Prognosis of IgA Nephropathy
IgA nephropathy has a highly variable but generally poor prognosis, with approximately 10-20% of patients progressing to end-stage renal disease within 10 years, and up to 50% reaching kidney failure or death within their lifetime if inadequately treated. 1, 2
Overall Disease Trajectory
The median kidney survival is approximately 11.4 years from diagnosis, with most patients progressing to kidney failure within 10-15 years and reaching kidney failure at a mean age of 48 years. 2 This underscores that IgA nephropathy is not a benign condition—based on eGFR and age at diagnosis, almost all patients are at risk of progression to kidney failure within their expected lifetime unless the rate of eGFR loss is maintained at ≤1 ml/min per 1.73 m² per year. 2
Clinical Risk Factors for Poor Prognosis
The prognosis depends critically on several clinical parameters that must be assessed at diagnosis and monitored during follow-up:
Proteinuria as the Primary Prognostic Marker
Proteinuria is the single most important clinical predictor of outcome in IgA nephropathy, with a much lower threshold for risk than other glomerular diseases. 3, 4
- Persistent proteinuria >1 g/day is associated with significant risk of GFR loss and progression to kidney failure. 3, 4
- Patients with proteinuria >3 g/day (heavy range) have only 69% renal survival at 5 years, compared to 87% for moderate proteinuria (1-2.9 g/day) and 100% for mild proteinuria (<1 g/day). 5
- Even patients traditionally considered "low risk" with proteinuria <0.88 g/g had approximately 20% progression to kidney failure within 10 years, and those with proteinuria 0.44-0.88 g/g had 30% progression. 2
- Time-averaged proteinuria is more predictive than single measurements—each 10% decrease in time-averaged proteinuria from baseline reduces the hazard ratio for kidney failure/death to 0.89. 2
- Reduction of proteinuria to <1 g/day is associated with favorable prognosis regardless of initial proteinuria level. 3
Blood Pressure and Hypertension
Uncontrolled hypertension is an independent predictor of adverse outcomes. 3, 4
- Hypertension at diagnosis is one of three key risk factors in the absolute renal risk (ARR) scoring system. 6
- Moderate or heavy proteinuria typically precedes the onset of hypertension and development of renal insufficiency. 5
- When hypertension control is achieved, the risk for death or dialysis is significantly reduced. 6
Baseline Kidney Function
Impaired GFR at presentation is associated with end-stage renal disease, though its association with rate of decline remains unclear. 3
- Lower GFR at presentation increases risk, but the relationship with progression rate is not definitively established. 3
- A 40% or greater decline in eGFR from baseline over 2-3 years indicates poor outcome. 7
Additional Metabolic Risk Factors
Hypertriglyceridemia and hyperuricemia at diagnosis are independent risk factors for progression that have been historically underestimated. 1
- These metabolic factors were significantly more common in patients with progressive versus stable disease. 1
- In patients with normal renal function at diagnosis, hypertriglyceridemia, hyperuricemia, hypertension, and proteinuria were all independent predictors in multivariate analysis. 1
Pathological Risk Factors
The Oxford MEST-C classification provides independent prognostic information beyond clinical parameters. 3, 7
The scoring system evaluates:
- M: Mesangial hypercellularity
- E: Endocapillary hypercellularity
- S: Segmental glomerulosclerosis
- T: Tubular atrophy/interstitial fibrosis
- C: Crescents
This pathologic scoring has been validated in independent pediatric and adult populations and adds statistically independent prognostic value. 3 However, the incremental clinical value beyond standard prognostic markers and its impact on therapeutic response selection remains unknown. 3
Absolute Renal Risk Stratification
A practical risk stratification system counts three risk factors present at diagnosis: hypertension, proteinuria ≥1 g/day, and severe pathologic lesions (global optical score ≥8). 6
The cumulative incidence of death or dialysis in adequately treated patients is:
- ARR = 0: 2% at 10 years, 4% at 20 years
- ARR = 1: 2% at 10 years, 9% at 20 years
- ARR = 2: 7% at 10 years, 18% at 20 years
- ARR = 3: 29% at 10 years, 64% at 20 years 6
Cardiovascular Risk
Sub-nephrotic-range proteinuria is a well-recognized risk factor for cardiovascular complications in IgA nephropathy, independent of renal function. 3, 8
- This cardiovascular risk exists even in patients with preserved eGFR and early disease stages. 8
- Any proteinuria >0.5 g/day warrants cardiovascular risk consideration and potential statin therapy. 8
Critical Caveats
- The ability to accurately predict individual patient-level risk currently is limited despite our understanding of these risk factors. 4
- Clinicians cannot fully account for outcome variability based on clinical features alone. 3
- Patients with persistently mild proteinuria at presentation rarely progress to higher levels, and serum creatinine never exceeded 2 mg/dl in this group. 5
- The threshold level of proteinuria that heralds risk is uncertain—most studies show 1 g/day, but some demonstrate 0.5 g/day as the threshold where risk begins to increase. 3