1. PL I. CKD at glance Screening to Update Latest Treatment.pdf

a

1. CKD at glance :
Screening to Update Latest Treatment
Haerani Rasyid
2025

2. Disclaimer
•All information presented in these slides are intended for scientific exchange and not to solicit off-label use.
•Please refer to local prescribing information for all drugs mentioned in this presentation for further details before prescribing.
•In Indonesia, Empagliflozin is indicated in adult patients with Type 2 Diabetes Mellitus to improve glycemic control, when Metformin used
alone does not provide adequate glycemic control. Empagliflozin is indicated as a combination with:
▪Metformin,
▪Metformin and a Sulfonylurea,
▪Metformin and Pioglitazone
when the existing therapy, along with diet and exercise, does not provide adequate glycemic control. For study results with respect to
combination, effects on glycemic control and cardiovascular events, and the populations studied, see sections Special warnings and precautions
for use, Interaction with other medicinal products and other forms of interactions, and Pharmacodynamic properties.
•In Indonesia, Empagliflozin is indicated in adults for the treatment of chronic heart failure.
•In Indonesia, Empagliflozin is indicated for the treatment of Kidney Disease.

3. Chronic Kidney Disease :
What do we know so far?

4. Chronic Kidney Disease
defined as abnormalities of kidney structure or function,presentfor >3 months,
with implications for health
1
CKD
Criteria for CKD (either of the following present for >3 months)
Markers of kidney damage
•Albuminuria (UACR ≥30 mg/g)
•Urine sediment abnormalities (e.g. dysmorphic
erythrocytes, acanthocytes)
•Electrolyte and other abnormalities due to tubular
disorders
•Abnormalities detected by histology
•Structural abnormalities detected by imaging
•History of kidney transplantation
Decreased excretory function
•eGFR <60 ml/min/1.73 m
2
CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; UACR, urine albumin-to-creatinine ratio;
1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppl 2013;3:1
KDIGO initiative classifies an individual as having CKD if structural or functional
abnormalities persist for >3 months, and if they have implications
for health.
Structural abnormalities include glomerulosclerosis and interstitial fibrosis; functional abnormalities
include a reduced GFR,loss of albumin or red blood cells into the urine (albuminuria or haema-
turia, respectively), and blood electrolyte disturbances.
CKD classification and staging takes into account the cause of kidney disease, and it
grades the severity of kidney dysfunction using two measurements:
GFR, either estimated GFR (eGFR) or measured GFR (mGFR), as an indicator-
for the excretory capacity of the kidneys (groups G1–G5)
The extent of albuminuria, a marker of impaired filtration barrier function (groups A1–A3)
Nature Reviews Disease Primers | (2025) 11:8

5. Criteria for diagnosis and risk stratification of CKD require both
eGFR and UACR
Abnormalities of kidney
structure and/or function for
>3 months with implications
for health
CKD
Decreased eGFR
<60 ml/min/1.73 m
2
Albuminuria A2–A3
(>30 mg/g)
and/or
*If no o ther markers of kidney disease, no CKD
CKD, chronic kidney d isea se; eGFR, estimated g lomerular filt ra tion rat e; KDI GO, Kidney Disease: Improv ing Glob al O utco mes; U ACR, urine albumin-to-creatinine ratio
Kid ney Disease: Improving Globa l Outcomes (KDIGO) Diab etes Work Group . Kid ney Int. 202 0;9 8(sup pl):S1-S115
Persistent albuminuria categories
Description and range
A1 A2 A3
Normal to mildly
increased
Moderately
increased
Severely
increased
<30 mg/g
<3 mg/mmol
30–300 mg/g
3–30 mg/mmol
>300 mg/g
>30 mg/mmol
eGFR categories
(ml/min/
1.73 m
2
)
description and
range
G1 Normal or high≥90 Low*
Moderately
increased
High
G2 Mildly decreased60–89 Low*
Moderately
increased
High
G3a
Mildly to
moderately
decreased
45–59
Moderately
increased
High Very high
G3b
Moderately to
severely decreased
30–44 High Very high Very high
G4Severely decreased15–29 Very high Very high Very high
G5 Kidney failure<15 Very high Very high Very high
KDIGO:
classification and prognosis
of CKD
Risk of progression
Risk of progression
Prognosis of CKD by GFR and Albuminuria

