Progressive Chronic

Kidney Disease
Cherelle Fitzclarence
August 2009

Overview
Case studies
Discussion
Take home messages

Case 1
50 yo diabetic 5 yr hx
Initial poor control but good last 3 years
with combo of insulin and oral
hypoglycaemics
Monitors own sugars
Post prandial BSLs <10mmol/L
HbA1c 5-7%
No peripheral neuropathy
No retinopathy
Albuminuria
Hypertension

Case 1 cont.
In large epidemiological surveys for
diabetes and chronic kidney disease,
which of the following are correct?
About 1 in 20 people have abnormalities on
urinalysis
About 8% of the general population have
evidence of diabetes mellitus
About 1 in 10 type 2 diabetics have evidence of
diabetic nephropathy
Those with diabetes are at risk of end stage
kidney disease

Case 1 cont.
Question 1
In large epidemiological surveys for
diabetes and chronic kidney disease,
which of the following are correct?
About 1 in 20 people have abnormalities on
urinalysis
About 8% of the general population have
evidence of diabetes mellitus
About 1 in 10 type 2 diabetics have evidence of
diabetic nephropathy
Those with diabetes are at risk of end stage
kidney disease

Discussion
Case 1
AusDiab 1 in 7 pts in Australia have
diabetes. This can be as high as 1 in 3 in
indigenous Australians
CKD was defined by presence of blood or
protein on urinalysis and/or serum
creatinine >150
8% of the surveyed group had diabetes
and half of them were unaware of Dx
30% of those surveyed had hypertension
with half being unaware of Dx
1 in 3 type 2 diabetics will develop
nephropathy

Take home message

Type 2 Diabetes is now worldwide, the
most common cause of end stage kidney
disease
Indigenous populations have much higher
rates of end stage kidney disease (ESKD)
Risk factors for ESKD

Hypertension
Diabetes
Family history
Ethnicity
Smoking
Obesity

Case 1
Question 2
Which of the following is the most
appropriate investigation when screening
for CKD?

24 hr urinary protein
24 hr urinary albumin excretion
Urinary prot/creat ratio on a spot urine
Urinary alb/creat ratio on a spot urine
MSU with dipstick, spot ACR, microscopy and
culture

Case 1
Question 2
Which of the following is the most
appropriate investigation when screening
for CKD?

24 hr urinary protein
24 hr urinary albumin excretion
Urinary prot/creat ratio on a spot urine
Urinary alb/creat ratio on a spot urine
MSU with dipstick, spot ACR, microscopy
and culture

Discussion
CARI/KCAT reviewed evidence
Combo screening the best

U/A
MSU - m,c,s
ACR
BP
Serum creatinine (GFR)

This should be done yearly in high risk

groups eg diabetics, ATSI
Further discussion

Take home message

Single urine dipstick for protein
limitations false positives, false negatives
Kidney function should be measured at
least yearly in those at increased risk CKD
Screening should include measurement of
BP, serum creatinine (GFR), MSU
Protein creatinine ratio or albumin
creatinine ration

Case 1
Question 3
Which of the following is/are true
statements concerning tests for assessing
CKD?
Serum creatinine is an accurate measure of
renal function and if <120 excludes
nephropathy
GFR estimated from a formula is an accurate
measure of renal function
A deterioration in eGFR or more than 15% over
a period of months is sign of acute renal failure
An eGFR of >20mls/min excludes clinically
relevant renal disease

Case 1
Question 3
Which of the following is/are true
statements concerning tests for assessing
CKD?
Serum creatinine is an accurate measure of
renal function and if <120 excludes
nephropathy
GFR estimated from a formula is an
accurate measure of renal function
A deterioration in eGFR or more than 15% over
a period of months is sign of acute renal failure
An eGFR of >20mls/min excludes clinically
relevant renal disease

