Transcript Management of CKD

Options of treatment for CKD
patients
What is Chronic Kidney Disease
• The presence of Kidney Damage or an
eGFR < 60 ml/min/1.73m2 and
• Present for ≥ 3 months and
• Not treated with dialysis or transplant
The diagnosis of CKD is only present in patients with eGFR ≥60ml/min if other
abnormalities (i.e. proteinuria, hematuria, anatomical) are also present.
Classification of CKD by Diagnosis
• Diabetic Kidney Disease
• Glomerular diseases (autoimmune diseases, systemic
infections, drugs, neoplasia)
• Vascular diseases (renal artery disease, hypertension,
microangiopathy)
• Tubulointerstitial diseases (urinary tract infection,
stones, obstruction, drug toxicity)
• Cystic diseases (polycystic kidney disease)
• Diseases in the transplant (Allograft nephropathy, drug
toxicity, recurrent diseases, transplant glomerulopathy)
Stages in Progression of Chronic Kidney
Disease and Therapeutic Strategies
Complications
Normal
Screening
for CKD
risk factors
Increased
risk
CKD risk
reduction;
Screening for
CKD
Damage
 GFR
Kidney
failure
Diagnosis
Estimate
Replacement
& treatment; progression;
by dialysis
Treat
Treat
& transplant
comorbid complications;
conditions;
Prepare for
Slow
replacement
progression
CKD
death
Target Audiences
• People with
- Diabetes
- Hypertension
- Family history of kidney failure
CKD stage
GFR (ml/min/1.73m2)
Description
1
>90
Normal renal function but
other evidence of organ
damage*
2
60-89
Mild reduction in renal
function with other
evidence of organ
damage*
3
30-59
Moderately reduced GFR
4
15-29
Severely reduced GFR
5
<15
End stage, or
approaching, end stage
renal failure
* Structural (eg APCKD), functional (eg proteinuria) or biopsy proven GN
O’Hare et al JASN 2007
The majority of patients with CKD 1-3 do
not progress to ESRF.
Their risk of cardiovascular death is higher
than their risk of progression.
CKD Predicts CVD
40
36.6
Age-Standardized Rate of Cardiovascular
Events (per 100 person-yr)
35
30
25
21.8
20
15
11.29
10
5
2.11
3.65
0
≥ 60
45-59
30-44
15-29
< 15
Estimated GFR (mL/min/1.73 m2)
Go, et al., 2004
Age-Standardized Rates of Death from Any
Cause (Panel A) and Cardiovascular Events
(Panel B), According to the Estimated GFR
among 1,120,295 Ambulatory Adults
Go, A, et al. NEJM 351: 1296
Secondary complications of CKD
What do the kidneys Do?
– produce EPO
– activate vit D ( maintain iCa levels)
– maintain homeostasis
• K+
– remove excess water
– maintain acid - base
– remove endogenous and exogenous toxins
What happens without dialysis?
• Factors affecting survival in advance CKD patients who
choose not to receive dialysis
•
CF Wong, Renal failure 2007
• 73 patients, mean age 79, 1:1 gender ratio, in a renal clinic
• Mean GFR 12 ml/min (range 4-31)
• Median life expectancy 1.95 years
– 28 died – 20 of those at home
• 58 admission to hospital in 30 patients
– 60% had no admission
CKD is Not Being
Recognized or Treated
• Most practices screen fewer than 20% of their Medicare
patients with diabetes*
• Patients are referred late to a nephrologist, especially
African-American men
• Less than 1/3 of people with identified CKD get an ACE
Inhibitor
Kinchen, et al., 2002;
McClellan et al.,1997
*Data provided by the USRDS based on 5 percent Medicare enrollment and claims data
NICE guidelines Sept 2008
• People who have or are at risk of developing CKD
• Those who need intervention to minimise
cardiovascular risk and what that intervention
should be
• Those who will develop progressive kidney
disease and how they can be managed
• Those who need referral for specialist kidney care
Offer testing for CKD
•
•
•
•
•
•
•
•
Diabetes
HTN
CV disease: IHD, CHF, PVD, CVD
Structural disease, calculi or BPH
Multisystem eg SLE
FHx CKD 5 or hereditary kidney disease
Nephrotoxins (CNIs or ACE inhibitors)
Opportunistic detection of h’turia or p’uria
Proteinuria
• Use albumin: creatinine ratio (ACR) (more
sensitive at low levels)
• ACR in diabetes
• PCR may be used for quanitification and
monitoring
Who needs a renal ultrasound?
