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Baseline Assessment at Biopsy

Sarah, 25

Baseline Assessment at Biopsy

Age

Race

Asian (Japanese)

eGFR

70 mL/min/1.73 m²

Systolic BP

130 mm Hg

Diastolic BP

80 mm Hg

Proteinuria

2.1 g/d

Use of ACE Inhibitor
or ARB at biopsy

None

MEST M-score

MEST E-score

MEST S-score

MEST T-score

MEST C-score

Immunosuppression use

None

PAS staining of M1 positive lesion.*

*Image used with permission from the Renal Fellow Network, from Gallan A. Kidney Biopsy of the Month. Published July 29, 2019. Available at: Kidney Biopsy of the Month: IgA Nephropathy - Renal Fellow Network/.

ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; eGFR, estimated glomerular filtration rate; HPF, high-power field; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); PAS, periodic acid-Schiff; RBC, red blood cells; UPCR, urine protein creatinine ratio.

Sarah, 25

Baseline Assessment at Biopsy

Age

Race

Asian (Japanese)

eGFR

70 mL/min/1.73 m²

Systolic BP

130 mm Hg

Diastolic BP

80 mm Hg

Proteinuria

2.1 g/d

Use of ACE Inhibitor
or ARB at biopsy

None

MEST M-score

MEST E-score

MEST S-score

MEST T-score

MEST C-score

Immunosuppression use

None

PAS staining of M1 positive lesion.*

Sarah, 25

Sarah is a 25-year-old Japanese American woman and recent law school graduate. She began working at a local, fast-paced law firm 6 months prior to her initial exam.

Sarah has been experiencing dark brown urine for the past 2 days following an upper respiratory tract infection. She is currently not menstruating and recalled a similar incident when she was a teenager.

•No remarkable findings upon physical exam
•Her urinalysis showed >25 RBC/HPF and 2+ protein

Sarah was referred to a nephrologist for subsequent workups:

UPCR 2.1 g/g (~24-hour urine
protein excretion of 2.1 g/d)

Kidney biopsy revealed dominant IgA staining and evidence of mesangial hypercellularity, which confirmed Sarah’s IgAN diagnosis

Click the arrows in the carousel below to explore Sarah’s baseline characteristics

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Age at Biopsy

25 years old

•IgAN is primarily diagnosed in adults 20-40 years of age^1,2
•Clinical presentation and disease progression can vary based on the patient’s age at diagnosis³

References: 1. Caster DJ, et al. Kidney Int Rep. 2023;8(9):1792-1800. 2. Lai KN, et al. Nat Rev Dis Primers. 2016;2:16001. 3. Gutierrez E, et al. Nephrol Dial Transplant. 2018;33:472-477.

Race

East Asian (Japanese)

•Clinical presentation and progression of IgAN can vary greatly depending on ethnicity¹
•Asian ethnicity is associated with faster disease progression and greater burden¹

–East Asian patients are 4x more likely to develop ESKD

ESKD, end-stage kidney disease.

Reference: 1. Yeo SC, et al. Nephrology (Carlton). 2019;24(9):885-895.

Estimated GFR at Biopsy

70 mL/min/
1.73 m²

•Sarah’s eGFR at biopsy indicated that she is in Stage 2 CKD: some kidney damage leading to a mild loss of kidney function
•eGFR decline is a validated risk factor of IgAN progression and is strongly associated with the risk of CKD progression and mortality¹

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

Reference: 1. Coresh J, et al. JAMA. 2014;311(24):2518-2531.

Blood Pressure at Biopsy

130/80 mm Hg

•Sarah’s blood pressure was slightly elevated at biopsy
•Hypertension can be a predictor of IgAN progression at the time of diagnosis¹
•Reduction of hypertension lowers the risk of progression to kidney failure²

References: 1. Maixnerova D, et al. J Nephrol. 2016;29(4):535-541. 2. KDIGO. Kidney Int. 2021;100:S1-S276.

Proteinuria at Biopsy

2.1 g/d

•Sarah had elevated proteinuria at the time of biopsy
•Proteinuria is a validated prognostic marker linked to long-term kidney outcomes, including eGFR decline and ESKD^1,2
•Proteinuria reduction inversely correlates with serum creatinine doubling, ESKD, and death^2,3

eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease.

References: 1. KDIGO. Kidney Int. 2021;100:S1-S276. 2. Thompson A, et al. Clin J Am Soc Nephrol. 2019;14(3):469-481. 3. Inker L, et al. Am J Kidney Dis. 2016;68(3):392-401.

