IgA nephropathy, also known as Berger’s disease, is one of the most common forms of glomerulonephritis. It occurs when Immunoglobulin A (IgA) deposits build up in the glomeruli—small filtering units in the kidneys—causing inflammation that can impair kidney function over time.

While some individuals may experience slow progression with minimal complications, others may face rapid deterioration of kidney health, leading to end-stage renal disease (ESRD). Understanding the risk factors that influence disease progression is crucial in managing IgA nephropathy effectively.

Proteinuria: A Key Indicator

Proteinuria, or the presence of excess protein in the urine, is one of the most significant predictors of disease progression in IgA nephropathy. Persistent proteinuria exceeding 1 gram per day is associated with a higher risk of kidney function decline. Protein leakage reflects underlying glomerular damage and ongoing inflammation, which accelerates renal scarring and leads to chronic kidney disease (CKD). Regular monitoring and control of proteinuria are essential to slow disease progression.

Hypertension and Its Impact

High blood pressure is another well-established risk factor for the worsening of IgA nephropathy. Hypertension exacerbates glomerular injury by increasing the pressure inside kidney filters, thereby accelerating damage. Patients with uncontrolled blood pressure are more likely to experience faster declines in their glomerular filtration rate (GFR), ultimately progressing to renal failure. Antihypertensive medications, particularly angiotensin-converting enzyme inhibitors (ACE inhibitors) or angiotensin receptor blockers (ARBs), are often prescribed to reduce blood pressure and control proteinuria simultaneously.

Reduced Kidney Function at Diagnosis

Initial kidney function, measured by the estimated glomerular filtration rate (eGFR), plays a pivotal role in determining disease outlook. Patients diagnosed with a low eGFR are at a higher risk of reaching ESRD. A reduced eGFR signifies advanced kidney damage already present at diagnosis, which limits the potential for recovery and response to treatment. Early detection, therefore, becomes essential for a more favorable long-term prognosis.

Renal Biopsy Findings

Renal biopsy results offer detailed insights into the extent of kidney damage. The Oxford Classification is a widely used histopathologic scoring system that evaluates features such as mesangial hypercellularity, endocapillary proliferation, segmental sclerosis, and tubular atrophy. Certain patterns—especially tubular atrophy and interstitial fibrosis—are strongly associated with disease progression. These findings help clinicians tailor treatment strategies based on individual risk profiles.

Episodes of Gross Hematuria

Whilemicroscopic hematuria is a hallmark of IgA nephropathy, recurrent episodes of gross hematuria, especially following respiratory infections, may also influence disease progression. Although not always directly correlated with worsening function, frequent visible blood in the urine suggests active glomerular inflammation. Over time, this can contribute to cumulative kidney damage.

Male Gender and Age

Several observational studies have identified male gender and older age at diagnosis as potential risk factors for more aggressive disease progression. Men tend to show higher levels of proteinuria and reduced renal survival compared to women. Age-related renal changes may also compound the impact of IgA deposits, making timely intervention more critical in older patients.

Smoking and Lifestyle Factors

Lifestyle choices such as smoking can significantly impact the course of IgA nephropathy. Smoking promotes vascular damage and inflammation, both of which can accelerate kidney injury. Obesity and poor dietary habits may also contribute to metabolic syndrome, hypertension, and worsening proteinuria. Adopting a kidney-friendly lifestyle—including regular physical activity, weight management, and a low-sodium, balanced diet—can support better long-term kidney health.

Genetic and Immune System Factors

Emerging research suggests that genetic predisposition and immune system irregularities may influence both the onset and progression of IgA nephropathy. Mutations affecting the glycosylation of IgA1 molecules are believed to contribute to immune complex formation and glomerular deposition. Additionally, abnormal immune responses to mucosal infections, especially in the respiratory and gastrointestinal tracts, are implicated in disease activity.

Managing Risk to Slow Progression

Effective management of IgA nephropathy involves identifying and modifying risk factors early in the disease course. Key strategies include controlling blood pressure, reducing proteinuria, maintaining a healthy lifestyle, and monitoring kidney function regularly. Immunosuppressive therapy may be considered in patients with rapidly deteriorating kidney function or persistent proteinuria despite optimal supportive care. However, treatment must be individualized based on clinical and histologic assessment.

Conclusion

IgA nephropathy is a complex disease with variable outcomes. While some individuals experience stable kidney function over decades, others face significant risk of progression to chronic kidney disease or renal failure. By understanding the risk factors—such as proteinuria, hypertension, initial kidney function, histological damage, and lifestyle choices—patients and healthcare providers can work together to create effective management plans. Early intervention remains the cornerstone of preventing disease advancement and preserving long-term renal health.