¿Qué aportan los Inhibidores SGLT2?Impacto sobre el riñón. Nefroprotección

Dr Jose Luis Górriz

Servicio de Nefrologia. Hospital Clínico Universitario. INCLIVA

Universidad de Valencia.

24 de Octubre de 2019

@jlgorriz

II Forum Multidisciplinar de Riesgo Multidisciplinar en Diabetes

Gorriz JL. Prim Care Diabetes. 2019 Aug 7

Kidney outcomes in SGLT-2 inhibitor trials(doubling of serum creatinine, ESKD, or death from renal causes)

Years since randomisation

Hazard ratio 0.60 (95% CI, 0.47-0.77)

2 3 4 5 610

Patients

with a

n e

vent

(%)

Placebo

Canagliflozin

0

1

2

3

4

5

6

7

8

0 6 12 18 24 30 36 42 48

HR 0.54 (95% CI 0.40, 0.75) Placebo

Empagliflozin

Months since randomization

Cum

ula

tive p

robabili

ty o

f event (%

)

20Hazard ratio 0.76 (95% CI, 0.67-0.87)

Placebo

Dapagliflozin

18

16

14

12

10

8

6

4

2

0

eGFR (ml/min/1.73m2): 74.0 76.5 86.1UACR (mg/g): 17.7 12.3 13.1

EMPA-REG CANVAS DECLARE

Wanner C et.al. NEJM 2016; Neal B. et.al. NEJM 2017; Wiviott S et.al. NEJM 2018

Efecto de la inhibición de SGLT2 en los objetivos renales en EMPA-REG y CANVAS

Muskiet MHA. Lancet Diabetes Endocrinol. 2018;6:674-676.

Dapagliflozin and Cardiovascular Outcomesin Type 2 Diabetes (DECLARE)

Wiviott SD. N Engl J Med. 2019 Jan 24;380(4):347-357

Mosenzon O. Lancet Diabetes Endocrinol. 2019;7(8):606-617.

Composite cardiorenal and renal-specific outcomes and their individual components for dapagliflozin versus placebo in the overall trial population

i-SGLT2: Efecto sobrealbuminuria

[.7.]

Porcentaje de pacientes con albuminuria en los estudios EMPA-REG, CANVAS, DECLARE y LEADER

39,9

28,9

11,0

30,1

23,0

7,1

30,2

23,4

6,8

0

5

10

15

20

25

30

35

40

45

Albuminuria > 30mg/g

Albuminuria 30-300mg/g

Albuminuria > 300mg/g

Pac

ien

tes,

%EMPA-REG CANVAS DECLARE

N=2800

N=2302

N=2049

N=2113 N=

772N=

720

IRMA 2: 950 pacientesRENAAL: 1513 pacientesIDNT: 1715 pacientes

N=5192

N=4023

N=

1169

Wanner C. New Engl J Med 2016, June 14Neal B. New Engl J Med 2017, 377(7):644-657

Perkovic V. Poster FR-PO 1058. ASN New Orleans. Novbre 2017Ratz I. Diabetes Obes Metab. 2018;20:1102–1110

Mann JFE. N Engl J Med 2017;377:839-48.

40

45

50

55

60

65

70

75

80

Week

Placebo

Empagliflozin

Ad

just

ed

mea

n (

95

% C

I) e

GFR

(mL/

min

/1.7

3m

2)

12 28 52 94 10880 12266 136 150 164 178 1920 4

Patients with normoalbuminuria

Patients with microalbuminuria

Patients with macroalbuminuria

Post-hoc analysis. MMRM using all data obtained until study end in patients treated with ≥1 dose of study drug. Normoalbuminuria: UACR <30 mg/g; microalbuminuria: UACR ≥30 to ≤300 mg/g; macroalbuminuria: UACR >300 mg/g.

