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Microalbuminuria
1. Dr A. AlfiDr A. Alfi
Consultant NephrologistConsultant Nephrologist
Transplant physicianTransplant physician
Head of Department of NephrologyHead of Department of Nephrology
KAAH& OC, JeddahKAAH& OC, Jeddah
Dr A. AlfiDr A. Alfi
Consultant NephrologistConsultant Nephrologist
Transplant physicianTransplant physician
Head of Department of NephrologyHead of Department of Nephrology
KAAH& OC, JeddahKAAH& OC, Jeddah
Dr M. Al-AmeenDr M. Al-Ameen
Nephrology SpecialistNephrology Specialist
Transplant physicianTransplant physician
KAAH& OC- JeddahKAAH& OC- Jeddah
Dr M. Al-AmeenDr M. Al-Ameen
Nephrology SpecialistNephrology Specialist
Transplant physicianTransplant physician
KAAH& OC- JeddahKAAH& OC- Jeddah
2.
3. CaseCase
50 year-old female.50 year-old female.
Known type 2 diabetes 5Known type 2 diabetes 5
years earlier.years earlier.
presented to OPD forpresented to OPD for
routine visit.routine visit.
No history ofNo history of
hypertension.hypertension.
Not known to have had aNot known to have had a
previous CV event.previous CV event.
She visits theShe visits the
ophthalmologist annuallyophthalmologist annually
with no retionopathywith no retionopathy
reported.reported.
Her medications include:Her medications include:
– an over-the-counteran over-the-counter
multivitamin.multivitamin.
– an oral hypoglycemican oral hypoglycemic
agent.agent.
– a statin for knowna statin for known
hypercholesterolemia.hypercholesterolemia.
She is otherwise well.She is otherwise well.
Findings on physicalFindings on physical
examination areexamination are
unremarkable.unremarkable.
Except that her BP thatExcept that her BP that
previously was less thanpreviously was less than
130/80, became130/80, became
135/85.135/85.
4. Case: QuestionsCase: Questions
Should the woman be screened forShould the woman be screened for
microalbuminuria on this visit ?microalbuminuria on this visit ?
What is the best way to screen for it ?What is the best way to screen for it ?
If the test result is positive, what does thisIf the test result is positive, what does this
mean in terms of the patient's risk formean in terms of the patient's risk for
cardiovascular and renal disease ?cardiovascular and renal disease ?
Is there anything that can be done medicallyIs there anything that can be done medically
for microalbuminuria ?for microalbuminuria ?
What follow-up is required, includingWhat follow-up is required, including
management of other risk factors ?management of other risk factors ?
SheldonSheldon et al; 2002CMAJ •et al; 2002CMAJ •
September 3, 2002; 167 (5)September 3, 2002; 167 (5)
5. Definition ofDefinition of
Microalbuminuria (MA)Microalbuminuria (MA)
Normally only a small amount of albumin is filteredNormally only a small amount of albumin is filtered
at the glomerulus, and most of that albumin isat the glomerulus, and most of that albumin is
degraded and reabsorbed by the proximal tubule.degraded and reabsorbed by the proximal tubule.
Usually only <1 mg/dl of albumin appears in theUsually only <1 mg/dl of albumin appears in the
urine.urine.
However, a number of conditions can temporarily orHowever, a number of conditions can temporarily or
permanently cause an increase in urinary proteinpermanently cause an increase in urinary protein
excretion by either altering glomerular membraneexcretion by either altering glomerular membrane
permeability, inducing glomerular capillarypermeability, inducing glomerular capillary
hypertension, or reducing tubular reabsorption.hypertension, or reducing tubular reabsorption.
Tobe et al; Can Med Assoc J 2002;167:499–503.Tobe et al; Can Med Assoc J 2002;167:499–503.
6. Definition ofDefinition of
Microalbuminuria (MA)Microalbuminuria (MA)
Microalbuminuria (MA) is defined as
the range in between: urinary
excretion of albumin of 20 to 200
ug/minute or 30 to 300 mg/24 hours.
7. Definition of MADefinition of MA
There is difference between proteinuria andThere is difference between proteinuria and
albuminuria.albuminuria.
Normal protein in urine should not exceedNormal protein in urine should not exceed
150 mg/day.150 mg/day.
This 150 mg protein includes Tamm HorsfallThis 150 mg protein includes Tamm Horsfall
protein (~70mg), protein of blood groupprotein (~70mg), protein of blood group
(~35mg), other proteins (enzymes,(~35mg), other proteins (enzymes,
hormones, Ig etc..) andhormones, Ig etc..) and Albumin (0-30mg)Albumin (0-30mg)..
So, Albumin in urine should not exceedSo, Albumin in urine should not exceed
30mg/day.30mg/day.
8. The standard urinalysis dipstick,
however, can detect albumin only at
levels greater than 300 mg/24 hours,
but MA can be accurately measured
by several widely available sensitive
methods (ELISA, RIA, nephelometry).
Definition of MADefinition of MA
9. Normalbuminuria = < 20 ug/minute or
< 30 mg/24 hours.
Microalbuminuria = the range in between:
urinary excretion of albumin of 20 to 200
ug/minute or 30 to 300 mg/24 hours.
Macroalbuminuria = more than 200
ug/min, or 300 mg/24 hours.
