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

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


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


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%


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

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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


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

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Fox

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Lan

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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

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et

al.,

Fox

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Lan

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80:

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: 16

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201

220

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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


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


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%)



Prevalence of stages 3-5 CKD in type 2 diabetesMDRD Study: 2,959 (18.8%)

CKD-EPI: 2,715 (17.2%)


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.


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


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


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


2. Renal impairment is common. Every second/third patient in our clinic might have signs of renal impairment.


4. Cystatin C


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


13.7%

9.7%

10.0%


8859 83


2. Renal impairment is common. Every second/third patient in our clinic might have signs of renal impairment.


4. Cystatin C

5. Measuring GFR


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)

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