SUMANEE PRAKOBSUK 24 Sep 2013

Chapter 1: Definition and classification of CKD

Chapter 2: Definition, identification, and
prediction of CKD progression
Chapter 3: Management of progression and
complications of CKD
Chapter 4: Other complications of CKD: CVD,
medication dosage, patient safety, infections,
hospitalizations, and caveats for investigating
complications of CKD
Chapter 5: Referral to specialists and models
of care

Conceptual model of CKD

 CKD: Whats NEW?

New CKD KDIGO Proposed Classification
New CKD Definition
New uACR
New eGFR Formula
Prevention & Treatment: Who & How?
How to assess CKD Progression?

CKD DEFINITION
CKD is defined as abnormalities of
kidney structure or function, present
for > 3 months, with implications for
health

STAGING OF CKD

Kidney Int 2011; 80: 17-28

Summary of categorical meta-analysis

(adjusted RRs) for general population
cohorts with ACR.

Kidney Int 2011; 80: 17-28

Summary of categorical meta-analysis

(adjusted RRs) for general population
cohorts with ACR.

Kidney Int 2011; 80: 17-28

Classification of CKD based on presence or absence of

systemic disease and location within the kidney of
pathologicanatomic findings

GFR categories in CKD

Albuminuria categories in CKD

Relationship among categories for

albuminuria and proteinuria

CGA staging of CKD: examples of

nomenclature

Evaluation of GFR
We recommend using serum creatinine and
a GFR estimating equation for initial assessment.(1A)
We suggest using additional tests (such as cystatin C or
a clearance measurement) for confirmatory testing in
specific circumstances when eGFR based on serum
creatinine is less accurate. (2B)
Report eGFRcreat in adults using the
2009 CKD-EPI creatinine equation.

Sources of error in GFR estimating

using creatinine

Performance of the CKD-EPI and MDRD Study

equations in estimating measured GFR in the external
validation data set

CKD-EPI

MDRD

Ann Intern Med 2009; 150(9): 604-612.

Meta-analysis of NRI for all-cause

mortality, CVD mortality, and ESRD

JAMA 2012; 307(18): 1941-1951

N Engl J Med 2012;367:20-9.

N Engl J Med 2013;369:932-43.

Sources of error in GFR estimating

using cystatin C

Evaluation of albuminuria

Factors affecting urinary ACR

DEFINITION AND IDENTIFICATION OF CKD

PROGRESSION

PREDICTORS OF PROGRESSION

Management of progression and

complications of CKD
PREVENTION OF CKD
PROGRESSION
BP and RAAS
interruption
Glycemic control
Hyperuricemia
Protein intake
Salt intake

COMPLICATIONS
ASSOCIATED WITH
LOSS OF KIDNEY
FUNCTION
Anemia
CKD-MBD
Acidosis

Management of progression and

complications of CKD
PREVENTION OF CKD
PROGRESSION
BP and RAAS
interruption
Glycemic control
Hyperuricemia
Protein intake
Salt intake

COMPLICATIONS
ASSOCIATED WITH
LOSS OF KIDNEY
FUNCTION
Anemia
CKD-MBD
Acidosis

Clinical Practice Guideline of HT in CKD

2004 KDOQI (Kidney disease Outcomes
Quality Initiative) Clinical Practice Guidelines
on Hypertension and Antihypertensive Agents
in Chronic Kidney Disease
KDIGO (The Kidney Disease Improving Global
Outcome) : Management of Blood Pressure in
Chronis Kidney Disease ; December 2012

KDIGO Clinical Practice Guideline for the Management

of Blood Pressure in Chronic Kidney Disease 2012
Non-diabetic

Diabetic

AER <30

140/90 (1B)

140/90 (1B)

AER >30

130/80 (2D,C)

130/80 (2D)

AER 30-300

ARB/ACEI (2B)

ACEI/ARB (2D)

AER>300

ARB/ACEI (1B)

ACEI/ARB (1B)

BP goal

Medication

Lawrence J.Appel ; NEJM 2010 363:918-29.

AASK : Conclusion
RCT in black with CKD
N = 1094
Randomly assigned : ramipril , metoprolol or amlodipine
Target mABP intensive arm : 92 mmHg
Target mABP standard arm : 102-107 mmHg
Result
Primary endpoint: No difference in rate of GFR decline
ACEI may be more effective than BB in slowing GFR decline
Subgroup
UPCR 0.22: No effect
UPCR>0.22: Intensive BP retard CKD progression (a doubling
sCr,ESRD or death)

Lawrence J.Appel ; NEJM 2010 363:918-29.

