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Albuminuria Versus GFR As Markers of Diabetic CKD Progression

1. Both albuminuria and GFR should be assessed as markers of diabetic CKD progression. 2. Changes in albuminuria are more variable than changes in GFR, which are usually progressive. 3. While a decline in GFR is usually accompanied by a rise in albuminuria, some patients follow a non-albuminuric pathway to renal impairment.

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38 views

Albuminuria Versus GFR As Markers of Diabetic CKD Progression

1. Both albuminuria and GFR should be assessed as markers of diabetic CKD progression. 2. Changes in albuminuria are more variable than changes in GFR, which are usually progressive. 3. While a decline in GFR is usually accompanied by a rise in albuminuria, some patients follow a non-albuminuric pathway to renal impairment.

Uploaded by

budi darmanta
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Albuminuria versus GFR as

markers of diabetic CKD


progression
KDIGO Controversies Conference:
“Diabetic Kidney Disease”
New Delhi, March 2012

Richard J MacIsaac
PhD FRACP

Director of Endocrinology & Diabetes, St Vincent's Hospital


Professorial Fellow, University of Melbourne
Evolution of Diabetic CKD
Incipient Overt
Nephropathy Nephropathy
GFR
100
(ml/min)
Log AER

GFR
10 15 20 yrs
Normoalbuminuria Microalbuminuria Macroalbuminuria
(AER < 20 µg/min) (AER 20-200 µg/min) (AER > 200 µg/min)
Stages of CKD
Stage eGFR Description Predominant
(ml/min/1.73 m2)
AER status

1 > 90 Kidney damage with normal/high GFR Normo- Micro-

2 60-89 Kidney damage with mild reduction in GFR Micro-

3 30-59 Kidney damage with moderate reduction in Micro/Macro-


GFR

4 15-29 Kidney damage with severe reduction in Macro-


GFR

5 < 15 Kidney failure


Albuminuria versus GFR as markers
of diabetic CKD progression

1. Albuminuria as a predictor of diabetic CKD


2. GFR as a predictor of diabetic CKD
3. Albuminuria & GFR uncoupling/coupling
4. Summary
Albuminuria as a marker of
diabetic CKD progression

• High Variability
M • Low Specificity
N
• Spontaneous Regression
µ • Δ AER ≠ Δ GFR
Higher levels of urinary albumin excretion within the
normal range predict faster decline in glomerular
filtration rate in diabetic patients
Babazono T et al. Diabetes Care 2009;32:1518-1520
Albuminuria versus GFR as markers of
diabetic CKD progression

1. Albuminuria as a predictor of diabetic CKD


2. GFR as a predictor of diabetic CKD
3. ALbuminuria & GFR uncoupling/coupling
4. Summary
GFR as index of diabetic CKD progression

120
15 • Low Variability
V
IV
I • High Specificity
30 90
III II
• Infrequent Regression
• GFR = best index of
60 kidney function
CKD-EPI formula underestimates measured
GFR > 90 ml/min/1.73m2 to the same extent
as the MDRD formula in type 2 diabetes
RJ MacIsaac (unpublished)

120 iGFR p<0.001


MDRD
† ‡
100 CKD-EPI
GFR (ml/min/1.73m2)

p=0.133
80

60 p=0.051
111.8
100.8 99.4

40 75.7 79.5 80.7

49.5
20 44.2 48.8

0
iGFR <60 (n=60) iGFR 60-90 (n=63) iGFR >90 (n=76)
Possible regression of eGFR with bardoxolone
Pergola PE NEJM 2011, 28, 327-36
eGFR (ml/min per 1.73m2)
Albuminuria versus GFR as markers
of diabetic CKD progression

1. Albuminuria as a predictor of diabetic CKD


2. GFR as a predictor of diabetic CKD
3. Albuminuria & GFR uncoupling/coupling
4. Summary
AER vs isotopic GFR in Type 2 Diabetes
RJ MacIsaac et al Diabetes Care 2004

Normoalbuminuria Microalbuminuria Macroalbuminuria


175

150
iGFR (ml/min/1.73m2)