EMPA-REG OUTCOME: Cambios en FGe según grado de albuminuria (empagliflozina vs placebo)

Cherney DZI. Lancet Diabetes Endocrinol. 2017; 5(8):610-621

Mayor beneficio en la progresión en pacientes con macroalbuminuria

Efecto de los iSGLT2 sobre la albuminuria

Perkovic V. Lancet Diabetes Endocrinol. 2018 Sep;6(9):691-704

CANVAS

normoalbuminúricos

microalbuminuria

Cherney DZI. Lancet Diabetes Endocrinol. 2017 Aug;5(8):610-621

EMPA- REG OUTCOME

macroalbuminuria

normoalbuminúricos

microalbuminuria

macroalbuminuria

CREDENCE

Perkovic V. New Eng J Med April 14, 2019

Definitions of Albuminuria Categories

Macroalbuminuria UACR ≥300 mg/g

Microalbuminuria UACR ≥30 to <300 mg/g

Normoalbuminuria UACR <30 mg/gMosenzon O. Lancet Diabetes Endocrinol. 2019;7(8):606-617

Ratz I. Presented at: ADA 79th Scientific Sessions; June 7-11, 2019; San Francisco, CA. 244-OR.

Dapagliflozin decreased the likelihood of patients deteriorating to a worse albuminuria category

Efecto de los iSGLT2 sobre la regresión de la albuminuria

Perkovic V. Poster FR-PO 1058. ASN New Orleans. Novbre 2017

CANVAS

Regresión de macro a micro o micro a normoCon >30 % del cambio respecto a basal

Cherney DZI. Lancet Diabetes Endocrinol. 2017 Aug;5(8):610-621

EMPA- REG OUTCOME

Regresión de micro a normo

Regresión de macro a micro/normo

Definitions of Albuminuria Categories

Macroalbuminuria UACR ≥300 mg/g

Microalbuminuria UACR ≥30 to <300 mg/g

Normoalbuminuria UACR <30 mg/g

Mosenzon O. Lancet Diabetes Endocrinol. 2019;7(8):606-617Ratz I. Presented at: ADA 79th Scientific Sessions; June 7-11, 2019; San Francisco, CA. 244-OR.

Dapaglflozin increased the likelihood of patients improving in albuminuria category, regardless of baseline UACR

iSGLT2: Datos enpacientes con FGe

reducido

[.14.]

Cardiovascular outcomes in patients with prevalent kidney disease* (EMPA REG OUTCOME)

Time to CV death Time to all cause mortality

Time to hospitalizationfor heart failure

Time to all cause hospitalization

Wanner C. Circulation. 2018 Jan 9;137(2):119-129*Defined as eGFR (MDRD) <60 mL/min/1.73m2 and/or macroalbuminuria (urine albumin-to-creatinine ratio >300 mg/g) at baseline.

New onset or worsening nephropathy in patients with prevalent kidney disease*

HR 0.58

(95% CI 0.47, 0.71)

p<0.001

Cum

ula

tive

pro

ba

bili

ty o

f e

ve

nt (%

)

*Defined as eGFR (MDRD) <60 mL/min/1.73m2 and/or macroalbuminuria (urine albumin-to-creatinine ratio >300 mg/g) at baseline.

Kaplan-Meier estimates in patients with prevalent kidney disease treated with ≥1 dose of study drug. Hazard ratios are based on Cox regression analyses. Post-hoc analyses.eGFR, estimated glomerular filtration rate. MDRD, Modification of Diet in Renal Disease.

Wanner C. New Engl J Med 2016, June 14

CREDENCEStudy Design and Population

Meg J. Jardine, MBBS, PhD, FRACP

Perkovic V. New Eng J Med April 14, 2019

The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation

Lower Baseline Renal Function in CREDENCE Participants

20% 26%

9%

60%

8% 11% 7%

88%-100

-80

-60

-40

-20

0

20

40

60

80

100

eGFR <60

UACR >300

1. Neal B, et al. N Engl J Med. 2017;377(7):644-657.2. Zinman B, et al. N Engl J Med. 2015;373(22):2117-2128.3. Raz I, et al. Diabetes Obes Metab. 2018;20(5):1102-1110.

CREDENCECANVAS

Program1

EMPA-REG OUTCOME2 DECLARE3

60

80

100

20

40

Prespecified Hierarchical Testing

Primary

1. ESKD, doubling of serum creatinine, or renal or CV death

Secondary

2. CV death or hospitalization for heart failure

3. CV death, MI, or stroke

4. Hospitalization for heart failure

5. ESKD, doubling of serum creatinine, or renal death

6. CV death

7. All-cause mortality

8. CV death, MI, stroke, hospitalization for heart failure, or hospitalization for unstable angina

Jardine MJ, et al. Am J Nephrol. 2017;46(6):462-472.