AASK

Lawrence J.Appel ; NEJM 2010 363:918-29.

study/year

outcome

intervention

control

HOPE
2001

MI, stroke in CKD

Ramipril

placebo

HOPE
2003

Dialysis, renal insufficiency

Ramipril

placebo

PREVEND
2004

CV events

Fosinopril

placebo

ALLHAT
2006

Renal failure &CAD with

CKD
In DM /non DM pt

lisinopril

Chlorthalidone

PEACE
2006,2007

CV mortality in CKD

trandolapril

placebo

TRANSCEN
2009

Dialysis/sCr doubling

telmisartan

placebo

Val-HeFT
2009

Death

valsartan

Placebo

William C.Cushman;NEJM 2010;362:1575-85

Action to Control Cardiovascular Risk

in Diabetes : ACCORD study

10251 patients from 77 centers US. And Canada

4377 patients in ACCORD BP trial
DM type II with HbA1C 7.5%
40 with CVD
55 with
Evidence of atherosclerosis ,albuminuria or LVH
2 additional CV risk factors

Assigned to either

Intensive BP control (systolic BP<120mmHg)

Conventional BP control (systolic BP<140 mmHg)
William C.Cushman;NEJM 2010;362:1575-85

William C.Cushman;NEJM 2010;362:1575-85

William C.Cushman;NEJM 2010;362:1575-85

ACCORD study : conclusions

Intensive BP control
Did not significantly reduce primary CV-event
Some possible harm
Hypotension
Arrhythmia or bradycardia
HyperK
Elevate SCr

William C.Cushman;NEJM 2010;362:1575-85

 Rationale
DM II with microalbuminuria increased risk kidney
failure and CV events
ACEI ,ARB reduce albuminuria in DM II with
microabluminia

 Ratinale
Pt with DM and high levels of urine albumin high
risk of adverse CV and kidney outcomes
Strong evidence from RCTs : ACEI &ARB protect
against kidney failure and reduce urine albumin
level

The Ongoing Telmisartan Alone and

in combinaion with Ramipril Global Endpoint Trial
ONTARGET

Multicenter RCT
2001-2007
Age >55 yrs with
Atherosclerotic disease
DM with end organ damage

25,630 were randomized to either

Tarmisartan 80 mg/day
Ramipril 10 mg/day
Tarmisartan 80mg+ramipril 10mg/day

The ONTARGET study : conclusions

Combination no benefit in primary outcome
compare to Ramipril
Combination Worse kidney outcome
Combination Significantly increase

Risk of hypotension
Syncope
Renal dysfuntion( requiring acute dialysis)
Hyperkalemia

Johannes F E Mann;Lancet 2008;372:547-53

Add on aliskiren 300mg

More hyperK in combine aliskiren group

Management of progression and

complications of CKD
PREVENTION OF CKD
PROGRESSION
BP and RAAS
interruption
Glycemic control
Hyperuricemia
Protein intake
Salt intake

COMPLICATIONS
ASSOCIATED WITH
LOSS OF KIDNEY
FUNCTION
Anemia
CKD-MBD
Acidosis

Management of progression and

complications of CKD
PREVENTION OF CKD
PROGRESSION
BP and RAAS
interruption
Glycemic control
Hyperuricemia
Protein intake
Salt intake

COMPLICATIONS
ASSOCIATED WITH
LOSS OF KIDNEY
FUNCTION
Anemia
CKD-MBD
Acidosis

Glycemic control

UKPDS( DM type II) extended follow up

DCCT/EDIC (DM type I)

Additional 11 years
A1C: 8% (equally)
Result: Intensive therapy Decrease
Microalbuminuria
Macroalbuminuria
Doubling SCr No
SCr > 2 Yes
HT
42% relative reduction in CV events
Decrease mortality

Guideline

KDOQI CLINICAL PRACTICE GUIDELINE FOR DIABETES

AND CKD: 2012 UPDATE

KDIGO CKD 2012

Kidney International Supplements (2013) 3, v

Management of progression and

complications of CKD
PREVENTION OF CKD
PROGRESSION
BP and RAAS
interruption
Glycemic control
Hyperuricemia
Protein intake
Salt intake

COMPLICATIONS
ASSOCIATED WITH
LOSS OF KIDNEY
FUNCTION
Anemia
CKD-MBD
Acidosis

Management of progression and

complications of CKD
PREVENTION OF CKD
PROGRESSION
BP and RAAS
interruption
Glycemic control
Hyperuricemia
Protein intake
Salt intake

COMPLICATIONS
ASSOCIATED WITH
LOSS OF KIDNEY
FUNCTION
Anemia
CKD-MBD
Acidosis

Serum Uric acid

Elevated SUA (>7 in men, >6 in woman)
Observational data: Elevate SUA

Progression of CKD
Increase All cause mortality
Increase CV mortality
CKD may be improved by specific uric acid lowering therapy.

