La Nefropatia Diabetica: nuove acquisizioni...
Transcript of La Nefropatia Diabetica: nuove acquisizioni...
La Nefropatia Diabetica: nuove acquisizioni
epidemiologiche e loro significato clinico dopo i
risultati dello Studio RIACE
Giuseppe Penno Dipartimento di Medicina Clinica e Sperimentale
Azienda Ospedaliera Universitaria di Pisa
RIACE is a multicentre observational prospective study that is being conducted in 19 collaborating centres in Italy
Recruitment of patients with T2DM (n. 15,993) started in 2007 and was completed in 2008
160 subjects were excluded due to missing or implausible values; data from the remaining 15,773 patients were than analyzed
Age: 66.0±10.3 years (median 67 years)
Diabetes duration: 13.2±10.2 years (median 11 years)
56.8% male and 43.2% female
13.593 subjects (86%) completed the 4 to 6 year follow-up NCT00715481; URL http://clinicaltrials.gov/show/NCT00715481
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Macro 4.7% Normo
73.1% Micro 22.2%
Albuminuria
30-59 17.1%
60-89 51.7%
≥90 29.6%
<30 1.7%
eGFR
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Penno G, et al., The RIACE Study Group. J Hypertens 29: 1802-1809, 2011
15,773 patients with type 2 diabetes from Italy
62.5% 12.0%
6.7%
17.1%
1.7%
Approximately 40% of patients with T2DM show signs of CKD Approximately 20% of patients with T2DM show reduced eGFR
Renal Dysfunction is Common in Patients with T2DM
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Prevalence of nephropathy in the German diabetes population
Pommer W. NDT Plus 1 (suppl 4) iv2-iv5, 2008
CKD stages 3-5 eGFR <60; n. 2,959 (18.8%)
Non-albuminuric CKD stages 3-5
n. 1,673 (56.6%)
Albuminuric CKD stages 3-5 n. 1,286 (43.4%)
No CKD eGFR ≥60 & no-albuminuria
n. 9,865 (62.5%)
CKD stages 1-2 eGFR ≥60 & albuminuria
n. 2,949 (18.7%) +
+
Micro-albuminuria n. 912 (30.8%)
Macro-albuminuria n. 374 (12,6%)
Penno G, et al., The RIACE Study Group. J Hypertens 29: 1802-1809, 2011
Micro-albuminuria n. 2,585 (87.7%)
Macro-albuminuria n. 364 (12.3%)
15,773 patients with type 2 diabetes from Italy
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Variable excluded: LDL-cholesterol
Penno G, et al., The RIACE Study Group. J Hypertens 29: 1802-1809, 2011
The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study
Independent correlates of Chronic Kidney Disease phenotypes 15,773 patients with type 2 diabetes from Italy
0
20
40
60
80
100
1st 691 (27.6%) 322 (21.6%) 2,506/1,489
2nd 854 (33.9%) 441 (28.6%) 2,225/1,542
3rd 960 (41.3%) 662 (36.2%) 2,324/1,827
4th 1029 (54.0%) 1049 (53,7%) 1,905/1,955
Perc
ent
Age, quartiles M: CKD+ n, (%) F: CKD+ n, (%)
n, M/F The RIACE Study Group, unpublished data
The RIACE (Renal Insufficiency and Cardiovascular Events) Italian Multicenter Study
15,773 patients with T2DM: CKD phenotypes by age quartiles
CKD stages 1-2 CKD stages 3-5 non-albuminuric
CKD stages 3-5 albuminuric
M F
M F
M F
M F
Normoalbuminuria Normal GFR
“Natural” history of Diabetic Nephropathy in type 1 and type 2 diabetes: new paradigms
Microalbuminuria
Macroalbuminuria
Reduced eGFR ESRD
Natural history of diabetic nephropathy: “albuminuric” pathway
Natural history of diabetic nephropathy: “non-albuminuric” pathway
Car
diov
ascu
lar e
vent
s, d
eath
Patients n.
