I FENOTIPI DI MALATTIA RENALE NEL DIABETICO: DAL RIACE ... · Data Source: National Health and...
Transcript of I FENOTIPI DI MALATTIA RENALE NEL DIABETICO: DAL RIACE ... · Data Source: National Health and...
Giuseppe PennoDipartimento di Medicina Clinica e
SperimentaleUniversitagrave di Pisa
I FENOTIPI DI MALATTIA RENALE
NEL DIABETICO DAL RIACE ALLA
NEFROPROTEZIONE
Dichiarazione esplicita di trasparenza delle fonti di finanziamentoe dei rapporti con soggetti portatori di interessi commerciali
Il sottoscritto Dr Giuseppe Penno
in qualitagrave diModeratore Relatore
ai sensi dellrsquoart 33 sul Conflitto di Interessi pag 17 del Reg Applicativo dellrsquoAccordo Stato-Regione del 5 novembre 2009
dichiarache negli ultimi due anni ha avuto i seguenti rapporti anche di finanziamento con soggetti
portatori di interessi commerciali in campo sanitario
AstraZeneca Boerhinger Ingelheim Eli-Lilly Janssen Merck Sharp amp Dohme
Novo Nordisk Takeda
Ancona 7 ottobre 2017
The changing face of DKD in diabetes
Adjusted for age sex and raceethnicity p-values are for trendUACR urine albumin-to-creatinine ratio
Prevalent cases of diabetic kidney disease in the United States accounting for persistence
Clinical manifestations of Kidney Disease among US Adults with Diabetes 1988-2014
p=039 plt0001
plt0001
Afkarian M et al JAMA 316 602-610 2016USRDS - 2016 Annual Data Report Vol 1 CKD Ch 1
40 30 20
Chart1
Sheet1
p=0001 p=015plt0001
plt0001
Adjusted for age sex and raceethnicity p-values are for trendUACR urine albumin-to-creatinine ratio
Adults aged lt65 Adults aged ge65 Adults aged lt65 Adults aged ge65
Prevalent cases of albuminuria and reduced eGFR in the United States by ageaccounting for persistence
Clinical manifestations of Kidney Disease among US Adults with Diabetes 1988-2014
Afkarian M et al JAMA 316 602-610 2016
Chart1
Sheet1
Vol 1 CKD Ch 1 6
Data Source National Health and Nutrition Examination Survey (NHANES) 2007ndash2012 participants aged 20 amp older Single-sample estimates of eGFR amp ACR eGFR calculated using the CKD-EPI equation
Afkarian M et al JAMA 316 602-610 2016
Clinical Manifestations of Kidney Disease among US Adults with Diabetes 1988-2014
Patientsn
DM
Follow-upyears
Renal impairment
No-albuminuric renal
impairment
Renal impairment with no albuminuria nor retinopathy
UKPDS Diabetes 55 1832-1839 2006
4006 100 15 28 67 (51) ---
MacIsaac RJ et al Diabetes Care 27 195-200 2004
301 100 --- 36 39 29
Kramer HJ et al NHANES III JAMA 289 3273-3277 2003
1197 100 --- 13 36 30
Thomas MC et al NEFRONDiabetes Care 32 1497-1502 2009
3893 100 --- 23 55 ---
Ninomiya T et al ADVANCEJ Am Soc Nephrol 20 1813-1821 2009
10640 100 --- 19 62 ---
Bakris GL et al ACCOMPLISHLancet 375 1173-1181 2010
11482 60 --- 95 468 ---
Tube SW et al ONTARGET TRASCENDCirculation 123 1098-1107 2011
23422 37 --- 24 68 ---
Drury PL et al FIELDDiabetologia 54 32-43 2011
9765 100 --- 53 590 ---
RIACE Study Group RIACEJ Hypertens 29 1802-1809 2011
15773 100 --- 188 566 432
In the last years progression of AER as an obligatorypredictorstep of DKD has been challenged
Schematic presentation of variable clinical courses of diabetic kidney disease
Boger CA et al PLOS Genetics 8 e1002989 2012 (modified)
Normoalbuminuria
Normal GFR
Normoalbuminuria
Normal GFR
0 5 10 15 20Duration of diabetes (years)
Increased GFR (hyperfiltration)
Reduced GFR ESRD
crosstalk between the two channels
Normoalbuminuria
Microalbuminuria
Macroalbuminuria
Normal GFR
The changing face of DKD in diabetes
RIACE and DKD phenotypes
30-59 mlmin173 m2
171Normo 731
Micro222
Macro47
60-89 mlmin173 m2
517
ge90 mlmin173 m2
296
lt30 mlmin173 m2
17
eGFR strata(mlmin173 m2)
Albuminuria strata(mlmin173 m2)
