Uricosuria: Biochemical Metabolic Dysfunction Footprint
recommendations?
Quím. José Ángel Flores Hernández
The Mexican Association of Clinical Laboratory Sciences16 – 17th November 2015
Cancun
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
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.
We can observe crystalline growth,
indicative of uric acid super saturation
in urine.
uric acid anhydrous
In this case uric acid dihydrate
We can also observe polycrystalline growth, indicative of
high levels of saturation and lithogenic risk.
uric acid anhydrous
Or, we can see growth
associated with other crystals.
calcium oxalate dihydrate
Amorphous urates
Druze of
uric acid anhydrous
Microscopía de luz polarizada
We can see these crystals associated with the
polymerization of proteins, they represent probable kidney
stone cores.
Microscopía de luz polarizada
Or, other shapes such as:
Cell debris
Urothelial cells
Intracellular
bacterial
community
Coagulated
protein
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
Is uric acid a marker of renal
dysfunction or urinary damage?
Generally, we think that diet is the responsible for high uric
acid levels among patients
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
Robert Terkeltaub, MD. Management of Gout: An Up-to-date Perspective
We can see the risk factors where major risk factors are
metabolic.
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.
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.
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
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.
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
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.
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.
hyperuricosuria
metabolic
risk factorseGFR
ml/minThen if there is a correct kidney
function, uric acid will be eliminated
through urine.
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).
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
Morphology cell death by apoptosis
Staining Sternheimer malvin
Morphology cell death
induced by cornification
Staining Sternheimer malvin
Or with atypia as polipoidia
and aneploudia which are
considered premalignant
injury.
Staining Sternheimer malvin
Is urinary uric acid a marker or renal
dysfunction and urinary tract ?
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.
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
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
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
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
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
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
%
Cellular alterations observed in urinary sediment of
patients with hyperuricosuria.
%
Staining Sternheimer malvin
39%
Staining Sternheimer malvin21%
Staining Sternheimer malvin15%
Staining Sternheimer malvin
12%
Staining Sternheimer malvin11%
Staining Sternheimer malvin
2%
%
Percentage of cellular alterations observed
Staining Sternheimer malvin
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?
It may be appropriate to combine the examination of the
urinary sediment with new biomarkers to provide a useful
diagnostic test battery.
Thank you for your attention