uricosuria: biochemical metabolic dysfunction footprint ......patient's health. it alerts the...
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Uricosuria: Biochemical Metabolic Dysfunction Footprint
recommendations?
Quím. José Ángel Flores Hernández
The Mexican Association of Clinical Laboratory Sciences16 – 17th November 2015
Cancun
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The search for new markers for kidney disease progresses
at a rapid pace.
Automation in the clinical laboratory has caused that
urinary sediments are less observed.
Mark A. Perazella, MD The Urine Sediment as a Biomarker of Kidney Disease.Am J Kidney Dis. 2015 May 2. pii: S0272-6386(15)00607-1.
automated equipment
but most of them do not centrifiged urine
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The urinalysis is a test that provides information about the
patient's health. It alerts the presence of systemic
diseases, or urinary tract, providing information on
diagnosis, prognosis. It is also a therapeutic guide.
In the examination of centrifuged urine, we can observe
different shapes. These suggest metabolic changes in the
patient.
Mark A. Perazella, MD The Urine Sediment as a Biomarker of Kidney Disease. Am J Kidney Dis. 2015 May 2.
pii: S0272-6386(15)00607-1.
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We can observe crystalline growth,
indicative of uric acid super saturation
in urine.
uric acid anhydrous
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In this case uric acid dihydrate
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We can also observe polycrystalline growth, indicative of
high levels of saturation and lithogenic risk.
uric acid anhydrous
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Or, we can see growth
associated with other crystals.
calcium oxalate dihydrate
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Amorphous urates
Druze of
uric acid anhydrous
Microscopía de luz polarizada
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We can see these crystals associated with the
polymerization of proteins, they represent probable kidney
stone cores.
Microscopía de luz polarizada
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Or, other shapes such as:
Cell debris
Urothelial cells
Intracellular
bacterial
community
Coagulated
protein
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6) ¿Cuál es el probable diagnóstico cristalográfico? 1) Riesgo litogénico tipo 22) Riesgo litogénico tipo 33) Riesgo litogénico tipo 44) Riesgo litogénico tipo 5
We can also see waxy casts indicative of severe kidney
suffering
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Is uric acid a marker of renal
dysfunction or urinary damage?
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Generally, we think that diet is the responsible for high uric
acid levels among patients
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Exogenus30% Endogenus
70%
Inosinic acid(IMP)
Ileana Ramazzina. et al., Completing the uric acid degradation pathway through phylogeneticcomparison of whole genomes. Nature Chemical Biology 2, 144 - 148 (2006)
But, exogenous production is 30%, and 70% is endogenous
Most endogenous
production by
pathway of PPRP
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Robert Terkeltaub, MD. Management of Gout: An Up-to-date Perspective
We can see the risk factors where major risk factors are
metabolic.
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Frances Rees, Michelle Hui & Michael Dohert. Optimizing current treatment of gout. Nature Reviews Rheumtology 10, 271–283 (2014)
GMPAMP
30%
70% Major sources
and routes of
elimination of uric
acid.
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Choi HK, Willett W, Curhan G. Fructose-rich beverages and risk of gout in women. JAMA. 2010 Nov 24;304(20):2270-8. Epub 2010
But, during the production of uric
acid, high activity is observed
the xanthine oxidase.
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Karen M Lounsbury. Calcium signaling and oxidant stress in the vasculature. Free Radical Biology and Medicine. Volume 28,Issue 9, 1 May 2000, Pages 1362–1369.
And an incremented oxidative stress in patient plasma
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We study the correlation between glomerular filtration
rate, uric acid in serum and different urinary markers of a
Mexican population group (n=79).
n=79Age
(years)
eGFR
(ml/min)
UA urinary
(mg/dl)
In serum (mg/dl)
UA Glucose Urea Creatinine
Mean 45.3 79.12 39.19 5.21 109.0 40.0 1.09
± SEM 2.0 2.01 2.10 0.20 4.2 2.5 0.07
We can observe the mean and the standard
error of the mean, for the following
variables.
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r = - 0.1737
Pearson r -0.1737
P value (two-tailed) 0.1257
P value summary ns
Is the correlation significant?
(alpha=0.05)No
Correlation between estimated glomerular filtration
rate (eGFR) and serum glucose
010
020
030
040
0
0
20
40
60
80
100
serum glucose (mg/dl)
eG
FR
(m
l/m
n)
Serum glucose has no correlation with eGFR
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minusr = - 0.6759
Pearson r -0.6759
P value (two-tailed) P<0.0001
P value summary ***
Is the correlation significant?
(alpha=0.05)Yes
Correlation between eGFR and serum urea
0 50 100
150
200
0
50
100
150
serum urea (mg/dl)
eG
FR
(m
l/m
n)
Serum urea has correlation with eGFR.
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0 2 4 6 8 10
0
50
100
150
UA serum (mg/dl)
eG
FR
(m
l/min
)
r = 0.01060
Pearson r 0.0.1060
P value (two-tailed) 0.9262
P value summary ns
Is the correlation significant?