Renal dysfunction is common in patients with T2DMThe RIACE Study 15773 patients with T2DM
Penno G et al The RIACE Study Group J Hypertens 29 1802-1809 2011
30 20
625120
67
171
17
No CKD
CKD stage 1
CKD stage 2
CKD stage 3
CKD stages 45
Approximately 40 of patients with T2DM show signs of CKD (stages 1-5)
Approximately 20 of patients with T2DM show signs of renal failure (eGFRlt60 mlmin173 m2)
Renal dysfunction is common in patients with T2DMThe RIACE Study 15773 patients with T2DM
Penno G et al The RIACE Study Group J Hypertens 29 1802-1809 2011
40
20
Severe(A3)
Mild(A2)
Normal(A1)
15-29
30-44
45-59
60-89
gt90
Albuminuria
Stage 2
Stage 1Stage 0(no CKD)
625
Stage 3
Stage 4
Stage 5
Stage 1-2albuminuric phenotype
187
Penno G et al J Hypertens 29 1802-1809 2011
Renal dysfunction is common in patients with T2DMThe RIACE Study 15773 patients with T2DM
eGFRmlmin173 m2
MDRD
lt15
G4
G3b
G3a
G2
G1
G5
Stage 35Non
albuminuricCKD
Phenotype
106
Stages 35
AlbuminuricCKD
Phenotype
82
Distribution of markers of CKD in RIACE and in NHANES participants with diabetes hypertension self-reported cardiovascular
disease amp obesity 2011ndash2014
Data Source National Health and Nutrition Examination Survey (NHANES) 2011ndash2014 participants age 20 amp older Single-sample estimates of eGFR amp ACR eGFR calculated using the CKD-EPI equation Abbreviations ACR urine albumincreatinine ratio BMI body mass index CKD chronic kidney disease SR CVD self-reported cardiovascular disease eGFR estimated glomerular filtration rate HTN hypertension
USRDS - 2016 Annual Data Report Vol 1 CKD Ch 1
106
82
187
De Cosmo S et al The AMD-Annals Study Group Nephrol Dial Transplant 29 657-662 2014
Kidney dysfunction and related cardiovascular risk factorsamong patients with type 2 diabetesClinical features of 120903 patients with type 2 diabetes whole sample and
divided according to the presenceabsence of albuminuria or low eGFR
106 187 82625
The changing face of DKD in diabetes
RIACE and DKD phenotypes
Different correlates for different phenotypes
Penno G et al The RIACE Study Group J Hypertens 29 1802-1809 2011
Independent correlates of nonalbuminuric and albuminuric renal impairment (eGFR lt60 mlmin per 173m2 stage ge3 CKD) and albuminuria with nonreduced eGFR (eGFR ge60 mlmin per 173m2 stages 1-2 CKD) vs no CKD (eGFR ge60 mlmin per 173m2 without albuminuria)
The RIACE (Renal Insufficiency and Cardiovascular Events) Italian Multicenter Study
106 187 82
Penno G et al The RIACE Study Group Diabetes Care 36 2301-2310 2013
HbA1c Variability as an Independent Correlate of Nephropathy but Not Retinopathy in Patients With Type 2 Diabetes
8260 patients with type 2 diabetes from Italy
106187 82
De Cosmo S et al The AMD-Annals Study Group Medicine 2016
Predictors of chronic kidney disease in type 2 diabetesA longitudinal study from the AMD Annals initiative
27029 patients with type 2 diabetes estimated eGFR ge60 mlmin173m2
and normoalbuminuria ndash observation over a period of 4 years
Independent correlates of nonalbuminuric and albuminuric renal impairment (eGFR lt60 mlmin per 173m2 stage ge3 CKD) and albuminuria with nonreduced eGFR (eGFR ge60 mlmin per 173m2 stages 1-2 CKD) vs no CKD (eGFR ge60 mlmin per 173m2 without albuminuria)
The RIACE (Renal Insufficiency and Cardiovascular Events) Italian Multicenter Study
106 187 82
Penno G et al The RIACE Study Group J Hypertens 29 1802-1809 2011
The changing face of DKD in diabetes
RIACE and DKD phenotypes
Different correlates for different phenotypes
Consequences of different phenotypes
0
10
20
30
40
50
CKD stages 1-2
n 2949
No CKD
n 9865
Maj
or C
VD e
vent
s
794(269)
1756(178)
Any CVD event by CKD phenotype
Chi square plt00001
CKD stages 3-5nonalbuminuric
n 1673
528(316)