Definition of MADefinition of MA
10. Condition
Urine
Dipstick
Daily urine
mg /d
Timed Urine
Collection
mcg/min
Normoalbuminuria Negative < 30 <20
Microalbuminuria Negative 30-299 20-199
Macroalbuminuria Positive >300 >200
Definition of MADefinition of MA
11. Race/ethnicity
Male gender
Older age
Low birth weight
Diabetes
Hypertension
Obesity
Smoking
Non-modifiableNon-modifiable ModifiableModifiable
well provenwell proven likelylikely
•High salt diet
• High protein diet
• Hyperlipidemia
• Fever
• Exercise
• CHF
• UTI
• Vaginal discharge
Causes of MACauses of MA
12. Causes of MACauses of MA
Langston C in 2004Langston C in 2004 classified MA as:classified MA as:
1.1. PrerenalPrerenal:: strenuous exercise, fever, hypothermia,strenuous exercise, fever, hypothermia,
seizures, and venous congestion.seizures, and venous congestion.
2.2. Renal MA:Renal MA: the goal of this lecturethe goal of this lecture
3.3. PostrenalPostrenal:: UTI and hematuriaUTI and hematuria if there is sufficientif there is sufficient
blood to cause the urine to be grossly pink or red.blood to cause the urine to be grossly pink or red.
Langston C;journal of A A H ALangston C;journal of A A H A 40:251-254 (2004)40:251-254 (2004)
So, before dignosis of renal MA, prerenal andSo, before dignosis of renal MA, prerenal and
postrenal causes shold be excludedpostrenal causes shold be excluded
13. Urine Tests for MAUrine Tests for MA
1.1. Albumin-to-Creatinine RatioAlbumin-to-Creatinine Ratio in ain a
random spot collectionrandom spot collection
2.2. 24-h Urine Collection24-h Urine Collection withwith
creatinine, allowing the simultaneouscreatinine, allowing the simultaneous
measurement of creatinine clearancemeasurement of creatinine clearance
3.3. TimedTimed (e.g., 4-h or overnight)(e.g., 4-h or overnight)
collection.collection.
14.
15. Albumin-to-Creatinine Ratio is
preferred (easy and accurate):
– First-void or other morning collections are
best because of the known diurnal
variation in albumin excretion
– If this timing cannot be used, uniformity of
timing for different collections in the same
individual should be employed.
Albumin-to-Creatinine Ratio is
preferred (easy and accurate):
– First-void or other morning collections are
best because of the known diurnal
variation in albumin excretion
– If this timing cannot be used, uniformity of
timing for different collections in the same
individual should be employed.
Urine Tests for MAUrine Tests for MA
16. Measurement of MAMeasurement of MA
1.1. Specific assaysSpecific assays ::
a.a. RadioimmunoassayRadioimmunoassay
b.b. Enzyme-linked immunosorbent assayEnzyme-linked immunosorbent assay
c.c. NephelometryNephelometry
2.2. Reagent tablets or dipsticksReagent tablets or dipsticks forfor
microalbumin may be carried out, sincemicroalbumin may be carried out, since
they show acceptable sensitivity (95%) andthey show acceptable sensitivity (95%) and
specificity (93%) when carried out byspecificity (93%) when carried out by
trained personnel.trained personnel.
All positive tests by reagent strips or tablets shouldAll positive tests by reagent strips or tablets should
be confirmed by more specific methods.be confirmed by more specific methods.
17. MA: SusceptibleMA: Susceptible
diabeticsdiabetics
If the urine albumin excretion is in the upperIf the urine albumin excretion is in the upper
range of normal (20–30 mg/d).range of normal (20–30 mg/d).
If the systolic blood pressure is greater thanIf the systolic blood pressure is greater than
130 mm Hg.130 mm Hg.
If the glycosylated hemoglobin level isIf the glycosylated hemoglobin level is
greater than 8. orgreater than 8. or
If the total cholesterol level is greater thanIf the total cholesterol level is greater than
5.24 mmol/L.5.24 mmol/L.
SheldonSheldon et al; 2002CMAJ • September 3, 2002;et al; 2002CMAJ • September 3, 2002;
167 (5)167 (5)
18. MA: PREVALENCES inMA: PREVALENCES in
the General Populationthe General Population
normal 0-10mg/lnormal 0-10mg/l
macroproteinuriamacroproteinuria
>200 mg/l>200 mg/l
microalbuminuriamicroalbuminuria
20-200 mg/l (~7%)20-200 mg/l (~7%)
high-normalhigh-normal
albuminuriaalbuminuria
10-20 mg/l10-20 mg/l
Hillege HL et al. J Int Med 2001;249:519-26Hillege HL et al. J Int Med 2001;249:519-26
Microalbuminuria was present in 7.2% of the subjects and independently
associated with age, gender, hypertension, diabetes, smoking,
previous myocardial infarction and stroke.
19. Incidence of MAIncidence of MA
Microalbuminuria is likely to be foundMicroalbuminuria is likely to be found
in one-third or more of diabeticin one-third or more of diabetic
patients.patients.
Sheldon et al; 2002 CMAJ • September 3, 2002; 167Sheldon et al; 2002 CMAJ • September 3, 2002; 167
(5)(5)
23. Pathogenesis:Pathogenesis:
Role of Endothelial DysfunctionRole of Endothelial Dysfunction
MA is thought to be the consequence ofMA is thought to be the consequence of
generalized endothelial damage along thegeneralized endothelial damage along the
vascular tree, including the glomerulus .vascular tree, including the glomerulus .
