La gestione del paziente diabetico: bisogni, percorsi e strumenti Metodi per lo studio della...
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Transcript of La gestione del paziente diabetico: bisogni, percorsi e strumenti Metodi per lo studio della...
La gestione del paziente diabetico: bisogni, percorsi e strumenti
Metodi per lo studio della nefropatia
GiuseGiuseppppe Pennoe Penno Dipartimento di Medicina Clinica e SperimentaleDipartimento di Medicina Clinica e Sperimentale
Azienda Ospedaliera Universitaria di PisaAzienda Ospedaliera Universitaria di Pisa
Pisa, 28-30 OTTOBRE 2013
1.1. Classification of chronic kidney Classification of chronic kidney disease (CKD) by albuminuria and disease (CKD) by albuminuria and eGFReGFR
Key pointsKey pointsKey pointsKey points
Levey AS et al, Kidney Int 80: 17-28, 2011
KDIGO: Classification of Kidney Disease by KDIGO: Classification of Kidney Disease by albuminuriaalbuminuria and Association with Adverse and Association with Adverse OutcomesOutcomes
Levey AS et al, Kidney Int 80: 17-28, 2011
KDIGO: Classification of Kidney Disease by KDIGO: Classification of Kidney Disease by eGFReGFR and Association with Adverse Outcomesand Association with Adverse Outcomes
Levey AS et al, Ann Intern Med 139: 137-147, 2003
National Kidney Foundation’s (NKF’s) Kidney Disease National Kidney Foundation’s (NKF’s) Kidney Disease Outcomes Quality Initiative (KDOQI) classificationOutcomes Quality Initiative (KDOQI) classification
Stage 0 - No CKDStage 1 CKDStage 2 CKDStage 3 CKDStage 4 CKDStage 5 CKD
MDRD
Tonelli M et al, Ann Intern Med 154: 12-21, 2011
MDRD
Alberta Kidney Disease Network classificationAlberta Kidney Disease Network classification
Risk category 0Risk category 1Risk category 2Risk category 3Risk category 4
Tonelli M et al, Ann Intern Med 154: 12-21, 2011
Alberta Kidney Disease Network classificationAlberta Kidney Disease Network classification
1.1. This risk classification system identifies This risk classification system identifies fewer patients as having advanced CKD fewer patients as having advanced CKD than the NFK staging systemthan the NFK staging system
2. This system could reduce unnecessary referral for care, at the cost of not referring or delaying referral for some patients who go on to develop ESRD or die
Take homeTake homeTake homeTake home
KDIGO, Kidney Int Suppl 3: 1-150, 2013
CKD-EPI
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
Low riskModerate riskHigh riskVery high risk
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
Low riskModerate riskHigh riskVery high risk
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
Low riskModerate riskHigh riskVery high risk
1.1. Classification of chronic kidney Classification of chronic kidney disease (CKD) by eGFR and disease (CKD) by eGFR and albuminuriaalbuminuria
2. Renal impairment is common. Every second/third patient in our clinic might have signs of renal impairment
Key pointsKey pointsKey pointsKey points
Stages of “Diabetic Stages of “Diabetic nephropathy”nephropathy”
NormoNormo 73,1%73,1%
MicroMicro 22,2%22,2%
MacroMacro 4,7%4,7%
eGFR strata eGFR strata (ml/min/1.73 m(ml/min/1.73 m22))
≥≥9090 29,6%29,6%
60-8960-89 51,7%51,7%
30-5930-59 17,1%17,1%
<30<30 1,7%1,7%
NKF’s KDOQI NKF’s KDOQI CKD stagesCKD stages
No CKDNo CKD 62,5%62,5%
Stage 1Stage 1
≥≥9090**6,7%6,7%
Stage 2Stage 2
60-8960-89**12,0%12,0%
Stage 3 Stage 3 30-5930-59 17,1%17,1%
Stages 4, 5Stages 4, 5 <30<30 1,7%1,7%
* * Plus “kidney damage”Plus “kidney damage”
MDRDMDRD
The RIACE (Renal Insufficiency and The RIACE (Renal Insufficiency and Cardiovascular Events) studyCardiovascular Events) study
15,773 patients with type 2 diabetes from Italy15,773 patients with type 2 diabetes from Italy