ACEi/ARB Use at the Time of Biopsy

None

While ACEi/ARBs are recommended as part of supportive care, Sarah had not initiated treatment at the time of her biopsy.¹

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker.

Reference: 1. KDIGO. Kidney Int. 2021;100:S1-S276.

MEST-C Score

M1 E0 S0 T0 C0

Sarah’s biopsy was evaluated using the Oxford classification, or MEST-C score. Her biopsy showed mesangial hypercellularity in >50% of glomeruli, but was absent of endocapillary hypercellularity, segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis, and crescents.

The MEST-C score can serve as a valuable early prognostic tool and should be considered when evaluating the risk of progression to ESKD.^1-3

ESKD, end-stage kidney disease; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C).

References: 1. Cattran DC, et al. Kidney Int Rep. 2023;8(12):2515-2528. 2. Haaskjold YL, et al. BMC Nephrology. 2022;23:26. 3. Coppo R, et al. Kidney Int. 2014;86(4):828-836.

Immunosuppression Use at or Prior to Biopsy

None

While the clinical benefits of immunosuppressive therapy have not been established in patients with IgAN, they may be used in specific patient populations if the risk/benefit profile is acceptable.¹

Reference: 1. KDIGO. Kidney Int. 2021;100:S1-S276.

*Image used with permission from the Renal Fellow Network, from Gallan A. Kidney Biopsy of the Month. Published July 29, 2019. Available at: https://www.renalfellow.org/2019/07/29/kidney-biopsy-of-the-month-iga-nephropathy/.

Sarah’s Risk of Progression

After Sarah’s IgAN diagnosis was confirmed by biopsy, she was prescribed an ACEi/ARB. One year later, her proteinuria stabilized to 1 g/d and her blood pressure was lowered to 120/80 with supportive care and lifestyle modifications.

Graph showing Sarah's risk of progression at age 27. 5 percent risk one year after stabilization on optimized supportive care

Graph showing Sarah's risk of progression at age 28. 11 percent risk two years after stabilization on optimized supportive care

Graph showing Sarah's risk of progression at age 29. 18 percent risk three years after stabilization on optimized supportive care

Graph showing Sarah's risk of progression at age 30. 25 percent risk four years after stabilization on optimized supportive care

Graph showing Sarah's risk of progression at age 31. 33 percent risk five years after stabilization on optimized supportive care

View the International
IgAN Prediction Tool

Current KDIGO guidelines do not recommend SGLT2i use in IgAN in the absence of diabetes, as additional data are needed to assess efficacy and safety. Treatments in hypothetical patient cases reflect current treatment guidelines.²

^aPredicted risk of progression was calculated using the International IgAN Prediction Tool and defined as the risk of a 50% decline in eGFR or ESKD.¹

ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; KDIGO, Kidney Disease: Improving Global Outcomes; SGLT2i, Sodium-Glucose Transport Protein 2 inhibitor.

References: 1. Barbour SJ, et al. Kidney Int. 2022;102(1):160-172. 2. KDIGO. Kidney Int. 2021;100:S1-S276.

Impact of Proteinuria

Despite decreasing her proteinuria level by half to 1 g/d,
Sarah remains at risk of progression.

A retrospective cohort study showed that patients perceived as low risk continue to remain at risk of progression to kidney failure within 10 years²

•30% risk in patients with proteinuria 0.5 to 1 g/d
•~20% risk in patients with proteinuria <0.5 g/d

Use the slider to see how reducing proteinuria below 1 g/d could reduce Sarah’s risk of progression.

23 percent risk progression at 5 years with proteinuria at 0.5 g/d

28 percent risk progression at 5 years with proteinuria at 0.75 g/d

33 percent risk progression at 5 years with proteinuria at 1 g/d

Reducing proteinuria from 1 g/d to 0.5 g/d lowers the risk of progression by ~10%

^aPredicted risk of progression was calculated using the International IgAN Prediction Tool and defined as the risk of a 50% decline in eGFR or ESKD.

eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease.

References: 1. Barbour SJ, et al. Kidney Int. 2022;102(1):160-172. 2. Pitcher D, et al. Clin J Am Soc Nephrol. 2023;18(6):727-738.

Changes in Proteinuria
and eGFR Over Time

Through medication and lifestyle changes, Sarah may be able to reduce her proteinuria and slow her eGFR decline.