RCT design
Small study show benefit in:

Reduced LV mass1
Improved endothelial function1
Decrease CV events2
Decrease hospitalization2
2

1 Kanbay

M, Clin J Am Soc Nephrol 2011; 6: 18871894.

Goicoechea M, Clin J Am Soc Nephrol 5: 13881393, 2010

KDIGO 2012 Clinical Practice Guideline for the Evaluation

and Management of Chronic Kidney Disease

Protein intake

We suggest lowering protein intake to

0.8 g/kg/day in adults with diabetes (2C) or
without diabetes (2B) and GFR <30 ml/min/
1.73 m2 (GFR categories G4-G5), with
appropriate education.
We suggest avoiding high protein intake
>1.3 g/kg/day in adults with CKD at risk of
progression. (2C)

Salt intake
We recommend lowering salt intake to < 90
mmol(<2 g) per day of sodium (corresponding
to 5 g ofsodium chloride) in adults. (1C)

Management of progression and

complications of CKD
PREVENTION OF CKD
PROGRESSION
BP and RAAS
interruption
Glycemic control
Hyperuricemia
Protein intake
Salt intake

COMPLICATIONS
ASSOCIATED WITH
LOSS OF KIDNEY
FUNCTION
Anemia
CKD-MBD
Acidosis

Management of progression and

complications of CKD
PREVENTION OF CKD
PROGRESSION
BP and RAAS
interruption
Glycemic control
Hyperuricemia
Protein intake
Salt intake

COMPLICATIONS
ASSOCIATED WITH
LOSS OF KIDNEY
FUNCTION
Anemia
CKD-MBD
Acidosis

Anemia in CKD patients

RAS blockade
Semin Nephrol 26:261-268

AJKD 2006;47(5):S81-85.

 1.2.1: Diagnose anemia in adults and children

>15 years with CKD when the
Hb concentration is
<13.0 g/dl in males
<12.0 g/dl in females. (Not Graded)

Investigation of anemia
1.3: In patients with CKD and anemia (regardless of age
and CKD stage), include the following tests in initial
evaluation of the anemia (Not Graded):
Complete blood count (CBC), which should
include Hb concentration, red cell indices, white
blood cell count and differential, and platelet count
Absolute reticulocyte count
Serum ferritin level
Serum transferrin saturation (TSAT)
Serum vitamin B12 and folate levels

USE OF IRON TO TREAT ANEMIA IN CKD

2.1.1: When prescribing iron therapy, balance

the potential benefits of avoiding or minimizing
blood transfusions, ESA therapy, and anemia
related symptoms against the risks of harm in
individual patients (e.g., anaphylactoid and
other acute reactions, unknown long-term
risks). (Not Graded)

2006

2012
2.1.2: For adult CKD patients with anemia not on
iron or ESA therapy we suggest a trial of IV iron
(or in CKD ND patients alternatively a 13
month trial of oral iron therapy) if (2C):
an increase in Hb concentration without
starting ESA treatment is desired* and
TSAT is <30% and ferritin is <500 ng/ml (500
mg/l)

2012
2.1.3: For adult CKD patients on ESA therapy who are
not receiving iron supplementation, we suggest a
trial of IV iron (or in CKD ND patients alternatively a
13 month trial of oral iron therapy) if (2C):
an increase in Hb concentration** or a decrease in
ESA dose is desired*** and
TSAT is <30% and ferritin is <500 ng/ml (500 mg/l)

ESA INITIATION
3.1: Address all correctable causes of anemia
(including iron deficiency and inflammatory
states) prior to initiation of ESA therapy. (Not
Graded)
3.2: In initiating and maintaining ESA therapy,
we recommend balancing the potential
benefits of reducing blood transfusions and
anemia-related symptoms against the risks of
harm in individual patients (e.g., stroke,
vascular access loss, hypertension). (1B)

 3.3: We recommend using ESA therapy with great

caution, if at all, in CKD patients with active
malignancyin particular when cure is the
anticipated outcome(1B), a history of stroke (1B),
or a history of malignancy (2C).

