Understand the Risk

Most IgAN patients will progress to kidney failure and dialysis or transplant within their lifetime1

EXPLORE RaDaR DATA right_arrow2

Focus on the Gut-Kidney Axis

The majority of Gd-IgA1 is thought to be produced in the gut—specifically the Peyer’s patches of the ileum3

SEE PATHOPHYSIOLOGY right_arrow2

Address Underlying Causes Early

Draft 2024 KDIGO guideline recommends managing IgAN causes and CKD consequences4

DRAFT 2024 KDIGO GUIDELINE right_arrow2
RaDaR

RaDaR

By the time IgAN symptoms present, significant, irreversible damage may have already occurred1

of adult patients are at
CKD stages 3, 4, or 5 at diagnosis1*

Preserving kidney function (eGFR) is the ultimate goal in IgAN management3

eGFR is the widely accepted endpoint to confirm kidney function benefit while UPCR is a surrogate biomarker for monitoring and treatment decisions5,6

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eGFR

  • Decline is directly associated with a worse renal prognosis in patients with IgAN6,7
  • Considered the optimal method for measuring kidney function6
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UPCR

  • Recognized risk factor to predict the progression of IgAN5,8
  • On its own, UPCR is not considered to be adequate evidence to predict long-term kidney benefit5

RaDaR data: slowing the rate of eGFR decline helps lower the risk of kidney failure1

RaDaR data are based on the IgAN cohort of the UK National Registry of Rare Kidney Diseases (RaDaR), a cohort study assessing relationships among key parameters such as proteinuria and eGFR to kidney survival1

This was a retrospective study of 2299 adults and 140 children over 5.9 years. To be included in the cohort, patients must have biopsy-proven IgAN diagnosis plus proteinuria >0.5 g/d or eGFR <60/mL/min/1.73 m2 at any time in their disease history1

Percent of patients at risk of reaching kidney failure in their lifetime†

Color-coded chart showing lifetime kidney failure risk by age and eGFR decline, with annotations for high-risk patient groups. Color-coded chart showing lifetime kidney failure risk by age and eGFR decline, with annotations for high-risk patient groups.

100% of patients 
at risk of kidney failure within their expected lifetime if1:

  • Younger than 40 years old at diagnosis
  • eGFR declines 3 mL/min/1.73 m2 annually

~40% of patients 
at risk of kidney failure within their expected lifetime if1:

  • Younger than 50 years old at diagnosis
  • eGFR declines 1 mL/min/1.73 m2 annually

UPCR: A PREDICTOR OF IgAN PROGRESSION

Even patients traditionally regarded as being 

“low risk” (proteinuria <0.88 g/g‡) may progress to kidney failure within 10 years1

RaDaR data: kidney failure risk 
based on time-averaged proteinuria1§

Bar chart showing kidney failure risk within 10 years based on time-averaged proteinuria levels, with risk percentages labeled. Bar chart showing kidney failure risk within 10 years based on time-averaged proteinuria levels, with risk percentages labeled.

Key findings

Earlier diagnosis and initiation of treatment should be considered for patients with IgAN, with diagnosis confirmed by kidney biopsy1

Waiting for proteinuria threshold of >0.88 g/g may not identify patients who have a significant lifetime risk of kidney failure1

RaDaR DATA UNDERSCORE
THE NEED FOR A MORE PROACTIVE APPROACH IN TREATING IgAN

DELVE INTO THE RaDaR DATA Arrow Right Icon

*Data are based on analysis of the RaDaR registry cohort.1

†Based on life expectancy of 81 years.1

‡Proteinuria 0.88 g/g may be considered comparable with protein excretion of 1 g/day.1

§Time-averaged proteinuria was defined as the time-weighted averages for UPCR.1

Pathophysiology

Pathophysiology

A key source of IgAN: the gut-kidney axis2,3

A growing body of evidence supports a “gut-kidney” axis in IgAN, with similarities between mesangial IgA deposits and mucosally derived IgA2,3

The mucosal immune system—particularly gut-associated lymphoid tissue (GALT)—is a major driver in the pathogenesis of IgAN9,10

Peyer’s patches are the most immunologically significant component of GALT11

video icon

The widely accepted 4-HIT model underscores the immune-mediated mechanisms specific to IgAN2,3

Circular graphic labeled HIT 1 showing Gd-IgA1 antibodies entering systemic circulation in early-stage IgAN. Circular graphic labeled HIT 1 showing Gd-IgA1 antibodies entering systemic circulation in early-stage IgAN.