• All people with CKD with
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–
–
–
–
–
Progressive CKD
Haematuria
Obstructive symptoms
> 20 yrs with FHx polycystic kidneys
CKD 4-5
Prior to biopsy
Who should be referred?
•
•
•
•
•
•
•
CKD 4 and 5 (with or without diabetes)
ACR > 70 unless diabetic and already treated
ACR > 30 and haematuria
GFR declining > 5 /yr or 10 in 5 yr
Uncontrolled HTN despite 4 agents
Suspect rare or genetic cause CKD
Suspect renal artery stenosis
Identify patients in your practice at high risk for Chronic Kidney Disease
- Patients with hypertension
- Patients with diabetes mellitus
- Patients with atherosclerotic coronary,
cerebral or peripheral vascular disease
eGFR <30
-Patients with heart failure
-Patients with unexplained anemia
-Patients with a family history of end stage renal disease
-First nations peoples
eGFR 30-60
Consider reversible factors:
-Medication
- Volume depletion
-Intercurrent illness
- Obstruction
Repeat tests in 2 - 4 weeks
eGFR <30
Nephrology referral
recommended
eGFR < 30
or progressive decline in eGFR
or persistent significant proteinuria
or inability to attain treatment targets
eGFR >60
Individualized follow up
and treatment
CKD is diagnosed in this group only
if other renal abnormalities are present
(i.e. proteinuria, hematuria, anatomical)
eGFR 30-60
Follow eGFR at 3 months then serially
Assess for persistent significant proteinuria
Implement risk reduction
Stable eGFR 30-60
and
no significant proteinuria
How to Test for Chronic
Kidney Disease*
In individuals with diabetes:
• “Spot” urine albumin to creatinine ratio
In others at risk:
• “Spot” urine albumin to creatinine ratio OR standard dipstick
(Bouleware, et al., 2003)
• Estimate GFR from serum creatinine using the MDRD prediction
equation
*24 hour urine collections are NOT needed. Diabetics should be
tested once a year. Others at risk testing less frequently as long as
normal.
Importance of Proteinuria in CKD
Interpretation
Explanation
Marker of kidney
damage
Spot urine albumin-to-creatinine ratio >30 mg/g or
spot urine total protein-to-creatinine ratio >200 mg/g
for >3 months defines CKD
Clue to the type
(diagnosis) of CKD
Spot urine total protein-to-creatinine ratio >5001000 mg/g suggests diabetic kidney disease,
glomerular diseases, or transplant glomerulopathy.
Risk factor for adverse Higher proteinuria predicts faster progression of
outcomes
kidney disease and increased risk of CVD.
Effect modifier for
interventions
Strict blood pressure control and ACE inhibitors are
more effective in slowing kidney disease
progression in patients with higher baseline
proteinuria.
Hypothesized
surrogate outcomes
and target for
interventions
If validated, then lowering proteinuria would be a
goal of therapy.
At What Level of Creatinine Does a 65-Year-Old Diabetic,
Hypertensive White Woman Weighing 50 Kilograms Have
CKD?
•
1.5 mg / dl
GFR = 37 mL/min/ 1.73 m2
Ccreat = 30 mL/min
• Creatinine = 1.0 for GFR = 59 mL/min/1.73 m2
What is an acceptable rise in creatinine?
Primary renal
damage
Loss of nephrons
Hyperfiltration of
remaining nephrons
Focal sclerosis
Mesangial cell proliferation
and matrix expansion
Increased glomerular
pressure
Mesangial cell and endothelial cell injury
Fig 2 Commonly used formulas for estimating renal function. MDRD=modification of diet
in renal disease
Traynor, J. et al. BMJ 2006;333:733-737
Copyright ©2006 BMJ Publishing Group Ltd.
