What is IgA (Immunoglobulin A) nephropathy?

From the Guidelines

IgA (Immunoglobulin A) nephropathy is a kidney disease characterized by the deposition of IgA antibodies in the glomeruli, leading to inflammation and damage.

Key Characteristics

• Can only be diagnosed with a kidney biopsy 1
• Determined by the MEST-C score (mesangial and endocapillary hypercellularity, segmental sclerosis, interstitial fibrosis/tubular atrophy, and crescents) according to the revised Oxford Classification 1
• No validated diagnostic serum or urine biomarkers for IgAN 1

Management

• Primary focus of IgAN management should be multifaceted, optimized supportive care, including RAS blockade, blood pressure control, cardiovascular risk minimization, adherence to lifestyle advice, and dietary counseling 1
• RAS blockade should be instituted irrespective of hypertension if the patient has proteinuria >0.5 g/d 1
• Glucocorticoid therapy may be considered for patients with high-risk features, but its use is based on relatively weak evidence and should be given with extreme caution or avoided entirely in patients with certain conditions (e.g., eGFR <30 ml/min per 1.73 m2, diabetes, obesity) 1

Treatment Targets

• Proteinuria reduction to under 1 g/d is a surrogate marker of improved kidney outcome in IgAN, and hence a reasonable treatment target 1
• New therapies for high-risk IgAN patients are currently being evaluated, including drugs that may augment the supportive care approach (e.g., SGLT2 inhibitors, sparsentan, atrasentan, hydroxychloroquine) or more specific approaches (e.g., enteric-coated budesonide, various complement inhibitors, therapies targeting B-cell development) 1

From the Research

Definition and Characteristics of IgA Nephropathy

• IgA nephropathy (IgAN) is considered an autoimmune disease characterized by the formation of IgA1-containing immune complexes in the circulation and glomerular immunodeposits 2.
• It is the most common form of primary glomerulonephritis, with clinical associations with a wide range of inflammatory and infectious diseases 3.
• The pathogenesis of IgAN is a multifactorial process involving the formation of immune complexes wherein aberrantly O-glycosylated IgA1 is recognized as an autoantigen 2.

Clinical Presentation and Prognosis

• The clinical presentation of IgAN is highly variable, with a wide spectrum of manifestations ranging from isolated microscopic hematuria or episodic macroscopic hematuria to nephrotic-range proteinuria 2.
• The exact prognosis of the individual IgAN course is often difficult to predict, with approximately one third of patients experiencing a stable benign course, and approximately 30% developing end-stage renal disease 4.
• Risk factors for disease progression include persistent microhematuria and proteinuria >1 g/day, arterial hypertension, and the extent of tubulointerstitial fibrosis at the time of diagnosis 4.

Pathogenesis and Treatment

• The pathogenesis of IgAN involves a "multi-hit" process, including an initial traumatic trigger and subsequent memory responses that are amplified in those with a genetic predisposition to the disease 3.
• Treatment options are currently limited, but new therapies are emerging that target different pathways, cells, and mediators involved in the disease pathogenesis, including B cell priming in the gut mucosa, cytokines, plasma cells, complement activation, and endothelin pathway activation 5.
• Intensive supportive care should be initiated as first-line treatment, and rare cases with progressive features may require treatment with corticosteroids 4.
• Future approaches may include the use of local budesonide or the inhibition of lymphocyte activation 4.