DIABETES COMPLICATION

KIDNEY AND CARDIOVASCULAR

ONE DAY SEMINAR ATLM
BANDUNG, 11 MARET 2018

!
Pisa, 28-30 OTTOBRE 2013!
 DIABETES MELITUS

Suatu kelompok penyakit

metabolik dengan karakteristik
hiperglikemia yang terjadi karena
kelainan sekresi insulin, kerja
insulin atau kedua-dua nya

Konsensus Pengelolaan dsn Pencegahan DM

type 2 di Indonesia 2015
 Classification of Diabetes
1.  Type 1 diabetes
–  β-cell destruction
2.  Type 2 diabetes
–  Progressive insulin secretory defect
3.  Gestational Diabetes Mellitus (GDM)
4.  Other specific types of diabetes
–  Monogenic diabetes syndromes
–  Diseases of the exocrine pancreas, e.g., cystic
fibrosis
–  Drug- or chemical-induced diabetes
American Diabetes Association Standards of Medical Care in Diabetes.

Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24!
 Criteria for the Diagnosis of Diabetes
Fasting plasma glucose (FPG)

≥126 mg/dL (7.0 mmol/L)$
OR
2-h plasma glucose ≥200 mg/dL

(11.1 mmol/L) during an OGTT$
OR
A1C ≥ 6.5%$
OR
Classic diabetes symptoms + random plasma glucose 

≥ 200 mg/dL (11.1 mmol/L)$
American Diabetes Association Standards of Medical Care in Diabetes.

Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24!
Risk factors for Prediabetes and T2D

American Diabetes Association Standards of Medical Care in Diabetes.


Classification and diagnosis of diabetes. Diabetes Care 2017; 40 (Suppl. 1): S11-S24!
 Recommendations: A1C Testing

•  Perform the A1C test at least 2x annually in

patients that meet treatment goals (and have
stable glycemic control).
•  Perform the A1C test quarterly in patients whose
therapy has changed or who are not meeting
glycemic goals.
•  Use of point-of-care (POC) testing for A1C
provides the opportunity for more timely treatment
changes.

American Diabetes Association Standards of Medical Care in Diabetes.


Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56!
 Mean Glucose Levels for Specified A1C Levels

Mean Glucose
Mean Plasma Glucose* Fasting Premeal Postmeal Bedtime
A1C% mg/dL mmol/L mg/dL mg/dL mg/dL mg/dL
6 126 7.0
<6.5 122 118 144 136
6.5-6.99 142 139 164 153
7 154 8.6
7.0-7.49 152 152 176 177
7.5-7.99 167 155 189 175
8 183 10.2
8-8.5 178 179 206 222
9 212 11.8
10 240 13.4
11 269 14.9
12 298 16.5
American Diabetes Association Standards of Medical Care in Diabetes.

Glycemic targets. Diabetes Care 2017; 40 (Suppl. 1): S48-S56!
 KELAINAN KOMORBID

•  Dislipidemia pada Diabetes Melitus

•  Hipertensi pada Diabetes Melitus
•  Obesitas pada Diabetes Melitus
•  Gangguan Koagulasi pada
Diabetes Melitus

Konsensus Pengelolaan dsn Pencegahan

DM type 2 di Indonesia 2015
 PENYULIT DIABETES MELITUS

•  Penyulit Akut
- Krisis Hiperglikemia
- Hipoglikemia
•  Penyulit Menahun
- Makroangiopati (CAD, Ulkus Iskemik
Stroke iskemik, Stroke hemoragik)
- Mikroangiopati ( Retinopati Diabetik,
Nefropati Diabetik, Neuropati,
 MASALAH-MASALAH KHUSUS
DIABETES MELITUS

DM-Cardiovascular Disease
 Cardiovascular Disease
•  CVD is the leading cause of morbidity & mortality for those
with diabetes.
•  Largest contributor to direct/indirect costs
•  Common conditions coexisting with type 2 diabetes (e.g.,
hypertension, dyslipidemia) are clear risk factors for
ASCVD.
•  Diabetes itself confers independent risk
•  Control individual cardiovascular risk factors to prevent/
slow CVD in people with diabetes.
•  Systematically assess all patients with diabetes for
cardiovascular risk factors.

American Diabetes Association Standards of Medical Care in Diabetes.