(alpha=0.05)no
Correlation between eGFR and serum uric acid
It can be observed that the excretion of uric acid depends
on eGFR.
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hyperuricosuria
metabolic
risk factorseGFR
ml/minThen if there is a correct kidney
function, uric acid will be eliminated
through urine.
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This could be cause we can see
morphology cell death by necrosis
Staining Sternheimer malvin
So injurious molecule increase in the first morning void
(urine).
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5) ¿Cómo se debe informar el crecimiento
señalado por la flecha?
1) Cristal
2) Macla
3) Drusa y cristal
4) Roseta
Or cell morphology
changes compatible
with autophagy
Staining Sternheimer malvin
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Morphology cell death by apoptosis
Staining Sternheimer malvin
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Morphology cell death
induced by cornification
Staining Sternheimer malvin
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Or with atypia as polipoidia
and aneploudia which are
considered premalignant
injury.
Staining Sternheimer malvin
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Is urinary uric acid a marker or renal
dysfunction and urinary tract ?
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r = 0.6678
0 20 40 60 80
0
50
100
150
UA urinary (mg/dl)
eG
FR
(m
l/m
n)
Data are expressed as the mean ± SEM, n = 3
animals/group.ND=Normocaloric diet, HDW= Hypercaloric diet and
water, HDCD= Hypercaloric diet and carbonated drinks. In signaled
cases, when compared, P≤0.05, if: [*] when compared with respective
control group.
Correlation between urinary uric acid and eGFR
Pearson r 0.6678
P value (two-tailed) p<0.0001
P value summary ***Is the correlation significant?
(alpha=0.05)Yes
A positive correlation was observed between urinary uric
acid and eGFR.
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r = 0.5789
Correlation between urinary uric acid and calcium
oxalate crystals
Number of XY Pairs 79
Spearman r 0.5789
95% confidence interval 0.4047 to 0.7126
P value (two-tailed) P<0.0001
P value summary ***
Exact or approximate P value? Gaussian Approximation
Is the correlation significant? (alpha=0.05) Yes
Staining Sternheimer malvin Staining Sternheimer malvin
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Correlation between urinary uric acid and uric acid
crystals
Number of XY Pairs 79
Spearman r -0.3695
95% confidence interval -0.5507 to -0.1551
P value (two-tailed) 0.0008
P value summary ***
Exact or approximate P value? Gaussian Approximation
Is the correlation significant? (alpha=0.05) Yes
r = 0.3695
Staining Sternheimer malvin Staining Sternheimer malvin
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Correlation between urinary uric acid and hyaline cast
Number of XY Pairs 79
Spearman r -0.4213
95% confidence interval -0.5920 to -0.2144
P value (two-tailed) 0.0001
P value summary ***
Exact or approximate P value? Gaussian Approximation
Is the correlation significant? (alpha=0.05) Yes
r = - 0.4213
Staining Sternheimer malvin Staining Sternheimer malvin
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Correlation between urinary uric acid and waxy cast
Number of XY Pairs 79
Spearman r -0.6070
95% confidence interval -0.7332 to -0.4403
P value (two-tailed) P<0.0001
P value summary ***
Exact or approximate P value? Gaussian Approximation
Is the correlation significant? (alpha=0.05) Yes
r = - 0.6070
Staining Sternheimer malvin Staining Sternheimer malvin
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Correlation between urinary uric acid and renal tubular
cells
Number of XY Pairs 79
Spearman r -0.4474
95% confidence interval -0.6125 to -0.2448
P value (two-tailed) P<0.0001
P value summary ***
Exact or approximate P value? Gaussian Approximation
Is the correlation significant? (alpha=0.05) Yes
r = - 0.4474
Staining Sternheimer malvin Staining Sternheimer malvin
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Correlation between urinary uric acid and urothelial
cells
Number of XY Pairs 79
Spearman r -0.3489
95% confidence interval -0.5340 to -0.1319
P value (two-tailed) 0.0016
P value summary **
Exact or approximate P value? Gaussian Approximation
Is the correlation significant? (alpha=0.05) Yes
r = - 0.3489
Staining Sternheimer malvin
Staining Sternheimer malvin
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%
Cellular alterations observed in urinary sediment of
patients with hyperuricosuria.
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%
Staining Sternheimer malvin
39%
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Staining Sternheimer malvin21%
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Staining Sternheimer malvin15%
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Staining Sternheimer malvin
12%
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Staining Sternheimer malvin11%
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Staining Sternheimer malvin
2%
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%
Percentage of cellular alterations observed
Staining Sternheimer malvin
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The following questions are:
- Uric acid is responsible for cell changes observed?
- Crystallization is a marker of increased metabolic
disorder?
- The automation allows the recognition of the
alterations observed in urinary sediment?
- The damage biomarkers are increasing first in urine?
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It may be appropriate to combine the examination of the
urinary sediment with new biomarkers to provide a useful
diagnostic test battery.