Hazard ratio (95% CI) P value

Primary composite outcome 0.70 (0.59–0.82) 0.00001

Doubling of serum creatinine 0.60 (0.48–0.76) <0.001

ESKD 0.68 (0.54–0.86) 0.002

eGFR <15 mL/min/1.73 m2 0.60 (0.45–0.80) –

Dialysis initiated or kidney transplantation 0.74 (0.55–1.00) –

Renal death* 0.39 (0.08–2.03) –

CV death 0.78 (0.61–1.00) 0.0502

CV death or hospitalization for heart failure 0.69 (0.57–0.83) <0.001

CV death, MI, or stroke 0.80 (0.67–0.95) 0.01

Hospitalization for heart failure 0.61 (0.47–0.80) <0.001

ESKD, doubling of serum creatinine, or renal death 0.66 (0.53–0.81) <0.001

Summary of Key Renal and CV Outcomes

Favors Canagliflozin Favors Placebo

0.25 0.5 1.0 2.0 4.0

*n=7 (2 / 5)

Perkovic V. New Eng J Med, April 14, 2019;

CREDENCE ha sido un gran estudio.

Comparación de datos de CREDENCE y EMPA REG

[.21.]

CREDENCE1 EMPA-REG OUTCOME®: Overall trial population2

Secondary composite kidney outcomes in

CREDENCE and EMPA-REG OUTCOME®

Comparison of trials should be interpreted with caution due to differences in study design, populations and methodology

ESKD, end-stage kidney disease.

1. Perkovic V et al. N Engl J Med 2019;DOI:10.1056/NEJMoa1811744; 2. Wanner C et al. N Engl J Med 2016;375:323.

Pa

rtic

ipa

nts

wit

h a

n e

ve

nt

(%)

Composite of ESKD, doubling of serum

creatinine or death from kidney causes

Composite of renal replacement therapy, doubling

of serum creatinine or death from kidney causes

22

Months

Pa

rtic

ipa

nts

wit

h a

n e

ve

nt

(%)

Months

46%34%

Comparator Placebo Hazard ratio(95% CI)

Hazard ratio(95% CI)n event/N n event/N

ESKD, sustained doubling of serum creatinine, and renal

or CV death

EMPA-REG OUTCOME® CREDENCE-like1 49/420 48/221 0.46 (0.31, 0.68)

CREDENCE2 245/2202 340/2199 0.70 (0.59, 0.82)

ESKD, sustained doubling of serum creatinine, and renal death

EMPA-REG OUTCOME® CREDENCE-like1 14/418 17/221 0.38 (0.18, 0.77)

CREDENCE2 153/2202 224/2199 0.66 (0.53, 0.81)

CV death

EMPA-REG OUTCOME® CREDENCE-like1 36/422 34/221 0.51 (0.32, 0.82)

CREDENCE2 110/2202 140/2199 0.78 (0.61, 1.00)

HHF or CV death*

EMPA-REG OUTCOME® CREDENCE-like1 57/422 46/221 0.56 (0.38, 0.83)

CREDENCE2 179/2202 253/2199 0.69 (0.57, 0.83)

0,25 0,5 1 2

Favors comparator Favors placebo

Cardiorenal outcomes in patients with proteinuric DKD in EMPA-REG OUTCOME®

versus CREDENCE

Comparison of trials should be interpreted with caution due to differences in study design, populations and methodology

*Excludes fatal stroke. Data for patients who did not have an event were censored on the last day they were known to be free of the outcome. ‘CREDENCE-like’ definition: eGFR ≥30 to <90

ml/min/1.73 m2 and UACR >300 mg/g. CREDENCE-like subgroup is reflected without corresponding all others subgroup from EMPA-REG OUTCOME but the data were consistent between

the analyzed subgroups and the overall population. ESKD defined as initiation of RRT or sustained eGFR <15 ml/min/1.73 m2. eGFR according to CKD-EPI. CV, cardiovascular; DKD,

diabetic kidney disease; eGFR, estimated glomerular filtration rate; ESKD, end-stage kidney disease; HHF, hospitalization for heart failure; RRT, renal replacement therapy.

