ΜΑΡΙΑ ΜΑΡΚΕΤΟΥ

ΔΙΕΥΘ. ΕΣΥ

ΠΑΝΕΠΙΣΤΗΜΙΑΚΟ ΝΟΣΟΚΟΜΕΙΟΗΡΑΚΛΕΙΟΥ

Υπερτασικός 69 ετώνμε διαβητική

νεφροπάθεια — νοσηλεία για οξύ στεφανιαίο

σύνδρομο για το οποίο θα κάνει προγραμματισμένη

PCI

Conflict of interest: none

Κλινικό Περιστατικόo Ασθενής 69 ετών

o Ιστορικό αρτηριακής υπέρτασης από 15-ετίας και ΣΔ τύπου 2 από 12-ετίας

o Αναφέρει προκάρδιοσυσφιγκτικό αλγος από 2ώρου και στηθάγχη προσπάθειάς από 3-μήνου

Φαρμακευτική αγωγήo Ιρμπεζαρτάνη/υδροχλωροθειαζίδη300/12,5 mg

o Συνδυασμό βιλδαγλιπτίνης και μετφορμίνης (50/1000mg)

oΓλικλαζίδη 3οmg

o ατορβαστατινη 20mg

Κατά την εισαγωγή του ….

o Glucose= 99mg/dL

o LDL-C=90mg/dL

oHbA1c = 7.1%

o ΑΠ = 185/105mm Hg

o Hct =42,5%

o S-crea = 1,3 mg/dl,

otroponine I=1,2ng/mL

Systolic BP and CV Death Rates in Type 2 Diabetes

Card

iovascu

lar

Mo

rtali

ty

Rate

/10,0

00P

ers

on

-yr

Stamler J et al. Diabetes Care. 1993;16:434-444.

Systolic Blood Pressure (mm Hg)

Nondiabetic Patients

Diabetic Patients

250

200

150

100

50

0<120 120–139 140–159 160–179 180–199 200

Screening Tools: eGFR

Considered the best overall index of kidney function.

Normal GFR varies according to age, sex, and body size, and declines with age.

CKD-EPI Creatinine Equation (2009) to estimate GFR.

Other useful calculators related to kidney disease include MDRD and Cockroft Gault.

GFR calculators are available online at www.kidney.org/GFR.

eGFR=58ml/min/1.73m2

Moderately reduced kidney

function

Screening Tools: ACRUrinary albumin-to-creatinine ratio (ACR) is calculated by dividing albumin concentration in milligrams by creatinine concentration in grams.

Creatinine assists in adjusting albumin levels for varying urine concentrations, which allows for more accurate results versus albumin alone.

Spot urine albumin-to-creatinine ratio for quantification of proteinuria

First morning void preferable

24hr urine test rarely necessary

365mg/dL

Hypertension-induced renal dysfunction

hypertension nephropathy – longterm hypertension causes kidney damage

ischaemic nephropathy - atherosclerotic changes in macrovessels (altogether with diabetes, hyperlipidaemia).. renovascular hypertension

vascular nephropathy (nephrosclerosis) –affection of smaller renal vessel causes kidney dysfunction

renovascular kidney disease – vascular nephrosclerosis + ischemic nephropathy

Επιπολασμός της Νεφρικής Νόσου Τελικού Σταδίου ανά αίτιο

0

40

80

120

160

1989 1990 1991 1992 1993 1994 1995 1996 1997 1998

Επ

ιπο

λα

σμ

ός α

νά

εκ

ατο

μύ

ριο

Πλ

ηθυ

σμ

ού

Σπειραματονεφρίτις Υπέρταση Διαβήτης

Έτος

United States Renal Data System (USRDS) 2000 Annual Data Report • WWW.USRDS.ORG

Diabetic nephropathy

A microvascular complication of diabetes

marked by albuminuria and a deteriorating

course from normal

renal function to ESRD.

