What’s hiding behind IgA nephropathy?

Case ReportCase Report

Bauerova L., Honsova E. Department of Pathology, the The First faculty of Medicine and General Teaching Hospital, Charles University PragueNephropathology training: Department of Clinical and Transplantant Pathology, IKEM

Clinical history: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

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), anti- nuclear antibodies (ANA), ds-DNA antibodies, ANCA, rheuma factor).

IgA

Diagnosis: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

IgG-IgA1, IgA1-IgA1 complexes

Complement components

Aberrantly glycosylated IgA1 Aberrantly glycosylated IgA1

Production of antiglycan antibodies

• Proliferation of mesangial cells • Expansion of ECM• Cytokines and growth factors production• Local complement activation

Podocytes and tubular cells

damage

FibronectinFibronectinTType IV ype IV collagencollagen

IgA nephropathyIgA nephropathy

Fabry´s diseaseFabry´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 diseaseFabry´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 sampleIn 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 cA case for second opinionase for second opinion

Differential diagnosisDifferential 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 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 The coexistence of IgA nephropathy and Fabry´s disease:Fabry´s disease:

• The coexistence of FD and immune disorders such as SLE, rheumatoid arthritis and pauci-immune 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: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:S-Cr: 65 μmol/l (0.71 mg/dl)• Proteinuria decreased (1g/day)• Peripheral edema disappeared• SStill suffering fromtill suffering from: fatigue, paresthesia, tinnitus,

and hearing loss

Thank YouThank You