Cardiovascular disease and risk management. Diabetes Care 2017; 40 (Suppl. 1): S75-S87!
 Diabetes and CVD
•  Atherosclerotic complications responsible for
–  80% of mortality among patients with diabetes
–  75% of cases due to coronary artery disease
(CAD)
–  Results in >75% of all hospitalizations for diabetic
complications

•  50% of patients with type 2 diabetes have

preexisting CAD. (This number may be less now
that more younger people are diagnosed with
diabetes.)

•  1/3 of patients presenting with myocardial

infarction have undiagnosed diabetes mellitus

Lewis GF. Can J Cardiol. 1995;11(suppl C):24C-28C

Norhammar A, et.al. Lancet 2002;359;2140-2144
 Most Cardiovascular Patients Have
Abnormal Glucose Metabolism
GAMI EHS CHS
n = 164 n = 1920 n = 2263

18% 27%
35% 31% 37% 37%

45% 36%
34%

Normoglyc Prediabetes Type 2 Diabetes

emia
GAMI = Glucose Tolerance in Patients with Acute Myocardial Infarction
study; EHS = Euro Heart Survey; CHS = China Heart Survey
Anselmino M, et al. Rev Cardiovasc Med. 2008;9:29-38.
Mechanisms by which Diabetes Mellitus
Leads to Coronary Heart Disease

Hyperglycemia Insulin Resistance

Inflammation HTN
Dyslipidemia
↑ AGE Endothelial
↑ Oxidative dysfunction
stress
↑ IL-6 ↑ LDL
Infection ↑ CRP ↑ TG
↓ HDL
Thrombosis
↑ SAA
↓ Defense ↑ PAI-1
mechanisms ↑ TF
↓ tPA
↑ Pathogen burden
Subclinical Atherosclerosis
Disease Progression

Atherosclerotic Clinical Events

AGE=Advanced glycation end products, CRP=C-reactive protein, CHD=Coronary heart disease
HDL=High-density lipoprotein, HTN=Hypertension, IL-6=Interleukin-6, LDL=Low-density lipoprotein,
PAI-1=Plasminogen activator inhibitor-1, SAA=Serum amyloid A protein, TF=Tissue factor,
TG=Triglycerides, tPA=Tissue plasminogen activator

Biondi-Zoccai GGL et al. JACC 2003;41:1071-1077.

 Glycemic Control and Risk of
Development of HF in Diabetes
 ADA Standards of Care

•  ADA recommends a general A1C target of <7%

•  The goal of therapy for the individual patient is to
achieve an A1C as close to normal (<6%) as possible
without hypoglycemia
•  More stringent glycemic goals may reduce the risk of
serious diabetes-related complications
•  Less stringent treatment goals may be appropriate for
certain patient populations and patients with severe or
more frequent hypoglycemia

American Diabetes Association Standards of Medical

American Diabetes Association. Diabetes Care. 2006;29:S4-S42. Care in Diabetes.
 Dislipidemia in Diabetes
•  Intensify lifestyle therapy & optimize
glycemic control for patients with:
–  Triglyceride levels >150 mg/dL
(1.7 mmol/L) and/or
–  HDL cholesterol <40 mg/dL (1.0 mmol/L) in
men and <50 mg/dL (1.3 mmol/L) in women
•  For patients with fasting triglyceride levels ≥ 500 mg/dL
(5.7 mmol/L), evaluate for secondary causes and consider
medical therapy to reduce the risk of pancreatitis.

American Diabetes Association Standards of Medical Care in Diabetes.


Cardiovascular disease and risk management. Diabetes Care 2017; 40 (Suppl. 1): S75-S87!
MASALAH-MASALAH KHUSUS
DIABETES MELITUS

Diabetes
dengan Nefropati Diabetik
•  The negative outcomes of chronic kidney disease
can be averted with early diagnosis and treatment.
•  In an effort to improve early diagnosis, the National
Kidney Foundation has issued standardized clinical
practice guidelines according to the Kidney Disease
Quality Initiative (K/DOQI).
•  In these guidelines and recommendations the
primary measure of renal function is the Glomerular
Filtration Rate (GFR).
Glomerular Filtration Rate (GFR)
•  The GFR is a measure of the rate at which
water and dissolved substances (low
molecular weight, ultrafiltrateable
compounds) are filtered out of the blood per
unit time.
•  Normal GFR’s for males are about of 150
mL/min per 1.73 m2 and 130 mL/min per
1.73 m2 for females.
 Measurement of GFR