6. Reduced eGFR and increased albuminuria are independently associated with
increased risk of CV death and kidney events
*
eGFR ≥90
eGFR 60-89
eGFR <60
0
1
2
3
4
5
6
A3 (sev erely increased)
A2 (m oderately increased)
A1 (norm al to mildly increased)
Risk of CV death (HR)
Baseline
eGFR
†
eGFR ≥90
eGFR 60-89
eGFR <60
0
5
10
15
20
25
A3 (sev erely
increased)
A2 (m oderately
increased)
A1 (norm al to
mi ldly increased)
Risk of kidney event (HR)
0.89
Baseline UACR
Baseline
eGFR
†
CV death Kidney events
‡
5.93
3.37
1.85
3.61
2.52
1.22
1.00
1.96
22.20
16.19
3.95
16.13
3.177.82
0.45
1.00
Baseline UACR
*Average time to follow-up for risk assessment was 4.3 years;
†
eGFR in ml/min/1.73 m
2
;
‡
A kidney event was defined as death as a result of kidney disease, requirement for
dialysis or transplantation, or doubling of serum creatinine to >2.26 mg/dl. Figure used with permission of The American Society of Nephrology, from Ninomiya T et al. J Am
Soc Nephrol 2009;20:1813; permission conveyed through Copyright Clearance Center, Inc
CV, cardiovascular; eGFR, estimated glomerular filtration rate; UACR, urine albumin-to-creatinine ratio
Ninomiya T et al.J Am Soc Nephrol 2009;20:1813
0.89

7. Worldwide, CKD as a cause of years of life lost has risen in importance and is
projected to continue to rise
1 Neonatal disorders
Leading causes 1990
1
2 Lower respiratory infections
3 Diarrhoeal diseases
4 Ischaemic heart disease
5 Stroke
6 Congenital anomalies
7 Tuberculosis
8 Road injuries
9 Measles
10 Malaria
11 COPD
12 Protein-energy malnutrition
13 Drowning
14 Self-harm
15 Meningitis
16 Cirrhosis
17 Lung cancer
18 Tetanus
19 HIV/AIDS
20 Interpersonal violence
24 Chronic kidney disease
28 Diabetes
1 Neonatal disorders
Leading causes 2007
1
2 Lower respiratory infections
3 Ischaemic heart disease
4 Diarrhoeal diseases
5 HIV/AIDS
6 Stroke
7 Malaria
8 Road injuries
9 Congenital anomalies
10 Tuberculosis
11 COPD
12 Cirrhosis
13 Self-harm
14 Lung cancer
15 Meningitis
16 Chronic kidney disease
17 Diabetes
18 Drowning
19 Protein-energy malnutrition
20 Interpersonal violence
1 Ischaemic heart disease
Leading causes 2017
1
2 Neonatal disorders
3 Stroke
4 Lower respiratory infections
5 Diarrhoeal diseases
6 Road injuries
7 COPD
8 HIV/AIDS
9 Congenital anomalies
10 Malaria
11 Tuberculosis
12 Lung cancer
13 Cirrhosis
14 Self-harm
15 Diabetes
16 Chronic kidney disease
17 Alzheimer’s disease
18 Interpersonal violence
19 Liver cancer
20 Meningitis
1 Ischaemic heart disease
Leading causes 2040
2
2 Stroke
3 Lower respiratory infections
4 COPD
6 Alzheimer’s disease
7 Diabetes
8 Road injuries
9 Lung cancer
10 Diarrhoeal diseases
11 Self-harm
12 HIV/AIDS
13 Liver cancer
14 Hypertensive heart disease
15 Colorectal cancer
16 Tuberculosis
17 Congenital defects
18 Neonatal preterm birth
19 Breast cancer
20 Falls
5 Chronic kidney disease
Red: Communicab le d iseases. Blue: Noncommunicable diseases. Green: Other ca uses
COPD, chronic obstructive pulmo nary disease; HIV/AIDS, human immunodeficiency virus/acquired immune deficiency s yndrome
Ref erences : 1. GBD 2017 Causes of Deat h Collaborators. Lancet 2018;392:1736; 2. Foreman K J et al. Lancet 2018;392:2052
The incidence of CKD continues to rise….
“The increase is like a train that keeps going”

8. 90
60
30
eGFR
Howcanwe
stopthetrain?
It’s important to early screening of CKD…