1. Wanner C et al. ISN World Congress of Nephrology 2019; poster; 2. Perkovic V et al. N Engl J Med 2019;DOI:10.1056/NEJMoa1811744.6

Presented at the 56th European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Congress; June 13, 2019; Budapest, Hungary.

Acute and Long-term Effects on eGFR

-20

-18

-16

-14

-12

-10

-8

-6

-4

-2

0

0 26 52 78 104 130 156 182LS

Mean

Ch

an

ge (

±S

E)

in e

GFR

(m

L/

min

/1

.73

m2)

Months since randomization

No. of Participants

Placebo 2178 2084 1985 1882 1720 1536 1006 583 210

Canagliflozin 2179 2074 2005 1919 1782 1648 1116 652 241

56.4 56.0

Canagliflozin Placebo

Chronic eGFR slopeDifference: 2.74/year (95% CI, 2.37–3.11)

–4.59/year

6 12 18 24 30 36 42

LS

mean

ch

an

ge (S

E) i

n

eG

FR

(m

L/

min

/1

.73

m2)

Baseline

60% reduction in the rate of eGFR decline with canagliflozin

On treatment

–1.85/year

Empagliflozin slowed the annual decline in eGFR in patient subgroups at higher risk for CKD progression assessed by mean eGFR slopes(Overall population)

*Adjusted mean eGFR over prespecified study periodsWanner C. J Am Soc Nephrol. 2018;29(11):2755-2769

In prevalent CKD, empagliflozin also slowed the annual decline in eGFR in patient subgroups at higher risk for CKD progression assessed by mean eGFR slopes

Wanner C. J Am Soc Nephrol. 2018;29(11):2755-2769

eGFR slopes depending on urinary albumin-to-creatinine ratio

Wanner C. J Am Soc Nephrol. 2018;29(11):2755-2769

EMPA-REG OUTCOME1: Renal Benefit of SGLT2-i

1. Wanner C. N Engl J Med. 2016;375:323–34; 2. Neal B. N Engl J Med. 2017;377:644–57

Week

Enf cardiovascular

+0.23 ml/min per year per 1.73 m2 (95%CI: +0.05 to 0.4)

EMPA-REG OUTCOME: incident for worsening nephropathy by baseline age

Monteiro P. Age Ageing. 2019 Oct 3. pii: afz096

T2DM is becoming a non-proteinuric state

Afkarian M. JAMA. 2016;316(6):602-610

RR of albuminuria (adjusted for eGFR): 0.73 vs 1988-1994

And a substantial % of DKD is now non-proteinuric

Halimi JM. Diabetes Metab. 2012 Oct;38(4):291-7

NHANES prevalence of non-proteinuric DKD : 50 %

Efecto de los iSGLT2 endiabéticos no proteinúricos

[.34.]

Trial design, key inclusion/exclusion criteria, and subgroup

definitions

Key inclusion criteria

• Adults (≥18 years of age) with T2DM

• HbA1c ≥7% and ≤10%*

• Established CV disease (prior MI, CAD, stroke, UA or occlusive PAD)

• BMI ≤45 kg/m2

Key exclusion criteria

• eGFR <30 ml/min/1.73 m2 (MDRD)

• Acute coronary syndrome, stroke or transient

ischemic attack within 2 months prior to informed

consent

35

Placebo (n=2333)

Pooled

Randomized

and treated

(n=7020)

Empagliflozin 10 mg (n=2345)

Empagliflozin 25 mg (n=2342)

Screening

(N=11,531)

*Stable background therapy for ≥12 weeks before randomization: for insulin, dose was to remain unchanged by >10% from the dose received 12 weeks

before randomization; for drug-naïve: HbA1c ≥7% and ≤9%. BMI, body mass index; CAD, coronary artery disease; CV, cardiovascular; DKD, diabetic

kidney disease; eGFR, estimated glomerular filtration rate; HbA1c, glycated hemoglobin; MDRD, Modification of Diet in Renal Disease; MI, myocardial

infarction; PAD, peripheral arterial disease; T2DM, type 2 diabetes mellitus; UA, unstable angina.

