TIME TO RETIRE MICROALBUMIN“the affirmative case”
Richard J MacIsaacPhD FRACP
Department of Endocrinology & Diabetes,St Vincent's Hospital & University of Melbourne
AACB 53rd Annual Scientific ConferenceSeptember 2015
TIME TO RETIRE MICROALBUMIN“the affirmative case”
Vs
It is time for micoalbuminuria to step down!
Microalbuminuria X• Microalbuminuria = A2• High Variability• Low Specificity• Spontaneous Regression• Δ AER ≠ Δ GFR
Microalbuminuria å Good prognostic marker
NM
µ
A paradigm of Diabetic Kidney Disease based solely onmicroalbuminuria needs to be questioned!
What is microalbuminuria?
Microalbuminuria refers to a range ofurinary albumin excretion
excretion
Microalbuminuria DOES NOT refer to fragments of urinary albumin
Immunochemically unreactive albumin in urine: fiction or reality? Speeckaert MM et al.Critical Reviews in Clinical Laboratory Sciences, 2011; 48(2): 87–96
Microalbuminuria as aprognostic marker
Higher levels of urinary albumin excretion within thenormal range predict faster decline in glomerular
filtration rate in diabetic patients
Babazono T et al. Diabetes Care 2009;32:1518-1520
WomenMen
Measurable Urinary Albumin Predicts Cardiovascular Risk evenamong Normoalbuminuric Patients with Type 2 Diabetes
Ruggenenti P et al. J Am Soc Nephrol 2012,23:1717
Why has microalbuminuria reigned solong as the preeminent marker of
diabetic kidney disease?
An Immunoassay method for urinary albumin at low concentrationsH.Keen & C. Chlouverakis
THE LANCET1963, 2(7314): 913-914
Summary of early studies demonstrating that microalbuminuriapredicts diabetic nephropathy* (DN) in type 1 diabetes
Viberti Parving Mogensen Mathiesen(1982) (1982) (1984) (1984)
No of patients 63 23 43 71
Age (years) 40 32 25 30
Follow-up (years) 14 6 10 6
Proposed discrimination 30 30 15 70rate (µg/min)
Development of DN below 2/55 2/15 0/29 3/64discrimination value
Development of DN above 7/8 6/8 12/14 7/7discrimination value (88%) (75%) (86%) (100%)
*Definition of DN included: protein excretion > 500 mg/24 h, AER > 150 µg/min, AER > 200 µg/min oralbustix positive depending on the study
MacIsaac RJ and Jermus G, Curr Opin Nephrol Hypertens 2011,20:246–257
UREMIA INVESTIGATION, 9(2), 85-95 (1985-86)Microalbuminuria: An Early MarkerOf Renal Invilvement in Diabetes
C. E. Mogensen, M.D.A.Chachati, M.D.C.K. Christensen, M.D.C.F. Close, M.D.T. Deckert, M.D.E. Hommel, M.D.J. Kastrup, M.D.P. Lefebvre, M.D.E.R. Mathiesen, M.D.B. Feldt-Rasmussen, M.D.A. Schmitz, M.D.G.C. Viberti, M.D.
“According to evaluations anddiscussions among the presentauthors, the following criteriamay be used for the classificationand renal involvement in theinsulin-dependent patient only,both in clinical work and inresearch projects.
Microalbuminuria is presentwhen urinary albumin excretionrate is greater that 20 µg/minless than or equal to 200µg/min.”
Log AER
Normoalbuminuria(AER < 20 g/min)
Microalbuminuria(AER 20-200 g/min)
Macroalbuminuria(AER > 200 g/min)
GFR100
(ml/min)
Evolution of Diabetic CKD
IncipientNephropathy
OvertNephropathy
GFR10 15 20 yrs
Microalbuminuria-variability
201612
840
ALBUMINEXCRETIONRATE(μg/min)
VARIANCEOF ALBUMINEXCRETIONRATE(μg/min)
NIGHT URINEDAY URINE
p< 0.0005
p< 0.05
CONTROLS DIABETICS
Mogensen CE et al Uremia Investigation 1985-86,9(2):85-95
400
300
200
100
0
High intra-individual day-to-day variation (CV) ofurinary albumin excretion (40-50%)
Seasonal variations of urinary albumin creatinineratio in Japanese subjects with type 2 diabetes
and early nephropathy?
Wada et al. Diabetic Medicine 2012,29:506-508
Microalbuminuria-specificity
The disease spectrum of microalbuminuriaand its role as an indicator of inflammation
Microalbuminuria as a Risk Predictor in Diabetes: The Continuing SagaBakris GL & Molitch M Diabetes Care 2014,37:867-875
The disease spectrum of albuminuria and itsassociated CV risk and kidney disease presence
Microalbuminuria as a Risk Predictor in Diabetes: The Continuing SagaBakris GL & Molitch M Diabetes Care 2014,37:867-875
Does microalbuminuria representan irreversible stage of
Diabetic Kidney Disease?
Type 1 diabetes Type 2 diabetesPerkins et al. NEJM (2003) 348: 2285 Aracki et al. Diabetes (2005) 54:2983
Factors associated with regression:Microalbuminuria of short duration,RAS blockers, low A1c/SBP
Factors associated with regression:Microalbuminuria of short duration,low A1c/SBP & lipid levels
Microalbuminuria: Rates ofremission/regression vs progression
216 patients with micro
113 patients studied
23/113 66/113 21/113(20%) (58%) (19%)
Normo Micro Macro
6 years 6 years
386 patients with micro
220 patients studied
88/220 99/220 33/220(40%) (45%) (15%)
Normo Micro Macro
Does kidney structure andfunction correlate with
microalbuminuria?
Prevalence of low glomerular filtration rate(GFR < 60 ml/min/1.73m2) and normoalbuminuria
'Progressive diabetic nephropathy. How useful is microalbuminuria?: contra‘MacIsaac et al RJ Kidney Int 2014, 86:50
GFR < 60 ml/min/1.73m2)
Biopsy findings in microalbuminuric patients with type2 diabetes and preserved renal function
I III
II
Fioretto et al., Diabetologia 1996, 39, 1569-1576
Interstitialchanges
Fioretto P, Mauer M, Brocco E et al. Patterns of renal injury in NIDDM patients withmicroalbuminuria. Diabetologia 1996; 39: 1569
Is microalbuminuria a validsurrogate end point in
clinical trials?
‘Progressive diabetic nephropathy. How useful is microalbuminuria?: contra’MacIsaac RJ et al Kidney Int 2014, 86:50
Microalbuminuria
Macroalbuminuria
Summary
IS IT TIME TO RETIRE MICROALBUMINURIA?
Vote: YES
Microalbuminuria = A2
High Variability
Low Specificity
Spontaneous Regression
Δ AER ≠ Δ GFR
Problems with urinary albumin within the microalbuminuric range
IS IT TIME TO RETIREMICROALBUMINURIA?
Retire the name- VOTE YES
Retire micro-albuminuriafrom its preeminentrole in CKD in diabetes VOTE YES
IS IT TIME TO RETIREMICROALBUMINURIA?
IS IT TIME TO RETIREMICROALBUMINURIA?
YES
Progression versus remission/regressionof microalbuminuria
‘Progressive diabetic nephropathy. How useful is microalbuminuria?: contra’MacIsaac RJ et al. Kidney Int 2014, 86:50
*regression