n Procedures for determining GFR with high

accuracy require the injection of exogenous
substances which are known to be only filtered
at the glomerulus and not absorbed or secreted
by the renal tubules.
n These gold standard procedures include Cr-
EDTA, radiological contrast media (Iohexol) and
inulin.
n Procedures determining GFR using exogenous
substances are invasive and carry some risk to
the patient which usually are considered too
expensive and time consuming for routine
clinical use.
 Measurement of GFR
Historically, Creatinine has been
considered the renal marker of choice
because it is a naturally occurring
endogenous compound that is freely
filtered at the glomerulus and has relatively
minor absorption and secretion by the
renal tubules.
 Calculation of GFR
24 Hours Creatinine Clearance:
Creatinine clearance (ml/min/1.73m2) =
U x V x 1.73 / P x 1440 x BSA
U is urinary creatinine (mg/dl)
V is urinary volume in 24 hours (ml)
P is serum creatinine (mg/dl)
BSA is body surface area.
1440 (Time in Minutes) = 24 x 60
 Measurement of GFR
Even though serum creatinine
determination remains the most commonly
used renal marker for estimation of GFR,
it is known to have a number of inherent
difficulties which limit its clinical reliability.
 Limitations of Creatinine as
a Marker for GFR
Limitation Comments
Non-Renal Gender
Factors Ethnicity
Diet
Muscle mass
Drugs which affect tubular secretion of creatinine
Clinical Poor sensitivity for Serum creatinine remains in the
Utility CKD “creatinine blind normal range until 50% of renal
function is lost. Insensitive to loss
range” of GFR in Stage 2 and Stage 3 of
CKD.
Analytical Non-specific bias frequently Use of enzymatic assays for
Problems reported with the commonly creatinine can significantly improve
used Jaffé Assay Method test performance by eliminating
(alkaline picrate ) many sources of analytical error.
 e GFR
•  In an attempt to improve the accuracy of
serum creatinine measurements the NKDEP
(National Kidney Disease Education
Program) has advocated the use of GFR
estimates, calculated from serum creatinine
levels.
•  The eGFR includes
–  Modification of Diet in Renal Disease (MDRD)
–  Cockroft-Gault (CG).
 Calculation of eGFR
•  Cockcroft- Gault estimated creatinine
clearance (ml/min) = (140-age) x (weight in
Kg) / serum creatinine (mg/dl) x 72 x (0.85 if
female).
•  MDRD estimated creatinine clearance (ml/
min/1.73m2) = 186 x [serum creatinine (mg/
dl)] -1.154 x (age in years) -0.203 x (0.742 if
female).
 Bias in the means of calculated GFR from conventional 24 hr
creatinine clearance in various stages of renal function.
24 Hr creatinine C&G creatinine MDRD creatinine
clearance clearance (ml/min) clearance (ml/min/
1.73m2)
Mean + SD Range Mean % Bias Mean % Bias

Overall (n = 369) 43.85 + 33.57 2 – 185 60.15 16.30 59.07 15.22

End stage renal failure (GFR <5 3.73 + 0.96 2–5 20.27 16.54 15.13 11.40
ml/min) (n = 15)

Severe renal failure (GFR 5 – 10 8.31 + 1.38 6 – 10 19.81 11.50 17.13 8.82
ml/min) (n = 32)

Moderate renal failure (GFR 19.80 + 5.63 11 – 30 33.20 13.40 32.75 12.95
10-30 ml/min) (n = 116)

mild renal failure (GFR 30-50 40.78 + 5.75 31 – 50 62.65 21.87 63.13 22.35
ml/min) (n = 88)

Minimal renal function 54.39 + 2.99 51 – 60 72.28 17.89 75.83 21.44

impairment (GFR 50-60
ml/min) (n = 18)

