Preserve and Prevent: Expert Perspectives on Optimizing Outcomes in Patients With IgAN

Jonathan Barratt, PhD, FRCP, and Jürgen Floege, MD, discuss IgA nephropathy in this CME activity titled "Preserve and Prevent: Expert Perspectives on Optimizing Outcomes in Patients With IgAN." For the full presentation, please visit us at www.peervoice.com/UQF870.

1. PeerVoice

Preserve and Prevent: Expert Perspectives on Optimizing
Outcomes in Patients With IgAN

Learning Objectives

Utilize evidence-based approaches to stratify risk and guide treatment decisions
in patients with IgA nephropathy (IgAN)

Appraise efficacy and safety data from pivotal clinical trials evaluating recently
approved therapies for IgAN

Recognize practical considerations for the use of recently approved therapies
used in the management of IgAN

Establish evidence-based treatment strategies to optimize outcomes in the
management of IgAN

This PeerVoice educational activity has been developed in partnership with KDIGO.
This activity is supported by an educational grant from Calliditas Therapeutics.

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2. PeerVoice

Jonathan Barratt, PhD, FRCP Jurgen Floege, MD
Professor of Renal Medicine Professor of Medicine
University of Leicester Division of Nephrology
Honorary Consultant Nephrologist RWTH Aachen University
The John Walls Renal Unit, University Hospital
University Hospitals of Leicester NHS Trust Aachen, Germany
Leicester, United Kingdom

This PeerVoice educational activity has been developed in partnership with KDIGO.

Copyright © 2010-2025, PeerVoice

3. PeerVoice

TT) "than Barratt, Pho, FRCP, has a financia interest/relationship or affiliation in the form of:
Consultant for Alexion Pharmaceuticals, Inc. AstraZeneca; Biogen Inc.; Calliditas Therapeutics AB;
AT F. Hoffmann-La Roche Ltd; Novartis AG; Otsuka Pharmaceutical Co, Ltd; Travere Therapeutics, Inc;
= Vera Therapeutics; and Vertex Pharmaceuticals Incorporated.
Grant/Research Support from Alexion Pharmaceuticals, Inc; Biogen Inc; Calliditas Therapeutics AB;
Novartis AG; Otsuka Pharmaceutical Co, Ltd; Travere Therapeutics, Inc; and Vertex Pharmaceuticals
Incorporated.

Júrgen Floege, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Alexion Pharmaceuticals, Inc. Amgen Inc; AstraZeneca; Bayer AG; Biogen Inc; Boehringer

y Ingelheim International GmbH; CSL Vifor; F. Hoffmann-La Roche Ltd; Novartis AG; Otsuka
TA Pharmaceutical Co, Ltd, STADA Arzneimittel AG; Travere Therapeutics, Inc;; Vera Therapeutics; and
Vertex Pharmaceuticals Incorporated.
Pm Speakers Bureau participant with Amgen Inc; AstraZeneca; CSL Vifor; F. Hoffmann-La Roche Ltd.

Novartis AG; Otsuka Pharmaceutical Co, Ltd; STADA Arzneimittel A\
Vera Therapeutics; and Vertex Pharmaceuticals Incorporated.
Advisory Board for Alexion Pharmaceuticals, Inc; Amgen Inc; AstraZeneca; Bayer AG; Biogen Inc;
Boehringer Ingelheim International GmbH; CSL Vifor; F. Hoffmann-La Roche Ltd; Novartis AG;

Otsuka Pharmaceutical Co, Ltd; STADA Arzneimittel AG; Travere Therapeutics, Inc.; Vera Therapeutics;
and Vertex Pharmaceuticals Incorporated.

ravere Therapeutics, In

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4. PeerVoice

Pathogenesis of IgA Nephropathy (IgAN):

The “Four Hit” Hypothesis

+ Hit 1: Increased production/

circulation of

galactose-deficient IgAl

Hit 2: Production of

auto-antibodies against

galactose-deficient IgAl

+ Hit 3: Formation of circulating
immune complexes

+ Hit 4: Deposition of circulating
immune complexes in glomerular
mesangium

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5. PeerVoice

+ Peyer's patches thought to be main
source of conventional surface
IgAl-expressing primed
mucosal B cells

