What’s hiding behind IgA
nephropathy?
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:
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•
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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
hematuria
• 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
factor).
IgA
Diagnosis:
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
complexes
• Proliferation of
mesangial cells
• Expansion of ECM
• Cytokines and
growth factors
production
• Local complement
activation
Fibronectin
Type IV
collagen
Podocytes and
tubular cells
damage
Fabry´s disease
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•
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
symptoms
• 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
disease
• 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
range
• 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