Signs and Symptoms of IgA Nephropathy

EP: 1.Advancing IgA Nephropathy Care: Emerging Therapies, Unmet Needs, and Economic Considerations

EP: 2.Introduction to IgA Nephropathy

EP: 3.Pathogenesis of IgA Nephropathy: The 4-Hit Cascade, A Proliferation-Inducing Ligand (APRIL), and cytokines

EP: 4.Diagnosing IgA Nephropathy

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EP: 5.Signs and Symptoms of IgA Nephropathy

EP: 6.Challenges in Timely Identification of IgA Nephropathy

EP: 7.Clinical Impact of IgA Nephropathy and Quality of Life

EP: 8.Overview of Treatment Landscape for IgA Nephropathy: Standard of Care and KDIGO Guidelines

EP: 9.Current Treatments for IgA Nephropathy and the 4-Hit Cascade

EP: 10.Gaps in Patient Care for IgA Nephropathy

EP: 11.Emerging Anti-BAFF and Anti-APRIL Therapies

EP: 12.Emerging Therapies: Other Strategies and Important Considerations

EP: 13.The Promise of Emerging Therapies for IgA Nephropathy and Future KDIGO Guidelines

EP: 14.Sequencing and Individualizing Treatments for IgA Nephropathy

EP: 15.Measuring Success in IgA Nephropathy in Clinical Practice

EP: 16.Economic Impact of IgA Nephropathy for Patients

EP: 17.Early Diagnosis and Cost Mitigation in IgA Nephropathy

EP: 18.Cost Implications of Modulating IgA Nephropathy Disease Course

EP: 19.Patient-Reported Outcomes in the Treatment of IgA Nephropathy

EP: 20.Future Possibilities for Step Therapy in IgA Nephropathy Treatment

EP: 21.Key Managed Care Considerations for IgA Nephropathy Treatment

EP: 22.Key Economic Considerations in IgA Nephropathy: Progression to Chronic Kidney Disease

EP: 23.Closing Thoughts About IgA Nephropathy Treatment

Clinical Presentation and Diagnostic Challenges in IgA Nephropathy

Common Presenting Signs and Symptoms

IgA nephropathy (IgAN) should be considered in patients presenting with the following:

• Microscopic hematuria: The most common finding, often persistent and may be discovered incidentally
• Episodic gross hematuria: Frequently coincides with mucosal infections, particularly upper respiratory tract infections (“synpharyngitic hematuria”)
• Proteinuria: Ranging from mild (< 1g/day) to nephrotic-range (> 3.5g/day)
• Hypertension: Present in 30%-40% of patients at diagnosis
• Acute kidney injury: May occur during episodes of gross hematuria
• Nephrotic syndrome: Less common but possible in 5%-10% of cases
• Recurrent macroscopic hematuria: Often triggered by intercurrent illnesses, physical exertion, or alcohol consumption
• Flank pain: Occasionally reported during episodes of gross hematuria

IgAN should be particularly considered in the following:

• Young adults (peak onset 20-30 years)
• Males (male:female ratio ~2:1)
• Asian and Caucasian populations (higher prevalence)
• Patients with family history of hematuria or kidney disease

Primary Diagnostic Challenges

1. Clinical heterogeneity: Presentation ranges from asymptomatic urinary abnormalities to rapidly progressive glomerulonephritis
2. Requirement for kidney biopsy: Definitive diagnosis requires invasive biopsy, which may be delayed or avoided in mild cases
3. Overlap with other glomerular diseases: Similar presentation to other forms of glomerulonephritis, including thin basement membrane nephropathy, Alport syndrome, and other immune complex-mediated glomerulonephritides
4. Timing of biopsy: Determining when urinary abnormalities warrant biopsy, especially in asymptomatic patients with isolated microscopic hematuria
5. Distinguishing primary IgAN from secondary forms: Associated with liver disease, inflammatory bowel disease, celiac disease, and various autoimmune conditions
6. Risk stratification: Identifying patients at high risk for progression vs those with benign disease course
7. Absence of specific biomarkers: No pathognomonic serological markers for noninvasive diagnosis
8. Variable natural history: Unpredictable disease trajectory, from spontaneous remission to progressive renal failure
9. Geographic and demographic variations: Different prevalence and phenotypes based on ethnicity and region, affecting pretest probability
10. Misdiagnosis during gross hematuria episodes: May be attributed to urinary tract infection or nephrolithiasis, delaying correct diagnosis

Renal biopsy remains the gold standard for diagnosis, with the pathognomonic finding of predominant or codominant mesangial IgA deposits on immunofluorescence.