Solini A et al The RIACE Study Group Diabetes Care 35 143-149 2012
CKD stages 3-5albuminuric
n 1286
576(448)
The RIACE (Renal Insufficiency and Cardiovascular Events) Italian Multicenter Study
Solini A et al The RIACE Study Group Diabetes Care 35 143-149 2012
Logistic regression analysis of CVD events by vascular bed with CKD phenotypes as covariates
The RIACE (Renal Insufficiency and Cardiovascular Events) Italian Multicenter Study
Penno G et al The RIACE Study Group Diabetes Care submitted
Nonalbuminuric renal impairment is a strong predictior of all-cause mortality in patients with in type 2 diabetes The RIACE Italian Multicentre Study
Cumulative survival by Kaplan Mayer analysis (A)
and Cox proportional hazards regression unadjusted (B)
and adjusted by age (C)
and multiple confounders (D)
according to DKD phenotypes
Penno G et al The RIACE Study Group Diabetes Care submitted
Nonalbuminuric renal impairment is a strong predictior of all-cause mortality in patients with in type 2 diabetes The RIACE Italian Multicentre Study
Survival analysis by Cox proportional hazards regression adjusted for confounders according to DKD phenotypes and age categories
A lt55 years
B 55-64 years
C 65-74 years
D gt75 years
The changing face of DKD in diabetes
RIACE and DKD phenotypes
Different correlates for different phenotypes
Consequences of different phenotypes
(hellip and type 1 diabetes)
The presence and consequence of nonalbuminuric chronic kidney disease in patients with type 1 diabetes
1 117
31
20 2431
76
012345678
CV events415 (115)
All-cause mortality406 (107)
no CKDStages 1-2 CKDStages 3-5 CKD Alb-Stages 3-5 CKD Alb+
Development of CV events and all-cause mortality 129 and 131 years of median follow-up respectively
HR
Thorn LM et al Diabetes Care 38 2128-2133 2015
Adjusted for sex age BMI sBP HbA1c non-HDL cholesterol history of retinal laser tx and current smoking Adjusted for age
0
5
10
50
75
100
No DKD
n 692
DKD stadi 1-2
n 53
DKDstadi ge3 Alb-
n 17
DKDstadi ge3 Alb+
n 12
894
68
22 16
207 of all subjects with DKD 586 of DKD stages ge3
774 patients with T1DM
The presence and consequence of nonalbuminuric chronic kidney disease in patients with type 1 diabetes all-cause mortality
M Garofolo et al unpublished data
The presence and consequence of nonalbuminuric chronic kidney disease in patients with type 1 diabetes all-cause mortality
M Garofolo et al unpublished data
Cum
ulat
ive
surv
ival
Follow-up years
K-M Log Rank testplt00001
No DKD (n 692)DKD stages 1-2 (n 53)DKD stages ge3 Alb- (n 17)DKD stages ge3 Alb+ (n 12)
30 Ref
500HR 20683
(8292-51587)
151HR 4504
(1992-10186)
294HR 8573
(3222-22815)
40 di 77452
626 x 1000anno
774 patients with T1DM follow-up 83plusmn23 years
The presence and consequence of nonalbuminuric chronic kidney disease in patients with type 1 diabetes all-cause mortality
M Garofolo et al unpublished data
HR 7441(2781-19911)
plt00001
HR 2970(1018-8662)
p=0046
Cum
ulat
ive
surv
ival
Follow-up years
No DKD (n 692)DKD stages 1-2 (n 53)DKD stages ge3 Alb- (n 17)DKD stages ge3 Alb+ (n 12)
Cox regression adjusted byage and gender
Ref
HR 3841(1686-8750)
p=0001
HR 95CI p
Age 1070 1044-1098 lt00001
Gender (M) 1922 0969-3813 =0061
The presence and consequence of nonalbuminuric chronic kidney disease in patients with type 1 diabetes all-cause mortality
M Garofolo et al unpublished data
HR 458(169-1242)
p=0003
HR 277(097-794)
p=0058
Cum
ulat
ive
surv
ival
Follow-up years
No DKDDKD stages 1-2DKD stage ge3 Alb-DKD stage ge3 Alb+
Ref
HR 257(111-594)
p=0027
HR 95CI p
Gender (M) 152 077-301 0225
EURODIAB risk scoreLow riskIntermediate riskHigh risk
13351174
---120-932
444-3104
lt00001
0021lt00001
p=0008
Cox regression adjusted byGender and EURODIAB risk score