9. Early Screening of CKD
•A systematic review suggested that screening for CKD is cost-effectivein people with
diabetes and hypertension.
•However, clinical trials have not been conducted to determine whether or not an
intervention to detect, risk-stratify, and treat CKD would improvethe health outcomes.
•Cost-effective analysis of population for CKD incorporating evidence-based treatment
with SGLT2i: concluded that screening adults for albuminuria to identify CKD could be
cost-effective.
•KDIGO: early identification of CKD in people at risk, who are usually asymptomatic,
would likely be beneficial in the community and primary care settings.
Kidney International (2024) 105 (Suppl 4S), S117–S314

10. Evaluation of cause of CKD
Kidney International (2024) 105 (Suppl 4S), S117–S314

11. Evaluation of cause of CKD
Kidney International (2024) 105 (Suppl 4S), S117–S314

12. When to refer to a nephrologist?
•Indications for referral to specialist kidney care services for people with
kidney disease
✓Acute kidney injury or abrupt sustained fall in eGFR
1
✓Progression of CKD
1
,

defined as:
•A decline in eGFR category accompanied by a
25% or greater drop in eGFR from baseline; and/or
•Rapid progression of CKD defined as a sustained
decline in eGFR of more than 5 ml/min/1.73 m
2
✓Moderately increased risk of CKD progression,
1–4
defined as:
•eGFR <30 ml/min/1.73 m
2
or
•Severely increased albuminuria*
i.e. UACR ≥300 mg/g or
•High risk of progression to kidney failure according
to KFRE (e.g. >3–5% risk at 5 years)
✓CKD and hypertension refractory to treatment with four
or more antihypertensive agents
1
✓Persistent abnormalities of serum
potassium, calcium or phosphate
1,5
✓Recurrent or extensive nephrolithiasis
1
✓Hereditary kidney disease
1
✓Signs of nephrotic syndrome (heavy
proteinuria with low serum albumin)
or unexplained haematuria
4
Kidney International (2024) 105 (Suppl 4S), S117–S314
See Guideline Recommendation

13. Guidelines recommend the use of SGLT2 inhibitors for their benefits across the
cardio, renal and metabolic spectrum
SGLT2 inhibitors are recommended by global guidelines and societies as first-line therapy for
people with T2D and at risk of cardio-renal disease
1–5

KDIGO 2024 clinical practice guideline
updates
for diabetes management in CKD
1
ADA-KDIGO 2022
consensus report
2
Recommend SGLT2 inhibitorsas
first-line therapy for people with diabetes and CKD
Primary Care Diabetes Europe 2022
position statement
5
Recommend SGLT2 inhibitors for
people with T2D and ASCVD, HF or
CKD (high CV risk)
including people who are
overweight/obese
5
Recommend SGLT2 inhibitorsas
initial therapy in T2D with or at high risk
of ASCVD, HF orCKD
3,4
ADA 2024 standards of
medical care
3
ADA-EASD 2022
consensus report
4
SGLT2 inhibitorsare listed as a
treatment option for people with T2D
who require glycaemic and weight
management
3,4
ADA, American Diabe tes Association; ASCVD, atheros cle rotic cardiovascular disease; CKD, chro nic kidne y dise ase; CV, cardio vascular; E ASD, Euro pean Association for the Study of Diabetes; HF, heart failure ;
KDIGO, Kidney Disease: Improving Global Outc omes ; SGLT2, sodium-glucose co-trans porter-2; T2D, type 2 diabetes. 1. Kidney Disease: Improving Global Outcome s (KDIGO) CKD Work Group. Kidney Int
2022;102:S1; 2. de Boer IH et al. Diabetes Care 2022;45:3075; 3. American Diabetes As sociation. Diabetes Care 2023;46:S1; 4. Davies M J et al. Diabetes Care 2022;45:2753; 5. Seidu S et al. Prim Care Diabetes
2022;16:223

14. KDIGO 2024 – New Recommendation Highlight
Holistic approach for improving outcomes in patients with T2DM & CKD
Kidney International (2024) 105 (Suppl 4S), S117–S317

15. SGLT2 inhibitors have come a long way in the past decade: from improving glucose control in people
with T2D, to CV and kidney benefits in people with CKD, independent of T2D
SGLT2 inhibitors have demonstrated…
Phase III
trials
Metabolic benefits in people
with T2D
1–4
CV and kidney benefits in
people with T2D and CVD
5–14
CVOTs
CV benefits in people
with HFrEF and HFpEF,
independent of T2D*
15–17
HF
trials
CKD
trials
Kidney benefits in people
with CKD, independent of T2D*
18,19
CKD
trials
People with CKD
± T2D
People with
HF ± T2D
People
with T2D
± CVD,
CKD or HF
†
R
E
NA
L
C
A
R
D
IO
M
ETA
B
O
L
I
C
Recent SGLT2i Studies on Delay
Progression for CKD

