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