Discussion
Serum creatinine can stay in the normal
range until more than 50% of GFR is lost
Serum creatinine is dependent on age,
weight, gender and muscle mass
Small people with low muscle mass,
elderly, female may have significant renal
impairment despite a normal creatinine
GFR falls over hours, days or weeks in
acute renal failure
GFR falls over months, years in chronic
renal failure
eGFR is used to stage kidney disease

Discussion
Stage

GFR mL/min/
1.73

Expected CMs

>90

None or the primary

disease process

60-89

None, hyperparathyroidism,
increased risk CVD

30-59

Nocturia, anaemia,
increased creat, decreased
vit D, dyslipidaemia, abN
extracellular volume

15-29

Uraemic symptoms,
abnomalities electrolytes

<15

Severe uraemic symptoms,

dialysis

Take home message

eGFR is useful as a screening tool for
CKD
Should be used in conjunction with BP, U/
A, ACR
eGFR can be used to stage CKD

Case 1 continues
Over next 12 months, renal disease
progresses
Creat 312
Risk factors for cardiovascular disease
poorly controlled
BP >150 with 4 drug therapy on board
ACEI, CCB, BB, Frusemide
Hyperlipidaemia despite statin therapy
ACR increasing despite ACEI

Case 1

Question 4
In slowing the progression of renal disease and
avoiding the development of malnutrition in CKD
patients with an eGFR 15-30 mls/min, which of the
following statements is/are correct?
Nephrotic patients need a high protein diet
Reducing proteinuria to <1g/24 hours is associated
with a reduction in rate of decline off renal function
Proteinuria is a good measure of renal dysfunction
Heavy proteinuria (>3g/24hrs) predicts the response
to ACEI

Case 1

Question 4
In slowing the progression of renal disease and
avoiding the development of malnutrition in CKD
patients with an eGFR 15-30 mls/min, which of the
following statements is/are correct?
Nephrotic patients need a high protein diet
Reducing proteinuria to <1g/24 hours is
associated with a reduction in rate of decline off
renal function
Proteinuria is a good measure of renal dysfunction
Heavy proteinuria (>3g/24hrs) predicts the
response to ACEI

Discussion
CARI guidelines advise against excessive
protein restriction for slowing renal function
decline
High protein diets do little to correct the
malnourished state
Control of BP can signifcantly reduce
proteinuria esp ACEI, AR2B, aldosterone
antagonists

Take home message

Low protein diets may slow progression
CKD but only a small impact and may
increase risk of malnutrition
High protein diets are not effective in
treating malnutrition and may accelerate
CKD
Lowering BP decreases proteinuria
Degree of preservation of renal function
achieved with AHA directly proportional to
decrease in proteinuria
ACEI/AR2Bs slow progression CKD more
than explained just be AHA

Case 1

Question 5
When a pt with T2DM is assessed for diabetic
nephropathy, which of the following is correct?
The absence of proteinuria excludes diabetic
nephropathy
Hypertension usually indicates the presence of
concomitant macrovascular disease
The severity of diabetic nephropathy is related to
the severity of hypertension
The absence of diabetic retinopathy excludes
diabetic nephropathy
Kimmelstiel-Wilson lesions must be present to
diagnose diabetic nephropathy

Case 1

Question 5
When a pt with T2DM is assessed for diabetic
nephropathy, which of the following is correct?
The absence of proteinuria excludes diabetic
nephropathy
Hypertension usually indicates the presence of
concomitant macrovascular disease
The severity of diabetic nephropathy is related to the
severity of hypertension
The absence of diabetic retinopathy excludes
diabetic nephropathy
Kimmelstiel-Wilson lesions must be present to
diagnose diabetic nephropathy

Discussion

NHANES 3 study T2DM with creat > 150 -1/3rd

had no evidence of proteinuria
Due to more of a Vasculopathy (particularly
microvascular) than by classic histological changes
of glomerular basement membrane thickening and
mesangial expansion
Vasculopathy is associated with hypertension and
may not be associated with proteinuria
Vasculopathy leads to progressive CKD,
accelerated by diabetic control, hypertension,
proteinuria