16. EMPA-KIDNEY was designed to investigate whether empagliflozin reduces the risk of
kidney disease progression or CV death in patients with CKD
Phase III randomised double-blind placebo-controlled trial
Population: designed to assess the effects of empagliflozin in a broad range of patients (~6000) with CKD at risk
of progression, including many patients without diabetes and patients with low levels of proteinuria
Placebo once daily +
standard of care*
EMPA-KIDNEY
Evidence of CKD at
risk of kidney disease
progression
Empagliflozin 10 mg once daily
+ standard of care*
Trial design
Kidney disease progression
Outcome
s
Composite primary outcome
CV deathOR
Kidney function loss defined as:
•Sustained reduction of ≥40%eGFR
decline from baseline
•Sustained decrease in
eGFR to<10 ml/min/1.73 m
2
End-stage kidney disease
•Defined as initiation of
chronic dialysis or
kidney transplant
Renal death
Key secondary
outcomes
‡
•All-cause hospitalisation
•First occurrence of hospitalisation for
heart failure or CV death
•All-cause mortality
Between 15 May 2019 and 16 April 2021, 6609 patients were randomised
*Guideline-directed medical therapy;
†
Other outcomes prespecified
CKD, chronic kidney disease; CV, cardiovascular; eGFR, estimated glomerular filtration rate
The EMPA-KIDNEY Collaborative Group. N Engl J Med 2023;388:117
Event driven: 1070 primary outcomes: 90%
power at p<0.05 to detect an 18% relative
risk reduction

17. Key exclusion criteria*
•Currently receiving an SGLT2 or dual SGLT1/2 inhibitor
•T2D and prior atherosclerotic CV disease with eGFR
>60 ml/min/1.73 m
2
•Receiving dual RAS inhibition (two of ACEi,
ARB, DRI)
•Any IV immunosuppression therapy in the
last3months or anyone currently on
>45mgprednisolone (or equivalent)
•Maintenance dialysis, functioning kidney transplant or
scheduled living donor transplant
•Polycystic kidney disease
•T1D
†
EMPA-KIDNEY: key inclusion and exclusion criteria
1,2
Key inclusion criteria*
•Age ≥18 years or at ‘full age’, as required by
local regulation
•Evidence of CKD at risk of kidney disease progression,
defined by ≥3 months before and at the time of
screening visit
–eGFR ≥45 to <90 ml/min/1.73 m
2
with
UACR A2–A3 (≥200 mg/g), or
–eGFR ≥20 to <45 ml/min/1.73 m
2
•Clinically appropriate doses of single-agent
RAS inhibition with either ACEi or ARB, unless either is
not tolerated or not indicated
•Neither requires an SGLT2 or SGLT1/2 inhibitor, nor that
such treatment is inappropriate
eGFR calc ulated using CKD-EPI formula. *For full details, refe r to publication s upplement;
†As o f January 2020, the proto col was amended to allo w c urrently enrolled patients with T1D to continue in the study and limit scre ening of new patients with T1D due to a sponsor decision. At that time,
the DMC did not report any safety co nc erns in patients with T1D
ACEi, angiotensin-converting enzy me inhibitor; ARB, ang iotensin rec eptor blocker; CKD, c hronic kidney diseas e; CKD-EPI, Chronic Kidney Dis ease Epidemiology Co llaboration; DMC, Data Monitoring Committe e; DRI, direct renin inhibitor; eGFR, e stimated glomerular filtration rate; IV,
intravenous; RAS, renin–ang io tensin sy ste m; SGLT, s odium-glucose co-trans porter; T1D, type 1 diabetes; T2D, ty pe 2 diabetes; UACR, urine albumin-to-cr eatinine ratio
1. The E MPA-KIDNEY Collaborative Group. N Eng l J Me d 2023;388:117. 2. The EMPA-KIDNEY Collaborative Group. Nephrol Dial Transplant 2022;37:1317
EMPA-KIDNEY population
1
eGFR ≥45 to
<90 ml/min/1.73 m
2
and
UACR ≥200 mg/g
or
eGFR ≥20 to <45 ml/min/1.73 m
2

