What`s hiding behind IgA nephropathy?

What’s hiding behind IgA
Case Report
Bauerova L., Honsova E.
Department of Pathology, the The First
faculty of Medicine and General Teaching
Hospital, Charles University Prague
Nephropathology training: Department of
Clinical and Transplantant Pathology, IKEM
Clinical history:
31– year – old woman
Proteinuria, fatigue, edema of the hands
Tinnitus and sudden hearing loss of the left ear
Arterial hypertension
Nephrotic proteinuria (5g/day) and microscopic
• Serum creatinine level of 73μmol/l (0,79mg/dl)
• Audiometry → hearing abnormalities
• Immunology was negative (ELISA testing – IgA, IgM, IgG, C3
and C4 complement, extractable nuclear antigen (ENA), antinuclear antibodies (ANA), ds-DNA antibodies, ANCA, rheuma
IgA nephropathy + suspicious Fabry´s disease
Genetic testing was recommended
(Low -galactosidase A activity in plasma and leucocytes)
Heterozygous mutation of α-Gal A gene
Aberrantly glycosylated IgA1
IgA nephropathy
Complement components
Production of antiglycan antibodies
IgG-IgA1, IgA1-IgA1
• Proliferation of
mesangial cells
• Expansion of ECM
• Cytokines and
growth factors
• Local complement
Type IV
Podocytes and
tubular cells
Fabry´s disease
X-linked recessive lysosomal storage disorder
Deficient activity of α-galactosidase A
Clinical manifestations are variable
Skin lesions, corneal dystrophy, paresthesias
and proteinuria
• During adulthood: heart disease, premature
cerebrovascular accidents, and progressive
renal disease
Fabry´s disease
• The link between the metabolic abnormality
in Fabry´s disease and kidney tissue injury is
still unclear
• In females, there are highly variable levels of
enzyme activity and broader range of clinical
• Most females are affected; in various studies,
12% of Fabry´s patients on dialysis are women
In a kidney biopsy sample
• Swollen, finely vacuolated podocytes in LM
• Dark blue bodies in semi-thin sections embedded in
epoxy resin
• Osmiophilic, lamellar bodies mainly in podocytes
(myelin figures, “zebra” bodies) in ELMI
• All renal cells can be affected
• Difficulties in cases with more advanced stages of FD
A case for second opinion
Differential diagnosis
• Myelin-like inclusions are not
entirely specific for Fabry´s
• Long-term treatment with
cationic amphiphilic drugs
(chloroquine and amiodarone)
• Chloroquine-induced lipidosis
in the kidney is not so rare
• Specific curvilinear inclusions
in podocytes are not present in
FD (Prof. Ferluga in his lecture,
23rd ECP, Helsinki 2011)
Dusan Ferluga: Electron microscopy of Fabry
nephropathy and drug-induced
phospholipidosis. 23rd ECP, Helsinki 2011
The coexistence of IgA nephropathy and
Fabry´s disease:
• The coexistence of FD and immune disorders
such as SLE, rheumatoid arthritis and pauciimmune and immune complex-mediated
necrotizing crescentic glomerulonephritis has
been described in the literature
• The combination of FD and IgAN is rare
Patient´s follow up:
• Human α-galactosidase A replacement therapy
• Antihypertensive drugs with diuretics
• Cardiac function and blood pressure in the normal
• S-Cr: 65 μmol/l (0.71 mg/dl)
• Proteinuria decreased (1g/day)
• Peripheral edema disappeared
• Still suffering from: fatigue, paresthesia, tinnitus,
and hearing loss
Thank You