerular basement membrane (GBM) glomerulonephritis model involving complement activation as its primary mechanism of action. CSL305 showed dose-dependent inhibition of disease as measured by urine albumin, with reductions in kidney cellular infiltration and plasma C3 cleaved fragments C3b/C3c/iC3b also observed. The second model was a collagen autoantibody-induced arthritis (CAIA) mouse model. Here, CSL305 showed a significant and dose-dependent inhibition of clinical score in both prophylactic and therapeutic settings, mediated exclusively via its FcRn mechanism of action. Although the animal models used in this study were found to preclude the demonstration of a synergistic effect on both mechanisms, CSL305 does act in vivo as both a complement inhibitor and as a FcRn antagonist to ameliorate disease.

Anti-glomerular basement membrane (GBM) disease is a rare autoimmune disorder characterized by circulating anti-GBM antibodies, rapidly progressive glomerulonephritis, and linear immunoglobulin G (IgG) deposition along the GBM. In contrast, atypical anti-GBM disease presents with an indolent course, absence of detectable antibodies, and variable histologic features. We report a 24-year-old male who presented with severe kidney failure (serum creatinine 17 mg/dL) and no pulmonary symptoms. Serologic tests for anti-GBM, ANCA, and ANA were negative, and complement levels were normal. Kidney biopsy revealed crescentic glomerulonephritis with 55% cellular crescents and linear polytypic IgG and C3 staining along the GBM. The patient was treated with hemodialysis, high-dose corticosteroids, cyclophosphamide, and plasma exchange according to standard anti-GBM protocols. Antibody titers remained undetectable throughout therapy. Despite aggressive treatment, kidney function did not recover, leaving the patient dialysis-dependent. This case represents an atypical manifestation of atypical anti-GBM disease, mimicking the severe phenotype of the classic form but lacking serologic confirmation. It highlights the diagnostic uncertainty and therapeutic challenges in seronegative presentations, in which antibody titers cannot guide treatment or transplantation decisions. Such cases may be more accurately described as crescentic glomerulonephritis with linear IgG staining, reflecting their overlap with classic anti-GBM disease.

Anti-glomerular basement membrane (anti-GBM) disease during pregnancy is rare and often life-threatening. We report a G4P1 woman who developed atypical anti-GBM disease at 13 weeks of gestation. Serial kidney biopsies demonstrated a reduction in active necrotizing lesions from 64.3% to 30.8% following early intensive immunosuppression and pregnancy termination. Western blot identified circulating autoantibodies against type IV collagen α1/α3 chains and laminin-521 (LM-521)-a novel finding in anti-GBM disease during pregnancy. Multidisciplinary management, including plasma exchange, high-dose methylprednisolone, hemodialysis, pregnancy termination, and obinutuzumab for serologic recurrence, enabled discontinuation of dialysis and partial renal recovery with stable kidney function. This case provides histological evidence, through sequential kidney biopsies, that early intensive immunotherapy combined with pregnancy termination can halt active necrotizing lesions and facilitate tissue repair. It also examines the potential association between specific autoantibody subtypes (anti-α1/α3 chains and LM521) and disease phenotypes, offering new insights into anti-GBM disease during pregnancy.

This narrative review examines acute and chronic kidney injury following COVID-19 infection and vaccination, discussing the mechanism of SARS-CoV-2 entry into host cells through the ACE2 receptor - highly expressed in renal tissues - facilitating the viral invasion. Viral RNA has been detected in the urine of patients infected with SARS-CoV-2, suggesting direct renal involvement. The incidence of Acute Kidney Injuriy (AKI) among hospitalized COVID-19 patients was particularly higher in the early stages of the pandemic and largely varied by 29%-46%, depending on population studied and COVID-19 wave. Pathological findings include Acute Tubular Injury (ATI), collapsing glomerulopathy, and focal segmental glomerulosclerosis. Major risk factors for AKI comprise older age, male sex, diabetes, hypertension, cardiovascular disease, and preexisting Chronic Kidney Disease (CKD). AKI significantly increases mortality of COVID-19 patients, particularly in advanced stages of renal failure. CKD is also associated with severe COVID-19 outcomes, including increased hospitalization, intensive care admission, and mortality. Patients with CKD show a dose-dependent relationship between disease stage and adverse patient outcomes. This review further addresses renal complications following COVID-19 vaccination, which, although rare, encompass various immune-mediated glomerular diseases. Minimal Change Disease (MCD) is most frequently reported after COVID-19 vaccination, followed by IgA nephropathy, membranous nephropathy, anti-glomerular basement membrane (anti-GBM) nephritis, and ANCA-associated vasculitis. These conditions commonly present with hematuria, proteinuria, or nephrotic syndrome, and many respond to corticosteroid or immunosuppressive therapy. Other less frequent renal complications include thrombotic microangiopathy, acute tubulointerstitial nephritis, and IgG4-related nephritis. In conclusion, both COVID-19 infection and vaccination can be associated with a spectrum of renal manifestations ranging from AKI to CKD and immune-mediated glomerulopathies. Awareness, early detection, and multidisciplinary management are essential to reduce renal morbidity and improve patient outcomes.

The non-collagenous domain 1 of the α3 chain of type IV collagen (α3(IV)NC1) is the primary autoantigen in anti-glomerular basement membrane (anti-GBM) disease. We previously developed a modified antigen-specific peptide, m-P14, derived from the nephritogenic epitope α3127-148, which ameliorated experimental anti-GBM nephritis. However, its short half-life limits clinical translation. This study evaluated a butyrate-conjugated derivative (m-P14-BA) to improve pharmacokinetic properties while preserving therapeutic efficacy. M-P14-BA and m-P14 were administered to α3127-148 immunized Wistar Kyoto rats in early and late treatment settings. Renal injury parameters and intrarenal inflammation were assessed, and pharmacokinetic profiles were evaluated following intraperitoneal administration in beagle dogs. M-P14-BA reduced proteinuria, crescent formation, glomerular IgG deposition, complement activation, and inflammatory cell infiltration, with overall efficacy comparable to m-P14 in early treatment settings. In late treatment settings, m-P14-BA was associated with a significant improvement in blood urea nitrogen levels and modest reductions in proteinuria and histopathological injury. Butyrate conjugation markedly improved pharmacokinetics, prolonging plasma elimination half-life by approximately 2.8-fold and increasing systemic exposure nearly fourfold. These pharmacokinetic improvements were associated with maintained therapeutic efficacy at a reduced dose, with 10 mg/kg m-P14-BA achieving effects broadly similar to those observed with 30 mg/kg m-P14. In summary, butyrate conjugation improves the pharmacokinetic profile of an antigen-specific therapeutic peptide while preserving therapeutic activity, suggesting a potential strategy to enhance the translational feasibility of peptide-based immunotherapy in anti-GBM disease.