Normal renal function (GFR > 89.94 + 24.85 61 -187 105.92 15.98 103.01 13.07
60 ml/min) (n = 100)
Even though creatinine based GFR equations
such as the MDRD improve the accuracy of
serum creatinine measurements, concentrations
of creatinine can be within the normal range
even with a GFR of around 40 mL/min/1.73 m2
resulting in a so called “creatinine blind” range.
This is due to the fact that MDRD understates
normal and elevated GFR’s and overstates
decreases in GFR
 Cystatin C as a GFR Marker
A substantial body of evidence has developed
over the past several years which supports the
use of Cystatin C as an alternative and more
sensitive endogenous marker for the
estimation of GFR than serum creatinine and
serum creatinine based GFR estimations
“Cystatin C is emerging as a biomarker superior
to serum creatinine for estimating GFR and
predicting the risk of death and cardiovascular
events”
(DIABETES, VOL 56, NOVEMBER 2007)
 Receiver operating characteristic plots of
serum creatinine and cystatin C
Villa et al. Critical Care 2005 9:R139   doi:10.1186/cc3044

•  Creatinine
–  Area under curve (95%
CI) 0.694
–  Sensitivity 54.1
–  Specificity 84.6
•  Cystatin C
–  Area under curve (95%
CI) 0.927
–  Sensitivity 86.1
–  Specificity 99.4
 Structure of Cystatin C

n Human Cystatin C (HCC) is

composed of 120 amino acids.
n Contains, four Cys residues
forming two characteristic
disulfides.
•  Cystatin C is a small 13 –kDa protein that is a member
of the cysteine proteinase inhibitor family that is
produced at a constant rate by all nucleated cells.
•  Due to its small size & positive charge at physiological
pH, it is freely filtered by the glomerulus, and is not
secreted but is fully reabsorbed and catabolized in
proximal renal tubules.
•  This means the primary determinate of blood Cystatin
C levels is the rate at which it is filtered at the
glomerulus making it an excellent GFR marker.
•  Normal serum Cystatin C values range from 0.6 to
1.0 mg/L.
•  Unlike creatinine, Cystatin C serum levels are virtually
unaffected by age (>1 yr), muscle mass, gender and
race.
•  A number of very simple formulas have been
introduced which can be used to obtain an estimated
GFR using Cystatin C.
•  Multiple studies have found Cystatin C to be more
sensitive to actual changes in GFR in the early stages of
CKD than creatinine based GFR estimates.
•  A significant advantage of Cystatin C based formulas,
unlike creatinine based equations, is that Cystatin C
based estimated GFR formulas are not biased
according to GFR and there is no GFR blind area with
Cystatin C.
 Assay Principle
Cystatin C in the sample
binds to the specific
anti-Cystatin C antibody,
which is coated on latex
particles, and causes
agglutination. The
degree of the turbidity
caused by agglutination
is measured optically
and is proportional to
the amount of Cystatin
C in the sample.
eGFR calculation by Cystatin C
An example of a Cystatin C estimated GFR
formula is the one proposed by Larson and
Grubb et al. In their study a Cystatin C–based
prediction equation using only concentration
in mg/L and a factor: GFR (ml/min) = 99.43
x (cys C)–1.5837 provided reliable and
readily available GFR data based on single
measurements of Cystatin C concentrations.
 CONTRAINDICATIONS