Enzymes involved in the metabolism ofEnzymes involved in the metabolism of
anionic components of the extracellularanionic components of the extracellular
matrix (e.g. heparan sulphate proteoglycan)matrix (e.g. heparan sulphate proteoglycan)
vulnerable to hyperglycaemia, seem tovulnerable to hyperglycaemia, seem to
constitute the primary cause of albuminuriaconstitute the primary cause of albuminuria
and the associated complications.and the associated complications.
Genetic polymorphism of such enzymes isGenetic polymorphism of such enzymes is
possibly the main reason for variation inpossibly the main reason for variation in
susceptibility.susceptibility.
DeckertDeckert
24. Natural History in DM 1Natural History in DM 1
Microalbuminuria is not usually aMicroalbuminuria is not usually a
presenting finding at the onset of DM1.presenting finding at the onset of DM1.
After a 5- to 10-yr duration of diabetes,After a 5- to 10-yr duration of diabetes,
susceptible patients developsusceptible patients develop
intermittent microalbuminuria beforeintermittent microalbuminuria before
having persistent microalbuminuriahaving persistent microalbuminuria
26. Natural History in DM 2Natural History in DM 2
Because of the insidious onset of DM2, theBecause of the insidious onset of DM2, the
true duration of the disease is often nottrue duration of the disease is often not
known. It has been reported that a durationknown. It has been reported that a duration
of >6 yr of diabetes may have existed beforeof >6 yr of diabetes may have existed before
diagnosisdiagnosis
Subjects often present with microalbuminuriaSubjects often present with microalbuminuria
at that point.at that point.
However, diabetic nephropathy in DM2 isHowever, diabetic nephropathy in DM2 is
similar to nephropathy in DM1 with similarsimilar to nephropathy in DM1 with similar
pathology, response to interventions ofpathology, response to interventions of
glucose control and anti-angiotensin IIglucose control and anti-angiotensin II
27.
28. Significance of MA inSignificance of MA in
Diabetic PatientsDiabetic Patients
MA predicts clinical nephropathy.MA predicts clinical nephropathy.
MA predicts an increased incidence ofMA predicts an increased incidence of
cardiovascular disease andcardiovascular disease and
cardiovascular mortality.cardiovascular mortality.
In other words, MA doubled the risk ofIn other words, MA doubled the risk of
having a cardiovascular event in diabetichaving a cardiovascular event in diabetic
pts.pts.
29. MA is a marker of early stage renalMA is a marker of early stage renal
damage.damage.
The degree of microalbuminuria isThe degree of microalbuminuria is
proportional to the degree of damage.proportional to the degree of damage.
Regression of MA decreases the risk.Regression of MA decreases the risk.
MA Predicts OvertMA Predicts Overt
NephropathyNephropathy
30. In type 1 Diabetes withoutIn type 1 Diabetes without
specific intervention:specific intervention:
– Only 80 % of microalbuminuric patients willOnly 80 % of microalbuminuric patients will
develop macroalbuminuria.develop macroalbuminuria.
– Only 50 % at 10 y and 75% at 20 y ofOnly 50 % at 10 y and 75% at 20 y of
macroalbuminuric patients willdevelopmacroalbuminuric patients willdevelop
ESRD.ESRD.
MA Predicts OvertMA Predicts Overt
NephropathyNephropathy
American Diabetic Association. Diab Care 2004
31. In type 2 Diabetes withoutIn type 2 Diabetes without
specific intervention:specific intervention:
– Only 20 – 40 % of microalbuminuricOnly 20 – 40 % of microalbuminuric
patients will develop macroalbuminuria.patients will develop macroalbuminuria.
– Only 20% of macroalbuminuric patientsOnly 20% of macroalbuminuric patients
over 20 y will develop ESRD.over 20 y will develop ESRD.
MA Predicts OvertMA Predicts Overt
NephropathyNephropathy
American Diabetic Association. Diab Care 2004
32. MA and CV RisksMA and CV Risks
MA is the strongestMA is the strongest
independent determinant ofindependent determinant of
ischaemic heart disease sinceischaemic heart disease since
confers a two to four-foldconfers a two to four-fold
increased risk for this illnessincreased risk for this illness
among diabetic andamong diabetic and
hypertensive or borderlinehypertensive or borderline
hypertensive subjects.hypertensive subjects.Jensen JS et al. Hypertension.2000; 35: 898–903.
33. All CV Risks Are RelatedAll CV Risks Are Related
to MAto MA
Microalbuminuria is related to aMicroalbuminuria is related to a
number of clinical variables such as:number of clinical variables such as:
Practically, all recognisedPractically, all recognised
cardiovascular risk factors are relatedcardiovascular risk factors are related
to microalbuminuria.to microalbuminuria.
1. Age
2. Male gender
3. Race
4. Hyperglycaemia
5. Hyperlipaemia
6. Hyperinsulinaemia
7. Hypertension
8. Obesity
9. LVH
10.Smoking habits
11.Diet
34. Microalbuminuria could simply reflectMicroalbuminuria could simply reflect
an augmented susceptibility toan augmented susceptibility to
atherosclerosis linked to commonatherosclerosis linked to common
pathogenetic factors (for instancepathogenetic factors (for instance
endothelial dysfunction).endothelial dysfunction).
