uricosuria: biochemical metabolic dysfunction footprint ......patient's health. it alerts the...

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 ***


(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 summary ns


(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.

http://www.google.com.mx/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&docid=G1HaxC5-jf1jFM&tbnid=IUD1sCJqOYHOGM:&ved=0CAUQjRw&url=http://bio-science-medical.com/productos.asp?producto=%C1CIDO %DARICO. Uricasa-PAP. Enz-Color.&id=19&ei=3jNXU6muMcac2QXQxYH4DA&bvm=bv.65177938,d.b2I&psig=AFQjCNED5n4dEr7QNeZEaCCjUyjw-qkJ4Q&ust=1398310213177532

http://www.google.com.mx/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&uact=8&docid=G1HaxC5-jf1jFM&tbnid=IUD1sCJqOYHOGM:&ved=0CAUQjRw&url=http://bio-science-medical.com/productos.asp?producto=%C1CIDO %DARICO. Uricasa-PAP. Enz-Color.&id=19&ei=3jNXU6muMcac2QXQxYH4DA&bvm=bv.65177938,d.b2I&psig=AFQjCNED5n4dEr7QNeZEaCCjUyjw-qkJ4Q&ust=1398310213177532

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


Morphology cell death by apoptosis


Morphology cell death

induced by cornification


Or with atypia as polipoidia

and aneploudia which are

considered premalignant

injury.


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 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


Spearman r -0.3695

95% confidence interval -0.5507 to -0.1551


P value summary ***



r = 0.3695


Correlation between urinary uric acid and hyaline cast


Spearman r -0.4213



P value summary ***



r = - 0.4213


Correlation between urinary uric acid and waxy cast


Spearman r -0.6070



P value summary ***



r = - 0.6070


Correlation between urinary uric acid and renal tubular

cells


Spearman r -0.4474



P value summary ***



r = - 0.4474


Correlation between urinary uric acid and urothelial

cells


Spearman r -0.3489



P value summary **



r = - 0.3489



%

Cellular alterations observed in urinary sediment of

patients with hyperuricosuria.

%


39%

Staining Sternheimer malvin21%


12%


2%

%

Percentage of cellular alterations observed


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

[email protected]

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