2006
2.1.2 In the opinion of the Work Group, in
dialysis and nondialysis patients with CKD receiving
ESA therapy, the selected Hb target should generally
be in the range of 11.0 to 12.0 g/dL.
2.1.3 In dialysis and nondialysis patients
with CKD receiving ESA therapy, the Hb target should
not be greater than 13.0 g/dL

ESA INITIATION : CKD ND

3.4.1: For adult CKD ND patients with Hb
concentration >10.0 g/dl (>100 g/l), we suggest that
ESA therapy not be initiated. (2D)
3.4.2: For adult CKD ND patients with Hb
concentration <10.0 g/dl (<100 g/l) we suggest that
the decision whether to initiate ESA therapy be
individualized based on

the rate of fall of Hb concentration

prior response to iron therapy,
the risk of needing a transfusion, the risks related to ESA
therapy and the presence of symptoms attributable to
anemia. (2C)

ESA INITIATION : CKD 5D

3.4.3: For adult CKD 5D patients, we suggest that
ESA therapy be used to avoid having the Hb
concentration fall below 9.0 g/dl (90 g/l) by
starting ESA therapy when the hemoglobin is
between 9.010.0 g/dl (90100 g/l). (2B)
3.4.4: Individualization of therapy is reasonable
as some patients may have improvements in
quality of life at higher Hb concentration and ESA
therapy may be started above 10.0 g/dl (100 g/l).
(Not Graded)

ESA MAINTENANCE THERAPY

3.5.1: In general, we suggest that ESAs not be used to
maintain Hb concentration above 11.5 g/dl (115 g/l) in
adult patients with CKD. (2C)
3.5.2: Individualization of therapy will be necessary as
some patients may have improvements in quality of life
at Hb concentration above 11.5 g/dl (115 g/l) and will
be prepared to accept the risks. (Not Graded)
3.6: In all adult patients, we recommend that ESAs not
be used to intentionally increase the Hb
concentration above 13 g/dl (130 g/l). (1A)

MEDICATION MANAGEMENT AND

PATIENT SAFETY IN CKD
We recommend that prescribers should take GFR
into account when drug dosing. (1A)
We recommend that adults with CKD seek
medical or pharmacist advice before using overthe-counter medicines or nutritional protein
supplements. (1B)
We recommend not using herbal remedies in
people with CKD. (1B)

MEDICATION MANAGEMENT AND

PATIENT SAFETY IN CKD
We recommend that metformin be continued in
people with GFR >45 ml/min/1.73 m2 (GFR
categories G1-G3a);
its use should be reviewed in those with GFR 30
44 ml/min/1.73 m2 (GFR category G3b);
it should be discontinued in people with GFR <30
ml/min/1.73 m2 (GFR categories G4-G5). (1C)

IMAGING STUDIES : Radiocontrast

We recommend that all people with
GFR <60 ml/min/1.73 m2 undergoing elective
investigation involving the IV iodinated radiocontrast
media should be managed according to the KDIGO
Clinical Practice Guideline for AKI including:
Avoidance of high osmolar agents (1B);
Use of lowest possible radiocontrast dose (Not Graded);
Withdrawal of potentially nephrotoxic agents before and
after the procedure (1C);
Adequate hydration with saline before, during, and after the
procedure (1A);
Measurement of GFR 4896 hours after the procedure (1C).

IMAGING STUDIES : Gadolinium-based

contrast media
Nephrogenic systemic fibrosis

IMAGING STUDIES : Gadolinium-based

contrast media
We recommend not using gadoliniumcontaining contrast media in people with GFR
<15 ml/min/1.73 m2 (GFR category G5) unless
there is no alternative appropriate test. (1B)
We suggest that people with a GFR <30
ml/min/1.73 m2 (GFR categories G4-G5) who
require gadolinium containing contrast media
are preferentially offered a macrocyclic
chelate preparation.

Bowel preparation
We recommend not to use oral phosphatecontaining bowel preparations in people with
a GFR < 60 ml/min/1.73 m2 (GFR categories
G3a-G5) or in those known to be at risk of
phosphate nephropathy. (1A)

Regimen : 45 ml two dose taken 10-12

hrs apart ,the evening before and the
morning of colonoscopy
Each 45 ml contain 5.8 g of elemental
phosphorus
Ramathibodi SWIFF solution
Kidney International (2009) 76,1027-103

REFERRAL TO SPECIALIST SERVICES

TIMING THE INITIATION OF RRT

We suggest that dialysis be initiated when one or more
of the following are present
symptoms or signs attributable to kidney failure (serositis,
acid-base or electrolyte abnormalities, pruritus)
inability to control volume status or blood pressure
a progressive deterioration in nutritional status refractory
to dietary intervention
cognitive impairment.

This often but not invariably occurs in the GFR range

between 5 and 10 ml/min/1.73 m2. (2B)

TIMING THE INITIATION OF RRT

Living donor preemptive renal transplantation
in adults should be considered when the GFR
is <20 ml/min/1.73 m2, and there is evidence
of progressive and irreversible CKD over the
preceding 612 months.(Not Graded)

IDEAL
Study