Take home message

Not all T2DM with CKD have proteinuria
Hypertension is common and is associated
with progressive CKD
If hypertension is resistant, think RAS
Diabetic retinopathy and nephropathy are
commonly but not always bound together

Case 1
Question 6
Which of the following is true regarding
treatment aimed at slowing the
progression of CKD and at preventing
cardiovascular events such as AMI and
CVA?
The target BP is <140/90
Only ACEI and AR2B slow progression CKD
In large studies, ACEi have been shown to
improve overall survival in diabetics with large
and small vessel vasculopathy
The presence of renovascular diesease is a
contraindication to the use of ACEI or AR2B

Case 1
Question 6
Which of the following is true regarding
treatment aimed at slowing the
progression of CKD and at preventing
cardiovascular events such as AMI and
CVA?
The target BP is <140/90
Only ACEI and AR2B slow progression CKD
In large studies, ACEi have been shown to
improve overall survival in diabetics with
large and small vessel vasculopathy
The presence of renovascular diesease is a
contraindication to the use of ACEI or AR2B

Discussion

Target BP should be <130/80

If diabetic with protenuria <1g/24 hours target
should be <120/75
BP decrease alone contributes to slowing CKD
All antihypertensives good for this but AR2B and
ACEI have greatest efficacy
HOPE and PROGRESS show ACEI in high risk
populations decrease cardiovascular events
Atherosclerotic renovascular disease with evidence
of RAS is not an absolute contraindication to the
use of ACEI or AR2B but you need to be very
careful

Take home message

Target BP
Proteinuria <1g/24hours 130/80
Proteinuria >1g/24hours 120/75

For diabetic CKD target BP <120/75

AR2B and ACEI preferred but any agent
ok as long as BP controlled
Atherosclerotic renovascular disease not
absolute contraindication to ACEi

Case 1
Question 7
In general, which of the following results in
50yo indicate need for referral to
Nephrologist?
Diabetic with eGFR <60 and poorly controlled
hypertension
A non diabetic with an eGFR 30-60mls,
proteinuria <0.5g/day, controlled BP
Proteinuria >1g/day with normal eGFR
Unexplained decline in kidney function (>15%
drop GFR over 3 months)

Case 1
Question 7
In general, which of the following results in
50yo indicate need for referral to
Nephrologist?
Diabetic with eGFR <60 and poorly
controlled hypertension
A non diabetic with an eGFR 30-60mls,
proteinuria <0.5g/day, controlled BP
Proteinuria >1g/day with normal eGFR
Unexplained decline in kidney function
(>15% drop GFR over 3 months)

Discussion
Late referral to Nephrologist associated
with poorer outcomes, greater morbidity
for RRT and pall care groups
Guidelines only and controversial if not
sure err on side of caution
In general, stable patients with eGFR >30
dont require referral but a significant
number can benefit from referral and
progression may be able to be averted

Take home message

Indications for referral to Nephrologist

Proteinuria > 1g/24 hrs

eGFR < 30mls in non diabetics
eGFR < 60mls in diabetics
Unexplained decline in kidney function
Glomerular haematuria with proteinuria
CKD with difficult to control hypertension
Otherwise unexplained anaemia

Case 1
Question 8
Pts Hb dropped to 90 and treatment with
epo commenced. Which of the following
are true?
Most common cause for anaemia in CKD with
GFR<60 is bleeding from the upper GIT
If pt on EPO, iron therapy is not required if
serum ferritin is >100
Treating the anaemia of CKD is not required
until HB<100
Anaemia occurs earlier in the course of CKD in
diabetic than non diabetic patients