+ By contrast, the adjacent lamina
propria is principally an effector site,
where surface IgA-expressing
primed mucosal B cells terminally
differentiate to plasma cells that
produce IgA

+ IgA is then transported across the
mucosal epithelium as secretory IgA

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6. PeerVoice

UK RaDak Registry: Kidney Outcomes for Patients With IgAN

Estimated Kidney Survival Rates Wi
Based on Time-Averaged Proteinuria

RaDaR

UK National Retrospective 2176 D ox
Registry of Rare’ cohort study
Kidney Diseases

2 o
ES
= œ
pl 3
8 2
® 3
8 3
E
£
5

2,299 adults and
140 children with 069
I I |

biopsy-proven IBAN

Time-Averaged
Proteinuria, g/g

10Y

Proteinuria >0.5 g/day or L
eGFR <60 mL/min/1.73m?
Median follow-up, 5.9 y o 02 04 06 08 1

Estimated Kidney Survival Rates

+ 50% of patients reached kidney failure or died

failure within lifetime

At a 1-mL/min/y decline in eGFR, -40% of adult patients aged <50 y at diagnosis reach kidney

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7. PeerVoice

US Kaiser Permanente Cohort: Kidney Outcomes for

Patients With IgAN

Incidence of Composite Kidney Endpoint
Kaiser Based on Time-Averaged UPCR
Permanente ross-sectional 1 >20 gle

Southern CA stud
Sa co IA 10-20 8/8
large integrat go
| healthcare system 5
| QQ, 655 adults with primary IgAN | Ss =
31% Asian/Pacific Islander Boa ilies
40% Hispanic/Latino 3
| 24% White and 3% Black Eos <05 g/g
5
6

o

‘Composite endpoint:
SP 250% eGFR decline
dd” Kidney failure or 0 25 8 75 0 vs 15

Mortality Follow-Up Time, y

+ 36% of patients reached composite kidney endpoint with 79.4 events per

1,000 patient-years (95% Cl, 69.6-90.7)
+ IgAN elevates risk for kidney outcomes starting at proteinuria levels 20.5 g/g

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8. PeerVoice

German CKD Cohort: Kidney Outcomes for Patients With IgAN

70| eGFR Slopes According to UACR Levels

GCKD

Prospective 5 60
en observational 8
Senn cohort study =
Kidney Disease 2010-2012 É 50 <01 8/8
£
A E 40! 20.1 to <0.6 g/g
© 421patients with E 20.6 to «14 g/g
qi | biopsy-proven IBAN CEA
nl A
[|
214 gig
| Median UACR, 04 g/g 20
Mean eGFR, 52.5 1 2 3 4 5 6
mL/min/1.73m? Time Since Baseline, y

Annual eGFR Loss, mL/mi

<0.1 g/g (n = 10)
20.1 to <0.6 g/g (n = 158)
20.6 to <1.4 g/g (n = 99)
214 g/g (n = 54)

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9. PeerVoice

Chinese Cohort: Kidney Outcomes for Patients With IgAN

Adjusted Hazard Ratios by Time-Averaged
Proteinuria (95% Cl)

Prospective
ity, cohort Complete Partial No
First Hospital EP Remission Remission Remission

<0.3g/d 03-05g/d 0.5-1.0 g/d 21.0 g/d

2,141 patients with
biopsy-proven IgAN
1.08 4.61 15.61

Ref (043-270) (237-896) (8:14-29,93)

Cox regression:
Time to kidney failure
= Mean follow-up, 5.8 + 4.4 y

+ 24% of patients reached kidney failure
+ Most patients progress to kidney failure within 15 years, and those with time-averaged proteinuria
levels 20.5 g/g experience worse outcomes

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10. PeerVoice

KDIGO 2025: Diagnosis of IgAN

IgA-dominant glomerulonephritis

Consider secondary causes:
+ IgA vasculitis
+ IRAN secondary to:
Viral infection (HIV, hepatitis)
~ Inflammatory bowel disease
Autoimmune disease
Liver cirrhosis
+ IBA-dominant infection-related GN

= i. ae
Treat primary
process

*Akey change in the 2025 guideline is a
recommendation to ensure an early diagnosis
and prompt treatment of IgAN

+ Akidney biopsy should be considered in all
adults with proteinuria 20.5 g/d (or equivalent)
in whom IgAN Is suspected