The changing face of DKD in diabetes
RIACE and DKD phenotypes
Different correlates for different phenotypes
Consequences of different phenotypes
(hellip and type 1 diabetes)
Nephroprotection
DKD diabetic kidney disease T1D type 1 diabetes T2D type 2 diabetes IDNT Irbesartan Type 2 Diabetic Nephropathy Trial RAAS reninndashangiotensin-aldosterone system RENAAL
1 Mogensen CE et al Br Med J (Clin Res Ed)1982285685 2 Parving HH et al Lancet 198311175 3 Lewis EJ et al N Engl J Med 19933291456 4 Lewis EJ et al N Engl J Med 2001345851 6 Brenner BM et al N Engl J Med
2001345861
Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan
1980 1990 2010 20152000
No new DKD-specific treatment in the last 15 years
High blood pressure
identified as DKD risk factor
szlig-blockers1
Hydralazine2
Captopril3
T1D
IDNT4 IRMA 25
Irbesartan T2D
RENAAL6
LosartanT2D
RAAS blockade
No new DKD-specific treatment in the last 15 years
Glucoseloweringagents
Glitazones(ADOPT)
Sulphonylureas(ADOPT)
Metiglinides andAlpha-Glucosidase
Inhibitors
Metformin(ADOPT)
GLP-1agonists
Insulin(ORIGIN)
DPP-4inhibitors
Key question are glucose-lowering agents able to improverenal end-points beyond their antihyperglycemic effect
SGLT-2inhibitors
The changing face of DKD in diabetes
RIACE and DKD phenotypes
Different correlates for different phenotypes
Consequences of different phenotypes
(hellip and type 1 diabetes)
Nephroprotection
DPP4-i and GLP-1 RA
∆ HbA1c 030
Worsening or improvement are defined as a shift from baseline ACR category (lt34 ge34 to le339 or gt339 mgmmol) Plt0001 vs placebo
16492 patients who had a history or were at risk for CV events
Scirica BM et al N Engl J Med 369 1317-326 2013
Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus
16492 patients who had a history or were at risk for CV events
Mosenzon O et al on behalf of the SAVOR-TIMI 53 Investigators EASD Stockholm 2015
Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus
16492 patients who had a history or were at risk for CV events
Mosenzon O et al Diabetes Care 40 69-76 2017
Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus
Effect of Saxagliptin on Renal Outcomes in the SAVOR-TIMI 53 Trial
Difference in mean change in ACR (mgg) as continuous variable among treatment arms by eGFR baseline categories
Beneficial non-insulin CV Outcomes Trials in T2DM
Outcomes
LEADERLiraglutide
9340 T2DM at high CV risk
SUSTAIN-6 Semaglutide3297 T2DM
at high CV riskThree-point MACE -13 -26CV death -22 -2
Fatal and non-fatal MI-14
non-fatal -12 not significant
non-fatal -26 not significant
Fatal and non-fatalstroke
-14non-fatal -11
both not significantnon-fatal -39
Heart failure -13 +11All-cause mortality -15 +5Nephropathy -22 -36
Marso SP et al for the SUSTAIN-6 Investigators N Engl J Med 375 1834-1844 2016 Marso SP et al for the LEADER Trial Investigators N Engl J Med 375 311-322 2016
Time to first renal eventMacroalbuminuria doubling of serum creatinine ESRD renal death
The cumulative incidences were estimated with the use of the KaplanndashMeier method and the hazard ratios with the use of the Cox proportional-hazard regression model The data analyses are truncated at 54 months because less than 10 of the patients had anobservation time beyond 54 months CI confidence interval ESRD end-stage renal disease HR hazard ratio
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso SP et al for the LEADER Trial Investigators N Engl J Med 375 311-322 2016
Liraglutide and Renal Outcomes in Type 2 Diabetes
Mann JFE et al for the LEADER Steering Committee and Investigators N Engl J Med 377 839-848 2017
Composite Renal Outcome and Individual Components of the Composite Outcome