MA and CV RisksMA and CV Risks
35. The relationship between
microalbuminuria and atherosclerotic
processes seems very tight and
increased urinary albumin excretion
(UAE) has been considered a marker
of prevalent subclinical
atherosclerosis.Jensen JS et al. J Hum Hypertens 1997; 11: 727–732.
Agrawal B et al. J Hypertens 1996; 14: 223– 228.
MA and CV RisksMA and CV Risks
36. In a large cross-sectional study of 11,343
nondiabetic hypertensive patients, those
with microalbuminuria had a significantly
higher prevalence (P < .001) of:
– Coronary artery disease (31% vs 22%)
– Left ventricular hypertrophy (24% vs14%)
– Previous stroke (6% vs 4%)
– Peripheral vascular disease (7% vs 5%).
Agrawal B et al.Agrawal B et al. J Hyperten 1996; 14:223–228.J Hyperten 1996; 14:223–228.
MA and CV RisksMA and CV Risks
37. Factors that cluster with microalbuminuria
Insulin resistance
Central obesity
Low levels of high-density lipoprotein cholesterol
High triglyceride levels
Systolic hypertension
Lack of nocturnal dip in blood pressure on 24-hour
monitoring
Salt sensitivity
Endothelial dysfunction
Hypercoagulability
Impaired fibrinolysis
Renal dysfunction
MA and CV RisksMA and CV Risks
38. Is the risk due to later
overt nephropathy?
HOPE study investigators found
that:
– Microalbuminuria was a strong predictor
of risk for cardiovascular disease even
after adjustment for renal function.
– Thirty eight percent of the HOPE study
patients had diabetes, mostly type 2.
Gerstein et al; Diabetes Care 2000; 23:B35–B39.
39. In type 1 diabetes, in contrast to type 2In type 1 diabetes, in contrast to type 2
diabetes, the relation betweendiabetes, the relation between
microalbuminuria and cardiovascularmicroalbuminuria and cardiovascular
morbidity and mortality has been mainlymorbidity and mortality has been mainly
attributed to the later development of overtattributed to the later development of overt
nephropathy.nephropathy.
However, in adults with type 1 diabetes,However, in adults with type 1 diabetes,
microalbuminuria alone has beenmicroalbuminuria alone has been
associated with excess cardiovascularassociated with excess cardiovascular
mortality.mortality.
Is the risk due to later
overt nephropathy?
Agardh CDet al. Diab Res Clin Pract 1997; 35(suppl):113–121.
40. MA in EssentialMA in Essential
HypertensionHypertension
Microalbuminuria can be detected in up toMicroalbuminuria can be detected in up to
40% of the population with established40% of the population with established
hypertension, particularly in those patientshypertension, particularly in those patients
not controlled satisfactorily by anti-not controlled satisfactorily by anti-
hypertensive therapy.hypertensive therapy.
Even blood pressure levels between 130Even blood pressure levels between 130
and 139/80 and 89 mmHg are significantlyand 139/80 and 89 mmHg are significantly
associated with microalbuminuriaassociated with microalbuminuria
Ruilope LM. Nephrol Dial Transplant (2004) 19: 524-528
41. MA and Metabolic Syndrome
Hyperinsulinaemia and peripheralHyperinsulinaemia and peripheral
resistance to insulin action seem to beresistance to insulin action seem to be
features of microalbuminuric patientsfeatures of microalbuminuric patients
Bigazzi et al; NephrolDial Transplant 1995; 10 [suppl 6]: 10-14
42. Microalbuminuria is also associated withMicroalbuminuria is also associated with
the metabolic syndrome, which includesthe metabolic syndrome, which includes
insulin resistance, low HDL cholesterolinsulin resistance, low HDL cholesterol
levels, high triglyceride levels, and truncallevels, high triglyceride levels, and truncal
obesity.obesity.
Current evidence strongly suggests thatCurrent evidence strongly suggests that
hyperinsulinemia is associated with ahyperinsulinemia is associated with a
greater risk for cardiovascular disease.greater risk for cardiovascular disease.
Patients with type 1 and type 2 diabetesPatients with type 1 and type 2 diabetes
mellitus with microalbuminuria are moremellitus with microalbuminuria are more
insulin-resistant than those withoutinsulin-resistant than those without
MA and Metabolic Syndrome
43. MA and Metabolic
Syndrome
Insulin promotes albumin transcapillary
excretion, thus determining albuminuria,
but preliminary studies do not seem to
support this conclusion. OR
MA could be the result of insulin actionMA could be the result of insulin action
at the renal level.at the renal level.
44. Palaniappan et al. NHANES III. Am J Hypertens 2003;16:952-8.Palaniappan et al. NHANES III. Am J Hypertens 2003;16:952-8.
Prevalence of MetS in subjects with microalbuminuria or normoalbuminuria
MA and Metabolic
Syndrome
46. MA and Salt Sensitivity
Salt-sensitive hypertensive patients showSalt-sensitive hypertensive patients show
higher albumin excretion rates than salt-higher albumin excretion rates than salt-
resistant patients.resistant patients.
Furthermore, when salt sensitive patientsFurthermore, when salt sensitive patients
are given a high-sodium diet they show anare given a high-sodium diet they show an
increase in fitration fraction, glomerularincrease in fitration fraction, glomerular
pressure, and albumin excretion rate.pressure, and albumin excretion rate.