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Idiopathic IgAN

Score kidney biopsy
using MEST-C score

I
‘Quantify progression risk
at diagnosis using
International IgAN Prediction Tool
to inform discussions with
patients for shared decision-making

Patients and their caregivers
should be provided information
on national and international
patient advocacy organizations
for disease management
education and peer support

Secondary causes of
disease must be
ruled out

Diagnosis requires a
kidney biopsy: There
are still no validated
blood or urine tests
to diagnose IgAN
The MEST-C

score from the
biopsy remains the
standard for
assessing kidney
tissue damage

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11. PeerVoice

KDIGO 2025: Intervention for All Patients With IgAN

nephron ose

Inspecill populations

facu der
ee hypertitration, proteinuria and Blood pressure
Dos doter En, =
notes Lim notin
co ad gene
Pe Aaron cr Data SLT itn
sae ci)
EC
Term eee)

Always conser the option ot a ciel rit

* Definition of at-risk patients .

- All patients with proteinuria 20.5 g/day -
(even on supportive therapy) are

considered at risk of progression =

Therapeutic goal
Reduce kidney function decline to physiological rate
(<I mL/min/y)

Aim for proteinuria <0.5 g/day, ideally <0.3 g/day

Two approved agents in US not yet addressed in the KDIGO 2025 guidelines: atrasentan and iptacopan

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12. PeerVoice

Abbreviations and References

Pathogenesis of IgA Nephropathy (IgAN): The “Four Hit” Hypothesis

Reference(s): Cheung CK et al. Front Nephrol. 2024;3:1346769.
Gentile M et al. Clin Kidney J. 2023;16:1059-1070.

Why Target the Gut to Treat IgAN?

Abbreviation(s): APRIL: a proliferation-inducing ligand; BAFF: B-cell-activating factor; DC: dendritic cell; FDC: follicular
DC; GALT: gut-associated lymphoid tissue; IBA-IC: IgA immune complex; SEM: scanning electron microscope; TGF:
transforming growth factor.

Reference(s): Barratt J et al. Kidney Int Rep. 2020;5:1620-1624.

UK RaDaR Registry: Kidney Outcomes for Patients With IgAN
Abbreviation(s): eGFR: estimated glomerular filtration rate.

Reference(s): Pitcher D et al. Clin J Am Soc Nephrol. 2023;18:727-738.

US Kaiser Permanente Cohort: Kidney Outcomes for Patients With IgAN

Abbreviation(s): UPCR: urine protein:creatinine ratio.
Reference(s): Sim JJ et al. Nephrol Dial Transplant. 2025 Apr 30:gfaf084. doi10.1093/ndt/gfafO84.

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13. PeerVoice

Abbreviations and References (Cont'd)

German CKD Cohort: Kidney Outcomes for Patients With IgAN

Abbreviation(s): CKD: chronic kidney disease; UACR: urine albumin:creatinine ratio.
Reference(s): Stamellou E et al. Clin Kidney J. 2024;17(8):sfae230.

Chinese Cohort: Kidney Outcomes for Patients With IgAN
Reference(s): Shen X et al. Nephrol Dial Transplant. 2025;40:1137-1146.

KDIGO 2025: Diagnosis of IgAN

Abbreviation(s): GN: glomerulonephritis; KDIGO: Kidney Disease: Improving Global Outcomes; MEST-C: mesangial (M)
and endocapillary (E) hypercellularity, segmental sclerosis (S), interstitial fibrosis/tubular atrophy (T),

and crescents (C).

Reference(s): Floege J et al. Kidney Int. 2025;108:548-554.

KDIGO IgAN and IgAV Work Group; Rovin BH et al. Kidney Int. 2025;108(4S)SI-S71.

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14. PeerVoice

Abbreviations and References (Cont'd)

KDIGO 2025: Intervention for All Patients With IgAN

Abbreviation(s): CV: cardiovascular; DEARA: dual endothelin angiotensin receptor antagonist; HC: hydroxychloroquine;
MMF: mycophenolate mofetil; RAS: renin-angiotensin system; SGLT2: sodium-glucose cotransporter 2; TRF: targeted-
release formulation.

Reference(s): Floege J et al. Kidney Int. 2025:108:548-554.