DM %
Follow-up years
Renal impairment
No-albuminuric renal
impairment
Renal impairment with no albuminuria nor retinopathy
UKPDS Diabetes 55: 1832-1839, 2006
4,006 100 15 28% 67% (51%) ---
DCCT/EDIC Diabetes Care 33: 1536-1543, 2010
1,439 100 (type 1) 19 6.2% 24% ---
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
1,197 100 --- 13% 36% 30%
Thomas MC et al., NEFRON Diabetes Care 32: 1497-1502, 2009
3,893 100 --- 23% 55% ---
Ninomiya T et al., ADVANCE J Am Soc Nephrol 20: 1813-1821, 2009
10,640 100 --- 19% 62% ---
Bakris GL et al., ACCOMPLISH Lancet 375: 1173-1181, 2010
11,482 60 --- 9.5% 46.8% ---
Tube SW et al., ONTARGET/ TRASCEND Circulation 123: 1098-1107, 2011
23,422 37 --- 24% 68% ---
Drury PL et al., FIELD Diabetologia 54: 32-43, 2011
9,765 100 --- 5.3% 59.0% ---
RIACE Study Group, RIACE J Hypertens 29: 1802-1809, 2011
15,773 100 --- 18.8% 56.6% 43.2%
“Natural” history of Diabetic Nephropathy in type 1 and type 2 diabetes: new paradigms
The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study
Results: stratification by CKD NKF’s KDOQI stage and retinopathy
No-retinopathy n. 2,027 (68.5%)
Retinopathy n. 932 (31.5%)
+
Non advanced Ret n. 472 (16.0%)
Advanced Ret n. 459 (15.5%)
No-retinopathy n. 2,067 (70.1%)
Retinopathy n. 882 (29.9%)
No CKD eGFR ≥60 & no-albuminuria
n. 9,865 (62.5%)
CKD stages 1-2 eGFR ≥60 & albuminuria
n. 2,949 (18.7%) +
CKD stages 3-5 eGFR <60; n. 2,959 (18.8%)
Penno G, et al., The RIACE Study Group. J Hypertens 29: 1802-1809, 2011
Concordance of CKD and Diabetic Retinopathy in subjects with type 2 diabetes
Out of 5,908 pts with CKD, only 1,814 (31%) had also retinopathy
Penno G, et al., The RIACE Study Group. Diabetes Care 35: 2317-2323, 2012
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study
Results: stratification by CKD NKF’s KDOQI stage and retinopathy
No-albuminuria no-retinopathy
n. 1,280 (43.2%)
No-albuminuria retinopathy
n. 393 (13.3%)
Albuminuria no-retinopathy n. 747 (25.3%)
Albuminuria retinopathy
n. 538 (18.2%)
+
No CKD eGFR ≥60 & no-albuminuria
n. 9,865 (62.5%)
CKD stages 1-2 eGFR ≥60 & albuminuria
n. 2,949 (18.7%) +
CKD stages 3-5 eGFR <60; n. 2,959 (18.8%)
Penno G, et al., The RIACE Study Group. Diabetes Care 35: 2317-2323, 2012
The Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study
Pugliese G et al., Atherosclerosis 218: 194-199, 2011
15,773 (100.0%)
258 (1.7%)
2,701 (17.1%)
1,897 (12.0%)
1,052 (6.7%)
9,865 (62.5%)
Total
304 (1.9%)
256 (1.6%)
48 (0.3%)
4-5
2,411 (15.3%)
2 (0.1%)
2,342 (14.8%)
23 (0.1%)
44 (0.3%)
3
1,743 (11.1%)
77 (0.5%)
1,591 (10.1%)
75 (0.5%)
2
1,260 (8.0%)
283 (1.8%)
977 (6.2%)
1
10,055 (63.8%)
234 (1.5%)
9,821 (62.3%)
No CKD 4-5 3 2 1 No CKD
Total MDRD Study CKD stage
CKD-EPI CKD Stage
Subjects moved by the
CKD-EPI equation
above
belove
Prevalence of stages 3-5 CKD in type 2 diabetes MDRD Study: 2,959 (18.8%)
CKD-EPI: 2,715 (17.2%)
The Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study
Pugliese G et al., Atherosclerosis 218: 194-199, 2011
Prevalence of stages 3-5 CKD in type 2 diabetes MDRD Study: 2,959 (18.8%)
CKD-EPI: 2,715 (17.2%)
Matsushita K et al, JAMA 307: 1941-1951, 2012
Comparison of risk prediction using the CKD-EPI Equation and the MDRD Study Equation for Estimated Glomerular Filtration Rate
Reclassification across estimated GFR categories
Matsushita K et al, JAMA 307: 1941-1951, 2012
Comparison of risk prediction using the CKD-EPI Equation and the MDRD Study Equation for Estimated Glomerular Filtration Rate Net reclassification improvements for all-cause mortality, cardiovascular mortality, and ESRD