“Since the introduction of eGFR reporting (together with a
programme of education in primary care), the proportion of
new dialysis patients referred late (defined as within 90
days) has fallen from 38% to 25% (p<0.01).”
BMJ 2007;334:1287 (23 June), doi:10.1136/bmj.39247.723206.3A
Who Should be Treated for
Chronic Kidney Disease
With diabetes:
• With urine albumin/creatinine ratios more than 30mg
albumin/1 gram creatinine
Without diabetes:
• With urine albumin/creatinine ratios more than 300mg
albumin/1 gram creatinine corresponding to about 1+
on standard dipstick
Or
Any patient:
• With estimated GFR less than 60 mL/min/1.73 m2
Chronic Kidney Disease Treatment
Objectives
Optimal management
• 􀂄Delaying progression
• 􀂄Treatment of Comorbidities
• 􀂄Transition to End Stage Renal Disease
What can be done to slow
progression of renal disease?
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•
•
•
Hypertension control
ACE-Inhibitors/A2R-Blockers
Blood sugar control
Moderate protein restriction
How to Treat for Chronic
Kidney Disease
• Maintain blood pressure less than
130/80 mmHg
• Use an ACE Inhibitor or ARB
• More than one drug is usually required and a diuretic
should be part of the regimen
• Continue best possible glycemic control in individuals with
diabetes
How to Treat for Chronic
Kidney Disease
(continued)
• Refer to dietician for a reduced protein diet
• Consult a nephrologist early
• Team with the nephrologist for care if GFR is less than 30
mL/min/1.73 m2
• Monitor hemoglobin and phosphorous with treatment as
needed
• Treat cardiovascular risk, especially smoking and
hypercholesterolemia
Early Treatment Makes
a Difference
Brenner, et al., 2001
Risk of progression to ESRD
ESRD
Death
5-year cumulative incidence
5 year cumulative incidence
<69
3%
12 %
70-79
1%
28 %
>79
1%
56 %
3047 patient with eGFR 30-59 in Norway
The progression of CKD: a 10 year population-based study of the effects of
gender and age. Eriksen and Ingebretsen, Kidney International 2006
Identify progressive CKD
• Obtain minimum 3 GFRs over not less than
90 days
• If new finding low GFR, repeat within 2
weeks to exclude ARF
Optimise risk factors
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Cardiovascular disease
Proteinuria
Hypertension
Diabetes
Smoking
Obesity
Exercise tolerance
Treatment to Prevent Progression of CKD
to Kidney Failure
• Intensive glycemic control lessens progression from
microalbuminuria in type 1 diabetes
- DCCT, 1993
• Antihypertensive therapy with ACE Inhibitors lessens
proteinuria and progression
- Giatras, et al., 1997
- Psait, et al., 2000
- Jafar, et al., 2001
Meta-Analyses
• Low protein diets lessen progression
- Fouque, et al., 1992
- Pedrini, et al., 1996
- Kasiske, et al., 1998
Meta-Analyses
Blood Pressure Targets
JAMA. 2003;289:2560–2571.
American Diabetes Association. Diabetes Care. 2002;25:134–147.