Zinman B et al. N Engl J Med 2015;373:2117.

2-week

placebo

run-in

Subgroup definitions

• Non-proteinuric DKD: eGFR <60 ml/min/1.73 m2 and UACR <300 mg/g

• All others: eGFR ≥60 ml/min/1.73 m2 or UACR ≥300 mg/g

The non-albuminuric phenotype represents an increasingly common form of

DKD, but clinical evidence in this important patient population is scarce

EMPA-REG OUTCOME®: Exploratory analysis

Different clinical phenotypes of DKD vs all others

Adapted from: Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. Kidney Int Suppl 2013;3:1.

DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; UACR, urine albumin-to-creatinine ratio.

https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf.

Albuminuria category, description and range (mg/g)

Normal to mildly

increased

Moderately

increased

Severely

increased

<30 30–300 >300

eG

FR

ca

teg

ory

, d

es

cri

pti

on

an

d r

an

ge

(m

l/m

in/1

.73

m2) Normal or high ≥90

Mildly decreased 60–89

Mildly to moderately

decreased45–59

Moderately to

severely decreased30–44

Severely decreased 15–29

Kidney failure <15

Non-albuminuric DKD

n=1290

All others

n=4893Albuminuric

DKD

n=769

18% of patients in

EMPA-REG OUTCOME®

met these criteria

Non-albuminuric DKDeGFR <60 ml/min/1.73 m2

and UACR ≤300 mg/g

= without overt albuminuria

11% of patients in

EMPA-REG OUTCOME®

met these criteria

Albuminuric DKDUACR >300 mg/g

= with overt albuminuria

Baseline characteristics:

Non-proteinuric DKD versus all others

Non-proteinuric DKD

N=1290

All others

N=5662P-value

Age, years 68.5±7.5 61.9±8.4 <0.0001

Time since diagnosis of T2DM >10

years862 (66.8) 3112 (55.0) <0.0001

Male 865 (67.1) 4098 (72.4) 0.0001

BMI, kg/m2 31.0±5.4 30.5±5.2 0.0019

HbA1c, % 8.03±0.84 8.08±0.85 0.0350

eGFR, ml/min/1.73 m2 (MDRD) 47.7±7.5 80.0±18.9 <0.0001

UACR, mg/g 50.8±65.0 202.8±675.1 <0.0001

Total cholesterol, mg/dl 160.6±42.3 163.5±44.1 0.0387

Overt CV disease* 1276 (98.9) 5620 (99.3) 0.2129

37

*Defined as history of stroke, coronary artery disease, myocardial infarction, coronary artery bypass graft, single vessel coronary

artery disease, multi-vessel coronary artery disease and peripheral artery disease. Data are n (%) or mean ± SD in patients treated

with ≥1 dose of study drug. BMI, body mass index; CV, cardiovascular disease; DKD, diabetic kidney disease; eGFR, estimated

glomerular filtration rate; HbA1c, glycated hemoglobin; MDRD, Modification of Diet in Renal Disease; T2DM, type 2 diabetes

mellitus; UACR, urine albumin-to-creatinine ratio.

Patients with non-proteinuric DKD were older, had a longer

time since diagnosis, and more often female

Background medications at baseline:

Non-proteinuric DKD versus all others

Non-proteinuric DKD

N=1290

All others

N=5662P-value

Glucose-lowering therapy

Metformin 751 (58.2) 4393 (77.6) <0.0001

Insulin 731 (56.7) 2620 (46.3) <0.0001

Sulfonylureas 508 (39.4) 2470 (43.6) 0.0054

Antihypertensive therapy 1265 (98.1) 5340 (94.3) <0.0001

ACE inhibitor/ARB 1099 (85.2) 4512 (79.7) <0.0001

Beta-blocker 889 (68.9) 3618 (63.9) 0.0007

Diuretic 770 (59.7) 2234 (39.5) <0.0001

Statin 1011 (78.4) 4344 (76.7) 0.2036

Aspirin 1056 (81.9) 4686 (82.8) 0.4407

38

Data are n (%) or mean ± SD in patients treated with ≥1 dose of study drug.