Bigazzi et al; NephrolDial Transplant 1995; 10 [suppl 6]: 10-14
47. MA and Atherogenic Serum
Lipid Profile
Microalbuminuria is associated with anMicroalbuminuria is associated with an
increased LDL:HDL cholesterol ratio andincreased LDL:HDL cholesterol ratio and
lower HDL cholesterol, as well as with higherlower HDL cholesterol, as well as with higher
uric acid levels.uric acid levels.
Furthermore, age, BMI, diastolic bloodFurthermore, age, BMI, diastolic blood
pressure, LDL cholesterol and uric acidpressure, LDL cholesterol and uric acid
independently and significantly influence theindependently and significantly influence the
variation of microalbuminuria.variation of microalbuminuria.
The relationship between these classicalThe relationship between these classical
atherogenic risk factors andatherogenic risk factors and
microalbuminuria suggest that the lattermicroalbuminuria suggest that the latter
could be a reflection of atherogenic vascularcould be a reflection of atherogenic vascular
damage.damage.
48. MA & EndothelialMA & Endothelial
DysfunctionDysfunction
Data support the concept that theData support the concept that the
presence of MA warning that there is apresence of MA warning that there is a
problem with the vasculature.problem with the vasculature.
The presence of MA is a marker ofThe presence of MA is a marker of
extensive endothelial dysfunction andextensive endothelial dysfunction and
a predictor of increased cardiovasculara predictor of increased cardiovascular
risk.risk.
Chugh A, Bakris GL. J Clin Hypertens (Greenwich). 2007 Mar;9(3):196-200.
49. Recent Report ofRecent Report of
Stehouwer and Smulders 2006Stehouwer and Smulders 2006
The most likely possibility is that aThe most likely possibility is that a
common pathophysiologic process, suchcommon pathophysiologic process, such
as endothelial dysfunction, chronic low-as endothelial dysfunction, chronic low-
grade inflammation, or increasedgrade inflammation, or increased
transvascular leakage oftransvascular leakage of
macromolecules, underlies themacromolecules, underlies the
association between microalbuminuriaassociation between microalbuminuria
and cardiovascular disease.and cardiovascular disease.
Stehouwer CD, Smulders YM.J Am Soc Nephrol. 2006 Aug;17(8):2106-11.
50. 0.5
0.6
0.7
0.8
0.9
1.0
0 1 2 3 4 5 6
Albuminuria and CV Risk inAlbuminuria and CV Risk in
Diabetics PtsDiabetics Pts
Normoalbuminuria
n = 191
Microalbuminuria
n = 86
Macroalbuminuria
n = 51
Status at baseline
Years
p < 0.01 normoalbuminuria vs. micro- and macroalbuminuria
p < 0.05 microalbuminuria vs. macroalbuminuria
Gall MA. et al. 1995
Survival
51. Days
0 200 400 600 800 1000 1200 1400
Fractionofsubjectsalive
0,00
0,85
0,90
0,95
1,00
0-10 mg/L
10-20 mg/L
20-200 mg/L
> 200 mg/L
Hillege HL et al Circulation 2002;106:1777-82Hillege HL et al Circulation 2002;106:1777-82
MORTALITY with albuminuriaMORTALITY with albuminuria
Normo albuminuria
High Normal
Microalbuminuria
Macroalbuminuri
a
52. RISK FACTORS andRISK FACTORS and
ALL CAUSE MORTALITYALL CAUSE MORTALITY
Diercks J et al. JACC 2002;40:1401Diercks J et al. JACC 2002;40:1401
Microalbuminuria
Hypertension
Hypercholest.
Smoking
Overweight
Diabetes
53. Mortality rate according to urine
albumin and proteinuria status
Valmadrid et al. Arch Intern Med. 2000; 160:1093-1100.
54. Verhave et alVerhave et al.. JASN 2003;14:1330-5JASN 2003;14:1330-5
Age (yrs)Age (yrs)
2020 3030 4040 5050 6060 7070 8080
UAE(mg/24h)UAE(mg/24h)
66
77
88
99
1010
1111
1212
1313
MaleMale
FemaleFemale
MA and AgeMA and Age
Urinary Albumin Excretion Increase with Age
55. Verhave J.C. et al. JASNVerhave J.C. et al. JASN 2003; 14:1330-52003; 14:1330-5
MA and BMIMA and BMI
BMI (kg/mBMI (kg/m22
))
2020 2222 2424 2626 2828 3030 3232
UAE(mg/24h)UAE(mg/24h)
66
77
88
99
1010
1111
1212
1313
MaleMale
FemaleFemale
Urinary Albumin Excretion Increase with BMI
56. MA and SMOKINGMA and SMOKING
Pinto-Sietsma SJ et al. Ann Int Med 2000;133:585-91Pinto-Sietsma SJ et al. Ann Int Med 2000;133:585-91
0 1 2 3 4
Microalbuminuria
nonsmokers
current smokers
≤20
>20
former smokers
Odds ratio (95% CI)
High normal albuminuria
nonsmokers
current smokers
≤20
>20
former smokers
57. MA and HormonalMA and Hormonal
TherapyTherapy
Oral contraceptivesOral contraceptives
Second generationSecond generation
Third generationThird generation
Hormone Replacement TherapyHormone Replacement Therapy
≤≤5 year used5 year used
>5 year used>5 year used
PremenopausalPremenopausal
1.90 (1.23 - 2.93)1.90 (1.23 - 2.93)
2.04 (1.28 - 3.25)2.04 (1.28 - 3.25)
1.39 (0.63 - 3.06)1.39 (0.63 - 3.06)
PostmenopausalPostmenopausal
2.05 (1.12 - 3.77)2.05 (1.12 - 3.77)
1.28 (0.37 - 4.50)1.28 (0.37 - 4.50)
2.56 (1.32 - 4.97)2.56 (1.32 - 4.97)
MonsterTBM et al. Arch Int Med 2001;161:2000-2005MonsterTBM et al. Arch Int Med 2001;161:2000-2005
58. So…So…
Microabuminuria is a sign of early renalMicroabuminuria is a sign of early renal
damagedamage
More importantlyMore importantly, it is an independent, it is an independent
sign of significantly increased risk of MI,sign of significantly increased risk of MI,
CVA and vascular death.CVA and vascular death.
