Understanding Risk Factors That Influence IgA Nephropathy Progression

IgA nephropathy, also known as Berger’s disease, is a chronic autoimmune kidney condition that often begins with blood in the urine but can silently progress to end-stage renal disease (ESRD). Identifying the risk factors for progression of IgA nephropathy is critical for managing outcomes, guiding treatment, and making decisions about long-term monitoring.

This article examines the clinical, pathological, and biochemical markers that predict a faster decline in kidney function among individuals with this condition.


Why Some Cases Progress and Others Don’t

IgA nephropathy has a highly variable clinical course. While some individuals live symptom-free for decades, others may experience a rapid progression toward chronic kidney disease (CKD) or even kidney failure.

Progression is influenced by a complex interplay of immune activity, genetic susceptibility, proteinuria, blood pressure control, and histologic damage seen on biopsy.


Key Risk Factors for Disease Progression

1. Persistent Proteinuria

Persistent proteinuria—especially levels above 1 gram/day—is the strongest predictor of poor long-term kidney outcomes. Even in patients with relatively preserved kidney function, high levels of urinary protein indicate active glomerular injury.

Lowering proteinuria through medication (e.g., ACE inhibitors or ARBs) is a core goal of management.

2. Hypertension

Elevated blood pressure, particularly uncontrolled or masked hypertension, accelerates kidney damage. Patients with systolic pressure >140 mmHg are at significantly higher risk for glomerular sclerosis and declining glomerular filtration rate (GFR).

3. Impaired Kidney Function at Diagnosis

An eGFR <60 ml/min/1.73m² at the time of diagnosis is associated with a higher risk of disease progression. Reduced kidney function suggests long-standing injury, even if symptoms were recently discovered.

4. Histologic Findings (Oxford Classification)

The Oxford MEST-C scoring system provides valuable insight into histologic damage and prognosis. Key components include:



  • M: Mesangial hypercellularity




  • E: Endocapillary hypercellularity




  • S: Segmental glomerulosclerosis




  • T: Tubular atrophy/interstitial fibrosis




  • C: Presence of crescents



Patients with segmental sclerosis (S1), tubular atrophy (T1/T2), or crescents (C1/C2) have agreater likelihood of progressive renal decline.

5. Male Sex

Several cohort studies have identified male gender as an independent risk factor for faster progression of IgA nephropathy, particularly in adult-onset cases. This may be due to hormonal influences or differences in immune regulation.

6. Age of Onset

Older age at diagnosis is associated with more rapid progression. While children and young adults often have a milder course, those diagnosed after age 40 tend to experience faster functional loss, even with less overt symptoms.

7. Recurrent Episodes of Macroscopic Hematuria

Frequent visible blood in the urine, especially following infections, can signal active disease flares that contribute to glomerular inflammation and injury over time.

8. Elevated Serum Creatinine and Low GFR

A steady rise in serum creatinine over time, even if mild, is a key marker of progression. A declining GFR trajectory—especially when accompanied by proteinuria—is a poor prognostic sign.


Additional Potential Risk Factors



  • High BMI or metabolic syndrome




  • Smoking and ongoing exposure to nephrotoxins




  • Delay in treatment initiation




  • Complement activation, especially elevated C3 or circulating immune complexes



Emerging biomarkers and genetic profiling may soon help predict which patients are more likely to progress to ESRD.


Slowing Disease Progression

Managing these risk factors can significantly delay or prevent kidney failure:



  • Blood pressure control (target <130/80 mmHg)




  • Proteinuria reduction with ACE inhibitors/ARBs




  • Immunosuppressive therapy in select cases (e.g., corticosteroids)




  • Dietary adjustments (low sodium, moderate protein intake)




  • Regular nephrology follow-up



Clinical trials are also exploring targeted therapies that inhibit immune pathways or prevent glomerular scarring.


Final Thoughts

Understanding the risk factors for progression of IgA nephropathy is essential for both patients and clinicians. While the course of this disease can be unpredictable, identifying early warning signs—like persistent proteinuria, high blood pressure, or specific biopsy features—can guide timely intervention.

Early action and individualized treatment may prevent the need for dialysis or transplantation in many patients living with IgA nephropathy.