Mucosal-type IgA1-induced renal injury occurs. 
Generic mechanisms of CKD, such as tubulointerstitial response to proteinuria, are thought to contribute to nephron loss2,3

FOCUS ON THE GUT-KIDNEY AXIS.

CHANGE THE COURSE OF TREATING IgAN

Downregulating mucosal Gd-IgA1 production is a compelling approach to reducing circulating IgA immune complex formation and effectively targeting the disease in its early stages1,9,10

Hear from an expert about the gut-kidney axis

Headshot of Dr. Jonathan Barratt beside the title "The Gut-Kidney Axis in IgAN."

EXPLORE A TREATMENT OPTION THAT CAN
MAKE A DIFFERENCE AT A KEY SOURCE OF IgAN

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gd iga

Gd-IgA1

Gd-IgA1: high levels have been associated with poor disease outcomes14

A prospective cohort study of 275 patients with biopsy-confirmed IgAN found an association between increased serum Gd-IgA1 levels and decreased renal survival15

Renal survival declines by quartile of serum Gd-IgA1 levels in patients with IgAN15

Graph showing renal survival over time in patients with IgAN stratified by quartiles of serum Gd-IgA1. Higher levels correlate with worse outcomes. Graph showing renal survival over time in patients with IgAN stratified by quartiles of serum Gd-IgA1. Higher levels correlate with worse outcomes.

There are data supporting that higher levels of Gd-IgA1 may be associated with15:

Circular callout referencing the overall progression of IgA nephropathy.

A trend for lower eGFR and higher proteinuria

Circular callout referencing the overall progression of IgA nephropathy.

Greater risk of kidney failure

Circular callout referencing the overall progression of IgA nephropathy.

Disease progression

kdigo

KDIGO

Draft-2024-KDIGO-Guideline-globe

Draft 2024 KDIGO guideline* supports the simultaneous management of IgAN-specific drivers and consequences4

Updated key considerations

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DIAGNOSIS

Biopsy should be performed in all adult patients with proteinuria ≥0.5 g/d in whom IgAN is a possible diagnosis without contraindications for biopsy4

Biopsy should be performed in all adult patients with proteinuria ≥0.5 g/d in whom IgAN is a possible diagnosis without contraindications for biopsy4

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PROGRESSION RISK

Risk of progressive kidney function loss is defined as proteinuria ≥0.5 g/d while on or off treatment, and (additional) treatment should be initiated4

Risk of progressive kidney function loss is defined as proteinuria ≥0.5 g/d while on or off treatment, and (additional) treatment should be initiated4

3

TREATMENT GOAL

Treatment goal is to reduce the rate of kidney function loss to <1 mL/min per year for the rest of the patient’s life4

Treatment goal is to reduce the rate of kidney function loss to <1 mL/min per year for the rest of the patient’s life4

4

PROTEINURIA MONITORING

Proteinuria should be maintained at <0.5 g/d (or equivalent), preferably <0.3 g/d [or equivalent]4

Proteinuria should be maintained at <0.5 g/d (or equivalent), preferably <0.3 g/d [or equivalent]4

5

TREATMENT TARGETS

For most patients, treatment management should focus on targeting IgAN-specific drivers for nephron loss, including reducing the production of pathogenic forms of IgA and IgA immune complex formation, while simultaneously addressing the generic response to IgAN-induced nephron loss4

For most patients, treatment management should focus on targeting IgAN-specific drivers for nephron loss, including reducing the production of pathogenic forms of IgA and IgA immune complex formation, while simultaneously addressing the generic response to IgAN-induced nephron loss4

draft 2024

IgAN treatment targets4†

DRIVERS FOR NEPHRON LOSS

TREATMENT GOALS

IgAN at risk of progressive kidney function loss
These should be managed simultaneously in all patients

IgAN-specific drivers for nephron loss

Reduce pathogenic forms of IgA and IgA immune complex formation

Reduce glomerular inflammation

Generic response to
IgAN-induced nephron loss

Blood pressure control

Reduce glomerular hyperfiltration and the impact of proteinuria on the tubulointerstitium

Cardiovascular risk reduction

IgAN at risk of progressive kidney function loss

These should be managed simultaneously in all patients

DRIVERS FOR NEPHRON LOSS

TREATMENT GOALS

IgAN-specific drivers for nephron loss

Reduce pathogenic forms of IgA and IgA immune complex formation

Reduce glomerular inflammation

Generic response to IgAN-induced nephron loss

Blood pressure control

Reduce glomerular hyperfiltration and the impact of proteinuria on the tubulointerstitium