Thyroid Function
•  Levels of Cystatin C are sensitive to changes in
thyroid function and should not be used without
knowledge of the patients thyroid status.
Corticosteroids
•  It has been reported that Cystatin C serum
concentrations are not affected by standardized
high-dose corticosteroid therapy but may be
increased in patients with impaired renal function
receiving corticosteroids.
 Advantages of Cystatin C as a GFR Marker
Advantage Comments
Virtually unaffected by non- Muscle Mass / Weight / Height
renal factors Age (>1 year) – Cystatin C parallels age related
decreases in GFR and may be used reliably with
children
Gender
Diet
Less inter individual variation than creatinine
Primary determinate of Cystatin Cystatin C is not secreted but is fully absorbed and
C levels are renal Factors broken down by tubular cell. Since there is no tubular
secretion of Cystatin C, it is extremely sensitive to
small changes in GFR in the earliest stages of CKD.
Sensitive to changes in the so- Enables early detection and treatment of CKD.
called creatinine blind GFR The creatinine blind area is demonstrated by the
range (40-70 ml/min/1.73 m2 ) lack of linearity in creatinine GFR equations. This
is probably due to increased secretion of
creatinine by the tubules in the GFR range 40-90
ml/min/1.73 m2
 Advantages of Cystatin C as a GFR Marker
Advantage
Demonstrates higher diagnostic accuracy
than MDRD, or C-G equations in
patients with diabetes
Can be used to detect and monitor
kidney disease in patients with hepatic
disease
Has been advocated as the preferred
endogenous marker for dosing
medication eliminated by the kidneys
Correlates to the appearance of
microalbumin
Comments
Enables early detection and treatment of
CKD in both Type 1 and Type 2 Diabetes.
Creatinine based GFR measurements are not
reliable and are not recommended in hepatic
disease. Cystatin C is reliable in cirrhotic
patients.
May detect mild to moderate decreases in
GFR that are not evident with serum
creatinine based measurements, thus avoiding
unnecessarily high drug doses which may pose
an increased risk to the patient and the
associated cost of possible resulting side
effects.
Recent studies suggest that very early
renal failure may be the first clinical
indication of the progressive kidney
damage associated with diabetes.
 Early Detection of Kidney Disease
in Type 1 and Type 2 Diabetes
Conclusions: Our study provides convincing
evidence that cystatin C may be more useful for
detecting early renal impairment in both type 1 and
type 2 diabetic patients than are creatinine and
commonly employed creatinine-derived formulas.
Cystatin C and Estimates of Renal Function:
Searching for a Better Measure of Kidney Function
in Diabetic Patients
Clinical Chemistry 53:3 480–488
(2007)
 Early Detection of Kidney Disease
in Type 1 Diabetes
Conclusion: Cystatin C was more accurate in detecting
decline in renal function than creatinine based
methods in this population of subjects with Type 1
and a normal mean baseline GFR.
Serial Measurements of Cystatin C Are More
Accurate than Creatinine-based Methods in
Detecting Declining Renal Function in Type 1
Diabetes
Diabetes Care.2008; 0: dc07-1588v1-0
 Early Detection of Kidney Disease
in Type 2 Diabetes
Conclusions: Cystatin C may be considered as an
alternative and more accurate serum marker than
serum creatinine or the Cockcroft and Gault estimated
GFR in discriminating type 2 diabetic patients with
reduced GFR from those with normal GFR.
Cystatin C Is a More Sensitive Marker Than
Creatinine for the Estimation of GFR in Type
2 Diabetic Patients
Kidney International, Vol. 61 (2002), pp. 1453–1461
Early Detection of Chronic Kidney
Disease
Conclusions: Among elderly persons without chronic
kidney disease, cystatin C is a prognostic biomarker
of risk for death, cardiovascular disease, and chronic
kidney disease. In this setting, cystatin C seems to
identify a “preclinical” state of kidney dysfunction
that is not detected with serum creatinine or
estimated GFR.
Cystatin C and Prognosis for Cardiovascular
and Kidney Outcomes in Elderly Persons
without Chronic Kidney Disease
Ann Intern Med. 2006;145:237-246
A recent meta-analysis demonstrated that serum
cystatin C is a better marker for GFR than serum
creatinine. In clinical practice, it has been suggested
that serum cystatin C can optimize early detection
for diabetic or hypertensive nephropathy. In
addition, the use of serum cystatin C is possibly
more appropriate for establishing an appropriate
dose adjustment of drugs that are mainly eliminated
by the kidney
A New Approach for Evaluating Renal
Function and Its Practical Application
J Pharmacol Sci 105, 1 – 5 (2007)
Early Detection of of Acute Renal
Failure
Conclusions: Serum cystatin C is a useful
detection marker of acute renal failure (ARF),
and may detect ARF one to two days earlier
than creatinine.
Early Detection of Acute Renal Failure
by Serum Cystatin C
Kidney Int 2004; 66:1115-1122
 Cardiovascular Risk
Conclusions: High cystatin C concentrations predict
substantial increased risks of all-cause mortality,
cardiovascular events, and incident heart failure
among ambulatory persons with CHD. This risk is
not completely captured by measures of kidney
function routinely used in clinical practice.
Association of Cystatin C With Mortality,
Cardiovascular Events, and Incident Heart
Failure Among Persons With Coronary Heart
Disease
Circulation. 2007;115:173-179
 T2DM and chronic kidney
disease (CKD) by albuminuria
and eGFR
KDIGO: Classification of Kidney Disease by
albuminuria and Association with Adverse
Outcomes$

Levey AS et al, Kidney Int 80: 17-28, 2011$

KDIGO: Classification of Kidney Disease by eGFR
and Association with Adverse Outcomes$