KDIGO IgAN and IgAV Work Group; Rovin BH et al. Kidney Int. 2025;108(4S):S1-S71

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15. PeerVoice

Part 2 of 2: Navigating Treatment Selection in IgAN: Optimizing Outcomes and
Preserving Kidney Function

Jonathan Barratt, PhD, FRCP Jürgen Floege, MD
Professor of Renal Medicine Professor of Medicine
University of Leicester Division of Nephrology
Honorary Consultant Nephrologist RWTH Aachen University
The John Walls Renal Unit, University Hospital
University Hospitals of Leicester NHS Trust Aachen, Germany
Leicester, United Kingdom

This PeerVoice educational activity has been developed in partnership with KDIGO.

Copyright © 2010-2025, PeerVoice

16. PeerVoice

TT) "than Barratt, Pho, FRCP, has a financia interest/relationship or affiliation in the form of:
Consultant for Alexion Pharmaceuticals, Inc. AstraZeneca; Biogen Inc.; Calliditas Therapeutics AB;
AT F. Hoffmann-La Roche Ltd; Novartis AG; Otsuka Pharmaceutical Co, Ltd; Travere Therapeutics, Inc;
= Vera Therapeutics; and Vertex Pharmaceuticals Incorporated.
Grant/Research Support from Alexion Pharmaceuticals, Inc; Biogen Inc; Calliditas Therapeutics AB;
Novartis AG; Otsuka Pharmaceutical Co, Ltd; Travere Therapeutics, Inc; and Vertex Pharmaceuticals
Incorporated.

Júrgen Floege, MD, has a financial interest/relationship or affiliation in the form of:
Consultant for Alexion Pharmaceuticals, Inc. Amgen Inc; AstraZeneca; Bayer AG; Biogen Inc; Boehringer

y Ingelheim International GmbH; CSL Vifor; F. Hoffmann-La Roche Ltd; Novartis AG; Otsuka
TA Pharmaceutical Co, Ltd, STADA Arzneimittel AG; Travere Therapeutics, Inc;; Vera Therapeutics; and
Vertex Pharmaceuticals Incorporated.
Pm Speakers Bureau participant with Amgen Inc; AstraZeneca; CSL Vifor; F. Hoffmann-La Roche Ltd.

Novartis AG; Otsuka Pharmaceutical Co, Ltd; STADA Arzneimittel A\
Vera Therapeutics; and Vertex Pharmaceuticals Incorporated.
Advisory Board for Alexion Pharmaceuticals, Inc; Amgen Inc; AstraZeneca; Bayer AG; Biogen Inc;
Boehringer Ingelheim International GmbH; CSL Vifor; F. Hoffmann-La Roche Ltd; Novartis AG;

Otsuka Pharmaceutical Co, Ltd; STADA Arzneimittel AG; Travere Therapeutics, Inc.; Vera Therapeutics;
and Vertex Pharmaceuticals Incorporated.

ravere Therapeutics, In

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17. PeerVoice

Managing IgA Nephropathy (IgAN):

Case of a 25-Year-Old Hispanic Female

+ Proteinuria: ~2.5 g/day

+ Microscopic hematuria: (10-20 RBCs/hpf)

+ Blood pressure: 110/70 mmHg

* eGFR: 70 mL/min/1.73m?

+ No prior kidney disease; abnormalities noted 6 months ago

Y

Should a kidney biopsy be done at this stage?

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18. PeerVoice

Managing IgA Nephropathy (IgAN):

Case of a 25-Year-Old Hispanic Female (Cont'd)

+ Biopsy findings: Primary IgAN confirmed
+ Oxford score: MIEOSITOCO

“ Y

At risk of progression
(moderate proteinuria, histologic risk markers)

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19. PeerVoice

NeflgArd: Composite Renal Endpoint

Nefecon ”
es HR (95% Cl)
ds 12 21 ' 0.45
All patients (21182) (39/182) —e— | (0.26-0.75)
1
8 14 o 051
UPCR <15 g/g (9/17) (16/18) 1 (0.21-112)
18 36 1 042
UPCR 21.5 g/g (12/65) (23/64) —e | (021-083)
1

0125 025 05 2
—
Favors nefecon Favors PBO

NeflgArd: Phase 3, global multicenter, randomized, double-blind, PBO-controlled trial of adult patients (aged 218 y) with primary IBAN,
eGFR 35-90 mL/min/178m°? and persistent proteinuria (UPCR 20.8 g/g or proteinuria 21 g/24 h) despite optimized RAS blockade.
Patients (N = 364) were randomly assigned (11) to receive 16 mg/day oral capsules of Nefecon (TRF-budesonide) or matching PBO for 9
months, followed by a 15-month observational follow-up period off study drug. Composite endpoint: time from randomization to
confirmed reduction in eGFR by 30% or kidney failure.

