Management of Chronic Kidney
Disease ( CKD )
CHRISTIAN W. MENDE, MD
FACP,FACN,FASN,FASH
Clinical Professor of Medicine,
University of California, San Diego
La Jolla, Calif.
FACULTY DISCLOSURE
Company
 Novartis
 Forest
 Boehringer
Ingelheim
 Lilly
 Janssen ( J&J )
 Astra-Zenika
Nature of Affiliation
Unlabeled Product
Usage
Speakers Bureau
Advisory Board
NONE
Speakers Bureau
Chronic Kidney Disease - CKD
( NKF and KDIGO Guidelines 2013 )
Definition :
Abnormalities of Kidney Structure or Function present > 3 months
( with health implication )
Incidence ( USA ) :
13 %
6–8%
( 10 -15 % world wide )
eGFR < 60 ml / min / 1.73m (1)
Classification by :
1)
2)
3)
Definition :
eGFR
Albuminuria
Cause
ALBUMINURIA ( AER )
Term
30 mg /d or ACR 30mg /g
“ Albuminuria “ prefered over Proteinuria ( Microalbuminuria term diluted )
(1) Grams ME et.al Am J Kidney Dis 2013 :62 (2) 253 -256
Criteria for CKD ( KDIGO 2013 )
1) Markers of Renal Damage
Albuminuria
( > 300 mg ACR )
Abnormal Urine sediment
Electrolyte disorders
( i.e. RTA )
Abnormal Kidney Biopsy
Abnormal Imaging
( Echo , CT )
2) Decreased Renal Function : eGFR < 60 ml = CKD
CKD Staging by eGFR
• G 1
• G 2
GFR
GFR
90 ml and above
60 – 90 ( mild renal insufficiency )
Chronic Kidney Disease ( CKD )
•
•
•
•
G
G
G
G
3a
3b
4
5
GFR
GFR
GFR
GFR
45 – 59
30 – 44
15 - 29
< 15 ml
(
(
(
(
moderate )
moderate to severe )
severe )
Renal Failure , ESRD )
CKD Staging by Albuminuria
Albuminuria
ACR :
AER :
( persistent > 3 months )
A 1 ACR < 30 mg / g
A 2 ACR
30 - 300 mg / g
A 3 ACR > 300 mg / g
Albumin / Creatinine Ratio in mg of Albumin
per gram of Creatinine
Albumin Excretion in mg per day
( ACR of 30 mg / g ~ AER of 50 mg / day )
Evaluation of CKD
Evaluate if present > 3 months
1) e GFR < 60 ml
< 50 ml
2) Albuminuria ACR
for Age 60 and younger
for Age 70 and older
> 30 mg / g
3) Obtain eGFR for Creatinine and Cystatin C in
eGFR 45-59 ml ( eGFR cyst / eGFR creat- cyst)
42% of CKD Diagnosis with eGFR creat using Cystatin C are
Reclassified with GFR > 60 ml and have NO CKD !
Shlipak MG et.al. NEJM 2013 ; 369 :932-943
Patients at Risk for CKD
1) Check BP in Office and at Home ( if possible )
2) Creatinine and eGFR
3) Urine for
RBC and WBC
ACR
NKF , 2013
ESTIMATING GFR FROM CREATININE
Estimated GFR from creatinine:
Cockroft-Gault Formula:
Cr Cl = [(140-age) x body weight (kg) x 0.85 if female] / [72 x SCr (mg/dL)]
Cockroft et al. Nephron 1976
MDRD Formula:
eGFR = 186 x SCr-1.154 x age (yrs)
-0.203
x (1.212 if black) x (0.742 if female)
Levey et al. Ann Intern Med 1999
CKD-EPI Formula
N= 8,254; 10 studies
eGFR = 141 x min(Scr/k, 1)a x max(Scr/k, 1)-1.209 x 0.993Age x 1.018 [if female] x 1.159 [if
black]
Levey et al. Ann Intern Med 2009
Estimated GFR ≠ GFR
NIH: eGFR >60 unreliable. Report as “>60”.
PROPERTIES OF CYSTATIN C
• Cystatin C – produced in all nucleated cells
• Constant release into blood, perhaps via cell
turnover
• Freely filtered at glomerulus
• No renal tubular secretion
• Cystatin C approximates GFR nearly independent
from age, sex, race, and muscle mass
RECLASSIFICATION BY eGFRcys AND
ASSOCIATED RISK
Mortality HR (95% CI)
1.36 (1.24, 1.48)
1.0
1.0
Mortality HR (95% CI)
0.88 (0.76, 1.01)
= same
1.57 (1.39, 1.78)
1.0
1.0
= worse
0.66 (0.57, 0.77)
0.77 (0.61, 0.98)
0.60 (0.27, 1.36)
1.67 (1.49, 1.88)
1.0
1.0
= better
1.0
1.0
1.72 (1.24, 2.37)
1.0
Adjusted for age, gender, race, smoking, systolic blood pressure, total cholesterol,
diabetes, history of cardiovascular disease, body mass index, and albuminuria.