0
10
20
30
40
50
CKD stages 1-2
n. 2,949
No CKD
n. 9,865
Maj
or C
VD e
vent
s, %
794 (26.9%)
1,756 (17.8%)
Results: Any CVD event by CKD phenotype
Chi square, p<0.0001
CKD stages 3-5 nonalbuminuric
n. 1,673
528 (31.6%)
Solini A. et al, The RIACE Study Group. Diabetes Care 35: 143-149, 2012
CKD stages 3-5 albuminuric
n. 1,286
576 (44.8%)
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Logistic regression analysis of all CVD events with CKD phenotypes as covariates
Solini A. et al, The RIACE Study Group. Diabetes Care 35: 143-149, 2012
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
CVD events in type 2 diabetic patients stratified by CKD and Diabetic Retinopathy
Penno G, et al., The RIACE Study Group. Diabetes Care 35: 2317-2323, 2012
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Logistic regression analysis of CVD events by vascular bed with CKD phenotypes as covariates
Solini A. et al, The RIACE Study Group. Diabetes Care 35: 143-149, 2012
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Reference category
Excess risk significant for eGFR values < 78 ml/min/1.73m2
CVD risk increases linearly by 12% for each decreasing decile of eGFR
Solini A. et al, The RIACE Study Group. Diabetes Care 35: 143-149, 2012
age-
and
sex
-adj
uste
d ris
k fo
r a C
VD e
vent
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Reference category
… CVD risk increases linearly by 9% for each increasing
decile of albuminuria
Excess risk was significant for AER values ≥10.5 mg/24h
age-
and
sex
-adj
uste
d ris
k fo
r a C
VD e
vent
Solini A. et al, The RIACE Study Group. Diabetes Care 35: 143-149, 2012
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
Reference category
… CVD risk increases linearly by 9% for each increasing
decile of albuminuria
Excess risk was significant for AER values ≥10.5 mg/24h
age-
and
sex
-adj
uste
d ris
k fo
r a C
VD e
vent
Solini A. et al, The RIACE Study Group. Diabetes Care 35: 143-149, 2012
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
11,538 (73.1%) of subjects with T2DM of the RIACE cohort have AER <30 mg/24h
n. 6,023 (52.2%)
n. 5,515 (47.8%)
AER <10 mg/24h
AER 10-29 mg/24h
The RIACE Study Group. Unpublished data.
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
OR 95%CI p Age, x 1 year 1.018 1.014-1.022 <0.0001 M/F Gender, male 1.238 1.070-1.432 0.004 Waist circumference, x 1 cm 1.050 0.996-1.106 0.070 HbA1c, x 1% 1.062 1.033-1.093 <0.0001 M Diastolic BP, x 1 mmHg 1.014 1.010-1.018 <0.0001 M/F Triglycerides, x 1 mg/dl 1.001 1.000-1.001 0.011 F RAS blockers 1.073 0.992-1.160 0.077 M DHP calcium channel blockers 1.171 1.053-1.302 0.004 M Glucose lowering agents (diet, REF): OHA insulin + OHA insulin
1.312 1.334 1.495
1.175-1.464 1.126-1.581 1.288-1.734
<0.0001 M/F
Smoking habits (no, REF): ex-smokers smokers
1.158 1.237
1.058-1.267 1.106-1.384
<0.0001 M
Family history for hypertension 1.325 1.207-1.455 <0.0001 M/F Family history for CVD 0.891 0.792-1.003 0.057 M Retinopathy (no ret, REF) non advanced advanced
1.141 1.095
1.010-1.288 0.942-1.271
0.072 F
Logistic regression 1 (n. 11,538)
Not in regression: diabetes duration, BMI (M), total cholesterol (M), HDL cholesterol, systolic BP (F), family history for diabetes The RIACE Study Group. Unpublished data.
1,673 patients with non-albuminuric stages 3-5 CKD excluded
9,865 (62.5%) of subjects with T2DM of the RIACE cohort have AER <30 mg/24h and eGFR >60 ml/min
n. 5,211 (52.8%)
n. 4,654 (47.28%)
AER <10 mg/24h
AER 10-29 mg/24h
The RIACE Study Group. Unpublished data.
The Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study
OR 95%CI p Age, x 1 year 1.018 1.014-1.022 <0.0001 M/F Gender, male 1.233 1.053-1.444 0.009 Waist circumference, x 1 cm 1.057 0.999-1.118 0.054 HbA1c, x 1% 1.066 1.034-1.099 <0.0001 M Diastolic BP, x 1 mmHg 1.014 1.010-1.019 <0.0001 M/F Triglycerides, x 1 mg/dl 1.001 1.000-1.001 0.058 F RAS blockers 1.069 0.982-1.163 0.122 M DHP calcium channel blockers 1.182 1.052-1.329 0.005 M Glucose lowering agents (diet, REF): OHA insulin + OHA insulin
1.293 1.277 1.470
1.150-1.454 1.062-1.536 1.247-1.733
<0.0001 M/F
Smoking habits (no, REF): ex-smokers smokers
1.188 1.286
1.077-1.310 1.142-1.448
<0.0001 M
Family history for hypertension 1.346 1.218-1.487 <0.0001 M/F Family history for CVD 0.898 0.790-1.021 0.100 M Retinopathy (no ret, REF) non advanced advanced
1.163 1.088
1.018-1.330 0.920-1.287
0.067
Logistic regression 2 (eGFR >60; n. 9,865)
Not in regression: duration of diabetes, BMI (M), HDL cholesterol, systolic BP (F), RAS blockers (M), family history for diabetes The RIACE Study Group. Unpublished data.
Avoid HbA1c variability
Penno G et al. Diabetes Care 36: 2301-2310 2013
8,260 patients with type 2 diabetes from Italy
Avoid HbA1c variability
Penno G et al. Diabetes Care 36: 2301-2310 2013
8,260 patients with type 2 diabetes from Italy
The RIACE Study Group. Submitted to NDT.
Independent association of hypertriglyceridemia with renal complications in subjects with type 2 diabetes.
10
9
8
7
6
5
4
3
2
1
0
OR
(95%
CI)
for C
KD s
tage
s 3-
5 no
n-al
bum
inur
ic
*
* *
*
* * * *
p=0.006
p=0.04 * *
subjects not on statins subjects on statins
1 2 3 4 5 6 7 8 9 10 <0.73 0.74- 0.90- 1.04- 1.19- 1.34- 1.51- 1.75- 2.05- >2.58 0.89 1.03 1.18 1.33 1.50 1.74 2.04 2.57
Independent association of hypertriglyceridemia with renal complications in subjects with type 2 diabetes.
The RIACE Study Group. Submitted to NDT.
10
9
8
7
6
5
4
3
2
1
0 1 2 3 4 5 6 7 8 9 10 <0.73 0.74- 0.90- 1.04- 1.19- 1.34- 1.51- 1.75- 2.05- >2.58 0.89 1.03 1.18 1.33 1.50 1.74 2.04 2.57
*
*
*
* *
* *
* * * *
p=0.004
p=0.015 p=0.042
p=0.004
p=0.040
14.629
OR
(95%
CI)
for C
KD s
tage
s 3-
5 al
bum
inur
ic
subjects not on statins subjects on statins
Independent association of hypertriglyceridemia with renal complications in subjects with type 2 diabetes.
The RIACE Study Group. Submitted to NDT.
Resistant hypertension in subjects with type 2 diabetes: clinical correlates and association with complications.
Resistant hypertension
Normotensive
Non-resistant hypertension
Uncontrolled hypertension
Solini A et al. J Hypertens 2014, Sept 5 (Epub ahead of print)
Resistant hypertension in subjects with type 2 diabetes: clinical correlates and association with complications.
Solini A et al. J Hypertens 2014, Sept 5 (Epub ahead of print)
Resistant hypertension in subjects with type 2 diabetes: clinical correlates and association with complications.
