Due to the lack of early symptoms, most patients with IgA nephropathy (IgAN) already have significant chronic kidney disease (CKD) at time of diagnosis.1

IgAN is the most common primary glomerulonephritis worldwide and is characterized by a progressive decline in kidney function, high rates of kidney failure leading to dialysis or transplant, and increased risk of early death.1,2

Stage 3 or higher CKD at diagnosis

in a retrospective cohort study of US patients,3 suggesting that they had already accumulated significant kidney damage.

Although IgAN can affect patients at any age, it is most commonly diagnosed among adults in their 20s and
30s.4 A kidney biopsy is required for a definitive IgAN diagnosis, leading to the possibility of underdiagnosis or
diagnostic delay, particularly in regions with limited access to biopsy.1,5

Learn how IgAN is diagnosed from Dr. Geetha,
Nephrologist, Johns Hopkins University School
of Medicine, USA

The mortality rate of patients with moderate- or high-risk IgAN was twice that of the general population in a large cohort study (N=665)*,6

  • A Norwegian cohort study in patients with IgAN (N=633), diagnosed between 1988 and 2004, compared the mortality rate by calculating the standardized mortality ratio (SMR; defined as the ratio between observed and expected numbers of deaths). The study showed that SMR did not
    increase in low-risk patients, while it significantly increased in moderate- and high-risk patients to 1.5 and 3.1, respectively.6

Kidney damage can progress over time and is often irreversible.1

IgAN disease progression

IgAN has a variable disease progression, ranging from asymptomatic
nonprogressive
to aggressive.5
However, nearly all patients with IgAN are at significant risk of developing
kidney failure within
their lifetime.7

Kaplan-Meier survival curve of time to kidney failure or death event in adult patients with IgAN

This data could suggest patients may require dialysis or transplant at a relatively young age.

of adult patients
develop kidney failure within
20 years of diagnosis7

Patients with IgAN have a high lifetime risk of kidney failure
unless eGFR decline can be minimized.

Graph depicting the percentage of patients who will reach kidney failure during life expectancy based on their eGFR at diagnosis

In patients aged 18 to 40 (the age
group when IgAN is commonly
diagnosed), almost all (80%–100%)
patients with annual eGFR decline
of 2–5 mL/min/1.73 m2 will reach
kidney failure within their lifetime.7

Learn how IgAN affects kidney function from
Dr. Cheung, Consultant Nephrologist and Honorary
Associate Professor, University of Leicester & John
Walls Renal Unit, UK

Higher proteinuria levels associated with more rapid progression to kidney failure or death7

Kaplan-Meier survival curves of time to kidney failure/death event on the basis of time-averaged proteinuria
1

of patients with
“low-risk” proteinuria
progress to kidney
failure within 10 years
of diagnosis.7

2

of patients with
“moderate-risk”
proteinuria

progress to kidney
failure within 10 years
of diagnosis.7

3

of patients with
“high-risk” proteinuria
progress to kidney
failure within 10 years
of diagnosis.7

Supportive therapy — the current standard of care —
does not stop kidney function decline8

Current management of patients with IgAN includes supportive therapy and treatment of CKD symptoms, such as regulating blood pressure and reducing proteinuria. However, these therapies do not actively prevent the formation of harmful immune complexes and do not stop kidney function decline.8

While optimized supportive therapy, including sodium-glucose cotransporter-2 (SGLT2) inhibitors, is beneficial, patients may still experience progressive eGFR decline that will lead to kidney failure within their lifetime, underscoring the unmet need for disease-specific therapies in IgAN.8,9

 

Average eGFR over time in the IgAN subanalysis of
the Dapagliflozin and Prevention of Adverse Outcomes in CKD
(DAPA-CKD) study of dapagliflozin, an SGLT2 inhibitor*,9

Graph depicting the change over time in eGFR in patients treated with dapagliflozin or placebo
1

Average
eGFR decline
with DAPA

mL/min/year9

2

Average
eGFR decline
with placebo

mL/min/year9

Patients with IgAN who received standard of care with an SGLT2 inhibitor had an eGFR decline of 3.5 mL/min per year, the rate at which most patients under age 50 progress to kidney failure.7,9

While supportive care such as SGLT2 inhibitors may decrease the rate of eGFR decline, there is still a steady overall decline that leaves patients at risk of end-stage kidney disease (ESKD).7,9

The optimal goal of therapy is to minimize loss of eGFR
to lower the lifetime risk of kidney failure.7

Learn about current treatment options for patients
with IgAN from Dr. Geetha, Nephrologist, Johns
Hopkins University School of Medicine, USA

Click on each box to learn more

Illustration of the four disease markers in IgAN: Gd-IgA1, hematuria, proteinuria, and kidney function (eGFR)

Gd-IgA1 levels are elevated in patients with IgAN and correlate with disease severity.8,10,11

Patients with IgAN have increased serum levels of galactose-deficient IgA1 (Gd-IgA1)—a pathogenic form of IgA1—which has an alteration in the hinge region and acts as an autoantigen. Recognition of Gd-IgA1 by autoantibodies results in the formation of nephrogenic immune complexes.8,10 Circulating immune complexes contain predominantly polymeric Gd-IgA1.10 Both Gd-IgA1 and its autoantibodies are produced by B cells.8

High Gd-IgA1 levels are associated with a greater risk of kidney function deterioration, ESKD, and death11

Graph depicting kidney cumulative survival in patients with IgAN based on serum Gd-IgA1 levels

Serum Gd-IgA1 and IgA/IgG immune complex levels are correlated with proteinuria severity12

Graph depicting the correlation between severity of proteinuria and levels of serum Gd-IgA1 or IgA-IgG immune complexes

Learn more

Illustration of the four disease markers in IgAN: Gd-IgA1, hematuria, proteinuria, and kidney function (eGFR)