Supplementary Figure 5B Kaplan Meier plot for time from randomisation to first EAC-confirmed new or worsening nephropathy using lsquoin-trialrsquo data from subjects in the full analysis set HR is from a proportional hazard model CI confidence interval EAC (external) event adjudication committee HR hazard ratio
Semaglutide 38
HR 064 (95 CI 046 088)Events 62 Semaglutide 100 PlaceboP=0005
Number of patients at risk
Semaglutide 1648 1630 1605 1580 1563 1541 1525 1518
Placebo 1649 1629 1570 1545 1518 1498 1471 1465
Placebo 61
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
New or worsening nephropathy
Marso SP et al for the SUSTAIN-6 Investigators N Engl J Med 375 1834-1844 2016
Chart1
Sheet1
Semaglutide Placebo HR(95 CI)
P valueNo () Incidence rate per 100 PYR
No () Incidence rate per 100 PYR
Retinopathy complications 50 (30) 149 29 (18) 086 176 111 278 002
Need for retinal
photocoagulation38 (23) 113 20 (12) 059 191 111 328 002
Vitreous haemorrhage 16 (10) 047 7 (04) 021 229 094 557 007
Need for treatment with
intravitreal agent16 (10) 047 13 (08) 038 125 059 256 058
Onset of diabetes-related
blindness5 (03) 015 1 (01) 003 501 059 4288 014
New or worsening
nephropathy62 (38) 186 100 (61) 306 064 046 088 0005
Persistent
macroalbuminuria44 (27) 131 81 (49) 247 054 037 077 0001
Persistent doubling of serum creatinine level and creatinine clearance per MDRD lt45 mlmin173m2
18 (11) 053 14 (08) 041 128 064 258 048
Need for continuous
renal-replacement therapy11 (07) 032 12 (07) 035 091 040 207 083
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Marso SP et al for the SUSTAIN-6 Investigators N Engl J Med 375 1834-1844 2016
Differences in glycaemic control with the study drug versus placebo in cardiovascular outcome studies assessing the safety of incretin‐based
therapies in patients with type 2 diabetes mellitus at high risk of cardiac events
Muskiet MHA et al Nature Review 4 september 2017
The changing face of DKD in diabetes
RIACE and DKD phenotypes
Different correlates for different phenotypes
Consequences of different phenotypes
(hellip and type 1 diabetes)
Nephroprotection
DPP4-i and GLP-1 RA
SGLT2-i
The effect of dapagliflozin on renal function in patientswith type 2 diabetes
Twelve double-blind placebo-controlled randomized clinical trials were analyzed up to 24 weeks (N = 4545) Six of the 12 studies included long-term data for up to 102 weeks (N = 3036)
Kohan DE et al J Nephrol 29 391-400 2016
Small transient reduction
Returned to near baseline by week 24
Returned to near baseline by week 24
gt90 of subjects had baselineeGFR gt60 mlmin173m2
Dapagliflozin reduces albuminuria over 2 years in patients with type 2 diabetes mellitus and renal impairment
minus264 (minus550 205)minus439 (minus643 minus120)
310 (minus190 1119)
Week 104 ∆ UACR
158
273
396
43
339
147
0
5
10
15
20
25
30
35
40
45Placebo DAPA 5 mg DAPA 10 mg
Shift to higher UACR level
Patients shifting UACR category ()
Shift to lower UACR level
Post hoc analysis included 166 patients with stage 3 chronic kidney disease (CKD) and increased albuminuria (ge34 mgmmol)
Fioretto P et al Diabetologia 59 2036-2039 2017
Canagliflozin slows progression of renal function decline independently of glycemic effects
Heerspink HJL et al
J Am Soc Nephrol 28 368-375 2017
Patients with an eGFR of lt55 mlmin per 173 m2 (or lt60 mlmin per 173 m2 if based on restriction of metformin use in the local label) or serum creatinine concentrations ge124 mmolL for men and ge115 mmolL for women were excluded
Canagliflozin slows progression of renal function decline independently of glycemic effects
Heerspink HJL et al J Am Soc Nephrol 28 368-375 2017
1450 T2DM patients receiving metforminEnd points were annual change in eGFR and albuminuria over 2 years of follow-up