Diabetic Nephropathy

Over 40% of new cases of end-

stage renal disease (ESRD) are

attributed to diabetes.

In 2001, 41,312 people with

diabetes began treatment for end-

stage renal disease.

In 2001, it cost $22.8 billion in

public and private funds to treat

patients with kidney failure.

Minorities experience higher than

average rates of nephropathy and

kidney disease

Incidence of ESRD

Resulting from Primary

Diseases (1998)

43%

23%

12%

3%

19%

Diabetes

Hypertension

Glomerulonephritis

Cystic Kidney

Other Causes

MicroalbuminuriaEarly indicator of diabetic nephropathy (diabetic damage to kidneys).

This is the presence of small particles of protein in the urine. Passage of protein through the glomeruli (or filtering units of the kidney, damages the kidney.)

-Detected in urinalysis (UA)

-Presence of microalbuminuria indicates 16.5X increased risk of cardiovascular mortality over 3.6 years (Bell, 2009).

Epidemiology About 20-30% of patients with type I DMdevelop microalbuminuria, less than halfprogress to overt nephropathy

Incidence of ESRD is 16% at 30 years.

5-60% of type II DM patients develop DN,depending on ethnicity

When diabetic retinopathy coexistswith albuminuria, the likelihood ofdiabetic nephropathy is very high

Suggests the presence of thespecific pattern of nodularglomerulosclerosis, the so calledKimmelstiel-Wilson lesion

PathophysiologyHyperglycaemia

Glycation endproducts (AGE)

activation of signal transduction

PKC, MAP kinase, NF-κB Reactive oxygen

radicals

Vasoactive systems

Hemodynamic

changes

Growth factors

Cell cycle changes

Tubulointerstitial fibrosisProteinuria

GlomerulosclerosisRenal failure

Pathogenesis

Genetic predisposition to or protection from diabetic nephropathy

◦ Differences in prevalence of microalbuminuria, ESRD in different patient populations

◦ Only half of patients with poor glycemic control will develop diabetic nephropathy

Multiple genes may be involved

Classification of CKD Based on GFR and Albuminuria Categories: “Heat

Map”

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work

Group. Kidney Int Suppls. 2013;3:1-150.

Treatment

Glycemic control

Hypertension control

Dietary protein restriction

RAS blockade

Blood pressure reduction is the most potent CVD risk reducer in type 2

diabetes

Meta Analysis: Lower Mean BP Results in Slower Rates of Decline in GFR in Diabetics and Non-

Diabetics

95 98 101 104 107 110 113 116 119

r = 0.69; P < 0.05

meanBP (mmHg)

GF

R (

mL

/min

/έτο

ς)

130/85 140/90

UntreatedHTN

0

-2

-4

-6

-8

-10

-12

-14

Bakris GL, et al. Am J Kidney Dis. 2000; 36: 646-661

Μεταβολή του GFR

Barnett et al; Acta Diabetol. 2005; 42 : S42 - S49

Anti-ischeamic drugs in the acute phase

2015 ESC guidelines

Oral antiplatelet therapy

2015 ESC guidelines

Anti-coagulation

2015 ESC guidelines

ESC/EAS 2016 guidelines

CKD patient safety approach

Fink et al. Am J Kidney Dis. 2009,53:681-668

Patient Safety

FollowingCKD detection

Improved diagnosis creates opportunity for strategic preservation of kidney function

Risk criteria mandating invasive therapy

2015 ESC guidelines

2015 ESC guidelines

Risk criteria mandating invasive therapy

GRACE score = 135Interpretation:■ Mortality in hospital: Intermediate risk -Mortality 2 - 5%■ Mortality at 6 months: High risk - Mortality >11%

Bleeding score

Bleeding score 43: High risk

Risk of in-hospital major bleeding 10,1%

Indications forrevascularization in patients

with nSTE-ACS

2014ESC/EACTS guidelines

2015 ESC guidelines

Prevention of contrast-induced nephropathy

2014ESC/EACTS guidelines

Although performing diagnostic and interventional procedures separately reduces the total volume exposure to contrast media, the risk of renal atheroembolicdisease increases with multiple catheterizations.

