IgA Nephropathy

(Berger Disease)
 CASE

A 24 year old female decided to be admitted due to recurrent gross hematuria for 6
episodes in a week & lasted for 1 month, edema of the face, both upper & lower extremities,
& the trunks, poor appetite, body malaise, & elevated BP. She claimed that recurrence of
gross hematuria noted 3 months after the resolution of gross hematuria 1 month ago.
BP=180/110. Serum Creatinine=1.8 mg/dl (Normal value = 0.5-1.5 mg/dl). Punch Biopsy
done of the kidney revealed (+) IgA deposits on immunofluorescent microscopy.
IgA Nephropathy

• Characterized by the presence of prominent IgA deposits in the mesangial regions and recurrent
hematuria
• Time of Diagnosis: 16 and 35 years.
• More frequently in males than in females
• 30% of patients will have progressive renal dysfunction and develop end-stage renal disease
• The most common cause of glomerulonephritis World Wide
Detsika, Maria & Lianos, Elias. (2021). Regulation of
Complement Activation by Heme Oxygenase-1 (HO-1) in Kidney
Injury. Antioxidants. 10. 60. 10.3390/antiox10010060.
Pathogenesis

Increase synthesis of polymeric IgA

Abnormal glycosylation of pIgA1 (best)

Abnormal IgA clearance:

• Liver
• Mesangial cells
 Synthesis of polymeric IgA

 IgA2 : mucosal surfaces

 IgA1 is mainly found in serum

Stevens, C.D. (2010).Clinical immunology and serology :

a laboratory perspective (3rd ed.). P61.
Abnormal glycosylation of pIgA1 and Abnormal IgA Clearance

Malik, IgA Nephropathy, 2019

 IgA1/ IgG
“Multi-Hit Etiology” Recognition

Mesangial
Increase synthesis of polymeric IgA Immune Mesangial
Hypercellularity
Deposition

Complement
Abnormal glycosylation of pIgA1
Activation

Cell lysis
Abnormal IgA clearance
IgA Deposition

• Henoch-Schönlein purpura
• Secondary IgA nephropathy occurs in patients with liver and intestinal diseases
Morphology

LIGHT MICROSCOPY:
• Glomeruli may be normal.
• Mesangial widening & proliferation (mesangioproliferative)
• Focal proliferative Glomerulonephritis Focal segmental sclerosis
• Crescentic Glomerulonephritis End Stage Renal Disease
 Morphology

Detsika, Maria & Lianos, Elias. (2021). Regulation of Complement Activation by Heme
Oxygenase-1 (HO-1) in Kidney Injury. Antioxidants. 10. 60. 10.3390/antiox10010060.
Morphology

Kumar, V., Abbas, A. K., & Aster, J. C. (Eds.). (2018). Robbins Basic Pathology (10th
ed.).p921.
Kidney Biopsy of the Month: What is Normal?, Renal Fellow Network,
https://www.renalfellow.org/2019/01/04/kidney-biopsy-of-the-month-
what-is-normal/
Morphology

IMMUNOFLUORESCENCE
• Mesangial deposition of IgA
• C3 and properdin
• Lesser amounts of IgG / IgM

Kumar, V., Abbas, A. K., & Aster, J. C. (Eds.). (2018). Robbins Basic Pathology (10th
ed.).p921.
Morphology

ELECTRON MICROSCOPY
• Electron dense deposits in the mesangium
• Prominent thickening of the arterioles
Clinical Pictures

• Microscopic/ Macroscopic hematuria with or without proteinuria : 30 - 40 %

• Acute Nephritic syndrome : 5 - 10 %

McPherson, R.A., Pincus, M. (2011). HENRY’S

Clinical Diagnosis and Management by Laboratory
Methods. (22nd ed.). P 458.
Treatment

• ACE inhibitors: in patients with proteinuria or declining renal function.

• Omega-3 (Fish oil)
 A 24 year old female decided to be admitted due to recurrent gross hematuria for 6
episodes in a week & lasted for 1 month, edema of the face, both upper & lower
extremities, & the trunks, poor appetite, body malaise, & elevated BP. She claimed that
recurrence of gross hematuria noted 3 months after the resolution of gross hematuria 1
month ago. BP=180/110. Serum Creatinine=1.8 mg/dl (Normal value = 0.5-1.5 mg/dl).
Punch Biopsy done of the kidney revealed (+) IgA deposits on immunofluorescent
microscopy.
References

• Kidney Biopsy of the Month: What is Normal?, Renal Fellow Network,

https://www.renalfellow.org/2019/01/04/kidney-biopsy-of-the-month-what-is-normal/
• Kumar, V., Abbas, A. K., & Aster, J. C. (Eds.). (2018). Robbins Basic Pathology (10th ed.).
Elsevier.
• Detsika, Maria & Lianos, Elias. (2021). Regulation of Complement Activation by Heme
Oxygenase-1 (HO-1) in Kidney Injury. Antioxidants. 10. 60. 10.3390/antiox10010060.
• McAninch, J. et.al. (2020).Smith & Tanagho’s General Urology. (9th ed). McGraw-Hill
Education.
• McPherson, R.A., Pincus, M. (2011). HENRY’S Clinical Diagnosis and Management by
Laboratory Methods. (22nd ed.). Elsevier Inc.
• Stevens, C.D. (2010).Clinical immunology and serology : a laboratory perspective (3rd
ed.).F.A. Davis Company.
• Strasinger, S.K, Di Lorenzo, M.S. (2008). Urinalysis and body fluids. (5th ed.). F.A. Davis
Company.