Levey AS et al, Kidney Int 80: 17-28, 2011$

Kidney Disease: Improving Global Outcomes (KDIGO)
classifica?on

Low risk
Moderate risk
High risk
Very high risk

KDIGO, Kidney Int Suppl 3: 1-150, 2013$

1.  Classification of chronic kidney
disease (CKD) by eGFR and
albuminuria
2.  Renal impairment is common.
Every second/third patient in our
clinic might have signs of renal
impairment
 The RIACE (Renal Insufficiency and
Cardiovascular Events) study
15,773 patients with type 2 diabetes from Italy

Stages of eGFR strata (ml/ NKF’s KDOQI

“Diabetic min/1.73 m2) CKD stages
nephropathy” ≥90 29,6% No CKD 62,5%
Normo 73,1% Stage 1
60-89 51,7% 6,7%
Micro 22,2% ≥90*
30-59 17,1% Stage 2
Macro 4,7% 12,0%
<30 1,7% 60-89*
Stage 3
MDRD
30-59
17,1%
Stages 4, 5
<30
1,7%
* Plus “kidney damage”
Penno G et al. J Hypertens 29: 1802-1809, 2011
Renal dysfunction is common in
patients with T2DM
The RIACE Study: 15,773 patients
No CKD
with T2DM
1.7% CKD stage 1
CKD stage 2
CKD stage 3
17.1% CKD stages 4/5

12.0% Approximately 40% of

62.5%
patients with T2DM show
signs of CKD (stages 1-5)
6.7%

Approximately 20% of
patients with T2DM show
signs of renal failure (eGFR
<60 ml/min/1.73 m2)
Penno G et al. J Hypertens 29: 1802-1809, 2011
Renal dysfunction is common in
patients with T2DM
The RIACE Study: 15,773 patients
with T2DM
Albuminuria
Normal Mild Severe
(micro) (macro)

>90 Stage 0 Stage 1-2
Stage 1
(no CKD) albuminuric phenotype

60-89
62.5% 18.7%

Stage 2
eGFR
ml/min/

1.73 m2 45-59 Stages 3/5
Stage 3/5

NON Stage 3
albuminuric
MDRD albuminuric CKD
30-44 CKD phenotype
phenotype

10.6% 8.2%
15-30 Stage 4

Penno G et al. J Hypertens 29: 1802-1809, 2011

1.  Classification of chronic kidney
disease (CKD) by eGFR and
albuminuria
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
Kidney Disease: Improving Global Outcomes (KDIGO)
classifica?on
Low risk
Moderate risk
High risk
Very high risk

KDIGO, Kidney Int Suppl 3: 1-150, 2013$

Associations of Kidney Disease measures with mortality and
ESRD in individuals with and without diabetes: a meta-analysis$
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
Fox CS et al., Lancet 380: 1662-1673, 2012!
 Risk of coronary events in people with chronic kidney disease
compared with those with diabetes:

a population-level cohort study$

1,268,029 participants; median follow-up of 48 months$

1,268,029 participants; median follow-up of 48 months;$
the Alberta Kidney Disease Network$

75,871$ 1,104,713$
12,960$ 15,368$ 59,117$
eGFR by the CKD-EPI equation! Tonelli M et al., Lancet, published online, June 19, 2012$
Risk of coronary events in people with chronic kidney disease
compared with those with diabetes:

a population-level cohort study$

Tonelli M et al., Lancet, published online, June 19, 2012$

 The Renal Insufficiency And Cardiovascular
Events (RIACE) Italian multicentre study

●  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$

1.  Classification of chronic kidney
disease (CKD) by eGFR and
albuminuria
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
Kidney Disease: Improving Global Outcomes
(KDIGO) classifica?on

KDIGO, Kidney Int Suppl 3: 1-150, 2013$

….. 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.

Inker LA et al, N Engl J Med 367: 20-29, 2012$

Cystatin C and estimates of renal function: searching for a
better measure of kidney function in diabetic patients

Pucci L et al., Clin Chem 53: 480-488, 2007$

Shlipak MG et al, N Engl J Med 369: 932-943, 2013$
 10.0%

13.7%
9.7%

Shlipak MG et al, N Engl J Med 369: 932-943, 2013$

59 83
88

Shlipak MG et al, N Engl J Med 369: 932-943, 2013$