Cardiovascular risk reduction

DRAFT 2024 KDIGO GUIDELINE

SUGGESTS A PROACTIVE TREATMENT APPROACH FOR PATIENTS AT RISK4

REVIEW THE DRAFT 2024 KDIGO GUIDELINE arrow-right
  • * Draft submitted for public comment and subject to change.
  • †IgAN treatment targets flowchart has been adapted. Access full draft 2024 KDIGO guideline via the button above.
Gd-IgA1-pipeline.pngStylized pipe image with a red Gd-IgA1 valve, illustrating changes in immune complex flow as a visual metaphor for disease modulation. Gd-IgA1-pipeline.pngStylized pipe image with a red Gd-IgA1 valve, illustrating changes in immune complex flow as a visual metaphor for disease modulation.

TURN DOWN THE RISK
OF KIDNEY DAMAGE AT A KEY SOURCE

Learn about an IgAN treatment option that can help

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Resources

Resources

Empower your patients with resources that can support them

IgA Nephropathy Foundation

Advancing research, advocacy, and support to improve outcomes for patients with IgAN

IGA Nephropathy Foundation logo
National Kidney Foundation

Empowering healthcare providers with education and resources to combat kidney disease across all stages

National Kidney Foundation logo
NephCure

Driving innovation and collaboration to accelerate breakthroughs in glomerular disease research and care

NephCure logo

Keep up with the latest innovations in IgAN management

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CKD=chronic kidney disease; eGFR=estimated glomerular filtration rate; Gd-IgA1=galactose-deficient IgA1; IgA=immunoglobulin A; IgA1=immunoglobulin A1; IgG=immunoglobulin G; KDIGO=Kidney Disease: Improving Global Outcomes; UPCR=urine protein-to-creatinine ratio.

References: 1. Pitcher D, Braddon F, Hendry B, et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. 2023;18(6):727-738. 2. Chang S, Li X-K. The role of immune modulation in pathogenesis of IgA nephropathy. Front Med (Lausanne). 2020;7:92. doi:10.3389/fmed.2020.00092 3. Lim RS, Yeo SC, Barratt J, et al. An update on current therapeutic options in IgA nephropathy. J Clin Med. 2024;13(4):947. doi:10.3390/jcm13040947 4. Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV) Public Review Draft; August 2024. Accessed March 1, 2025. https://kdigo.org/igan-igav-public-review-draft/ 5. Thompson A, Carroll K, Inker LA, et al. Proteinuria reduction as a surrogate end point in trials of IgA nephropathy. Clin J Am Soc Nephrol. 2019;14(3):469-481. 6. Levey AS, Gansevoort RT, Coresh J, et al. Change in albuminuria and GFR as end points for clinical trials in early stages of CKD: a scientific workshop sponsored by the National Kidney Foundation in collaboration with the US Food and Drug Administration and European Medicines Agency. Am J Kidney Dis. 2019. 7. Goto M, Waiai K, Kawamura T. A scoring system to predict renal outcome in IgA nephropathy: a nationwide 10-year prospective cohort study. Nephrol Dial Transplant. 2009;24:3068-3074. 8. Reich HN, Troyanov S, Scholey JW. Remission of proteinuria improves prognosis in IgA nephropathy. J Am Soc Nephrol. 2007;18:3177-3183. 9. Coppo R. The gut-renal connection in IgA nephropathy. Semin Nephrol. 2018;38:504-512. 10. Han L, Fang X, He Y, Ruan XZ. ISN Forefronts Symposium 2015: IgA nephropathy, the gut microbiota, and gut-kidney crosstalk. Kidney Int Rep. 2016;1:189-196. 11. Morbe UM, Jorgensen PB, Fenton TM, et al. Human gut-associated lymphoid tissues (GALT); diversity, structure, and function. Mucosal Immunology. 2021;14:793-802. 12. Jung C, Hugot J-P, Barreau F. Peyerʼs patches: the immune sensors of the intestine. Int Journal Inflammation. 2010;1-12. https://doi.org/10.4061/2010/823710 13. Van Kruiningen H, West AB, Freda BJ, et al. Distribution of Peyerʼs patches in the distal ileum. Inflammatory Bowel Dis. 2002;8(3):180-185. https://doi.org/10.1097/00054725-200205000-00004 14. Canetta PA, Kiryluk K, Appel GB. Glomerular diseases: emerging tests and therapies for IgA nephropathy. Clin J Am Soc Nephrol. 2014;9(3):617-625. 15. Zhao N, Hou P, Lv J, 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. doi:10.1038/ki.2012.197

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