Case 1
Question 8
Pts Hb dropped to 90 and treatment with
epo commenced. Which of the following
are true?
Most common cause for anaemia in CKD with
GFR<60 is bleeding from the upper GIT
If pt on EPO, iron therapy is not required if
serum ferritin is >100
Treating the anaemia of CKD is not required
until HB<100
Anaemia occurs earlier in the course of CKD
in diabetic than non diabetic patients

Discussion
Small increased risk in GIH
Anaemia of CKD is due to relative
erythropoietin deficiency and show up in
stage 3 and is more severe in diabetics
Prior to epo, iron deficiency was rare due
to blood transfusions
Now relative iron deficiency is a problem
EPO can only be prescribed once Hb <100
Aim Hb 120
Worse outcomes if Hb higher than this
Renal anaemia is often iron responsive

Discussion

Aims
Prior to starting epo ferritin >100
Once epo started ferritin 400-600
Transferrin saturation >20% prior to epo
therapy
Transferrin saturation 30-40% post epo
starting
Adequate iron stores required for epo to
work
Iron deficiency is most common cause of
hyporesponsiveness to epo

Take home message

Impaired absorption of oral iron and
increased utilization of iron with EPO
therapy have contributed to the
development of iron deficiency
Optimize responsiveness to EPO targets
for ferritin 300-600 and saturation 30-40%

Case 1

CKD progresses and he needs dialysis. GP

questions whether other therpay may have
prevented such a rapid progression to ESKD
Question 9
For which of the following therapies is there level 1
evidence for efficacy in the CKD population
Cholesterol lowering with statins both to slow
progressive decline of renal function and to
reduce the increased cardiovascular risk
associated with CKD
Uric acid reduction slows progression
Exercise and weight loss improve insulin
resistance and slow progression
Aldosterone blockade can further slow
progression
AR2B can further slow progression in pts on
ACEI

Case 1

CKD progresses and he needs dialysis. GP

questions whether other therpay may have
prevented such a rapid progression to ESKD
Question 9
For which of the following therapies is there level 1
evidence for efficacy in the CKD population
Cholesterol lowering with statins both to slow
progressive decline of renal function and to
reduce the increased cardiovascular risk
associated with CKD
Uric acid reduction slows progression
Exercise and weight loss improve insulin
resistance and slow progression
Aldosterone blockade can further slow
progression
AR2B can further slow progression in pts on
ACEI

Discussion
Decrease uric acid, cessation of smoking,
weight loss all slow progression but
evidence is poor; studies small, non
randomised, case studies
Statins thought to help but again studies
not good no RCT
AR2B and ACEI combo thought to help if
patient proteinuric COOPERATE study

Take home message

Allopurinol, weight loss, cessation of
smoking, exercise may all slow
progression of CKD but no level one
evidence
Beneficial effect of lipid though to be
present but still waiting level 1 evidence
AR2B and ACEi together can help delay
progression in pt with proteinuria

Case 1
Question 10
In type 2 DM ACEi and AR2B have been
shown to slow the development of
progression of nephropathy in pts who are

Normoalbuminuric and normotensive

Normoalbuminuric and hpertensive
Microalbuminuric and hypertensive
Macroalbuminuric and hypertensive

Case 1
Question 10
In type 2 DM ACEi and AR2B have been
shown to slow the development of
progression of nephropathy in pts who are

Normoalbuminuric and normotensive

Normoalbuminuric and hypertensive ***
Microalbuminuric and hypertensive
Macroalbuminuric and hypertensive

Discussion
BENEDICT study
ACEi decreased albumuria in T2DM with
hypertension and normal albumin excretion

RENAAL study
Similar results with AR2B

Take home message

ACEi and AR2B have been proven in
hypertensive type 2 diabetics to slow
progression of CKD, development of
microalbuminuria, macroalbuminuria
Dont use combination in patients who are
simply hypertensive

Conclusion
Keep your chronic disease protocols
handy

Acknowledgements
Information taken from chapter 11 Clinical
Cases in Kidney Disease by David Harris
and colleagues