18. EMPA-KIDNEY included understudied CKD Patients with Low eGFR and
without Albuminuria
A1 A2 A3
Normal to mildly increasedModerately increasedSeverely increased
<30 30–300 >300
G1 ≥90
G2 60–89
G3a 45–59
G3b 30–44
G4 15–29
G5 <15
eGFR Category, Description, and Range (ml/min/1.73 m
2
)
Low risk* Moderately increased riskHigh riskVery high risk
Albuminuria Stage, Description, and Range (mg/g)
FIDELIO-DKD
1
eGFR ≥25 - <60ml/min/1.73
m
2
and UACR ≥30 mg/g –
<300 mg/g and presence of
diabetic retinopathy
or
eGFR ≥25 - <75ml/min/1.73
m
2
and UACR≥300 mg/g
EMPA-KIDNEY
Population
3
eGFR ≥20 to <45
ml/min/1.73m
2
or
eGFR ≥45 to
<90ml/min/1.73m
2

and UACR ≥200 mg/g
eGFR ≥25 to
≤75ml/min/1.73m
2
and UACR ≥200 mg/g to
≤5000 mg/g
DAPA-CKD
2
Compa rison of studies sho uld be interp reted with ca ution due to dif fere nc es in study d esig n, pop ula tions and method ology
Adapted from Ki dney Disease: Improving Global Outcomes (KDIGO) CKD Work Group.Kidney Int S uppl2013;3:1.
*Defi ned as l ow ri sk for developing mineral bone disorder and cardiovascular compli cat ions if t here are no ot her markers of kidney di sease or CKD
eGFR, estimat ed glomerular fil trat ion rate; UACR, urine albumin-to-creat inine rati o
1. Bak ris GL et al. Am J Nephrol 2019;50:333; 2. Heerspi nk H et al. Nephrol Dial Transplant 2020; doi: 10.1093/ndt/gf z290; ; 3. Cl inic alTri als.gov. NCT03594110 (accessed Aug 2020)

19. EMPA-KIDNEY Studies a CKD Population With an Unmet Clinical Need
CKD patients with low eGFR and no or mildly increased albuminuria make up to one third of the
total CKD population
CKD patients with low eGFR and no or mildly increased albuminuria have a high unmet clinical
need, since therapeutic options are limited. RAASi has not been demonstrated to lower kidney
function decline in this patient population
EMPA-KIDNEY includes patients over a broad eGFR range with- and without albuminuria as well as
with- and without diabetes
EMPA-KIDNEY covers a large range CKD patients at various stages of disease, and exclusively also
includes CKD patients with low eGFR and no or only mildly elevated albuminuria. The patients
have a relevant risk for CKD progression, with an annual eGFR decline of 4-7%
CKD, chronic kidney disease; eGFR, estimated glomerular filtration rate; RAASi, renin-angiotensin-aldosterone system inhibition

20. Summary of baseline characteristics
1,2
31%
22%
25%
22%
PRIMARY KIDNEY DIAGNOSIS
Diabetic kidney
disease
HTN/renovascular
Glomerular disease
Other/unknown
6609
had an eGFR
<30 ml/min/1.73 m
2
35%
48%
had
CV disease*
27%
had no prior
history of diabetes
54%
had a UACR <300 mg/g
randomised participants from 8 countries, of which
*Prior CV disease defined as self-reported history of myocardial infarction, heart failure, stroke, TIA or PAD. CV, cardiovascular; eGFR, estimated glomerular filtration rate; HTN, hypertensive;
PAD, peripheral artery disease; TIA, transient ischaemic attack; UACR, urine albumin-to-creatinine ratio
1. The EMPA-KIDNEY Collaborative Group. N Engl J Med 2023;388:117; 2. The EMPA-KIDNEY Collaborative Group. Nephrol Dial Transplant 2022;37:1317

