IgA nephropathy, also known as Berger's disease, is a kidney disorder characterized by the deposition of immunoglobulin A (IgA) in the glomeruli—the specialized filtering units of the kidneys. This condition often leads to inflammation, progressive kidney damage, and variable clinical outcomes. It is one of the most common primary glomerulonephritides worldwide and can range from asymptomatic urinary abnormalities to chronic kidney disease.

Causes and Risk Factors

IgA nephropathy is believed to arise from an abnormal immune response. Excessive or altered IgA molecules accumulate in the glomerular mesangium, triggering inflammation. Several factors may contribute to disease development and progression:

• Immune system dysfunction: Production of IgA with aberrant glycosylation leads to immune complex formation and glomerular deposition.


• Genetic influences: Family history appears to increase susceptibility, suggesting inherited predisposition.


• Environmental triggers: Mucosal infections—particularly of the respiratory or gastrointestinal tract—often coincide with flares.


• Other contributing factors: High blood pressure, obesity, and metabolic disorders may exacerbate kidney injury.

Clinical Presentation and Symptoms

Clinical manifestations of IgA nephropathy vary widely:

• Hematuria: Blood in the urine is the most common sign. It may appear as dark or pink urine after an infection (gross hematuria) or be detected only microscopically (microscopic hematuria).


• Proteinuria: Leakage of protein appears as foamy urine. Persistent proteinuria may indicate ongoing glomerular damage.


• High blood pressure: Common in many patients, particularly in advanced stages.


• Edema: Swelling in the hands, feet, or around the eyes may occur when protein loss is significant.


• Renal function decline: Measured by increasing serum creatinine or decreasing estimated glomerular filtration rate (eGFR).

Diagnosis

Diagnosis includes clinical evaluation and laboratory investigations:

• Urinalysis: Detects red blood cells, protein, and casts.


• Blood tests: Assess kidney function via creatinine, eGFR, and measure proteinuria.


• Imaging studies: Ultrasound may be used to assess kidney structure and exclude other causes.


• Kidney biopsy: Definitive diagnosis is established by observing IgA deposits in glomeruli under immunofluorescence microscopy.

Clinical Course and Prognosis

IgA nephropathy has a variable course. While some individuals maintain stable kidney function with minor urinary findings, others experience progression to chronic kidney disease over years or decades. Risk indicators include:

• Persistent proteinuria greater than 1gram per day


• Reduced eGFR at time of diagnosis


• Frequent episodes of gross hematuria


• High blood pressure that is difficult to control

Early detection and intervention can slow progression, but the disease remains unpredictable and requires ongoing monitoring.

Treatment and Management Strategies

There is no cure for IgA nephropathy, but therapies aim to protect kidney function and reduce inflammation:

Supportive Treatments

• Blood pressure control: ACE inhibitors or ARBs are the first-line therapy, lowering both blood pressure and proteinuria.


• Proteinuria reduction: Dosing is adjusted to achieve optimal reduction of proteinuria, often guided by protein/creatinine ratio.


• Lifestyle measures: Dietary changes, weight control, and regular exercise support overall kidney health.

Immunosuppressive Therapies

• Corticosteroids: May be prescribed in patients with high-risk features or persistent proteinuria despite supportive care.


• Advanced immunomodulatory agents: Cyclophosphamide, mycophenolate mofetil, or calcineurin inhibitors may be considered in steroid-resistant cases.

Emerging and Adjunctive Options

• SGLT2 inhibitors: Initially used in diabetes, evidence suggests kidney-protective effects in patients with IgA nephropathy.


• Targeted therapies: Ongoing trials are investigating complement inhibitors and other agents to reduce inflammatory signaling in glomeruli.

Monitoring and Follow-Up

Regular follow-up is vital in managing IgA nephropathy:

• Urine tests: Monitor for proteinuria and hematuria every 3–6 months.


• Kidney function assessment: eGFR and serum creatinine every 3–6 months or more frequently if there is decline.


• Blood pressure monitoring: Self-monitoring combined with clinic measurements to ensure targets are met.


• Specialist referral: In cases of rapidly worsening function or heavy proteinuria, nephrology involvement is recommended.

Long-Term Outlook and Lifestyle Impact

With effective management, many individuals retain adequate kidney function for years. However, a subset will progress to end-stage kidney disease, requiring dialysis or transplantation. Lifestyle support, emotional care, and patient education are essential for maintaining adherence to treatment and monitoring plans.

Conclusion

IgA nephropathy is a complex and variable kidney condition. Early identification, close monitoring, and a balanced management plan that combines blood pressure control, proteinuria reduction, and targeted therapies offer the best chance of preserving kidney health. Regular follow-up with healthcare providers and timely adjustment of therapy are key. Although a cure remains elusive, proactive care can significantly improve long-term outcomes and quality of life.