Microalbuminuria should be looked forMicroalbuminuria should be looked for
in all pts with DM and hypertension.in all pts with DM and hypertension.
59. MA: PracticalMA: Practical
Perspective
Screening of all diabetic and hypertensive
patients by conventional dipstick for urinary
albumin.
If +ve means that albumin > 300 mg/ 24h
Renal damage started evaluate for CKD
staging and management
If dipstick is –ve Test for MA (UAE 30-
300mg/24h) Evaluate for underlying risk
factors immediately start management
strategy.
60. MA: PracticalMA: Practical
Perspective
• Determination of MA is recommended in the
initial work-up of subjects with primary hypertension
Verdecchia P, Reboldi G P. Blood Pressure. Volume 13, Number 4/August 2004
62. Diabetes
Mellitus
• Glycemic Control
• BP Control
• ACE-I/ARBs
• nd CCB
Primary
Prevention
Microalbuminuria D. Nephropathy
ESRD/ Death
Secondary
Prevention
Tertiary
Prevention
• BP Control
• ACE-I/ARBs
• Anemia Control
• Ca/Po4 Control
• BP Control
• ACE-I/ARBs
• nd CCB
PreventivePreventive
StrategyStrategy
MA: PracticalMA: Practical
Perspective
67. Among available antihypertensive drugs,Among available antihypertensive drugs,
angiotensin-converting enzyme (ACE)angiotensin-converting enzyme (ACE)
inhibitors and the angiotensin II receptorinhibitors and the angiotensin II receptor
antagonists seem to be superior to otherantagonists seem to be superior to other
antihypertensive drugs in reducing UAE.antihypertensive drugs in reducing UAE.
The dual blockade of the renin-angiotensinThe dual blockade of the renin-angiotensin
system with an ACE inhibitor and ansystem with an ACE inhibitor and an
angiotensin II receptor antagonist is a newangiotensin II receptor antagonist is a new
and promising approach to control UAE inand promising approach to control UAE in
hypertensive patientshypertensive patients
Verdecchia P, Reboldi G P. Blood Pressure. Volume 13, Number 4/August 2004
Management StrategyManagement Strategy
68. MA: Primary PreventionMA: Primary Prevention
1.1. Patients with family history of HTN and/ orPatients with family history of HTN and/ or
cardiovascular events in 1st degree relatives.cardiovascular events in 1st degree relatives.
2.2. Hypertensive patients or even have smallHypertensive patients or even have small
increase in systemic BP, within the normalincrease in systemic BP, within the normal
range or loss of nocturnal dipping.range or loss of nocturnal dipping.
Hovind P et al. (2004). Br Med J 328:1105Hovind P et al. (2004). Br Med J 328:1105
Daneman D et al (1994) Kidney Int 46:1154–1159Daneman D et al (1994) Kidney Int 46:1154–1159
3.3. Patients with poor glycemic control:Patients with poor glycemic control:
Sustained hyperglycemia HbA1c > 8.6.Sustained hyperglycemia HbA1c > 8.6.
4.4. Patients who have retinopathy.Patients who have retinopathy.
5.5. Dyslipidemic patients.Dyslipidemic patients.
6.6. Smokers.Smokers.
1.1. Patients with family history of HTN and/ orPatients with family history of HTN and/ or
cardiovascular events in 1st degree relatives.cardiovascular events in 1st degree relatives.
2.2. Hypertensive patients or even have smallHypertensive patients or even have small
increase in systemic BP, within the normalincrease in systemic BP, within the normal
range or loss of nocturnal dipping.range or loss of nocturnal dipping.
Hovind P et al. (2004). Br Med J 328:1105Hovind P et al. (2004). Br Med J 328:1105
Daneman D et al (1994) Kidney Int 46:1154–1159Daneman D et al (1994) Kidney Int 46:1154–1159
3.3. Patients with poor glycemic control:Patients with poor glycemic control:
Sustained hyperglycemia HbA1c > 8.6.Sustained hyperglycemia HbA1c > 8.6.
4.4. Patients who have retinopathy.Patients who have retinopathy.
5.5. Dyslipidemic patients.Dyslipidemic patients.
6.6. Smokers.Smokers.
Target Diabetic PopulationsTarget Diabetic Populations
69. 7.7. Patients with protein intakes greater thanPatients with protein intakes greater than
20% of energy intake.20% of energy intake.