Solini A et al. J Hypertens 2014, Sept 5 (Epub ahead of print)
Solini A et al. J Am Geriatr Soc 61: 1253-1261, 2013
CVD (%)
1st quartile by age CVD (%)
2nd quartile by age
CVD (%)
CVD (%)
3rd quartile by age 4th quartile by age
0
10
20
30
40
50
3-4 (<60) 2 (60-89) 1 (≥90)
Met yes
Met no
0
10
20
30
40
50
Met yes
Met no
0
10
20
30
40
50
Met yes
Met no
0
10
20
30
40
50
Met yes
Met no
1,733 561 61
609 267 102 401
411 172
1,118 969 157
682 1,336 312
281 655
370
161 1,100 513
74 826
776
eGFR category (ml/min/1.73 m2)
3-4 (<60) 2 (60-89) 1 (≥90) eGFR category (ml/min/1.73 m2)
3-4 (<60) 2 (60-89) 1 (≥90) eGFR category (ml/min/1.73 m2)
3-4 (<60) 2 (60-89) 1 (≥90) eGFR category (ml/min/1.73 m2)
p=0.002
p<0.001 p=0.023
p<0.001 p<0.001
p=0.001
p=0.245
p<0.001
p=0.010
p=0.311
p<0.001
p<0.001
Solini A et al. J Am Geriatr Soc 61: 1253-1261, 2013
Retnakaran R et al., Diabetes 55: 1832-1839, 2006
Challenging conventional paradigms: Diabetic kidney disease with and without albuminuria
UKPDS; 4006 type 2 DM patients followed over a median of 15 years
0
10
20
30
40
50
60
70
1534 (38%) developing albuminuria
1132 (28%) developing renal impairment
64%
24%
12%
Patie
nts
%
51%
16%
33%
no renal impairment
renal impairment subsequent to albuminuria
renal impairment before albuminuria
no albuminuria
albuminuria subsequent to renal impairment
albuminuria before renal impairment
Challenging conventional paradigms: Diabetic kidney disease with and without albuminuria
Molitch ME et al., Diabetes Care 33: 1536-1543, 2010
DCCT/EDIC; 1439 type 1 DM patients followed over a median of 19 years
0
10
20
30
40
50
60
70
1350 (93.8%) with no sustained eGFR <60
89 (6.2%) developing sustained eGFR <60
50%
42%
8%
Patie
nts
%
24% 16%
61%
no albuminuria
microalbuminuria
macroalbuminuria
no albuminuria
microalbuminuria before renal impairment
macroalbuminuria before renal impairment
Krolewski AS et al., Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care 37: 226-234, 2014.
CKD stages 3-5 eGFR <60
n. 29 (3.7%)
No CKD eGFR ≥60 & no-albuminuria
n. 695 (89.4%)
CKD stages 1-2 eGFR ≥60 & albuminuria
n. 53 (6.8%)
Micro-albuminuria n. 46 (86.8%)
Macro-albuminuria n. 7 (13.2%)
Non-albuminuric CKD stages 3-5 n. 17 (58.6%)
Albuminuric CKD stages 3-5 n. 12 (41.4%)
Micro-albuminuria n. 4 (33.3%)
Macro-albuminuria n. 8 (66.7%)
Heterogeneity of CKD phenotypes among 777 subjects with type 1 diabetes
Russo E et al., Diabetologia 56 (suppl 1) S472, 2013; EASD, Barcelona, 23-27 September 2013
Variables CKD 1-2 CKD 3-5
MODEL 2 OR 95%CI p OR 95%CI p
Age, x year 0.956 0.923-0.990 0.012 1.048 0.999-1.098 0.054 Diabetes Duration, x year -- -- -- -- -- -- HbA1c 1.354 1.024-1.790 0.033 -- -- -- Total-C 1.011 1.002-1.020 0.015 -- -- -- Gamma-GT 1.006 1.001-1.012 0.029 1.014 1.003-1.026 0.017 Fibrinogen 1.004 1.000-1.009 0.073 1.010 1.002-1.017 0.010 Hypertension 4.260 1.999-9.078 0.0001 5.783 0.960-34.833 0.055 PAS -- -- -- 1.025 0.998-1.052 0.066
Retinopathy No Background Proliferative
1.0
1.666 10.778
0.660-4.207 4.380-26.523
0.0001
0.280 0.0001
1.0
1.747 7.684
0.367-8.314 1.877-31.450
0.002
0.483 0.005
Variables not in the Equation Sex, BMI, Smokers, PAD, HDL-C, Triglycerides, Uric Acid
Heterogeneity of CKD phenotypes among 777 subjects with type 1 diabetes