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20. PeerVoice

NeflgArd: Proteinuria

o .
&

ge

E

$3

so

GE -404 e Nefecon 16 mg/d

SE A Placebo

E

= Treatment period, mo Observational follow-up period, mo

6 E 2 18 24
169 166 157 155 145
169 164 160 151 142
281 336 “613 4a 307
(29510161) (-39610-270) (-66210458) (-490t0-266) (28910 -218)
vs placebo. -a3 “73 -52 -32 -29 10
(1091029) (1801012) (881042) (1281075) (0083) (288 24)

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21. PeerVoice

NeflgArd: eGFR

© Nefecon 16 mg/d
A Placebo

Treatment period, mo Observational follow-up period, mo

Mean Absolute Change in eGFR
From Baseline, mL/min/1.73m?

o 3 6 9 2 18 24
Nefecon n 182 m 167 167 153 155 149
Placebo, n 182 178 m 164 161 150 146

m/min fen?
Nofecon 1 mg/d (16210399) (-00810284) (-080t0 215) (-296 100.08) (6.46 to -268) (804 10-41)

122 088 182 450 on
vs placebo. -950. 1200

~208 ~328 -456 -585
(-807 10 -0.98) (-44810 -204) (-686 10-322) (-716 10-451) (-n2ite-772) (137610 -1015)

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22. PeerVoice

NeflgArd: Adverse Events

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AE n(%) 8

Peripheral edema 3117) 7(4)

Hypertension 22 (12) 6(3)

Muscle spasms 22 (12) 7(4)

Acne 20 (M) 2m

Headache 19 (10) 14 (8)
Nasopharyngitis 17(9) 19 (10)
Face edema 14 (8) 1(05)
Dyspepsia Ea) 40)

Arthralgia 12(7) 4(2)

URTI 10 (5) 10 (5)
Insomnia 10 (5) 7(4)

Fatigue 10 (5) 7(4)

Rash 10 (5) 7(4)

Increase in weight 10 (5) 5(3)

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23. PeerVoice

TESTING: Composite Renal Endpoint

æ 80
e.
E
s 3
2852 ° PBO, 431%
CERES
SIE 40
ES Methylprednisolone, 28.8%
2579
805%
205020
Es" HR, 0.53
gt = (95% Cl, 0.39-0.72; P < 001)
& o

o 1 2 3 4 5 6

Time to Event, y

TESTING: Multicenter, double-blind, randomized clinical trial of patients with IgAN, proteinuria 21 g/day, and eGFR of 20 to 120
mL/min/1.73m? after at least 3 months of optimized background care. Patients (N = 503) were randomized in a 1 ratio to receive oral
methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or PBO (n = 126). After 262 patients
were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning
by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent patients (121 in the oral
methylprednisolone group and 120 in the PBO group). Composite endpoint: 40% decline in eGFR, kidney failure (dialysis, transplant), or
death due to kidney disease.

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24. PeerVoice

TESTING: Proteinuria and eGFR

Proteinuria eGFR
=
E
a
< E
N =
> E

ui
5 $
E
É
[o]
®
03612 24 36 48 60 72 84 96
036 12 24 36 48 60 72 84 96
Mean Plot Over Time, h (95% Cl) Mean Plot Over Time, h (95% Cl)
= Methylprednisolone —— Placebo

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25. PeerVoice

TESTING: Adverse Events

Serious AE, n (%) i a)
Hospitalization/

prolonged hospitalization 28 (1) 7@)
Death 4(2) 00)
life-threatening 40) 0(0)
Severe infection requiring

hospitalization um) 30
P.jirovecii pneumonia 42) 0)
Pneumonia/respiratory tract

infection 30m AE)
Sepsis 2(0.8) 1(0.4)
Urinary tract infection 2(0.8) 00)
Gastrointestinal bleeding

requiring hospitalization 30 1(0.4)
Clinical evidence fractures/

osteonecrosis 30 00)
New-onset diabetes mellitus 2(0.8) o(o)