Marion J et al.Marion J et al. Current Diabetes Reports 2003, 3:412-417Current Diabetes Reports 2003, 3:412-417
8.8. Patients who have slightly elevated urinaryPatients who have slightly elevated urinary
albumin excretion: upper limit of normal.albumin excretion: upper limit of normal.
Rossing P et al. (2002). Diabetes Care 25: 859Rossing P et al. (2002). Diabetes Care 25: 859––864864..
9.9. Patients with short stature or History of LowPatients with short stature or History of Low
Birth weight.Birth weight. Hovind P et al. (2004). Br Med J 328:1105Hovind P et al. (2004). Br Med J 328:1105
10.10. Women using Oral contraceptive.Women using Oral contraceptive.
Ahmed SB et al (2005). Diabetes Care 28:1988Ahmed SB et al (2005). Diabetes Care 28:1988––1994.1994.
11.11. Presence of Cardiovascular risk markers.Presence of Cardiovascular risk markers.
7.7. Patients with protein intakes greater thanPatients with protein intakes greater than
20% of energy intake.20% of energy intake.
Marion J et al.Marion J et al. Current Diabetes Reports 2003, 3:412-417Current Diabetes Reports 2003, 3:412-417
8.8. Patients who have slightly elevated urinaryPatients who have slightly elevated urinary
albumin excretion: upper limit of normal.albumin excretion: upper limit of normal.
Rossing P et al. (2002). Diabetes Care 25: 859Rossing P et al. (2002). Diabetes Care 25: 859––864864..
9.9. Patients with short stature or History of LowPatients with short stature or History of Low
Birth weight.Birth weight. Hovind P et al. (2004). Br Med J 328:1105Hovind P et al. (2004). Br Med J 328:1105
10.10. Women using Oral contraceptive.Women using Oral contraceptive.
Ahmed SB et al (2005). Diabetes Care 28:1988Ahmed SB et al (2005). Diabetes Care 28:1988––1994.1994.
11.11. Presence of Cardiovascular risk markers.Presence of Cardiovascular risk markers.
Target Diabetic PopulationsTarget Diabetic Populations
MA: Primary PreventionMA: Primary Prevention
70. MA: 1ry PreventiveMA: 1ry Preventive
MeasuresMeasures
1.1. Glycaemic controlGlycaemic control should be optimised,should be optimised,
with FBSwith FBS << 6 mmol/l and/or HbA1c6 mmol/l and/or HbA1c << 7%7%
2.2. Mentain Target BPMentain Target BP << 130/80130/80
3.3. ACE-I/ ARBs:ACE-I/ ARBs:
4.4. Cigarette smokingCigarette smoking should be activelyshould be actively
discourageddiscouraged
5.5. Mentian Lipid ProfileMentian Lipid Profile::
a.a. LDL<100 mg/dl (<2.6 mmol/l) LDL<100 mg/dl (<2.6 mmol/l)
b.b. Triglycerides<150 mg/dl (<1.7 mmol/l) Triglycerides<150 mg/dl (<1.7 mmol/l)
c.c. HDL>40 mg/dl (>1.0 mmol/l)HDL>40 mg/dl (>1.0 mmol/l)
1.1. Glycaemic controlGlycaemic control should be optimised,should be optimised,
with FBSwith FBS << 6 mmol/l and/or HbA1c6 mmol/l and/or HbA1c << 7%7%
2.2. Mentain Target BPMentain Target BP << 130/80130/80
3.3. ACE-I/ ARBs:ACE-I/ ARBs:
4.4. Cigarette smokingCigarette smoking should be activelyshould be actively
discourageddiscouraged
5.5. Mentian Lipid ProfileMentian Lipid Profile::
a.a. LDL<100 mg/dl (<2.6 mmol/l) LDL<100 mg/dl (<2.6 mmol/l)
b.b. Triglycerides<150 mg/dl (<1.7 mmol/l) Triglycerides<150 mg/dl (<1.7 mmol/l)
c.c. HDL>40 mg/dl (>1.0 mmol/l)HDL>40 mg/dl (>1.0 mmol/l)
72. 6.6. Protein IntakeProtein Intake
– Not to exceed a protein intake of 20% of total energy.Not to exceed a protein intake of 20% of total energy.
Toeller et al. Diabetologia. 1997 Oct;40(10):1219-26.Toeller et al. Diabetologia. 1997 Oct;40(10):1219-26.
– FishFish:: Diet including a high amount of fish protein lessen the risk of DN.Diet including a high amount of fish protein lessen the risk of DN.
Mollsten AV et al. Diabetes Care 24:805–810, 2001Mollsten AV et al. Diabetes Care 24:805–810, 2001
– ChickenChicken:: A normoproteic diet with chicken as the only source of meatA normoproteic diet with chicken as the only source of meat
may represent an alternative strategy for treatment of patients with typemay represent an alternative strategy for treatment of patients with type
2 diabetes and microalbuminuria.2 diabetes and microalbuminuria.
Gross JL et al. Diabetes Care, April 1, 2002; 25(4): 645 - 651.Gross JL et al. Diabetes Care, April 1, 2002; 25(4): 645 - 651.