National Kidney Foundatrion. Am J KidnDis. 2002;39(suppl 1):S1–S266
Meta Analysis: Lower Mean BP
Results in
Slower Rates of Decline in GFR in Diabetics and
Non-Diabetics
Am J Kidney Dis.2000;36(3):646-661
Blood pressure control
• Systolic < 140 (aim 120-139 mm Hg)
• Diastolic < 90 mm Hg
• If diabetes or proteinuria, aim 130/80 mm
Hg
ACE inhibitor/ ARBs
• Offer to:
– Diabetes and ACR > 2.5 ± HTN/CKD
– Non-diabetic with CKD and high BP and ACR
30+ mg/mmol (0.5g/24 hrs)
– Non-diabetic with CKD and ACR > 70
regardless of blood pressure or risk factors
– Titrate to maximum tolerated dose before add
in second agent
Clinical Practice Guidelines for
Management of Hypertension in CKD
Type of Kidney Disease
Blood Pressure
Target
(mm Hg)
Preferred Agents
for CKD, with or
without
Hypertension
Other Agents
to Reduce CVD Risk
and Reach Blood
Pressure Target
ACE inhibitor
or ARB
Diuretic preferred,
then BB or CCB
Diabetic Kidney Disease
Nondiabetic Kidney Disease
with Urine Total Protein-toCreatinine Ratio 200 mg/g
Nondiabetic Kidney Disease
with Spot Urine Total
Protein-to-Creatinine ratio
<200 mg/g
Kidney Disease in Kidney
Transplant Recipient
<130/80
None preferred
Diuretic preferred,
then ACE inhibitor,
ARB, BB or CCB
CCB, diuretic, BB,
ACE inhibitor, ARB
The metabolic complications of CKD
Uraemia
Stage 5
Hypertriglyceridaemia
Hyperphosphataemia
Stage 4
Ca absorption and
lipoprotein activity reduced
Malnutrition, LVH, anaemia
Metabolic acidosis
Hyperkalaemia
Stage 3
PTH increases at GFR
50-60
Stage 2
Stage 1
Targets
Parameter
Target
Haemoglobin
>11 g/dl
Ferritin (patients on EPO)
>150µg/l
Calcium
2.10 – 2.60 mmol/l
Phosphate
0.84 – 1.45 mmol/l
Parathyroid hormone
< 4 x upper limit of range
Bicarbonate
22-26 mmol/l
Potassium
3.5-6.0 mmol/l
Referral to smoking cessation
programme
100% of smokers
Management of Comorbidities
• Anemia
• Renal Osteodystrophy
• Hyperlipidemia
Etiology and Workup of Anemia in
Renal Failure
Benefits of Correction of Hb
• Raising Hematocrit to 30-36% improves:
–
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–
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Brain and cognitive function
Quality of Life
Exercise capacity/muscle function
?LVH
?Survival
Principles of Anemia Treatment
• Erythropoietin
– Epoetinalfa
– DarbepoietinAlpha
• Targets
– Hgb=11 to 12 g/dL
– Hct=33% to 36%
• Sufficient iron should be administered to
maintain
– TSAT of >20%,
– Serum ferritinlevel of >100 ng/mL
Treatment of Calcium, Phosphate
Levels and Osteodystrophy
• AIM: To Normalize– Serum calcium
– Serum Phosphorus
– PTH levels
• Methods:
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–
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Oral Calcium
Vitamin D analogs
Phosphate binders (sevelamer)
Calcimimetics(cinacalcet)
Dyslipidemiain Renal Patients
Am J Kidney Dis. 1998 Nov;32(5 Suppl3):S142-56
Atorvastatinin Patients with Type 2
Diabetes Mellitus Undergoing
Hemodialysis
Primary end point of cardiovascular death, nonfatal myocardial
infarction, and stroke in diabetic hemodialysis pts
N Engl J Med 2005;353:238-248
Management of Dyslipidemia in CKD
• NCEP guidelines recommended:
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–
–
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Cholesterol<200
LDL-C<100
HDL-C>45 (M), 55(F)
Triglycerides<150
Preparation for renal replacement
• Choice of renal replacement
• Timely access surgery
• Timely dialysis initiation
Dealing with Stage 5 CKD
• When GFR decreases below 30ml/min, advice
about options for kidney failure such as dialysis or
kidney transplant
• When GFR decreases to less than 15ml/min,
advice to start treatment with above options.
What is Dialysis?
• Dialysis is a treatment that cleanses blood of excess water
and waste that has built up due to kidney failure.
• There are 2 kinds of dialysis: hemodialysis and peritoneal
dialysis
• When GFR decreases to below 20ml/min the doctor will
advise for arrangement of a permanent access to either of
the above 2 options
Hemodialysis
• In hemodialysis, a dialysis machine which contains a
special filter, a dialyzer, will become the substitute of your
kidney.