In CKD patients with diffuse atherosclerosis, a single invasive approach (diagnostic angiography followed by ad hoc PCI) may be considered, but only if the contrast volume can be maintained, 4 mL/kg.

The risk of CIN increases significantly when the ratio of total contrast volume to GFR exceeds 3.7:1

Angiography and PCI: two in one?

Recommendation for the type of revascularization(CABG or PCI) in patients with SCAD with suitable coronary anatomy

for both procedures and low predicted surgical mortality

Stone et al. Circulation 2001;104:642-647

Diabetes and PCI: Factors influencing outcome

Eur Heart J 2004;25:190-8

Inflammation

Atherosclerosis burden

Renal dysfunctionLV dysfunction

PAD

Prothromboticstate

Endothelial dysfunction Restenosis

CAD progression and/or worse

outcome in PCI

Patti et al. Am J Cardiol 2008; 102:2555-2583

Akin et al. Am J cardiol 2010;106:1201-1207

Blood pressure treatment strategies

ESH ESC guidelines 2013

Διαβήτης: Αυστηρός γλυκαιμικός έλεγχοςvs αυστηρού ελέγχου της ΑΠ και

Καρδιαγγειακά συμβάματα στη UKPDS

AEEΌλα τα σχετιζόμενα με το διαβήτη συμβάματα

Θάνατοι λόγω

Διαβήτη

Μικροαγγειακές

επιπλοκές

-50

-40

-30

-20

-10

0

% R

ed

uc

tio

n In

Re

lati

ve

Ris

k

Αυστηρός γλυκαιμικός έλεγχος(HbA1C : 8,2%)

Αυστηρός έλεγχος της ΑΠ(Μέση ΑΠ 144/82 mmHg)

32%

37%

10%

32%

12%

24%

5%

44%

Bakris GL, et al. Am J Kidney Dis. 2000;36(3):646-661

*

*

*

*

*P <0.05 σε σύγκριση με αυστηρό γλυκαιμικό έλεγχο

Primary Outcome Experience in the Six Pre-specified Subgroups of Interest

*Treatment by subgroup interaction

Intensive StandardEvents %/yr Events %/yr HR (95% CI) P

Participants with

CKD at Baseline

Primary CKD

outcome14 0.33 15 0.36 0.89 (0.42,

1.87)

0.76

≥50% reduction in

eGFR*

10 0.23 11 0.26 0.87 (0.36, 2.07) 0.75

Dialysis 6 0.14 10 0.24 0.57 (0.19, 1.54) 0.27Kidney transplant 0 - 0 - - .

Secondary CKD

OutcomeIncident albuminuria** 49 3.02 59 3.90 0.72 (0.48, 1.07) 0.11

Participants

without CKD at

Baseline

Secondary CKD

outcomes≥30% reduction in

eGFR*127 1.21 37 0.35 3.48 (2.44, 5.10) <.000

1

Incident albuminuria** 110 2.00 135 2.41 0.81 (0.63, 1.04) 0.10

Renal Disease Outcomes

*Confirmed on a second occasion ≥90 days apart **Doubling of urinary albumin/creatinine ratio from <10 to >10 mg/g

Glucose Control in CKD

Target HbA1c ~7.0%

Can be extended above 7.0% with comorbidities or limited life expectancy, and risk of hypoglycemia

Risk of hypoglycemia increases as kidney function becomes impaired

Declining kidney function may necessitate changes to diabetes medications and renally-cleared drugs

Recommendations for long term management

Combined effect of ARB/ACEi with MRB may further decrease

microalbuminuria

Healthy Lifestyle

The Persistence of memory Salvador Dali