Renal Pathology Case Studies
Moderators: J. Charles Jennette
Case 4 -
San Carlo Borromeo Hospital
A 58 years old man reported since 1991 recurrent episodes of leg's purpura.
April 1992 : paresis a "frigore" of facial nerve.
October 1994: for the presence of fever, unresponsive to
antibiotic therapy, diffuse edema and leg purpura he was admitted to our Nephrology Department.
Exames : acute renal failure (S. Creatinine 1,2 → 3,5 mg/dl), hypoalbuminemia, nephrotic range
proteinuria (5,5 gr/24 h) with microhematuria.
Sonography: normal kidneys.
First Renal Biopsy (#4A):
Case 4 - Slide 1
the renal sample presented 7 glomeruli. No glomeruli showed global sclerosis . All glomeruli showed
mild expansion of mesangial matrix, very intense hypercellularity due to mesangial cell proliferation and
massive intracapillary infiltration of inflammatory cells (exudative lesion). Diffuse thickening of the
glomerular basement membrane with diffuse and conspicuous double-contour appearance.
Presence of intraluminal thrombi variable for size and diffusion, entirely filling the capillary
lumen. They appeared amorphous, eosinophilic, PAS positive and Congo red negative. Monoclonal
antibodies against leukocyte population demonstrated a prevalent and massive intracapillary infiltration
of monocyte-macrophages (CD68 pos cells).
Interstitium and vessels were normal.
By Immunofluorescence an intense staining of intraluminal thrombi for IgG and IgM was present; only
faint segmental staining of peripheral loops was present.
Electron Microscopy confirmed the presence of massive infiltration of monocyte-macrophages in close
contact with subendothelial and intraluminal deposits. Moreover these deposits have a randomly arranged
Further exams: Reduced C3 and markedly reduced C4, RA test and Waaler Rose positive, rise of Hepatic
indexes, ANA and Anti-DNA negative, ANCA negative. Antibody anti HCV and HCV-RNA positive; IgG-IgM/K
Cryoglobulins with serum and urinary monoclonal component of IgM/K; Cryocrit 80%.
Hepatic biopsy: active chronic hepatitis.
After 3 months normal renal function (S. Creatinine 0,95 mg/dl), proteinuria 0,5 gr/24 h.
- Interpheron α 3.000.000 UI (9 per week)
- Metilprednisolone pulses (1 gr x 3 days) + oral corticosteroid 0,5 mg/kg/d
- Oral Cyclophosphamide 2 mg/kg per 8 weeks
- Plasma exchange (classic treatment)
After 6 months normal renal function, proteinuria 0,3 gr/24 h.
Second Renal Biopsy (#4B):
Case 4 - Slide 2
The renal sample presented 33 glomeruli. No glomeruli showed global sclerotic lesions. All glomeruli
appeared a little enlarged without evident mesangial matrix expansion or mesangial cell proliferation.
No intracapillary inflammatory cells were seen. Only few and segmental thickening of glomerular basement
membrane without double-contour appearance. No intraluminal thrombi were present.
By Immunofluorescence faint segmental parietal deposits of IgG and IgM were detected.
Differential Hitological Diagnosis
Waldenstrom's macroglobulinemia : characterized by intracapillary deposits
frequently very huge strongly positive, by Immunofluorescence, for IgM. Usually there is not evident
hypercellularity and the glomerular basement membranes are normal.
Idiopathic Membranoproliferative glomerulonephritis: characterized by
marked mesangial matrix expansion, mesangial cells proliferation and diffuse tickening of glomerular
basement membrane with double-countour appearance. Intracapillary inflammatory cells infiltration, when
present, is usually mild.
By Immunofluorescence parietal deposits of C3 are prevalent on Electronic Microscopy never
show structured deposits.
Diffuse Lupus Nephritis : in few cases some intracapillary "thrombi" can
be present such as intracapillary inflammatory cells.
Wire loop aspect of capillary walls and "full house" pattern at Immunofluorescence are
characteristic of this disease.
By Electron Microscopy in rare cases is possible to find a structured deposits with a
peculiar characteristic called "finger prints" (not randomly arranged).
Henoch-Schonlein purpura: in some cases a morphological pattern of
membranoproliferative lesion is present without evidence of tuft necrosis. The prevalent
mesangio-parietal deposits of IgA is diagnostic of this disease.
Thrombotic Microangiopathy (Thrombotic Thrombocytogenic purpura):
characterized by the presence of thrombi predominantly in small-size arteries, arterioles and also
Mesangial cells proliferation is usually absent or very mild, endothelial edema and
degeneration is very common and "double contour" appearance of basement membrane is usual.
This newly formed sub-endothelial space is not occupied by Immunodeposits but is filled
with fluffy materials.
In severe cases collapse of the tuft with wrinkling of the capillary walls is common.
Immunofluorescence is negative except for Fibrinogen positivity in vessels thrombosis.
Cryoglobulinemic glomerulonephritis : typically characterized by
membranoproliferative-exudative pattern, with massive intracapillary moncyte-macrophages accumulation,
diffuse basement membrane tickening with "double contour" appearance and in many cases diffuse
intracapillary "thrombi" strongly positive for IgG and IgM (Cryoglobulin precipitation).
By electron microscopy frequent presence of structured deposit characterized by randonly
arranged microtubular structures.
Diagnosis: Morphological lesions of the biopsy case is highly suggestive of Cryoglobulinemic glomerulonephritis.
Further exams: ANA, Anti-DNA, ANCA negative Hypo C3 and marked Ipo C4, Ra
Test and Waaler-Rose positive; antibody anti HCV and HCV-RNA positive; IgG-IgM/K; Cryocrit 80%. These
data confirmed a diagnosis of Cryoglobulinemic Glomerulonephritis.
Therapy with Interpheron α, Metilprednisolone pulses, Cyclophosphamide
and plasma exchange. The patient, after 6 months, was in complete clinical remission (S. Creatinine
0,95 mg/dl – Proteinuria 0,3 gr/24h).
The second renal biopsy showed a quite complete resolution of histological and Immunohistological
These data further confirme a diagnosi of Cryoglobulinemic Glomerulonephritis that usually present a
very good renal follow-up with rare progression to End Stage Kidney.
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