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26. PeerVoice

PROTECT: Proteinuria

Interim analysis Final analysis

en sen
$ Irbesartan
© -20
5
ö
& =“ ® Sparsentan
3 -60 Y

o 36 10

Time, wks

Ry

Sparsentan M 31% Y vs Irbesartan @ 11%

More patients achieved
complete proteinuria
remission (UPE <0.3 g/d)

PROTECT: Phase 3 double-blind, randomized, active-controlled international trial of adult patients (aged 218 y) with biopsy-proven
primary IgAN and proteinuria of at least 10 g/day despite maximized RAS inhibition for at least 12 weeks, Patients (N = 406) were
randomly assigned (11) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral
irbesartan once daily) based on a permuted-block randomization method

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27. PeerVoice

PROTECT: eGFR, Kidney Survival, and Adverse Events

eGFR Change,
mL/min/1.73m?
bobro

3

o 36
Time, wk

Chronic Slope Total Slope
(Wks 8-10) (OFWitio)

mSparsentan

mibesaran

Sparsentan | Irbesartan

Absoluto change in
GFR (mL /min/1.73m2)

Sparsentan vs Irbesartan
Baseline to Wk 110
5.8 vs |] -9.5

* 40% eGFR reduction, end-stage kidney disease, death,

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Sparsentan | Composite kidney
failure endpoint* ax 13%
Irbesartan isfation of wiih
initiation of IST wit
no renal indication = ex
Safety

Sparsentan had a safety profile
comparable to irbesartan
Peripheral edema was similar in
both groups, with no increases in

body weight

No drug-induced liver injury

occurred

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28. PeerVoice

STOP-IgAN: Effects of Two Immunosuppressive Treatment

Protocols for IgAN

Events/N

Full Clinical Remission

OR (97.5% Cl)

Subgroup = | a
= en
Tigh GFR
FAS 3/54 1/55 5.31 (107-2636) 02
Available cases 3/51 1/47 5.38 (1-26.28) 018
Tow GFR
fas ins am 358 020-5580) | 202
ae va 3/24 224 (016.072) | 491
[arr oecrease | Evente/N
218 min 7am Supportive Conisosteroid CR(E/S% CI)
Subgroup ie Ben
Tigh GFR
FAS 16/54 12/55 0.64 (0.24-175) 324
Available cases 14/52 10/53 0.62 (0.22-18) 318
Ton FR
FAS 6/26 9/27 167 (0.41-6.79) 415
Available cases 4/24 7/25 179 (0.37-8.64) Al

STOP-IgAN: To assess the role of IST in IgAN, patients (N = 162) with IBAN and proteinuria >0.75 g/d after 6 months of optimized
supportive care were randomized into two groups: continued supportive care or additional immunosuppression (GFR 260
mL/min/1.73m?: 6-month corticosteroid monotherapy; GFR = 30 to 59 mL/min/1.73m:: cyclophosphamide for 3 months followed by
azathioprine plus oral prednisolone).

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29. PeerVoice

STOP-IgAN: Adverse Events

Serious AE, n

High GFR

Mor

Atleast I serious AE 6

Total serious AES 19 14 9 19
Total infectious events 69 15 48 59
aes a A a A
Death 1 o o 1
DER ® o a 5
Leukopenia 3 1 o 1
Malignancy o o o 2
Impaired glucose

tolerance/diabetes 1 9 1 1
mellitus

a © = o a
Fracture o 1 o o
Osteonecrosis o o o o

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30. PeerVoice

EMPA-KIDNEY: Kidney Disease Progression

Glomerular Diseases

1
\ R

1 HR (95%

1

IgAN 51/413 eras | _ gi 0.67(0.46-0.97)

Focal segmental 1

glomerulosclerosis Lie 1807: 135 (0.65-2.81)
H

Other

eritema 471342 59/316 078 (053-116)

‘All participants 0.71(062-080)

0.4 06 081012 16

— —
Favors Empagliflozin Favors PBO

EMPA-KIDNEY: Phase 3 international randomized controlled trial of patients with eGFR 20 to <45 mL/min/1.73m, or 45 to <90
mL/min/1.73m? with UACR) of 200 mg/g or higher at screening. Patients (N = 6,609) were randomly assigned (1:1) to 10 mg oral
‘empagliflozin once daily or matching PBO. There were 817 patients with IBAN enrolled (49% of glomerular disease subgroup).