Changes in proteinuria and eGFR over time

Use the slider to see how Sarah’s proteinuria and eGFR may change over time

Graph modeling proteinuria progression over time with and without intervention, starting at biopsy

Graph showing proteinuria level with and without intervention, after two years

Graph showing proteinuria progression with and without intervention, at four years

Graph showing proteinuria with and without intervention, at six years

Graph modeling eGFR decline over time with and without intervention, starting at biopsy

Graph showing eGFR with and without intervention, after two years

Graph showing eGFR with and without intervention, after four years

Graph showing eGFR with and without intervention, after six years

Changes in proteinuria and eGFR, as well as the differences between "With intervention" and "Without intervention", are hypothetical and based on trends seen in clinical trials and cohort studies.^1-4

eGFR, estimated glomerular filtration rate.

References: 1. Pitcher D, et al. Clin J Am Soc Nephrol. 2023;18(6):727-738. 2. Faucon AL, et al. Nephrol Dial Transplant. 2024;30:gfae085. 3. Rovin BH, et al. Lancet. 2023;402(10417):2077-2090. 4. Lafayette R, et al. Lancet. 2023;402:859-870.

Impact of eGFR Decline on
Progression to Kidney Failure

If Sarah’s eGFR decline stabilizes, this can delay the onset of kidney failure.

Select a button below to see how different rates of eGFR decline can impact progression to kidney failure.

Graph depicting changes in eGFR over time

Graph depicting changes in eGFR over time at a loss of 2 mL/min/1.73 m2 per year

Graph depicting changes in eGFR over time at a loss of 3 mL/min/1.73 m2 per year

Graph depicting changes in eGFR over time at a loss of 5 mL/min/1.73 m2 per year

CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.

A Considerable Impact on Physical, Mental, and Emotional Health^1,2

~25% of patients with IgAN experience anxiety^1,a

~30% of patients with IgAN experience depression^2,b

~40% daily activity impairment reported^3,c

Up to 40% overall work impairment reported^3,c

^aSurvey of U.S. patients on coping with IgAN from the NKF Voice of the Patient Report.

^bProspective observational study of adult patients with biopsy-confirmed IgAN.

^cBased on real-world data from the Adelphi IgAN Disease Specific Programme (DSP), a point-in-time survey of IgAN-treating nephrologists and their patients in the United States, EU5 (France, Germany, Italy, Spain, and the United Kingdom), Japan, and China between June and October 2021. Data presented are for patients with IgAN in the United States, and are based on the average impairment reported by participants.

References: 1. The Voice of the Patient. National Kidney Foundation. December 8, 2020. Accessed June 10, 2024. https://www.igan.org/wp-content/uploads/2021/01/VOP_IgAN_12-7-20__FNL.pdf. 2. Zhao Y, et al. J Int Med Res. 2020;48(1):300060519898008. 3. Lafayette R, et al. Poster. International Symposium on IgA Nephropathy; Tokyo, Japan. September 28-30, 2023 (poster P-51).

SELECT ANOTHER HYPOTHETICAL PATIENT

Carlos

Mark

Discover the pathogenesis of IgAN

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This website is for Healthcare Professionals Only

What is the MEST-C score? The Oxford classification describes 5 features associated with adverse kidney outcomes.1,2

Baseline Assessment at Biopsy

Baseline Assessment at Biopsy

Sarah is a 25-year-old Japanese American woman and recent law school graduate. She began working at a local, fast-paced law firm 6 months prior to her initial exam.

Sarah was referred to a nephrologist for subsequent workups:

Age at Biopsy

25 years old

Race

East Asian (Japanese)

Estimated GFR at Biopsy

70 mL/min/1.73 m2

Blood Pressure at Biopsy

130/80 mm Hg

Proteinuria at Biopsy

2.1 g/d

ACEi/ARB Use at the Time of Biopsy

None

MEST-C Score

M1 E0 S0 T0 C0

Immunosuppression Use at or Prior to Biopsy

None

Sarah’s Risk of Progression

Impact of Proteinuria

Changes in Proteinuria and eGFR Over Time

Impact of eGFR Decline on Progression to Kidney Failure

A Considerable Impact on Physical, Mental, and Emotional Health1,2

SELECT ANOTHER HYPOTHETICAL PATIENT

Carlos

Mark

What is the MEST-C score? The Oxford classification describes
5 features associated with adverse kidney outcomes.^1,2

70 mL/min/
1.73 m²

Changes in Proteinuria
and eGFR Over Time

Impact of eGFR Decline on
Progression to Kidney Failure

A Considerable Impact on Physical, Mental, and Emotional Health^1,2