Transcript AAIM 2015 Charlotte A. Lee, MD, FLMI, DBIM

Proteinuria and
Microalbuminuria
Optimum Re 2015
Charlotte A. Lee, M.D., FLMI, DBIM
General Considerations
◼ Evidence
now suggests that
proteinuria has implications for allcause mortality and cardiovascular
outcomes at a general population level,
not only in individuals with chronic
kidney disease (CKD).
Risk of Proteinuria
◼
◼
Cardiovascular risk appears to be increased even at
levels of urinary protein excretion that are not
considered to be pathological.*
Increasing albuminuria is associated with a graded
increase in risk.+
*Hillege HL, Janssen WM, Bak AA, et al. Prevend Study Group Microalbuminuria is
common, also in a nondiabetic, nonhypertensive population, and an independent
indicator of cardiovascular risk factors and cardiovascular morbidity. J Intern
Med. 2001;249(6):519–526
+Wachtell
K, Ibsen H, Olsen MH, et al. Albuminuria and cardiovascular risk in
hypertensive patients with left ventricular hypertrophy: the LIFE study. Ann Intern
Med. 2003;139(11):901–906
Risk of Proteinuria
A 2010 meta-analysis of studies totaling
48,000 participants reported that the
presence of microalbuminuria was
associated with a future stroke risk 90%
greater than that of normoalbuminuric
individuals.*
*Lee M, Saver JL, Chang KH, Liao HW, Chang SC,
Ovbiagele B. Impact of microalbuminuria on incident
stroke: a meta-analysis. Stroke. 2010;41(11):2625–2631.
PREVEND Study
◼ Prevention
of Renal and Vascular Endstage
Disease
◼ Studied over 40,000 individuals
◼ Found that a 2-fold increase the ACR
(albumin-creatinine ratio) causes a 30%
increase in cardiovascular mortality
Hillege HL, Fidler V, Diercks GF, et al. Prevention of Renal
and Vascular End Stage Disease (PREVEND) Study Group
Urinary albumin excretion predicts cardiovascular and
noncardiovascular mortality in general
population. Circulation. 2002;106(14):1777–1782
HOPE Study
◼ Heart
Outcomes Prevention Evaluation
◼ Found that proteinuria was associated
with adverse outcome independently of
traditional cardiovascular risk factors.
Gerstein HC, Mann JF, Yi Q, et al. HOPE Study
Investigators Albuminuria and risk of cardiovascular
events, death, and heart failure in diabetic and
nondiabetic individuals. JAMA. 2001;286(4):421–426
Normal Values
Serum creatinine
0.5-1.50 mg/dL (44-132 umol/L)
Urine Creatinine
10-300 mg/dL
Urine Total Protein 0-30 mg/dL (0.3 g/L)
Protein Creatinine Ratio (PCR) 0-200mg/g creatinine
(0-.20gm/gm)
24 hr. Protein 30-150 mg/24 hr (0.03-0.15g/24 hr)
GFR
>90 ml/min/1.73m2 (1.5 mL/sec/1.73m2)
◼= SI Units
Proteinuria
◼Normally
always present in small
amounts, less than 150 mg/24 hr
◼Standard laboratory testing
includes all proteins, such as
albumin, globulins, peptides, any
protein-containing sediment or
inclusions
◼Up to 30% of all urine protein is
albumin
Tamm-Hosfall Protein
◼A
mucoprotein produced by
the ascending limb of the loop
of Henle that is a normal
constituent of urine and is the
major constituent of urinary
casts
Incidental Causes of Proteinuria:
◼Bacteria
◼Spermatozoa
◼WBC’s (UTI)
◼Blood (even if
no RBC’s but “heme
positive”)
◼Vaginal secretions
◼Cellular debris
◼Pregnancy
◼Fever
Reliability of the “HOS”
(Home Office Specimen, UA, Urinalysis)
Rate of urinary protein excretion may
vary with:
◼ Alcohol intake
◼ Diet
◼ Hydration levels
◼ Time of day
◼ Heavy exercise
◼ Fever
24 hr. Urine Protein vs. Spot
Collection
◼ 24
hr. collection—Inconvenient
◼ 24 hr. collection—Often unreliable due
to inadequate collection
◼ Spot urine is accurate regardless of
age and sex
◼ Spot urine is inexpensive and adapts to
lab automation
Why use the PCR instead of
Total Protein?
Based on the fact that there is a normal
acceptable range of protein excretion
and there is a normal daily range of
creatinine excretion over time in a given
individual.
Urine Creatinine
◼ Based
on the premise that urine
creatinine (by-product of muscle
metabolism) production is constant
and can be used as a measure of urine
concentration
Urine Creatinine
Normal Daily Excretion
12-24 mg/kg/day in females
◼ 16-26 mg/kg/day in males
Example:
135 (61kg) woman excretes ~723 —1464
mg/day
( Average = ~1000mg/day )
◼
Varying Laboratory Reporting of
the Normal PCR:
◼0-.2 mg(protein)/mg(creatinine)*
◼0-20 mg/dl+
◼0-200 mg/gm*
◼0-200
mcg/mg
+ SI units
* Insurance Laboratories
“Spot” Urine (HOS) vs.
24-hr. collection
Normal = 0-200 mg/g
creatinine
◼ Estimation of 24-hr. urinary
protein excretion based on
calculation of the
protein/creatinine ratio
◼
Formula Calculation:
Protein (mg/dL)
Creatinine (mg/dL)
x 1000 mg/g
Comparative Values
Normal protein excretion: <150mg/24
hr.
◼ PCR of 200mg/gm is roughly 300 mg/24
hr., hence the reason for 200mg/gm
being the upper limit of normal.
◼
Microalbumin
The “Mini-Me” of Albuminuria
MA—Normal Values
◼ 0-3
mg/dL (0-30 mg/L)
◼ 30-300 mg/24 hr.
◼ 0-30 mg/gm creatinine
Disorders Associated with
Microalbuminuria
Renal:





Diabetes mellitus
Nephrotoxic drugs
Bence Jones proteinuria
Myoglobinuria
Hemoglobinuria
Disorders Associated with
Microalbuminuria
Non-Renal:
◼ Atherosclerosis
◼ Lipid
abnormalities
◼ Insulin resistance
◼ Hypertension
◼ Myocardial infarction
Microalbumin

Strokes, myocardial infarctions
and peripheral vascular disease
are 2 to 10 times more frequent
in diabetics than non-diabetics.*
*Schmitz A., et al. “Microalbuminuria: A major
risk factor in non-insulin dependent
diabetics. A 10 year follow-up study of 503
patients.” Diabetic Med 1988; 5:126-34.
“Persistent or increasing
microalbuminuria indicates early
diabetic nephropathy and represents
a twenty-fold greater risk for the
development of clinically overt renal
disease in patients with IDDM and
NIDDM.”
Bennett, et al. Ad Hoc Committee, Council on D.M.,
National Kidney Foundation, 1995
Effect of ACE Inhibitors
◼ Lowering
of blood pressure by
lowering arteriolar resistance
by inhibiting angiotensin I→
angiotensin II
◼ Decrease the degradation of
bradykinin (a vasodilator)
ACE Inhibitors
◼ Aid
excretion of sodium
(natriuresis)
◼ Reduce the progression of
diabetic nephropathy (and thus
proteinuria) independently from
the blood pressure-lowering effect
Underwriting Application
When reflexed from elevated
glucose, fructosamine, or
glycohemoglobin:
◼33%
>3mg/dL (>30 mg/L)*
◼67%
0-3 mg/dL (0-30 mg/L)
*Likely to be at greater risk of
complications