125
n=192
100

75

50

25
n=109
39 % 35% 26%
0
10 100 1000
1
AER (µg/min)
AER vs eGFR in Type 1 Diabetes
ME Molitch et al Diabetes Care, 33, 1536-1543 2010
Microalbuminuria and the risk for early progressive
renal function decline in type 1 diabetes
Perkins BA et al. JASN 2007, 18, 1353-1361

Baseline GFR (ml/min/1.73m2)


155 143

Early decline
GFR > - 3.3%/year

9% 31% Stable

Early decline

ESRD
Early Renal Function Decline in Type 2 Diabetes
Pavkov ME et al CJASN 2011

Initial GFR > 150 ml/min


% with early decline GFR > 3.3%/year
(urinary iothalamate clearance)

32% 42%

Normoalbuminuria Microalbuminuria
(n = 68) (n = 88)
Microalbuminuria and the risk for early progressive
renal function decline in type 1 diabetes
Perkins BA et al. JASN 2007, 18, 1353-1361
Frequency of early progressive renal function decline in patients with T1DM and normoalbuminuria
or microalbuminuria divided according to the 4-year course of microalbuminuria

Frequency
of early
progressive
renal
function
decline-
(>3.3%/yr)
Early Renal Function Decline in Type 2 Diabetes
Pavkov ME et al CJASN 2011
Decline in early renal function and subsequent development of ESRD is
strongly dependent on progression to macroalbuminuria in type 2 diabetes
Relationship between initial change in AER and overall change
in GFR per year in type 1 diabetes: Intention to treat analysis
Jerums et al . Am J Nephrol(2008) 28:614.

23 study groups (9 studies)


Early DN
n=1181

10 study groups (5 studies)


Late DN
n=510
Intensified multifactorial intervention in patients
with T2 DM and microalbuminuria: STENO 2 Study
P Gaede et al. Lancet (1999) 353:617-622, P Gaede et al. N Engl J Med (2003) 348:383-393

Analysis according to intention to treat (n=160)


Standard Intensive
n = 80 n = 80
Median AER Baseline 69 78
(mg/24h) 3.8 yr 79 66*
7.8 yr 99 58* (p < 0.01)
Mean iGFR Baseline 118 116
(ml/min/1.73m2) 3.8 yr 105 105
7.8 yr 86 86
Intensified multifactorial intervention in patients
with T2 DM and microalbuminuria: STENO 2 Study
P Gaede et al. Nephrol Dial Transplant (2004) 19:2784-8

Post Hoc Analysis: according to AER during follow-up (n = 151)


Baseline AER Micro Micro Micro

Follow-up AER Normo Micro Macro


n = 46 58 47
GFR Decline 2.3 ± 0.4 3.7 ± 0.4 5.4 ± 0.5
(ml/min/year) (Anova,
p < 0.001)

Conclusion Remission to normoalbuminuria is associated with decreased


GFR decline during 7.8 yr follow-up
Albuminuria and GFR as markers
of diabetic CKD progression

1. Albuminuria as predictor of diabetic CKD


2. Estimating or measuring GFR in diabetic CKD
3. Albuminuria & GFR uncoupling/coupling
4. Summary
Conclusions
• Both albuminuria and GFR should be assessed as markers
of diabetic CKD progression
• Changes in albuminuria are variable whereas changes in
GFR are usually progressive
• A decline in GFR is usually accompanied by a rise in
albuminuria but some patients follow a non-albuminuric
pathway to renal impairment (GFR < 60 ml/min/1.73m2)
• Progression to ESRD is usually strongly dependent on
progression to macroalbuminuria
• Albuminuria and GFR have complementary roles in staging
and stratifying the risk of progressive diabetic CKD
The definition, classification, and prognosis of chronic kidney
disease: a KDIGO Controversies Conference report
Levey A et al Kidney International (2011) 80, 17–28
Acknowledgements

G Jerums
S. Panagiotopoulos
E. Premaratne
E. Ekinci
K. Cheong
S. Verma
S. Finch

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