21. Primary composite outcome
Kidney disease progression or CV death
1,2

0 0.5 1 1.5 2 2.5
30
10
0
Years of follow-up
Empagliflozin 10 mg
Participants with event (%)
Placebo40
20
Placebo N(%):
558 (16.9%)
Events/100 PY: 8.96
Empagliflozin N(%):
432 (13.1%)
Events/100 PY: 6.85
Placebo 3305 3250 3129 2243 1496 592
Empagliflozin3304 3252 3163 2275 1538 624
Patients at risk, n
HR 0.72
(95% CI 0.64, 0.82)
p<0.001
RRR
28%
NNT=28*
ARR: 3.6 %
†
*NNT: 28 (95% CI 19 , 53) per 2 years a t risk
2
;
†
ARR for the p rimary composite outcome o f kidney d isea se prog ression or CV death is 3.6% per PY a t risk. Figure ada pted from Figure 1 of reference.
Kid ney disease progression defined as end-stag e kidney d isea se, a sustained decline in eGFR to <10 ml/min/1.73 m
2
, renal deat h, or a susta ined d ecline of ≥ 40% in eGFR from ra nd omisat io n
ARR, absolute risk reduction; CV, cardiova scular, eGFR, estima ted glomerula r filtration rate; NNT, number needed t o t rea t; PY, pat ient-years; RRR, rela tive risk reduction
1. The EMPA-KIDNEY Co lla borative Group. N Eng l J Med 202 3;3 88:117; 2 . Boehring er Ingelheim. Data o n file. 2022

22. Key secondary outcome:
all-cause hospitalisation (first and recurrent)
1,2
0.5 1.0 1.5 2.0 2.5
1.0
0.8
0.6
0.4
0.2
Mean number of events
Placebo
Empagliflozin 10 mg
Years of follow-up
0
0
Placebo 29.2% per year
Empagliflozin 24.8% per year
Patients at risk, n
Placebo 3305 3283 3241 2500 1705 775
Empagliflozin3304 3283 3245 2493 1719 798
HR 0.86
(95% CI 0.78, 0.95)
p=0.003
RRR
14%
Key s econdary outc omes we re prespecified to be adjus ted for multiple testing using the Hochberg 'step-up' procedure with a family-wis e error rate of 0.029; semi-parame tric joint frailty model was used. The analy sis of ho spitalis atio ns for any cause include d the first and all subsequent
events , so o nly the rates are shown; 1611 hospitalisations occurred among 960 patients in the empagliflozin group, and 1895 hospitalisations occurred among 1035 patients in the placebo group
RRR, re lative risk reduction
1. The E MPA-KIDNEY Collaborative Group. N Engl J Me d 2023;388:117; 2. Boehringer Ingelheim. Data on file. 2022

23. Subgroup analysis of primary endpoint:
key subgroups of interest
Empagliflozin 10 mg Placebo
n with event/N analysed HR (95% CI) HR (95% CI)
Overall 432/3304 558/3305 0.72 (0.64, 0.82)
Baseline diabetes
No 214/1779 252/1790 0.82 (0.68, 0.99)
Yes 218/1525 306/1515 0.64 (0.54, 0.77)
Baseline eGFR
<30 247/1131 317/1151 0.73 (0.62, 0.86)
30 to <45 140/1467 175/1461 0.78 (0.62, 0.97)
≥45 45/706 66/693 0.64 (0.44, 0.93)
Baseline UACR, mg/g
A1 (<30) normal to mildly increased 42/665 42/663 1.01 (0.66, 1.55)
A2 (30 to ≤300) moderately increased 67/927 78/937 0.91 (0.65, 1.26)
A3 (>300) severely increased 323/1712 438/1705 0.67 (0.58, 0.78)
0.25 0.5 1 2
Favours empagliflozinFavours placebo
Primary outco me was kidney disease progression (defined as E SKD, sustained eGFR decline o f ≥40% or to <10 ml/min/1.73 m
2
, o r adjudicated renal death) o r CV death. E vents co nfirme d or unrefuted by
adjudication are considered as an endpoint eve nt
CV, cardiovascular; eGFR, e stimated glomerular filtration rate; ESKD, e nd-stag e kidney disease; U ACR, urine albumin-to-creatinine ratio
The EMPA-KIDNEY Collaborative Group. N Engl J Me d 2023;388:117
What’s the effect
on progression for
eGFR?