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31. PeerVoice

KDIGO 2025: Practical Therapeutic Considerations for

25-Year-Old Female

+ 25-year-old Hispanic female + No prior kidney disease;

Proteinuria: -2.5 g/day abnormalities noted 6 mo ago
Microscopic hematuria Biopsy findings: Primary IgAN confirmed
(10-20 RBCs/hpf) Oxford score: MIEOSITOCO

Blood pressure: 110/70 mmHg

- eGFR: 70 mL/min/1.73m?

Treatments for IgAN itself Treatments for CKD/nephron loss
Nefecon (TRF-budesonide) RAS inhibition
Systemic glucocorticoids Sparsentan
Iptacopan® SGLT2 inhibition
Atrasentan®

* Approved in US; not yet addressed in KDIGO 2025 guidelines.

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32. PeerVoice

Abbreviations and References

Managing IgA Nephropathy (IgAN): Case of a 25-Year-Old Hispanic Female
Abbreviation(s): eGFR: estimated glomerular filtration rate; RBCs/hpf: red blood cells per high power field.
Reference(s): Courtesy of Jonathan Barratt, PhD, FRCP; Jurgen Floege, MD; September 2025.

Managing IgA Nephropathy (IgAN): Case of a 25-Year-Old Hispanic Female (Cont'd)
Reference(s): Courtesy of Jonathan Barratt, PhD, FRCP; Jürgen Floege, MD; September 2025.

NeflgArd: Composite Renal Endpoint
Abbreviation(s): PBO: placebo; RAS: renin-angiotensin system; TRF: targeted-release formulation; UPCR: urine

protein:creatinine ratio.
Reference(s): Lafayette R et al. Lancet. 2023;402:859-870.

NeflgArd: Proteinuria
Reference(s): Lafayette R et al. Lancet. 2023;402:859-870.

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33. PeerVoice

Abbreviations and References (Cont'd)

NeflgArd: eGFR
Reference(s): Lafayette R et al. Lancet. 2023;402:859-870.

NeflgArd: Adverse Events

Abbreviation(s): AE: adverse event; URTI: upper respiratory tract infection.
Reference(s): Lafayette R et al. Lancet. 2023:402:859-870.

TESTING: Composite Renal Endpoint

Reference(s): Lv J et al. JAMA. 2022;327:1888-1898.

TESTING: Proteinuria and eGFR

Abbreviation(s): CKD-EPI: Chronic Kidney Disesas Epidemiology; UPE:urins protein exertion.
Reference(s):

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34. PeerVoice

Abbreviations and References (Cont'd)

TESTING: Adverse Events
Reference(s): Lv J et al. JAMA. 2022:3:

1888-1898.

PROTECT: Proteinuria
Reference(s): Rovin BH et al. Lancet. 2023;402:2077-2090.

PROTECT: eGFR, Kidney Survival, and Adverse Events

Abbreviation(s): IST: immunosuppressive therapy.
Reference(s): Rovin BH et al. Lancet. 2023;402:2077-2090.

STOP-IgAN: Effects of Two Immunosuppressive Treatment Protocols for IgAN

Abbreviation(s): FAS: full analysis set.
Reference(s): Rauen T et al. J Am Soc Nephrol. 2018;29:317-325.

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35. PeerVoice

Abbreviations and References (Cont'd)

STOP-IgAN: Adverse Events
Reference(s): Rauen T et al. J Am Soc Nephrol. 2018;29:317-325.

EMPA-KIDNEY: Kidney Disease Progression
Reference(s): EMPA-KIDNEY Collaborative Group. Lancet Diabetes Endocrinol. 2024;12:51-60.

KDIGO 2025: Practical Therapeutic Considerations for 25-Year-Old Female

Abbreviation(s): SGLT2: sodium-glucose cotransporter 2.

Reference(s): Courtesy of Jonathan Barratt, PhD, FRCP; Jürgen Floege, MD; September 2025.
Floege J et al. Kidney Int. 2025:108:548-554.

KDIGO IgAN and IgAV Work Group; Rovin BH et al. Kidney Int. 2025;108(4S):S1-S71.

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