Introduction

Autoimmune kidney diseases represent a significant subset of renal disorders, where the immune system mistakenly targets renal structures, leading to inflammation, tissue damage, and progressive loss of kidney function. Among them, lupus nephritis stands as the most extensively studied condition, being one of the severe organ manifestations of systemic lupus erythematosus (SLE). Lupus nephritis is characterized by immune complex deposition in the glomeruli, complement activation, and subsequent inflammatory injury that may lead to renal failure if not appropriately managed. It not only contributes substantially to morbidity and mortality in SLE patients but also poses a challenge in treatment due to its heterogeneity and variable response to therapy. Beyond lupus nephritis, other autoimmune kidney diseases such as anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, anti-Glomerular Basement Membrane (anti-GBM) disease, and IgA nephropathy involve complex immune dysregulation and distinct pathogenic pathways. Each of these diseases shares common features of immune-mediated injury but differs in clinical presentation, histopathology, and therapeutic strategies. Understanding lupus nephritis and related autoimmune nephropathies provides critical insight into the interplay between systemic immunity and renal health [1].

Description

Lupus nephritis exemplifies how systemic autoimmunity translates into severe renal involvement. Immune complexes formed by autoantibodies against nuclear antigens deposit in the glomeruli, triggering complement activation and recruitment of inflammatory cells. Histologically, lupus nephritis is classified into six classes by the International Society of Nephrology/Renal Pathology Society (ISN/RPS), ranging from minimal mesangial involvement (Class I) to advanced sclerosing disease (Class VI). Clinical manifestations may vary from asymptomatic hematuria and proteinuria to nephrotic syndrome and rapidly progressive glomerulonephritis. Current management emphasizes early detection through urine analysis, renal biopsy, and biomarker assessment, as delayed diagnosis often results in irreversible damage. Treatment strategies rely on immunosuppressive agents such as corticosteroids, cyclophosphamide, and mycophenolate mofetil, while newer biologics like belimumab and rituximab target specific immune pathways. Despite advancements, treatment response is often incomplete, highlighting the need for novel therapies that address both inflammation and long-term preservation of renal function [2].

ANCA-Associated Vasculitis (AAV) represents another major autoimmune kidney disease, characterized by small vessel inflammation mediated by antibodies against neutrophil cytoplasmic antigens, most commonly proteinase 3 (PR3) and Myeloperoxidase (MPO). Renal involvement in AAV typically manifests as pauci-immune crescentic glomerulonephritis, often leading to rapidly progressive renal failure. AAV is clinically diverse, encompassing granulomatosis with polyangiitis, microscopic polyangiitis, and eosinophilic granulomatosis with polyangiitis. Treatment involves induction of remission using glucocorticoids and cyclophosphamide or rituximab, followed by maintenance therapy with azathioprine or methotrexate. Relapse remains a major challenge, and ongoing research explores targeted therapies against complement factor C5a and B-cell pathways. The integration of biomarkers, such as ANCA titers and urinary chemokines, holds promise for guiding individualized treatment and predicting disease activity [3].

Anti-glomerular basement membrane (anti-GBM) disease, also known as Goodpastureâ??s disease, is a rare but aggressive autoimmune kidney disorder characterized by autoantibodies directed against type IV collagen in the glomerular and alveolar basement membranes. Clinically, it often presents with a combination of rapidly progressive glomerulonephritis and pulmonary hemorrhage, forming the classic Goodpastureâ??s syndrome. Pathologically, linear deposition of IgG along the glomerular basement membrane is the hallmark finding. Due to its fulminant course, rapid diagnosis is essential, typically achieved through serological testing and kidney biopsy. Despite advances in therapy, outcomes remain poor if treatment is delayed, underscoring the need for heightened clinical awareness. Emerging research is examining the role of complement activation and genetic susceptibility in disease pathogenesis, which may inform future therapeutic targets [4].

IgA nephropathy, while traditionally classified as a primary glomerulonephritis, also demonstrates features of autoimmune dysregulation. It is caused by abnormal glycosylation of IgA1 molecules, leading to the formation of pathogenic immune complexes that deposit in the mesangium and incite inflammation. Clinically, IgA nephropathy presents with recurrent episodes of hematuria, often following upper respiratory infections, and can progress to chronic kidney disease over time. Unlike lupus nephritis and AAV, IgA nephropathy often follows a slower course, though risk factors such as proteinuria, hypertension, and male gender accelerate progression. Management strategies emphasize supportive care with reninâ??angiotensin system inhibitors to reduce proteinuria and blood pressure, while immunosuppression is reserved for high-risk patients. Recently, targeted therapies such as corticosteroid-sparing regimens, B-cell inhibitors, and agents modulating mucosal immunity have shown promise in clinical trials. The growing understanding of its autoimmune underpinnings blurs the distinction between primary and secondary nephropathies, placing IgA nephropathy within the broader spectrum of autoimmune renal diseases [5].

Conclusion

Autoimmune kidney diseases, with lupus nephritis as a central example, highlight the complex interplay between systemic immunity and renal pathology. While these conditions share a common foundation of immune-mediated injury, they differ significantly in mechanisms, presentation, and therapeutic approaches. Advances in immunology and molecular medicine are reshaping our ability to diagnose and treat these diseases, offering hope for precision-based interventions that reduce relapses and preserve renal function. Despite progress, challenges remain in achieving sustained remission and preventing long-term kidney damage. Continued research into novel biomarkers, immune-modulating therapies, and patient-specific treatment strategies is essential for improving outcomes in lupus nephritis and beyond.

Acknowledgment

None.

Conflict of Interest

None

References

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