Russo E et al., Diabetologia 56 (suppl 1) S472, 2013; EASD, Barcelona, 23-27 September 2013
Variables CKD 3-5 Non-albuminuric
CKD 3-5 albuminuric
MODELLO 2 OR 95%CI p OR 95%CI p Age, x year 1.090 1.030-1.153 0.003 1.092 1.008-1.184 0.031 HbA1c -- -- -- 2.262 1.020-5.016 0.044 HDL-C -- -- -- 0.950 0.890-1.013 0.117 GammaGT 1.016 1.002-1.030 0.022 -- -- -- Fibrinogen -- -- -- 1.016 1.003-1.028 0.012
Hypertension 15.725 1.432-172.655 0.024 -- -- --
PAD -- -- -- 1.092 0.996-1.198 0.062
Retinopathy No Background Proliferative
1.0
0.779 4.147
0.137-4.417 0.964-17.844
0.028
0.778 0.056
-- -- --
Variables not in the Equation Sex, Diabetes Duration, BMI, Smokers, PAS, Total-C, Triglycerides, Uric Acid
Heterogeneity of CKD phenotypes among 777 subjects with type 1 diabetes
Russo E et al., Diabetologia 56 (suppl 1) S472, 2013; EASD, Barcelona, 23-27 September 2013
CKD stages 3-5 eGFR <60
n. 18 (1.9%)
No CKD eGFR ≥60 & no-albuminuria
n. 736 (78.6%)
CKD stages 1-2 eGFR ≥60 & albuminuria
n. 182 (19.5%)
Micro-albuminuria n. 128 (70.3%)
Macro-albuminuria n. 54 (29.7%)
Non-albuminuric stages 3-5 CKD n. 5 (27.8%)
Albuminuric stages 3.5 CKD n. 13 (72.2%)
Micro-albuminuria n. 4 (30.8%)
Macro-albuminuria n. 9 (69.2%)
*
*p=0.039 vs cohort 1 Russo E et al., Diabetologia 57 (suppl 1), 2014; EASD, Vienna, 15-19 September 2014
Heterogeneity of CKD phenotypes among 936 subjects with type 1 diabetes (EURODIAB-Italy)
777 T1DM eGFR MDRD (ml/min/1.73 m2)
Total >90 75-89 60-74 <60 N. 445 232 71 29 ACR (<10 mg/g), n (%) 353 (79.3) 187 (80.6) 50 (70.4) 10 (34.5) 600 (77.2)
ACR (10-29 mg/g), n (%) 61 (13.7) 31 (13.4) 13 (18.3) 7 (24.1) 112 (14.4)
Microalbuminuria (30-299 mg/g), n (%) 25 (5.6) 14 (6.0) 7 (9.9) 4 (13.8) 50 (6.4)
Macroalbuminuria (>300 mg/g), n (%) 6 (1.3) --- 1 (1.4) 8 (27.6) 15 (1.9)
936 T1DM eGFR MDRD (ml/min/1.73 m2) Total >90 75-89 60-74 <60
N. 794 84 40 18 ACR (<10 mg/g), n (%) 407 (51.3) 35 (41.7) 13 (32.5) 4 (22.2) 459 (49.0)
ACR (10-29 mg/g), n (%) 242 (30.5) 25 (29.8) 14 (35.0) 1 (5.5) 282 (30.1)
Microalbuminuria (30-299 mg/g), n (%) 106 (13.4) 16 (19.0) 6 (15.0) 4 (22.2) 132 (14.1)
Macroalbuminuria (>300 mg/g), n (%) 39 (4.9) 8 (9.5) 7 (17.5) 9 (50.0) 63 (6.7)
*p=0.006
*p<0.0001
Heterogeneity of CKD phenotypes among subjects with type 1 diabetes
NA
NA
Garofolo M et al., 25° Congresso Nazionale SID, Bologna, 28-31 Maggio 2014
93,8
82,4
70,6 64,7
90
58,3 58,3
16,7
0
10
20
30
40
50
60
70
80
90
100
Hypertension Treatment with BP-lowering
agents
Treatment with RAS blockers
Treatment with statins
11,8 8,3
76,5
66,7
11,8 25
CKD 3-5 Alb- CKD 3-5 Alb +
HbA1c > 9% HbA1c 7-9% HbA1c < 7%
777 T1DM: clinical features CKD 3-5 Alb- vs CKD 3-5 Alb+
ns ns
ns p = 0.010
ns
Garofolo M et al., 25° Congresso Nazionale SID, Bologna, 28-31 Maggio 2014
38,3
20,6 17,5 15,9
100
87,5
75
12,5
0
10
20
30
40
50
60
70
80
90
100
Hypertension Treatment with BP-lowering
agents
Treatment with RAS blockers
Treatment with statins
22,6 25
75,8
37,5
1,6
37,5
CKD 2b Alb- CKD 2b Alb +
p=0,001 p<0,001
p <0,001
ns
p <0,001
777 T1DM: clinical features CKD 3-5 Alb- vs CKD 3-5 Alb+
HbA1c > 9% HbA1c 7-9% HbA1c < 7%
Garofolo M et al., 25° Congresso Nazionale SID, Bologna, 28-31 Maggio 2014
Conclusions (1)
Non-albuminuric renal impairment is the predominant clinical phenotype in patients, particularly women, with reduced eGFR.