Penno G et al. J Hypertens 29: 1802-1809, 2011
62.5%12.0%
6.7%
17.1%
1.7%
No CKD
CKD stage 1
CKD stage 2
CKD stage 3
CKD stages 4/5
Approximately 40% of patients with T2DM show signs of CKD (stages 1-5)
Approximately 20% of patients with T2DM show signs of renal failure (eGFR <60 ml/min/1.73 m2)
Renal dysfunction is common in Renal dysfunction is common in patients with T2DMpatients with T2DM
The RIACE Study: 15,773 patients The RIACE Study: 15,773 patients with T2DMwith T2DM
Penno G et al. J Hypertens 29: 1802-1809, 2011
Severe(macro)
Mild(micro)
Normal
eGFR
ml/min/1.73 m2
MDRD
15-30
30-44
45-59
60-89
>90
Albuminuria
Stage 2
Stage 1Stage 0(no CKD)
62.5%
Stage 3
Stage 4
Stage 1-2albuminuric phenotype
18.7%
Stages 3/5albuminuric
CKDphenotype
8.2%
Stage 3/5NON
albuminuricCKD
phenotype
10.6%
Penno G et al. J Hypertens 29: 1802-1809, 2011
Renal dysfunction is common in Renal dysfunction is common in patients with T2DMpatients with T2DM
The RIACE Study: 15,773 patients The RIACE Study: 15,773 patients with T2DMwith T2DM
Patientsn.
DM%
Follow-upyears
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/EDICDiabetes 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., NEFRONDiabetes Care 32: 1497-1502, 2009
3,893 100 --- 23% 55% ---
Ninomiya T et al., ADVANCEJ Am Soc Nephrol 20: 1813-1821, 2009
10,640 100 --- 19% 62% ---
Bakris GL et al., ACCOMPLISHLancet 375: 1173-1181, 2010
11,482 60 --- 9.5% 46.8% ---
Tube SW et al., ONTARGET/ TRASCENDCirculation 123: 1098-1107, 2011
23,422 37 --- 24% 68% ---
RIACE Study Group, RIACEJ Hypertens 29: 1802-1809, 2011
15,773 100 --- 18.8% 56.6% 43.3%
““Natural” history od Diabetic Retinopathy in Natural” history od Diabetic Retinopathy in type 1 and type 2 diabetes: new paradigmstype 1 and type 2 diabetes: new paradigms
NormoalbuminuriaNormoalbuminuriaNormal GFRNormal GFR
““Natural” history od Diabetic Retinopathy in Natural” history od Diabetic Retinopathy in type 1 and type 2 diabetes: new paradigmstype 1 and type 2 diabetes: new paradigms
MicroalbuminuriaMicroalbuminuria
MacroalbuminuriaMacroalbuminuria
Reduced eGFRReduced eGFRESRDESRD
Natural history of diabetic nephropathy: “albuminuric” pathway
Natural history of diabetic nephropathy: “non-albuminuric” pathway
Ca
rdio
vasc
ula
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ven
ts, d
eath
Ca
rdio
vasc
ula
r e
ven
ts, d
eath
1.1. Classification of chronic kidney Classification of chronic kidney disease (CKD) by eGFR and disease (CKD) by eGFR and albuminuriaalbuminuria
2. Renal impairment is common. Every second/third patient in our clinic might have signs of renal impairment
3. Albuminuria and eGFR: complementary measures of (diabetic) CKD
Key pointsKey pointsKey pointsKey points
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
Low riskModerate riskHigh riskVery high risk
Associations of Kidney Disease measures with mortality and Associations of Kidney Disease measures with mortality and ESRD in individuals with and without diabetes: a meta-analysisESRD in individuals with and without diabetes: a meta-analysis
Fox
CS
et
al.,
Fox
CS
et
al.,
Lan
cet
Lan
cet 3
80:
1662
-167
3,
380
: 16
62-1
673,
201
220
12
Data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts
Associations of Kidney Disease measures with mortality and Associations of Kidney Disease measures with mortality and ESRD in individuals with and without diabetes: a meta-analysisESRD in individuals with and without diabetes: a meta-analysis
Fox
CS
et
al.,
Fox
CS
et
al.,
Lan
cet
Lan
cet 3
80:
1662
-167
3,
380
: 16
62-1
673,
201
220
12
Data for 1,024,977 participants (128,505 with diabetes) from 30 general population and high-risk cardiovascular cohorts and 13 chronic kidney disease cohorts
