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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).
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.
Baseline Assessment at Biopsy
Carlos, 40
Baseline Assessment at Biopsy
Age
40
Race
Hispanic
eGFR
47 mL/min/1.73 m2
Systolic BP
160 mm Hg
Diastolic BP
84 mm Hg
Proteinuria
6 g/d
Use of ACE Inhibitor
or ARB at biopsy
None
MEST M-score
1
MEST E-score
1
MEST S-score
1
MEST T-score
0
MEST C-score
0
Immunosuppression use
None
PAS staining showing sclerosis in the upper left portion of the glomerulus as indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.
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/.
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; eGFR, estimated glomerular filtration rate; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); PAS, periodic acid-Schiff.
Assessment after 2 years
Carlos, 42
Assessment after 2 years of maximal supportive care
Age
42
Race
Hispanic
eGFR
45 mL/min/1.73 m2
Systolic BP
140 mm Hg
Diastolic BP
80 mm Hg
Proteinuria
3 g/d
Use of ACE Inhibitor
or ARB at biopsy
Yes
MEST M-score
1a
MEST E-score
1a
MEST S-score
1a
MEST T-score
0a
MEST C-score
0a
Immunosuppression use
Yes
PAS staining showing sclerosis in the upper left portion of the glomerulus as indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.
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/.
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; eGFR, estimated glomerular filtration rate; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); PAS, periodic acid-Schiff.
Carlos, 40
Baseline Assessment at Biopsy
Age
40
Race
Hispanic
eGFR
47 mL/min/1.73 m2
Systolic BP
160 mm Hg
Diastolic BP
84 mm Hg
Proteinuria
6 g/d
Use of ACE Inhibitor
or ARB at biopsy
None
MEST M-score
1
MEST E-score
1
MEST S-score
1
MEST T-score
0
MEST C-score
0
Immunosuppression use
None
PAS staining showing sclerosis in the upper left portion of the glomerulus as indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.
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/.
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; eGFR, estimated glomerular filtration rate; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); PAS, periodic acid-Schiff.
Carlos, 40
Carlos is a 40-year-old Hispanic man and
IT professional who runs his own
business.
Over the past 3 months, Carlos began experiencing fatigue, weight gain, and swelling in his ankles, which he noticed because his shoes were fitting more tightly than usual. Carlos remembers when he was a child, his father experienced similar symptoms of fatigue and swollen ankles.
- •High blood pressure and grade 2 edema were found upon physical exam
Carlos followed up with a nephrologist
Reduced renal function
suggesting stage 3a CKD
Microscopic hematuria,
and proteinuria of 6 g/d
Kidney biopsy with staining revealed IgA deposits, mesangial and
endocapillary hypercellularity, and segmental sclerosis, confirming
a
diagnosis of IgAN
CKD, chronic kidney disease; IgA, immunoglobulin A.
Age at Biopsy
40 years old
- •Most patients with IgAN are diagnosed by 40 years of age1
- •Clinical presentation and disease progression can vary based on the patient’s age at diagnosis2
SwipeClick the arrows to learn more about
Carlos’ baseline characteristics at biopsy
References: 1. Pitcher D, et al. Clin J Am Soc Nephrol. 2023;18(6):727-738. 2. Gutierrez E, et al. Nephrol Dial Transplant. 2018;33:472-477.
Race
Hispanic
- •Clinical presentation and progression of IgAN can vary greatly depending on ethnicity1
- •Hispanic patients with IgAN have a high rate of CKD progression and ESKD, with a median age at ESKD of 46 years2
CKD, chronic kidney disease; ESKD, end-stage kidney disease.
References: 1. Yeo SC, et al. Nephrology (Carlton). 2019;24(9):885-895. 2. Sim J, et al. Kidney Int Rep. 2024;9(suppl 4):S157-S158.
Estimated GFR at Biopsy
47 mL/min/1.73 m2
- •Carlos’ eGFR at biopsy indicated that he was in Stage 3a CKD: some kidney damage causing 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
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
160/84 mm Hg
- •Carlos’ 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
6 g/d
- •Carlos 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, Carlos 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 S1 T0 C0
Carlos’ biopsy was evaluated using the Oxford classification, or MEST-C score. His biopsy showed mesangial hypercellularity in >50% of glomeruli, presence of endocapillary hypercellularity and segmental glomerulosclerosis, and no tubular atrophy/interstitial fibrosis or 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.
Carlos, 40
Baseline Assessment at Biopsy
Age
40
Race
Hispanic
eGFR
47 mL/min/1.73 m2
Systolic BP
160 mm Hg
Diastolic BP
84 mm Hg
Proteinuria
6 g/d
Use of ACE Inhibitor
or ARB at biopsy
None
MEST M-score
1
MEST E-score
1
MEST S-score
1
MEST T-score
0
MEST C-score
0
Immunosuppression use
None
PAS staining showing sclerosis in the upper left portion of the glomerulus as indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.
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/.
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; eGFR, estimated glomerular filtration rate; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); PAS, periodic acid-Schiff.
Carlos’ Risk of Progression
Based on Carlos’ clinical features at the time of his biopsy, he may be at risk of developing ESKD before he turns 50. The International IgAN Prediction Tool can be used to estimate his risk of progression.
