¿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, …
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