In IgAN:
Each incremental gram per day above 1g results in a 10- to 25-fold faster rate of decline in kidney function and survival6
PROTEINURIA IS A
KEY FEATURE OF GLOMERULAR DISEASE1–4
Risk factor:
Proteinuria is a major RISK FACTOR for glomerular disease, if left unchecked it can lead to end-stage kidney disease (ESKD), dialysis, and even death2–6
Predictor:
Proteinuria is the single strongest modifiable PREDICTOR of the rate of kidney function decline in glomerular diseases such as IgA nephropathy (IgAN)1,2,5,6
Glomerular diseases:
Glomerular diseases such as IgAN are characterized by high levels of proteinuria6
Proteinuria is a key factor in the progression of IgAN
Proteinuria contributes to disease progression1,4,5,7
Proteinuria is primarily associated with a progressive loss of kidney function leading to kidney failure.5,9 The pathophysiologic link between proteinuria and progressively declining kidney function is complex, however there is evidence to suggest that tubular epithelial cells play a central role4
This effect of proteinuria in disease progression occurs through various processes:1,4,5,7,8
Induction of tubular chemokine expression and complement activation, leading to inflammatory interstitial cell infiltration and sustained fibrogenesis1,4,5,7,8
Activated angiotensin II (ANG II) produces vasoactive, inflammatory, and profibrotic cytokines, including the vasoconstrictor, endothelin-1
(ET-1)4,7,8
Disease progression is accelerated by a cycle of inflammation and activated tubular response, leading to tubular damage/apoptosis, podocyte damage, and ultimately interstitial fibrosis4,8
Proteinuria is a key marker of prognosis and disease severity in IgAN2,5,9,10
Proteinuria and reduced estimated glomerular filtration rate (eGFR) are joint contributors to glomerular disease progression2,5
Kidney function in IgAN
High proteinuria and declining eGFR are associated with an increased risk of disease progression in IgAN2,3
Slower decline in kidney function
Higher proteinuria levels are associated with a faster decline in eGFR;3,5 conversely, patients within normal proteinuria levels show a slower decline in eGFR2
Increased proteinuria was a stronger predictor of disease progression than a reduced eGFR2
Target proteinuria to slow progression to kidney failure
Reducing proteinuria is associated with improved patient outcomes1,4–6,10–16
Proteinuria is a modifiable risk factor: the more it is reduced, the greater the protective effect against decline in kidney function to ESKD1,4–6,10–16
In patients with IgAN (N=81):
delay in the median time to kidney failure14
In IgAN, 30% reduction in proteinuria is estimated to reduce risk for ESKD by 50%, which is consequently estimated to increase the median time to ESKD. The median time to ESKD or eGFR <15mL/min/1.73m2 was extended in this model from 12.4 years to 23.1 years14
