La Nefropatia Diabetica: nuove acquisizioni ...· La Nefropatia Diabetica: nuove acquisizioni epidemiologiche

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  • 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: 66.010.3 years (median 67 years)

    Diabetes duration: 13.210.2 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

    http://clinicaltrials.gov/show/NCT00715481
  • Macro 4.7% Normo

    73.1% Micro 22.2%

    Albuminuria

    30-59 17.1%

    60-89 51.7%

    90 29.6%

  • 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

  • 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    n, M/F The RIACE Study Group, unpublished data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 NKFs 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

  • 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 NKFs 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

  • 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

  • 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