Associations of Kidney Disease measures with mortality and Associations of Kidney Disease measures with mortality and ESRD in individuals with and without diabetes: a meta-analysisESRD in individuals with and without diabetes: a meta-analysis
Fox
CS
et
al.,
Fox
CS
et
al.,
Lan
cet
Lan
cet 3
80:
1662
-167
3,
380
: 16
62-1
673,
201
220
12
Data for 13 chronic kidney disease cohorts
Risk of coronary events in people with chronic kidney disease Risk of coronary events in people with chronic kidney disease compared with those with diabetes:compared with those with diabetes:a population-level cohort studya population-level cohort study
1,268,029 participants; median follow-up of 48 months
Tonelli M et al.,Tonelli M et al., Lancet,Lancet, published online, June 19, published online, June 19, 20122012
1,268,029 participants; median follow-up of 48 months;the Alberta Kidney Disease Network
1,104,71375,87159,11715,36812,960
eGFR by the CKD-EPI equation
Tonelli M et al.,Tonelli M et al., Lancet,Lancet, published online, June 19, published online, June 19, 20122012
Risk of coronary events in people with chronic kidney disease Risk of coronary events in people with chronic kidney disease compared with those with diabetes:compared with those with diabetes:a population-level cohort studya population-level cohort study
Intra-individual CV:32.5% (14.3-58.9)
Concordance rate between a single UAE and the geometric mean:
• Two UAE: normo: 94.6%;micro: 83.5%;macro: 91.1%;micro/macro: 90.6%;
• Three UAE:normo: 94.6%;micro: 84.2%;macro: 86.8%;micro/macro: 90.8%.
Predictive performance for the mean of 3 UAE values
Reference line
UAEone valueUAEtwo values
4,062 subjects with at least two UAE measurements
The The RRenal enal IInsufficiency nsufficiency AAnd nd CCardiovascular ardiovascular EEvents (vents (RIACERIACE) Italian multicentre study) Italian multicentre study
Pugliese G et al., Nephrol Dial Transplant 26: 3950-3954, 2011
The The RRenal enal IInsufficiency nsufficiency AAnd nd CCardiovascular ardiovascular EEvents (vents (RIACERIACE) Italian multicentre study) Italian multicentre study
Summary of results and conclusions
A single UAE value, thought to be encumbered with high intra-individual variability, is an accurate predictor of the stage of nephropathy in subjects with type 2 diabetes.
Multiple UAE measurements may not be necessary for classification purposes in both clinical and epidemiological settings.
Pugliese G et al., Nephrol Dial Transplant 26: 3950-3954, 2011
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
The The RRenal enal IInsufficiency nsufficiency AAnd nd CCardiovascular ardiovascular EEvents (vents (RIACERIACE) Italian multicentre study) 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
4-5321No CKD
TotalMDRD StudyCKD stage
CKD-EPICKD Stage
Soggetti riclassificati
con la equazione
CKD-EPI
sopra
sotto
Prevalence of stages 3-5 CKD in type 2 diabetesMDRD Study: 2,959 (18.8%)
CKD-EPI: 2,715 (17.2%)
The The RRenal enal IInsufficiency nsufficiency AAnd nd CCardiovascular ardiovascular EEvents (vents (RIACERIACE) Italian multicentre study) Italian multicentre study
Pugliese G et al., Atherosclerosis 218: 194-199, 2011
Prevalence of stages 3-5 CKD in type 2 diabetesMDRD Study: 2,959 (18.8%)
CKD-EPI: 2,715 (17.2%)
The The RRenal enal IInsufficiency nsufficiency AAnd nd CCardiovascular ardiovascular EEvents (vents (RIACERIACE) Italian multicentre study) Italian multicentre study
Summary of results and conclusions
Estimating GFR in patients with type 2 diabetes using the CKD-EPI equation provides a better definition of the cardiovascular burden associated with CKD, in terms of CVD prevalence and CHD risk score.