ACE, angiotensin-converting enzyme; ARB, angiotensin receptor blocker; DKD, diabetic kidney disease.

Patients with non-proteinuric DKD tended to use insulin,

ACEi/ARBs, beta-blockers and diuretics more frequently

Empagliflozin Placebo

HR (95% CI) p-valuen event/N analysed (%)

ESKD, sustained 40% eGFR decline, or CV or renal death*

EMPA-REG OUTCOME1 overall population 275/4648 216/23250.61 (0.51,

0.73)

Albuminuric DKD2 90/506 68/2600.56 (0.41,

0.77)

Non-albuminuric DKD2 66/839 45/4390.73 (0.50,

1.07)

All others2 116/3253 103/16100.54 (0.42,

0.71)

39

Favours empagliflozin Favours placebo

0,25 0,5 1 2

*ESKD defined as initiation of RRT or sustained eGFR <10 ml/min/1.73 m².

CV, cardiovascular; DKD, diabetic kidney disease; eGFR, estimated glomerular filtration rate; RRT, renal replacement therapy.

1. Wanner C et al. N Engl J Med 2016;375:323; 2. Wanner C et al. EASD 2019; Barcelona, Spain; 16–20 September 2019.

Empagliflozin reduced the risk of cardio-renal outcomes,

regardless of DKD phenotype

Nominal p-value <0.0001

Interaction p-

value 0.4265

40

†ESKD defined as initiation of RRT or sustained eGFR <15 ml/min/1.73 m². ‡ESKD defined as initiation of RRT or sustained eGFR <10 ml/min/1.73 m². Albuminuric DKD defined as UACR >300 mg/g with any eGFR [CKD-

EPI]; non-albuminuric DKD group defined as eGFR <60 ml/min/1.73 m2 and UACR ≤300 mg/g; all others group defined as eGFR ≥60 ml/min/1.73 m2 or UACR ≤300 mg/g. DKD, diabetic kidney disease; eGFR, estimated

glomerular filtration rate; MDRD, Modification of Diet in Renal Disease; n/a, not applicable; NC, not calculated; RRT, renal replacement therapy; UACR; urinary albumin-to-creatinine ratio.

Source: Wanner C et al. EASD 2019; Barcelona, Spain; 16–20 September 2019.

Empagliflozin Placebo Hazard ratio

(95% CI)

Hazard ratio

(95% CI)

Interaction

p-valuen event/N % n event/N %

Incident or worsening nephropathy*

All patients 525/4124 12.7 388/2061 18.8 0.61 (0.53, 0.70)

0.1145Albuminuric DKD n/a n/a n/a n/a NC

Non-albuminuric DKD 150/829 18.1 128/431 29.7 0.53 (0.42, 0.67)

All others 332/3219 10.3 228/1589 14.3 0.67 (0.56, 0.79)

ESKD, sustained doubling of creatinine, or renal death†

All patients 31/4645 0.7 37/2323 1.6 0.40 (0.25, 0.64)

0.4462Albuminuric DKD 17/504 3.4 19/260 7.3 0.40 (0.21, 0.77)

Non-albuminuric DKD 6/838 0.7 5/438 1.1 NC

All others 7/3253 0.2 13/1609 0.8 0.26 (0.10, 0.64)

ESKD, sustained 40% eGFR decline, or renal death‡

All patients 108/4645 2.3 87/2323 3.7 0.59 (0.45, 0.78)

0.9858Albuminuric DKD 49/504 9.7 36/260 13.8 0.56 (0.36, 0.86)

Non-albuminuric DKD 21/838 2.5 18/438 4.1 0.56 (0.30, 1.06)

All others 36/3253 1.1 33/1609 2.1 0.53 (0.33, 0.85)

0,125 0,25 0,5 1 2

Empagliflozin reduced the risk of adverse kidney outcomes,

regardless of DKD phenotype

Cox regression analyses in patients treated with ≥1 dose of study drug. Interaction p-value is for test of homogeneity of treatment group difference

between subgroups with no adjustment for multiple tests. Data for patients who did not have an event were censored on the last day they were known

to be free of the outcome. *Defined as progression to macroalbuminuria (UACR >300 mg/g); a doubling of serum creatinine, accompanied by an

eGFR of ≤45 ml/min/1.73 m2 (MDRD formula); initiation of RRT; or renal death (patients with albuminuric DKD were excluded from this analysis).Favours empagliflozin Favours placebo

