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What is the MEST-C score? The Oxford classification describes
5 features associated with adverse kidney outcomes.1,2
ESKD, end-stage kidney disease; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C).
a©2021, with permission from the National Kidney Foundation, Inc. Available from: https://www.sciencedirect.com/journal/american-journal-of-kidney-diseases
b©2016, with permission from the National Kidney Foundation, Inc. Available from: https://www.sciencedirect.com/journal/american-journal-of-kidney-diseases
References: 1. Pattrapornpisut P, et al. Am J Kidney Dis. 2021;78(3):429-441. 2. Lusco MA, et al. Am J Kidney Dis. 2016;67(6):e33-e34.
International IgAN Prediction Tool1,2
The International IgAN Prediction Tool was developed to help nephrologists determine their patients’ risk of progression to ESKD or 50% decline in eGFR
Factors used to determine risk:
- •age
- •race
- •eGFR
- •blood pressure
- •proteinuria
- •presence of MEST lesions
- •ACE inhibitor or ARB use
- •immunosuppression use
Although crescents have been shown to increase risk of IgAN progression, they are not included in the Prediction Tool.1-3
To fully appreciate a patient’s risk, HCPs may need to account for additional disease features, such as the presence of crescents.
Continue to learn how crescents can impact IgAN progression
ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; eGFR, estimated glomerular filtration rate; HCP, healthcare provider; MEST, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T).
References: 1. Barbour SJ, et al. JAMA Intern Med. 2019;179(7):942-952. 2. Barbour SJ, et al. Kidney Int. 2022;102(1):160-172. 3. Du Y, et al. Front Med (Lausanne). 2022;9:864667.
Baseline Assessment at Biopsy
Mark, 34
Mark, 34
Baseline Assessment at Biopsy
Age
34
Race
White
eGFR
54 mL/min/1.73 m2
Systolic BP
140 mm Hg
Diastolic BP
80 mm Hg
Proteinuria
2.5 g/d
Use of ACE Inhibitor
or ARB at biopsy
None
MEST M-score
1
MEST E-score
1
MEST S-score
0
MEST T-score
0
MEST C-score
1
Immunosuppression use
None
H&E staining showing mesangial hypercellularity, endocapillary hypercellularity, and crescent formation. Crescent formation indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.*
*Image source: Luis Fernando Arias-Restrepo, MD, Universidad de Antioquia, Medellín, Colombia. Available from: https://kidneypathology.com/English_version/IgA_Nephropathy.html. Used with permission.
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; H&E, hematoxylin and eosin; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C).
Mark, 34
Baseline Assessment at Biopsy
Age
34
Race
White
eGFR
54 mL/min/1.73 m2
Systolic BP
140 mm Hg
Diastolic BP
80 mm Hg
Proteinuria
2.5 g/d
Use of ACE Inhibitor
or ARB at biopsy
None
MEST M-score
1
MEST E-score
1
MEST S-score
0
MEST T-score
0
MEST C-score
1
Immunosuppression use
None
H&E staining showing mesangial hypercellularity, endocapillary hypercellularity, and crescent formation. Crescent formation indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.*
Mark, 34
Mark is a 34-year-old avid runner who travels
frequently for his new position
at work.
Over the past 2 weeks, Mark has occasionally noticed his urine had blood in it and was frothy.
- •Blood tests revealed his creatinine was elevated at 1.7 mg/dL
- •Mark was referred to a nephrologist, where additional tests revealed he had a proteinuria level of 2.5 g/d and stage 3a CKD
Based on these results, his nephrologist performed a kidney biopsy, which confirmed IgAN, and showed mesangial hypercellularity, endocapillary hypercellularity, and 15% glomerular crescents.
Click the arrows in the carousel below to explore Carlos’ baseline characteristics
Swipe in the carousel below to explore Mark’s baseline characteristics
Age at Biopsy
34 years old
- •IgAN is often diagnosed in adults aged 20-40 years1,2
- •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
White
- •IgAN incidence and progression can vary by region and ethnicity1
- –Annual incidence in the US is ~1.29/100,000 persons, compared to ~1-2/100,000 persons in Europe and ~4.2/100,000 persons in Japan2-4
References: 1. Yeo SC, et al. Nephrology (Carlton). 2019;24(9):885-895. 2. Kwon CS, et al. J Health Econ Outcomes Res. 2021;8(2):36-45. 3. Willey C, et al. Nephrol Dial Transplant. 2023;38(10):2340-2349. 4. Kiryluk K, et al. Kidney360. 2023;4(8):1112-1122.
Estimated GFR at Biopsy
54 mL/min/
1.73 m2
- •Mark’s eGFR at biopsy indicated that he was in stage 3a CKD: some kidney damage leading to a mild to moderate loss of kidney function
- •eGFR decline is a validated risk factor of IgAN progression. Declines in eGFR are strongly associated with the risk of CKD progression and mortality1,2
CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.
Reference: 1. Coresh J, et al. JAMA. 2014;311(24):2518-2531. 2. KDIGO. Kidney Int. 2021;100:S1-S276.