View the International
IgAN Prediction Tool
Based on the patient’s characteristics at biopsy, what would you estimate as Carlos’ risk of progression 5 years after his biopsy?a
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
eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease.
Reference: 1. Barbour SJ, et al. JAMA Intern Med. 2019;179(7):942-952.
Carlos, 40
Baseline Assessment at Biopsy
Age
40
Race
Hispanic
eGFR
47 mL/min/1.73 m2
Systolic BP
160 mm Hg
Diastolic BP
84 mm Hg
Proteinuria
6 g/d
Use of ACE Inhibitor
or ARB at biopsy
None
MEST M-score
1
MEST E-score
1
MEST S-score
1
MEST T-score
0
MEST C-score
0
Immunosuppression use
None
PAS staining showing sclerosis in the upper left portion of the glomerulus as indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.
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/.
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; eGFR, estimated glomerular filtration rate; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); PAS, periodic acid-Schiff.
Carlos’ Risk of Progression
At 5 years, Carlos’ risk of progression is 25%.a
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
eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease.
Reference: 1. Barbour SJ, et al. Kidney Int. 2022;102(1):160-172.
Carlos, 42
Assessment after 2 years of maximal supportive care
Age
42
Race
Hispanic
eGFR
45 mL/min/1.73 m2
Systolic BP
140 mm Hg
Diastolic BP
80 mm Hg
Proteinuria
3 g/d
Use of ACE Inhibitor
or ARB at biopsy
Yes
MEST M-score
1a
MEST E-score
1a
MEST S-score
1a
MEST T-score
0a
MEST C-score
0a
Immunosuppression use
Yes
PAS staining showing sclerosis in the upper left portion of the glomerulus as indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.
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/.
ACE, angiotensin-converting enzyme; ARB, angiotensin II receptor blocker; BP, blood pressure; eGFR, estimated glomerular filtration rate; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); PAS, periodic acid-Schiff.
Carlos’ Risk of Progression
After Supportive Care
Carlos was promptly started on maximal supportive care including immunosuppression. Two years after his initial diagnosis, he was able to reduce his blood pressure and reduce his proteinuria by half to 3 g/d.
Although he began treatment with supportive care soon after
his diagnosis,
Carlos’ risk of progression has increased.
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
aMEST-C score obtained from initial baseline biopsy
bPredicted 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
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.
Histopathological Changes
Caused by IgAN
Carlos was able to lower his proteinuria and blood pressure; however, Gd-IgA1 immune complexes can continue to deposit in his kidneys, causing histopathological changes and kidney damage.1
Patients with IgAN may continue to lose functional kidney tissue over time even when treated with supportive care to improve other clinical parameters like blood pressure and/or proteinuria.2
Changes in renal histopathological features
Use the slider to see how histopathological features can change over time and impact kidney survival.
At biopsy, Carlos had mesangial and endocapillary hypercellularity. Part of the glomerulus had developed sclerosis as indicated by the black arrow in the image below.a
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/.
Mesangial and endocapillary cells continue to proliferate, and the glomerulus has developed more scarring.
Excess ECM is deposited within the mesangium, and tubular atrophy develops.
Mesangial cells and inflammatory cells continue to proliferate, and scarring spreads to more of the glomerulus.
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.3-6
aPAS staining showing sclerosis in the upper left portion of the glomerulus as indicated by black arrow. A single glomerulus may not capture all components of the MEST-C score.
eGFR, estimated glomerular filtration rate; Gd-IgA1, galactose-deficient IgA1; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C); PAS, periodic acid-Schiff.
References: 1. Lai KN, et al. Nat Rev Dis Primers. 2016;2:16001. 2. Barratt J, et al. Kidney Int. 2023;103(2):391-402. 3. Pitcher D, et al. Clin J Am Soc Nephrol. 2023;18(6):727-738. 4. Faucon AL, et al. Nephrol Dial Transplant. 2024;30:gfae085. 5. Rovin BH, et al. Lancet. 2023;402(10417):2077-2090. 6. Lafayette R, et al. Lancet. 2023;402:859-870.
Impact of MEST-C Lesions
These histopathological lesions may indicate Carlos has an increased risk of developing elevated proteinuria levels or progressing to ESKD.
Click below to learn more about the impact of MEST-C lesions on kidney outcomes.
aHistopathologic samples were retrieved from the Norwegian Kidney Biopsy Registry; 306 patients were included in the study.
bHazard ratio compared to patients without these lesions.
ESKD, end-stage kidney disease; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C).
Reference: 1. Haaskjold YL, et al. BMC Nephrol. 2022;23(1):26.
aBased on a subset of 219 patients with initial proteinuria < 0.5 g/d within a larger cohort of patients from 13 countries across Europe.
bHazard ratio compared to patients without these lesions.
ESKD, end-stage kidney disease; MEST-C, mesangial hypercellularity (M), endocapillary hypercellularity (E), segmental sclerosis (S), tubular atrophy and interstitial fibrosis (T), crescent (C).
Reference: 1. Coppo R, et al. Kidney Int. 2014;86(4):828-836.
Impact of eGFR Decline
on Progression to ESKD
Based on how quickly Carlos’ eGFR declines, he may reach
kidney failure within 10 years.
If Carlos’ 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 ESKD.
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