Hematuria is a common feature of IgAN, and may be associated with worse clinical outcomes13

Hematuria is a common clinical manifestation of IgAN, with more than 70% of patients developing microscopic hematuria.13

In IgAN, the deposition of immune complexes in the kidney induces the release of cytokines, chemokines, and complement activation, leading to inflammation. Local inflammation, in turn, causes glomerular capillary damage—which allows the passage of red blood cells into the urine—and the development of hematuria.8

Both the presence and persistence over time of hematuria are associated with higher rates of kidney function loss and kidney failure.14

Persistent microscopic hematuria was associated with a significant 87% increase in the risk of kidney failure in the long term.15

Although the current Kidney Disease Improving Global Outcomes (KDIGO) guidelines single out proteinuria as an independent risk factor for IgAN progression, several studies suggest hematuria as a potential predictor of progression to ESKD.2,12,13,15

Long-term cohort study of patients with IgAN (n=112)

Graph depicting the proportion of patients who progressed to ESKD based on their level of hematuria

Both time-averaged hematuria and proteinuria were independent
predictive factors for ESKD.14


Resolution of microscopic hematuria has been associated with
improved kidney outcomes in patients with IgAN.14

Illustration of the four disease markers in IgAN: Gd-IgA1, hematuria, proteinuria, and kidney function (eGFR)

Higher proteinuria is associated with worse kidney outcomes.16

In a study of 542 patients with IgAN from the Toronto Glomerulonephritis Registry, the level of proteinuria was associated with the rate of eGFR decline. Patients with proteinuria > 3 g/day (n=121) lost kidney function 25-fold faster than those with < 1 g/day.16

Although proteinuria levels 0.44 to < 0.88 g/g (~0.5 to 1.0 g/day) are traditionally regarded as “low risk,” 30% of these patients progressed to kidney failure within 10 years.7

Reductions in proteinuria are associated with improved kidney outcomes: an analysis of data from 13 controlled trials showed an association between treatment effects on percent reduction of proteinuria and treatment effects on a composite of time to doubling of serum creatinine, ESKD, or death.17

Learn more

Illustration of the four disease markers in IgAN: Gd-IgA1, hematuria, proteinuria, and kidney function (eGFR)

Decreased eGFR predicts worse clinical outcomes in patients
with IgAN.

eGFR and proteinuria can be quantified to determine kidney outcomes for patients with IgAN.2 A retrospective cohort study of adult and pediatric patients with IgAN (N=2,439) demonstrated that:7

  • Patients with an eGFR loss
    of ≥ 1 mL/min/1.73 m2 per year are at high risk of kidney failure within their lifetime.
  • Minimizing eGFR loss to
    ≤ 1 mL/min/1.73 m2 per year from diagnosis can help reduce the risk of progression to kidney failure.

Why is it important to treat IgAN early?

References:

  1. Kwon CS et al. A systematic literature review of the epidemiology, health-related quality of life impact, and economic burden of immunoglobulin A nephropathy. J Health Econ Outcomes Res. 2021;8(2):36–45.
  2. Kidney Disease: Improving Global Outcomes (KDIGO) Blood Pressure Work Group. KDIGO 2021 clinical practice guideline for the management of blood pressure in chronic kidney disease. Kidney Int. 2021;100(45):S1–S276.
  3. Caster DJ et al. Clinicopathological characteristics of adult IGA nephropathy in the United States. Kidney Int Rep. 2023;8(9):1792–1800.
  4. Penfold RS et al. Primary IgA nephropathy: current challenges and future prospects. Int J Nephrol Renovasc Dis. 2018:11:137–148.
  5. Jarrick S et al. Mortality in IgA nephropathy: a nationwide population-based cohort study. J Am Soc Nephrol. 2019;30(5):866–876.
  6. Knoop T et al. Mortality in patients with IgA nephropathy. Am J Kidney Dis. 2013;62(5):883–890.
  7. Pitcher D et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2023;18(6):727–738.
  8. Cheung CK et al. The role of BAFF and APRIL in IgA nephropathy: pathogenic mechanisms and targeted therapies. Front Nephrol. 2024;3:346769. doi: 10.3389/fneph.2023.1346769.
  9. Wheeler DC et al. A pre-specified analysis of the DAPA-CKD trial demonstrates the effects of dapagliflozin on major adverse kidney events in patients with IgA nephropathy. Kidney Int. 2021;100(1):215–224.
  10. Knoppova B et al. The origin and activities of IgA1-containing immune complexes in IgA nephropathy. Front Immunol. 2016:7:117. doi: 10.3389/fimmu.2016.00117.
  11. Zhao N et al. The level of galactose-deficient IgA1 in the sera of patients with IgA nephropathy is associated with disease progression. Kidney Int. 2012;82(7):790–796.
  12. Suzuki Y et al. Serum levels of galactose-deficient immunoglobulin (Ig) A1 and related immune complex are associated with disease activity of IgA nephropathy. Clin Exp Nephrol. 2014;18(5):770–777.
  13. Zand L et al. Microscopic hematuria as a risk factor for IgAN progression: considering this biomarker in selecting and monitoring patients. Clin Kidney J. 2023;16(Suppl 2):ii19–ii27.
  14. Sevillano AM et al. Remission of hematuria improves renal survival in IgA nephropathy. J Am Soc Nephrol. 2017;28(10):3089–3099.
  15. He P et al. Hematuria was a high risk for renal progression and ESRD in immunoglobulin A nephropathy: a systematic review and meta-analysis. Ren Fail. 2021;43(1):488–499.
  16. Reich HN et al. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. 2007;18:3177–3183.
  17. Thompson A et al. Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clin J Am Soc Nephrol. 2019;14:469–481.
  Sign Up For Updates