Shlipak MG. et al. N Eng J Med, 2013
KDIGO SUGGESTION #1
• Estimating GFR:
1. Use creatinine eGFR
2. Are you confident that this is accurate?
3. If no, use either:
Cystatin C
Direct measure GFR
KDIGO SUGGESTIONS #2
Confirming CKD:
Your patient’s eGFR creat is 45-60 and is not
known to have kidney disease:
1. Measure Cystatin C
2. If eGFR < 60 by Cystatin C = CKD present
> 60 by Cystatin C = NO CKD
KDIGO SUGGESTION #3
When using cystatin C:
• Use eGFR equation
• Use standardized measure
• For medical dosing of potentially toxic
agents ( i.e.Chemotherapy )
use Cystatin C
Clinical Implication in Using GFR and
Albuminuria for Classification
Monitoring GFR and Albuminuria
Yearly :
G 1 A 1 , G 1 A 2, G 2 A 1, G 2 A 2 and G 3 a A 1
2 X per Year :
G 1 A 3 , G 2 A 3,G 3 a A 2 ,G 3 b A 1
3 X per Year :
G 3 a A 3 , G 3 b A 2 ,G 3 b A 3 ,G 4 A1 ,G 4 A 2, G 4 A 3
G5A1,G5A2,G5A3
KDIGO , 2 013
Definition of CKD Progresssion
1) Decline by 1 category ( i.e. Stage 3a to 3b )
2) Loss of 25% or more from Baseline eGFR
3) Rapid Progression > 5 ml eGFR Loss / Year
KDIGO , 2013
Risk Factors for CKD
Hypertension
Diabetes
Cardiovascular Disease
Age
( GFR loss of 1ml / year starting at age 40 )
Obesity
Ethnicity Afro Americans , Native Americans , Hispanic
Positive Family History
Albuminuria < 300 mg /d with eGFR > 60 ml = NO Mortality increase
Risk of CVD greater than Progression of CKD in eGFR < 60
70 % Patients die from CVD
4 % reach ESRD / Dialysis
Risk Factors , cont’d
AKI
Recovery from AKI even within 10% of baseline value leads
to increased Risk and Progression of CKD
( AKI definition : SCr increase by 0.3mg in 48hrs, or < 0.5ml/kg urine in 6hrs )
Nephrotoxic agents
Dye studies , Antibiotics , NSAID
Smoking
Albuminuria increased , Nephrosclerosis
Ethnicity
Afro-Americans ( 3.5x ESRD risk ) and Native Americans
Hispanics
Positive Family History of CKD , ESRD
Aging
Loss of 1 ml / year of GFR starting age 40
Risk Factors for CKD and Predictors of
Progression
•
•
•
•
•
•
•
Hypertension
Diabetes
Albuminuria > 300 mg /d
CKD stage 3 b ( eGFR < 45 ml )
Cardiovascular Disease ( CAD , PAD , CHF )
Hyperlipidemia ( Nephrosclerosis )
Obesity ( see separate slides )
Risk Modification in CKD
•
•
•
•
•
•
Stop Smoking
Exercise 150 min / week at least
Keep BMI < 25
Statin therapy ( see separate slide )
A1C < 7 % in Diabetes ( if tolerated )
BP control to < 140/90 mmHg
< 130/90 with Albuminuria ( > 300mg )
• Correct Anemia to Hgb to 11- 12 gm range
• Treat Albuminuria with ACEI or ARB
Obesity has a 3.5 x CKD Risk
USA Adults :
> 33 % have BMI > 30
> 35 % with Metabolic Syndrome
Obesity is associated with
Albumiuria increase
Insulin Resistance
RAAS activation ( incl. elevated Aldosterone )
Increased Sympathetic Activity
Inflammatory State ( high hCRP, Leptin )
Hypertension risk or increasing of BP
Metabolic Syndrome has a 55 % increased Risk of CKD ( < 60 ml )
Met-analysis: Thomas G et.al. 2011 Clin J Am Soc Nephrol 6: 2364
CKD and Cardiovascular Risk
Age < 60
Linear relationship between eGRF < 60 ml and
CV Risk ( CVA , CAD , MI , CHF , PAD )
Age > 60 and eGFR < 60
Creatinine not useful , unless both
Creatinine and Cystatin C used
ACR > 300
is a Risk for CVD irrespective of eGFR
Van der Velde M et al Clin J Am Soc Nephrol 2010; 5 :2053
Lipids in CKD
AGE > 50 years old with eGFR < 60
STATIN or STATIN / EZETIMIBE Combo
AGE > 50 years old with eGFR > 60
( G 1 , G 2 , mostly patients with Albuminuria )
STATINS only
AGE < 50 years old with CKD use STATINS