– Fish and ChickenFish and Chicken:: A normoproteic diet with chicken and fish as theA normoproteic diet with chicken and fish as the
only meat protein source decreases the GFR in the hyperfilteringonly meat protein source decreases the GFR in the hyperfiltering
normoalbuminuric IDDM patients. The GFR reduction after this diet isnormoalbuminuric IDDM patients. The GFR reduction after this diet is
similar to that observed after an LPD.similar to that observed after an LPD.
Pecis M et al. Diabetes Care 17:665–672, 1994Pecis M et al. Diabetes Care 17:665–672, 1994
6.6. Protein IntakeProtein Intake
– Not to exceed a protein intake of 20% of total energy.Not to exceed a protein intake of 20% of total energy.
Toeller et al. Diabetologia. 1997 Oct;40(10):1219-26.Toeller et al. Diabetologia. 1997 Oct;40(10):1219-26.
– FishFish:: Diet including a high amount of fish protein lessen the risk of DN.Diet including a high amount of fish protein lessen the risk of DN.
Mollsten AV et al. Diabetes Care 24:805–810, 2001Mollsten AV et al. Diabetes Care 24:805–810, 2001
– ChickenChicken:: A normoproteic diet with chicken as the only source of meatA normoproteic diet with chicken as the only source of meat
may represent an alternative strategy for treatment of patients with typemay represent an alternative strategy for treatment of patients with type
2 diabetes and microalbuminuria.2 diabetes and microalbuminuria.
Gross JL et al. Diabetes Care, April 1, 2002; 25(4): 645 - 651.Gross JL et al. Diabetes Care, April 1, 2002; 25(4): 645 - 651.
– Fish and ChickenFish and Chicken:: A normoproteic diet with chicken and fish as theA normoproteic diet with chicken and fish as the
only meat protein source decreases the GFR in the hyperfilteringonly meat protein source decreases the GFR in the hyperfiltering
normoalbuminuric IDDM patients. The GFR reduction after this diet isnormoalbuminuric IDDM patients. The GFR reduction after this diet is
similar to that observed after an LPD.similar to that observed after an LPD.
Pecis M et al. Diabetes Care 17:665–672, 1994Pecis M et al. Diabetes Care 17:665–672, 1994
MA: 1ry PreventiveMA: 1ry Preventive
MeasuresMeasures
73. 7.7. Sodium IntakeSodium Intake:: High sodium intake should beHigh sodium intake should be
avoided.avoided.
8.8. Avoidance of Oral Contraceptive.Avoidance of Oral Contraceptive.
9.9. Correction of CV Risk Factors.Correction of CV Risk Factors.
10.10. Life Style ChangesLife Style Changes::
Moderate weight loss (7% body weight)Moderate weight loss (7% body weight)
Regular physical activity (150 min/week)Regular physical activity (150 min/week)
Dietary fiber (14 g fiber/1,000 kcal) and foodsDietary fiber (14 g fiber/1,000 kcal) and foods
containing whole grainscontaining whole grains
Reduced intake of fat to reduce calories.Reduced intake of fat to reduce calories.
7.7. Sodium IntakeSodium Intake:: High sodium intake should beHigh sodium intake should be
avoided.avoided.
8.8. Avoidance of Oral Contraceptive.Avoidance of Oral Contraceptive.
9.9. Correction of CV Risk Factors.Correction of CV Risk Factors.
10.10. Life Style ChangesLife Style Changes::
Moderate weight loss (7% body weight)Moderate weight loss (7% body weight)
Regular physical activity (150 min/week)Regular physical activity (150 min/week)
Dietary fiber (14 g fiber/1,000 kcal) and foodsDietary fiber (14 g fiber/1,000 kcal) and foods
containing whole grainscontaining whole grains
Reduced intake of fat to reduce calories.Reduced intake of fat to reduce calories.
MA: 1ry PreventiveMA: 1ry Preventive
MeasuresMeasures
Editor's Notes
What is Microalbuminuria (MA)?
MA defined: 30-300mg albumin in urine over 24 hrs or (20-200 µg/min). Not detected on ‘protein’ dipstick. Most accurate assessment is 24hr collection, however most convenient and sufficient screening test is an Albumin : Creatinine ratio on spot urine (usually first morning)
Why is Microalbuminuria important?
MA is a marker of early stage renal damage. The degree of microalbuminuria is proportional to the degree of vascular damage.
Regression decreases risk. MA is a signal from the kidney that CV risk is increased.
American Diabetes Association (ADA). Diabetic Nephropathy. Diabetes Care. 2004; 27: (Suppl 1): S79-83
Garg JP, Bakris GL. Microalbuminuria: marker of vascular dysfunction, risk factor for cardiovascular disease. Vasc Med 2002;7:35-43
CV Risk increases with Degree of Proteinuria – so microalbuminuria is as important as proteinuria.
Proteinuria is a window into blood vessel integrity and its presence predicts poor survival. The impact of microalbuminuria and macroalbuminuria on mortality was evaluated prospectively in 328 Caucasian patients with type 2 diabetes who were followed for 5 years.
Over 6 years 8% of patients with normoalbuminuria, 20% of patients with microalbuminuria, and 35% of patients with macroalbuminuria died - predominantly from cardiovascular disease; P &lt; 0.01 [normoalbuminuria versus micro- and macroalbuminuria] and P &lt; 0.05 [microalbuminuria versus macroalbuminuria].
1. Gall MA, Borch-Johnsen K, et al. Diabetes 1995; 44(11):1303-1309.