• An access is needed to be able to filter blood from the
bloodstream into the tubes going to the machine.
• Treatments should be done at least three times a week
• Each dialysis session lasts 3-5 hours
• The “access” can be through a fistula or a catheter
• Catheters are usually used as temporary access
only.
• They can be attached at the side of the neck for
jugular catheters, in the upper chest for subclavian
catheters and through the inguinal area for
femoral catheters
Jugular catheter
• Fistulas are used for more permanent access.
These are inserted by surgeons by connecting an
artery to a nearby vein in the arm.
• Fistulas can take a month to a few months to
enlarge before it can be ready for access.
• The advantages of fistulas are that they are less
prone to infections and clogging and they are less
visible because they are under the skin.
Peritoneal Dialysis
• In peritoneal dialysis, there is no machine. Instead of an
artificial filter, the lining of the abdomen, the peritoneum is
used as a natural filter. The peritoneum has a lot of small
vessels in it.
• Excess waste and water from the blood can travel from the
peritoneum into a dialysate solution that can be infused
into the belly.
• The access for infusing the dialysate solution is a
peritoneal catheter.
Kidney transplant
• Surgery can be planned. This is an operation that
involves the transfer of a healthy kidney into a CKD
patient’s body. A donor of a healthy kidney is required
for this treatment.
• This treatment starts with finding a willing donor. Once
found, tests are done to match the blood and tissue types
of the patient and the donor. This is to lessen the chance
of rejection of the transplanted kidneys. Once a match
is available, surgery can be planned
What can Primary Care
Providers do?
• Recognize who is at risk
• Provide testing and treatment
• Encourage labs to provide and report estimated GFR and
spot urine albumin/creatinine ratios
CKD 3 management in primary care
• Diabetes, ischaemic heart disease, hypertension
• Risk factor management
• Not much specialist renal medicine involved in
majority of CKD 3
• Refer if refractory hypertension, complications of
renal failire, renal artery stenosis etc…
• Identify those with progressive CKD and refer
“Patients receiving comprehensive care by
the renal team have shown:
– slower rates of decline in renal function
– greater probability of starting dialysis with
higher haemoglobin, better calcium control and
permanent access
– a greater likelihood of choosing peritoneal
dialysis.”
Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. for the
Collaborative Study Group. Renoprotective effect of the angiotensin-receptor
antagonist irbesartan in patients with nephropathy due to type 2 diabetes N
Engl J Med 2001. 345:851–860.
Reasons for a National Kidney
Disease Education Program
1) Kidney failure is a public health problem
2) Economical, effective testing and therapy exist
3) Testing and therapy are inadequately applied
Preservation of Kidney Function:
9-Pronged Approach
LDL-C = low-density lipoprotein cholesterol; NSAID = nonsteroidal antiinflammatorydrug.
b SI conversion factor: To convert LDL-C values to mmol/L, multiply by 0.0259.
Mayo Clin Proc. • September 2008;83(9):1064-1069
Summary
• Assess risk for CKD progression
– serial eGFR
– proteinuria
• Assess CV Risk
– as per high risk group guidelines
• Assess for CKD complications
– anemia
Clinical Practice Guidelines for the Detection,
Evaluation and Management of CKD
Stage
Description
GFR
Evaluation
Management
At increased
risk
Test for CKD
Risk factor management
1
Kidney
damage with
normal or 
GFR
>90
Diagnosis
Comorbid
conditions
CVD and CVD
risk factors
Specific therapy, based on diagnosis
Management of comorbid conditions
Treatment of CVD and CVD risk factors
2
Kidney
damage with
mild  GFR
60-89
Rate of
progression
Slowing rate of loss of kidney function 1
3
Moderate 
GFR
30-59
Complications
Prevention and treatment of complications
4
Severe  GFR
15-29
Preparation for kidney replacement therapy
Referral to Nephrologist
Kidney Failure
<15
Kidney replacement therapy
5
1
Target blood pressure less than 130/80 mm Hg. Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot
urine total protein-to-creatinine ratio of greater than 200 mg/g.
Summary
Optimal Management of CKD
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