Pugliese G et al., Atherosclerosis 218: 194-199, 2011
Matsushita K et al, JAMA 307: 1941-1951, 2012
Comparison of risk prediction using the CKD-EPI Comparison of risk prediction using the CKD-EPI Equation and the MDRD Study Equation for Equation and the MDRD Study Equation for Estimated Glomerular Filtration RateEstimated Glomerular Filtration Rate
Distribution of estimated GFRData from 1.1 million adults from 25 general population cohorts, 7 high-risk cohorts (of vascular disease), and 13 CKD cohorts
Matsushita K et al, JAMA 307: 1941-1951, 2012
Comparison of risk prediction using the CKD-EPI Comparison of risk prediction using the CKD-EPI Equation and the MDRD Study Equation for Equation and the MDRD Study Equation for Estimated Glomerular Filtration RateEstimated 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 Comparison of risk prediction using the CKD-EPI Equation and the MDRD Study Equation for Equation and the MDRD Study Equation for Estimated Glomerular Filtration RateEstimated Glomerular Filtration RateNet reclassification improvements for all-cause mortality, cardiovascular mortality, and ESRD
1.1. Classification of chronic kidney Classification of chronic kidney disease (CKD) by eGFR and disease (CKD) by eGFR and albuminuriaalbuminuria
2. Renal impairment is common. Every second/third patient in our clinic might have signs of renal impairment.
3. Albuminuria and eGFR: complementary measures of (diabetic) CKD
4. Cystatin C
Key pointsKey pointsKey pointsKey points
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm
Inker LA et al, N Engl J Med 367: 20-29, 2012
….. the combined equation improved the classification of measured GFR ….. and correctly reclassified 16.9% of those with an estimated GFR of 45 to 59 ml per minute per 1.73 m2 as having a GFR of 60 ml or higher per minute per 1.73 m2.
Pucci L et al., Clin Chem 53: 480-488, 2007
Cystatin C and estimates of renal function: searching for a better measure of kidney function in diabetic patients
Shlipak MG et al, N Engl J Med 369: 932-943, 2013
Shlipak MG et al, N Engl J Med 369: 932-943, 2013
13.7%
9.7%
10.0%
Shlipak MG et al, N Engl J Med 369: 932-943, 2013
8859 83
Shlipak MG et al, N Engl J Med 369: 932-943, 2013
Shlipak MG et al, N Engl J Med 369: 932-943, 2013
1.1. Classification of chronic kidney Classification of chronic kidney disease (CKD) by eGFR and disease (CKD) by eGFR and albuminuriaalbuminuria
2. Renal impairment is common. Every second/third patient in our clinic might have signs of renal impairment.
3. Albuminuria and eGFR: complementary measures of (diabetic) CKD
4. Cystatin C
5. Measuring GFR
Key pointsKey pointsKey pointsKey points
KDIGO, Kidney Int Suppl 3: 1-150, 2013
Kidney Disease: Improving Global Outcomes (KDIGO) Kidney Disease: Improving Global Outcomes (KDIGO) classificationclassification
Pucci L et al, Diabet Med 18: 116-120, 2001
Agarwal R et al, Clin J Am Soc Nephrol 4: 77-85, 2009
We suggest an eight-sample technique to adequately capture the entire plasma pharmacokinetic profile. Sampling at 5, 15, 30, 45, 60, 120, 240, and 360 (or longer) min after bolus iothalamate should adequately capture the distribution and elimination phase of this drug. Others have suggested a similar approach (Pucci L et al. Diabet Med, 2001)