in
CAD ( prior MI , post Revasculaarization )
Diabetes
Post Ischemic CVA
Estimated 10 year CAD Risk > 10%
KIDIGO “Lipid Management in CKD” J. Kidney Int. , Nov. 2013
Albuminuria : Risk for CVD and CKD
1) Albuminuria > 300 mg /d
with or without Diabetes
increases CVD Risk ( HOPE )
2) Albuminuria > 300 mg /d
Risk increased for Dementia , Mortality and
Myocardial infarction = Independent of CKD
3) Albuminuria and CKD ( eGFR < 60 ) have “SYNERGISTIC “ effect for
accelerated Rate of CVD events ( HUNT 2 )
4) Risk of CVD with eGFR < 60 ml greater than Progression of CKD
70 % Mortality from CVD
4 % ESRD ( Dialysis ,Transplant )
Albuminuria and CKD in Diabetes
ACR mg / g
10 %
20 %
70 %
300 ( ~ 500 mg / day )
30 – 300 mg / g
No Albuminuria
CKD 3 ( eGFR < 60 )
11 % < age 65
26 % > age 65
Coresh J.et al. J Am Soc Nephrol 2005;16:180-188
CKD Management ( KDIGO 2O13 )
Hypertension
( BP Goals in next slide )
ACEI or ARB use in
Diabetes > 30 mg / d Albuminuria
All others > 300 mg / d Albuminuria
Diabetes
HbA1c < 7%
Sodium intake
< 5 gm Salt ( 2500 mg Na )
Protein intake
< 0.8 g / kg /d
Healthy Lifestyle
150 min /week of Physical Activity
BMI 20 - 25 ( most desirable )
NO Smoking
ONLY if GFR < 30 ml
CKD
Blood Pressure
( With or Without
Guidelines
DIABETES - KDIGO 2013 )
NO Albuminuria
BP < 140 / 90 mmHg
Albuminuria
> 30 mg / d
BP < 130 / 80 mmHg
Use ACEI or ARB’S if > 30mg /d Albuminuria
Lifestyle :
BMI > 20 – 25 , Salt < 5 gm ( 2000 mg Na )
Exercise 30 min 5 X / week
NSAID use in Hypertension / CKD
Lower Efficacy of ALL Antihypertensive Drugs , incl.
Diuretics by 15-20% ( exception CCB’s )
Cause Salt Sensitivity
( > 3-4 day use )
Use in CKD 3 ( < 60 ml GFR ) only short term , if absolutely needed
Reduce GFR by 10-15 % ( while in use )
Risk of Hyperkalemia , AKI and CHF
CKD 4 ( < 30 ml GFR ) --- Contraindicated ( absolute )
CKD and Imaging Studies
• Avoid high osmolar Agents
• Use lowest possible Dose
• Stop Nephrotoxic drugs before tests ( RAAS,
blockers , NSIAD )
• Adequate Hydration before ,during ,after study
• Obtain eGFR 48 -96 hrs post tests
• No Gadolinium if eGFR < 15 ml
• No oral Phosphate Bowel prep if eGFR < 60
CKD and Medication Use
Be aware of all RENAL excreted Drugs in eGFR < 60
Avoid NSAID
Reduce dosing
Metformin
max 1000 mG for GFR < 45
If GFR < 30ml STOP
Digoxin , Lithium , Aminoglycosides,Ciprofloxin ,etc.
Observe K
with ACEI , ARB , Aldactone , K-sparing Diuretics , KCl
( Baseline K > 4.5 and / or eGFR < 45 ml = “ High Risk “ )
NO Herbal drugs
Anemia in CKD
Definition
Male < 13 gm/dl Hb
Female < 12 gm/dl Hb
Incidence of ANEMIA with eGFR
45 - 59 ml
30 - 44 ml
< 30 ml
12.3 %
22.7 %
51.5 %
Evaluate
Fe ,IBC, Ferritin , Fe sat.% , stools OB , B12, Folic Acid , TSH .
Goal
Correct to max 12 gm/dl Hgb
( Do not use ESA in active or recent Malignancy )
CKD and Bone Disease
Measure yearly ( at least ) for eGFR < 45 ml
Calcium , Phosphate , PTH , Alkaline
Phosphatase , HCO3 (Bicarbonate )
Vitamin D 25 OH
Maintain / Correct :
PO4 to normal range 3.5- 4.5 ( mg% )
PTH levels ?
HCO3 > 22 meq/L ( oral Bicarbonate tablets)
Specialist Referral for CKD
AKI
CKD 4
Albuminuria
( Acute Kidney Injury )
( eGFR < 30 ml )
> 300mg ACR
CKD Progression
> 5 ml Loss / year or change in Stage
Red cell cast ( Glomerular Disease ) or > 20 RBC w/o cause
CKD and Resistent Hypertension
Not at Goal on 3 Drugs ( CCB, RAAS ,Diuretic)
Recurrent Nephrolithiasis
Hyperkalemia
Hereditary Kidney Disease
( 2 or more episodes )
( persistent )
( i.e. PCK )