Indicaciones de i-SGLT2 según filtrado glomerular

Clinical Practice Guideline on management of diabetes and CKD. Nephrol Dial Transplant (2015) 30: ii1–ii142Martinez-Castelao A, Gorriz JL, Sola E, Morillas C et al. Nefrologia 2012;32(4):419-26Modificado de RedGDPS. Enfermedad renal crónica y Diabetes Mellitus Autor: Dr. Antonio Rodríguez-PoncelasFichas técnicas de Dapagliflozina, Empagliflozina y Canagliflozina

FGe/Fármacos >60 45-59 30-44 15-29 < 15

Inhibidores SGLT2

Dapagliflozina No ajusteNo iniciar

Mantener. No ajuste(10 mg/dia)

No No No

Empagliflozina No ajusteNo iniciar. Mantener

Si FG< 60 en tto, 10 mg/diaNo No No

Canagliflozina No ajusteNo iniciar. Mantener.

Si FG< 60 en tto, 100 mg/diaNo No No

Recomendaciones actuales

Marzal D. SEC Monogr. 2018;6(2):35‐38

Diabetologia. 2018 Oct 5. [Epub ahead of print]ASCVD: atherosclerotic CV diseaseCKD: chronic kidney disease Davies MJ. Diabetes Care 2019;42(Suppl. 1):S90–S102

Presented at the 56th European Renal Association - European Dialysis and Transplant Association (ERA-EDTA) Congress; June 13, 2019; Budapest, Hungary.

ADA Standards of Care Updated With Renal Guidance Based on CREDENCE

• “The CREDENCE trial was the first sodium-glucose cotransporter 2 (SGLT2) inhibitor trial to assess renal-specific primary outcomes and ended early due to efficacy. Incorporating these findings into the Standards of Care now gives providers the latest evidence-based recommendations to treat people with type 2 diabetes and diabetes-related chronic kidney disease…”

– William T. Cefalu, MD, Chief Scientific, Medical and Mission Officer of the ADA1

• Based on the Grade A evidence from the CREDENCE trial, the ADA living guidelines (updated on June 3, 2019)2 propose the following:

– “For patients with type 2 diabetes and diabetic kidney disease, consider use of an SGLT2 inhibitor in patients with an eGFR ≥30 mL/min/1.73 m2 and particularly in those with >300 mg/g albuminuria to reduce risk of CKD progression, cardiovascular events, or both.”

1. American Diabetes Association. http://www.diabetes.org/newsroom/press-releases/2019/updates-standards-medical-care-diabetes.html. Accessed June 5, 2019.2. American Diabetes Association. Standards of Medical Care in Diabetes–2019. http://care.diabetesjournals.org/content/42/Supplement_1. Last updated June 3, 2019. Accessed June 5, 2019.

Futuro de la enfermedad renal

diabética

Renal Clinical outcome trials in DKD on going

Trial Drug (class) n Main inclusión criteria

Trial status Renal outcome

Fidelio-DKD Finerenone 4800 Type 2 DM eGFR 25-75, macroalbuminruia. K<4.8

Ongoing.April 2020

Composite: >40% eGFR reduction, dScr, ESKD, renal death

DAPA-CKD Dapagliflozin 4000 eGFR 25-75, proteinuria Ongoing.Ends: Nov 2020

Composite: >50% eGFR reduction, dScr, ESKD, cardiovascular death, renal death

EMPA-KIDNEY

Empagliflozin 5000 eGFR 20-45 or 40-90 with albuminuria

OngoingEmds: June 2022

Composite: kidney disease progression (ESKD, eGFR <10, renal death, or ≥40% reduction in eGFR) or cardiovascular death)

*DKD: diabetic kidney diseaseModificado de: Muskiet M. Lancet Diabetes Endocrinol. 2018 Dec 19

Otros: aR GLP-1 (FLOW) , selonseertib, Imarikiren, …