Do Females with Fabry Disease frequently

have major Organ Involvement?

Alberto Ortiz, MD, PhD

Nephrology

IIS-Fundacion Jimenez Diaz, UAM

IRSIN, REDINREN

Madrid, Spain

Conflict of interest

• Consultant: Sanofi

• Speaker fees: Sanofi, Shire, Amicus

key questions

1. How many women with Fabry

disease?

2 key questions

http://www.fabry.org/fsig.nsf/PDFs/PDFsR/$File/2013_Annual_Report.pdf

Approximately equal numbers of male or female patients

XY XX

Women have double the

chances of having a

Fabry gene mutation

There should be double the

number of women than men

in Fabry registries

1 1 2

The guy looks so

normal…

…may be u do not need 2 X

chromosomes after all

If I can live with only one X chromosome…..

….. why not get rid of the second one?

Cheaper to maintain!

XX

X

Unfortunately,

XX XX XX XX

XX XX XX XX

XX XX XX XX

XX XX XX XX

XX

XX

XX

XX

XX XX XX XX

XX XX XX XX

XX XX XX XX

XX XX XX XX

XX

XX

XX

XX

Cells are dumb!

#

women

http://www.fabry.org/fsig.nsf/PDFs/PDFsR/$File/2013_Annual_Report.pdf

Who is missing?

There should double the women than men

XY XX XX

#

women

The less

severely

affected!

Registry data may

overestimate the

severity of Fabry

disease among women

populations

1. How many women with Fabry

disease?

2 key questions

2. What is major organ involvement?

This is a frequent

chronological order

in classical Fabry

Functions of the kidney

Filters the blood

But does not lose proteins in urine!!

NOT beer!

Eliminates toxins in urine

Getting proteins: our perspective

Getting proteins: our ancestors perspective

Only injured kidneys

leak protein in urine

• Albuminuria

• Proteinuria

Functions of the kidney

Filters the blood

But does not lose proteins in urine!!

NOT beer!

Eliminates toxins in urine

Any more functions?

EPO: prevents anemia

Hormone production

Klotho: prevents

Calcitriol (active vitamin D):

prevents bone disease

aging

Fortunately renal function can be replaced!

Peritoneal dialysis at home

Hemodialysis

Transplantation: British transplant games

Ortiz et al. NDT 2009

Age at first renal replacement therapy in Fabry

Approximately 10X less females require RRT

Females have 20X lower chances of requiring RRT

Fabry nephropathy is a progressive proteinuric

kidney disease of metabolic origin

Males Females

What is chronic kidney disease?

Abnormalities of kidney structure or function, present

for >3 months, with implications for health.

KDIGO 2012, Kidney Int Suppl 2013

What is chronic kidney disease?

Criteria for CKD (either of the following present for >3

months)

1. Markers of kidney damage (one or more)

– Albuminuria (>30 mg/g creatinine)

– Other

2. Decreased renal function: GFR <60 ml/min/1.73 m2

(<50% of normal)

KDIGO CKD 2012. Kidney Int Suppl 2013. CKD, chronic kidney disease; GFR, glomerular filtration rate.

or

Where do the GFR and albuminuria thresholds

come from?

Risk ■ For CKD progression

■ For premature all-cause and cardiovascular

death

2012 CGA Classification of CKD

Albuminuria (proteinuria) Cause GFR

KDIGO CKD 2012. Kidney Int 2013.

The meaning of albuminuria in Fabry disease

et al. CJASN 2010

Men Women

“Physiological” rate of eGFR

decline above age 40

-1.0 ml/min/1.73 m2/year

Time

Renal

function

According to severity of

proteinuria

2012 CGA Classification of CKD

Albuminuria (proteinuria) Cause GFR

KDIGO CKD 2012. Kidney Int 2013.

Beware of underestimating CKD in late onset variants!

The fact that end-stage kidney disease is uncommon does not

mean that kidney involvement is mild

0

10

20

30

40

50

60

70

80

90

100

1 2

% of natural history patients, not yet on RRT,

over the age of 40, that fulfill renal function criterion (GFR <60

ml/min/1.73 m2) for chronic kidney disease

Since approx. 50% of women are missing from Registries, we may

assume that between 10 and 20% of women aged over 40 have

low renal function CKD

Since approx. 50% of women are missing from Registries, we may

assume that between 10 and 20% of women aged over 40 have

low renal function CKD

What about the general population?

In Spain, approx. 9 % of women aged over 40 have

low renal function CKD

1. Less women with known Fabry disease than expected:

severity of Fabry disease in the women population

probably overestimated

2 key concepts

2. However, major organ involvement does occur

Need for RRT 20x lower than in men

But do not underestimate milder CKD

Which may occur with a frequency approx 2x higher than

in general population for decreased renal function

1. How many women with Fabry

disease?

2 key questions

2. What is major organ involvement?