Change in eGFR over 192 weeks
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes
Wanner C et al N Engl J Med 375 323-334 2016
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes
-39 -46New-onset or worsening nephropathy including new onset of macroalbuminuria (UACR gt300 mgg)
reduction started very early with curves separating after 3 months
Composite outcome bull Doubling of serum creatinine accompanied by
an eGFR of 45 mlmin173 m2 or lessbull Initiation of renal replacement therapybull Death due to renal disease
Wanner C et al N Engl J Med 375 323-334 2016
Incident or Worsening Nephropathy Renal Composite Outcome
Empagliflozin Placebo
no with event
analyzed ()
rate1000pt-yr
no with event
analyzed ()
rate1000pt-yr
Hazard Ratio (95 CI)
p-value
Incident or worsening nephropathy or CV death
6754170(162)
607 4972102(236)
959 061 (055ndash069) lt0001
Incident or worsening nephropathy 5254124(127)
478 3882061(188)
760 061 (053ndash070) lt0001
Progression to macroalbuminuria 4594091(112)
418 3302033 (162)
649 062 (054ndash072) lt0001
Doubling of serum creatinine 704645(15)
55 602323(26)
97 056 (039ndash079) lt0001
Initiation of renal replacement therapy 134687(03)
10 142333(06)
21 045 (021ndash097) 004
Doubling of serum creatinine initiation of renal replacement therapy or death due to renal disease
814645(17)
63 712323(31)
115 054 (040ndash075) lt0001
Incident albuminuria in patients with normoalbuminuria at baseline
14302779(515)
2525 7031374(512)
2660 095 (087ndash104) 025
Favors placeboFavors empagliflozin
Hazard ratio (95 CI)
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes
Wanner C et al N Engl J Med 375 323-334 2016
Chart1
CVd
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes
Wanner C et al N Engl J Med 375 323-334 2016
Pre-specified subgroup analyses for incident or worsening nephropathy
HR 061 (95CI 053-070) plt0001
-39
Composite of doubling of serum creatinine initiation of renal replacement therapy or death due to renal disease
Empagliflozin Placebop-value for interactionPatients analyzed
All patients 4645 2323Urine albumin-to-creatinine ratio 051lt30 mgg 2766 1376ge30 to 300 mgg 1325 671gt300 mgg 504 260
Estimated glomerular filtration rate 018ge90 mLmin173m2 1043 48660 to lt90 mLmin173m2 2406 123245 to lt60 mLmin173m2 822 416lt45 mLmin173m2 374 189
Favors placeboFavors empagliflozin
Hazard ratio (95 CI)
Wanner C et al N Engl J Med 375 323-334 2016
054 (040ndash075)
Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes
HR 054 (95CI 040-075) plt0001
-46
Grafico1
CVd
Sheet2
Sheet3
Cherney D et al Lancet Diabetes Endocrinol June 27 2017
4171 with normo- (A) 2013 with micro- (B) 769 with macro-albuminuria (C)
Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease an exploratory
analysis from the EMPA-REG OUTCOME randomised placebo-controlled trial
-7 p=0013
-25 plt00001
-32 plt00001
Cherney D et al Lancet Diabetes Endocrinol June 27 2017
2013 with microalbuminuria (A) 769 with macroalbuminuria (B)
Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease an exploratory
analysis from the EMPA-REG OUTCOME randomised placebo-controlled trial
new onset of sustainednormoalbuminuria in patientswith microalbuminuria atbaseline
new onset of sustainednormoalbuminuria or microalbuminuria in patientswith macroalbuminuria atbaseline
Cherney D et al Lancet Diabetes Endocrinol
June 27 2017
4171 with normo- 2013 with micro- 769 with macro-albuminuriaEstimated eGFR over 192 weeks by albuminuria categories
Effects of empagliflozin on the urinary albumin-to-creatinine ratio in patients with type 2 diabetes and established cardiovascular disease an exploratory
analysis from the EMPA-REG OUTCOME randomised placebo-controlled trial