Concordance between CKD and diabetic retinopathy is low, with only a minority of patients with renal dysfunction presenting with any or advanced retinal lesions.
The non-albuminuric form is associated with a significant prevalence of CVD, especially at the level of the coronary vascular bed.
Even within the normoalbuminuric range, in type 2 diabetic patients, AER is correlated with several risk factors which are potentially susceptible of therapeutic intervention.
Conclusions (2)
CKD is associated with HbA1c variability more than with average HbA1c, whereas retinopathy and CVD are not.
CKD is associated with hypertriglyceridemia and with resistant hypertension (likely bidirectional?).
Non-albuminuric renal function impairment is also detectable in a high proportion of patients with type 1 diabetes.
The RIACE Steering Committee
Giuseppe Pugliese (Coordinator), Giuseppe Penno (Secretariat), Anna Solini, Enzo Bonora, Emanuela Orsi, Roberto Trevisan, Luigi Laviola, Antonio Nicolucci. The Diabetic Nephropathy Study Group, SID
Giuseppe Pugliese, Salvatore De Cosmo, Gabriella Gruden, Susanna Morano, Giuseppe Penno, Francesco Pugliese, Giampaolo Zerbini, Luigi Laviola, Anna Solini, Roberto Trevisan. Participating diabetes centers
1. Azienda Ospedaliera Sant'Andrea, Roma (Coordinating Center): Giuseppe Pugliese, Paola Simonelli, Laura Salvi, Alessandra Bazuro. 2. Ospedale Le Molinette, Torino: Paolo Cavallo-Perin, Gabriella Gruden, Bartolomeo Lorenzati. 3. Ospedale San Luigi Gonzaga, Orbassano: Mariella Trovati, Giovanni Anfossi, Franco Cavalot, Massimo Chirio. 4. Ospedale San Raffaele, Milan: Gianpaolo Zerbini, Valentina Martina. 5. IRCCS “Cà Granda – Ospedale Maggiore Policlinico”, Milan: Emanuela Orsi, Alessia Dolci. 6. Ospedale San Paolo, Milan: Antonio Pontiroli, Marco Laneri. 7. Ospedale San Giuseppe, Milan: Maura Arosio, Antonio Rossi, Laura Montefusco. 8. Ospedali Riuniti, Bergamo: Roberto Trevisan, Anna Corsi. 9. Università e Azienda Ospedaliera Universitaria Integrata di Verona: Enzo Bonora, Giacomo Zoppini. 10. Policlinico Universitario, Padova: Angelo Avogaro, Monica Vedovato, Elisa Pagnin. 11. Azienda Ospedaliero-Universitaria Pisana, Pisa: Giuseppe Penno, Laura Pucci, Daniela Lucchesi, Eleonora Russo, Monia Garofolo. 12. Ospedale Santa Chiara, Azienda Ospedaliero-Universitaria Pisana, Pisa: Anna Solini. 13. Ospedale Le Scotte, Siena: Francesco Dotta, Cecilia Fondelli, Laura Nigi. 14. Policlinico Umberto I, Roma: Susanna Morano, Alessandra Gatti, Elisabetta Mandosi e Mara Fallarino. 15. Ospedale S. Maria Goretti, Latina: Raffaella Buzzetti, Gaetano Leto. 16. Ospedali Riuniti, Foggia: Mauro Cignarelli, Olga Lamacchia, Sabina Pinnelli. 17. Policlinico Universitario, Bari: Francesco Giorgino, Luigi Laviola, Sebastio Perrini. 18. Policlinico Mater Domini, Catanzaro: Giorgio Sesti, Francesco Andreozzi. 19. Università e Azienda Ospedaliera Universitaria di Cagliari, Policlinico Universitario: Marco Giorgio Baroni, Giuseppina Frau.
Thanksgiving
Thanksgiving
MD Monia Garofolo
Eleonora Russo
Rosalia Bellante
BD Daniela Lucchesi
Laura Giusti
Veronica Sancho-Bornez
Laura Pucci
Thank you for your attention!