Blood Pressure at Biopsy
140/80 mm Hg
- •Mark’s blood pressure was found to be elevated at biopsy
- •Hypertension has been shown to serve as a clinical 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
2.5 g/d
- •Mark had elevated proteinuria at the time of biopsy
- •Proteinuria is a validated prognostic marker linked to long-term kidney outcomes, including eGFR decline and ESKD1,2
- •Proteinuria reduction inversely correlates with serum creatinine doubling, ESKD, and death2,3
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, Mark had not initiated treatment at the time of his 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 E1 S0 T0 C1
Mark’s biopsy was evaluated using the Oxford classification, or MEST-C score. His biopsy showed mesangial hypercellularity in >50% of glomeruli, endocapillary hypercellularity, and crescents in 15% of glomeruli, but was absent of segmental glomerulosclerosis and tubular atrophy/interstitial fibrosis.
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 source: Luis Fernando Arias-Restrepo, MD, Universidad de Antioquia, Medellín, Colombia. Available from: https://kidneypathology.com/English_version/IgA_Nephropathy.html. Used with permission.
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; H&E, hematoxylin and eosin; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C).
Impact of Crescents
on IgAN Progression
The International IgAN Prediction Tool indicates Mark has 12% risk of progression after 5 years. However, his biopsy revealed crescents, which are not included in the risk prediction model but have been associated with poor prognosis and more rapid decline in kidney function.1-3,a
Given Mark’s risk, he was started on supportive care.
View the International
IgAN Prediction Tool
Changes in renal histopathological features
Use the slider to see how histopathological features can change over time and impact kidney survival.
Mark’s biopsy at diagnosis showed mesangial hypercellularity, endocapillary hypercellularity, and crescents. Crescent formation indicated by black arrow in the image below.b
Image used with permission.*
Cells continue to accumulate in the capillaries and mesangium, and inflammatory cells infiltrate the crescent.
Excess ECM is deposited within the mesangium and the crescent spreads throughout the glomerulus. Tubules begin to show signs of atrophy.
Cells continue to accumulate in the capillaries and mesangium. Inflammatory cells continue to infiltrate the crescent, and tubular atrophy worsens.
Red blood cell
Crescent (epithelial
and immune cells)
Protein
ECM
Gd-IgA1 immune
complexes
Immune cells
Mesangial cells
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.4
The graphic shown above is for illustrative purposes only and is intended to educate on potential histopathological changes that could occur during IgAN. It is not intended to provide specific information about the progression of these changes or inform treatment decisions. Changes in proteinuria and eGFR are hypothetical and are based on trends seen in clinical trials and cohort studies.5-8
*Image source: Luis Fernando Arias-Restrepo, MD, Universidad de Antioquia, Medellín, Colombia. Available from: https://kidneypathology.com/English_version/IgA_Nephropathy.html. Used with permission.
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.3
bH&E staining showing mesangial hypercellularity, endocapillary hypercellularity, and crescent formation. Crescent formation indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.
eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; H&E, hematoxylin and eosin; KDIGO, Kidney Disease: Improving Global Outcomes; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); SGLT2i, Sodium-Glucose Transport Protein 2 inhibitor.
References: 1. Pattrapornpisut P, et al. Am J Kidney Dis. 2021;78(3):429-441. 2. Cattran DC, et al. Kidney Int Rep. 2023;8(12):2515-2528. 3. Barbour SJ, et al. JAMA Intern Med. 2019;179(7):942-952. 4. KDIGO. Kidney Int. 2021;100:S1-S276. 5. Pitcher D, et al. Clin J Am Soc Nephrol. 2023;18(6):727-738. 6. Faucon AL, et al. Nephrol Dial Transplant. 2024;30:gfae085. 7. Rovin BH, et al. Lancet. 2023;402(10417):2077-2090. 8. Lafayette R, et al. Lancet. 2023;402:859-870.
Impact of Crescents
on IgAN Progression
The International IgAN Prediction Tool indicates Mark has 12% risk of progression after 5 years. However, his biopsy revealed crescents, which are not included in the risk prediction model but have been associated with poor prognosis and more rapid decline in kidney function.1-3,a
Given Mark’s risk, he was started on supportive care.
The presence of crescents signals an urgent need to treat
- •Crescents indicate active glomerular inflammation from GBM rupture, leading to cell and protein accumulation in Bowman’s space4
- •Early crescents may be reversible, but a high C score suggests rapid kidney failure5,6
High C scores are indicative of active glomerular injury and rapid disease progression6,7
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; GBM, glomerular basement membrane; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C).
References: 1. Pattrapornpisut P, et al. Am J Kidney Dis. 2021;78(3):429-441. 2. Cattran DC, et al. Kidney Int Rep. 2023;8(12):2515-2528. 3. Barbour SJ, et al. JAMA Intern Med. 2019;179(7):942-952. 4. Mushafi AA, et al. Front Physiol. 2021;12:724186. 5. Trimarchi H, et al. Kidney Int. 2017;91(5):1014-1021. 6. Shen XH, et al. J Nephrol. 2015;28:441-449. 7. Rodrigues JC, et al. Clin J Am Soc Nephrol. 2017;12:677-686.
Learn more about how Mark’s eGFR may decline over time
Impact of eGFR Decline
on Progression to Kidney Failure
Based on how quickly Mark’s eGFR declines, he may reach
kidney failure within 10 years.
If Mark’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.
CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate.
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