24. Empagliflozin reduced the rate of progression of CKD by
approximately 50%
Empagliflozin reduced eGFR decline across UACR subcategories
25
30
35
40
0 6 12 18 24 30 36
eGFR (ml/min/1.73 m
2
)
Month
Placebo Empagliflozin 10mg
2Baseline
Chronic slope,*
mean (SE)
†
Empagliflozin Placebo Difference (95% CI)
-1.37 (0.08)-2.75 (0.08) 1.37 (1.16, 1.59)
UACR ≥300
-0.11
-0.49
-2.35
-0.89
-1.69
-4.11
-4.5
-4
-3.5
-3
-2.5
-2
-1.5
-1
-0.5
0
Rate of change in chronic eGFR
slope (ml/min/1.73m
2
/year)
UACR <30UACR ≥30 to <300
Prespeci fied tertiary outcomes incl uded the mean annual rates of change in eGFR in ml/min/1.73 m
2
/year from 2 months to t he final fol low-up visit (chronic slope, ref erred to as 'Long-term’ i n f igure 3) bytreat ment all ocation were esti mated usi ng shared
paramet er model s. For t he pl ot, li near MM RM analyses were used t oesti mate mean eGFR by tre atm ent allocation at each schedule d fol low-up visit (prespec ifi ed ex plorat ory assessment ). *MMRM result s over t ime (adjusted mean, 95% CI); model inc ludes
age, sex, di abetes status, UACR, region, treat ment by visit i nteract ion, baseli ne value by visit i nteract ion;
†
Mean annual rates of change in eGFR from 2 months to t he final fol low-up visit (chronic slope, ref erred to as 'Long-term') by treatment al locat ion
were esti mated usi ng shared parameter models.
eGFR, estimat ed glomerular fil trat ion rate; MMRM , mixed model repeated measures; UACR, urine albumi n-to-creat inine ratio.
The EMPA-KIDNEY Collaborat ive Group. N Engl J Med 2023;388:117;EMPA-KIDNEY Collaborat ive GroupWCN2023; oral present ati on (WCN23-0342)
Mean eGFR decline per year in participants with:
Empagliflozin 10 mg
Placebo
Empagliflozin’s Mechanism of Action

25. Insulin-independent glucose excretion MoA: SGLT2i facilitate the renal excretion of excess glucose
Glucose reabsorption
through SGLT2
2,11
Filtered glucose
(~180 g/day) and
sodium
3
Na
+
Na
+
Na
+
Na
+
Glucose
K
+
Na
+
SGLT2
Proximal
tubular cells
SGLT2
inhibitor
Glucose
GLUT2
Blood Lumen
SGLT2 inhibitors
reduce glucose and
sodium reabsorption in the
proximal tubule
1
leading to:
Glucose
excretion
1,2
Natriuresis
1
Diuresis
1
SGLT2: ∼97% of
filtered glucose
reabsorbed in
normoglycaemia
Urinary glucose
excretion:
78 g/day
4
1.Heise T et al. Clin Ther201 6;3 8:2 265; 2.Vallon V & Thomso n S C. Diabetologia201 7;6 0:2 15; 3.Bakris GL et al. Kidn ey Int 200 9;7 5:1 272; 4.Boeh ringer Ingelhe im Pha rmace uticals, Inc. Jardian ce
®
(empa gliflo zin) summary o f prod uct ch aracte ristics. Ja n 2 020

26. Mechanisms of Kidney protection in response to SGLT-2 Inhibition
Nature Reviews Nephrology 2020;16:317
What to expect when your patients
using SGLT2i

27. Source : Practical considerations for the use of SGLT2 inhibitors in the Asia-Pacific countries-An expert consensus. Liw A, Lydia A, et al. Wiley Nephrology. Feb 2023. Available on:
DOI: 10.1111/nep.14167

28. Summary
•Progression of CKD are associated with many factors and comorbidities
•Compared with placebo, empagliflozin reduced the relative risk of kidney disease progression* or CV death by 28% in a
broad range of patients with CKD, including a large proportion of those without T2D, across the spectrum of eGFR (and down
to an eGFR of 20 ml/min/1.73 m
2
), with various underlying causes of CKD, and in those with and without RASi treatment (HR
0.72; 95% CI 0.64, 0.82; p<0.001)
•Treatment effect was demonstrated irrespective of underlying cause of CKD across a broad range of eGFR down to 20
ml/min/1.73 m
2
, as well as in a large proportion of patients without diabetes
•Compared with placebo, empagliflozin approximately halved the rate of progression of kidney disease
(chronic slope reduced from -2.75 ml/min/1.73 m
2
/year with placebo to -1.37 ml/min/1.73 m
2
/year with
empagliflozin)
•A statistically significant relative risk reduction of 14% was observed with treatment with empagliflozin compared with
placebo in all-cause hospitalisation (HR 0.86; 95% CI 0.78, 0.95; p=0.003), which is impactful for patients, care providers and
hospital administrators
•Overall, safety data are generally similar to the previous known safety profile of empagliflozinn