Glomerulonephritis/Nephritic Syndrome (Thurman)

Question 1

Post-infectious glomerulonephritis.

Answer 1

Diagnosis considered for patients with nephritic syndrome, positive strep test, and low C3 levels. Classically presents 14-21 days after an acute Group A Streptococcus infection. Often seen in children, sometimes with findings of endocarditis, empyema, etc. M protein driven. Positive streptolysin if due to strep. Prognosis is good, as most resolve spontaneously and leave no permament damage (in kids).

Pathology: Diffuse, global endocapillary proliferative glomerulonephrosis is the light microscopy diagnosis. Hypercellular glomeruli with closed/stuffed capillary loops (endocapillary proliferation - diffuse) as well as PMN in the capillary loops. Hump-like subendothelial deposits (EM and light microscopy). IF shows “starry sky” pattern of IgG and C3 (lights up everywhere, not limited to a specific region [subepithelial, mesangial and subendothelial]).

**Nephritic syndrome, so can present with rales, HTN, CVA tenderness, etc.

Question 2

IgA Nephropathy aka Berger disease

Answer 2

A MESANGIAL PROLIFERATIVE glomerulonephritis involving IgA deposits in the mesangium. Classically seen in 15-35 y/o men.

Most patients present with asymptomatic microhematuria, nonnephritic proteinuria and good kidney function.

MICROHEMATURIA is CONCURRENT with viral illness (unlike post-infectious GN)

Tx with steroids, few respond. Some cases are stable, some progress to ESRD.

Pathology: Hypercellular mesangial regions with sclerosis (fibrosis). IM shows IgA/C3 in the mesangium (“burning bush” pattern)

***Biopsy of the skin shows IgA deposits termed Henoch-Sholein purpura. (systemic IgA disease)

Question 3

Membranoproliferative glomerulonephritis (MPGN)

Answer 3

Classically associated with HCV or HIV infection, though the idiopathic form is most often seen in adolescents, particularly girls. Light microscopy shows a lobulated appearance of the glomerulus, mesangial cell proliferation, and a thickening of the GBM. Complement mediated disease with low C3 and C4 levels. Prognosis is poor with most progressing to end stage renal disease. IF shows C3 and IgG deposits in the capillary walls and the mesangium. Hypertension is a common feature early in the disease, often preceding loss of kidney function.

Question 4

Anti-GBM Disease

Answer 4

Includes Goodpasture syndrome if pulmonary hemorrhage involved, or can be “renal limited.” Results from IgG binding to Type IV collagen in the GBM. Complement activation and neutrophil infiltrates lead to rapid renal failure. If present, pulmonary hemorrhage often precedes renal symptoms, and intrapulmonary blood loss is the reason for the iron deficiency anemia seen in Goodpasture. Aggressive treatment with steroids, immunosuppressive agents and plasma exchange is required before transplantation, b/c circulating GBM Ab will destroy the new kidneys, too.

Question 5

Goodpastures disease is classically seen in young males (rare), and consists of the triad of:

Answer 5

PULMONARY HEMORRHAGE
Iron deficiency ANEMIA
GLOMERULONEPHRITIS assx with circulating ab to the GBM

**Crescentic disease (Diffuse crescentic glomerulonephritis) with NEPHRITIC components. IF you forget this has linear IF staining I will reach out of the ipad and strangle your useless ass.

Question 6

Pauci-immune renal vasculitis

Answer 6

Patients with small vessel vasculitis who DO NOT show evidence of immune complex deposition are considered to have a pauci-immune vasculitis. Classically see fibrinoid necrosis and crescents. Immune complexes must be absent (by definition). 90% of patients are ANCA positive, including myeloperoxidase (MPO) and proteinase 3 (PR-3). Patients generally present with nephritic disease, and often the lungs are involved (pulmonary-renal symdrome). Tx with immunosuppressive drugs incl cyclophosphamide, high-dose steroids, and rituxumab.

Question 7

Lupus Nephritis

Answer 7

About 1/2 of patients with Lupus develop renal disease, and these patients have higher mortality rates. Generally patients present with proteinuria or hematuria, but either a nephritic or nephrotic pattern can present. Tx with mycophenolate mofatil or cyclophosphamide and high-dose steroid. Can present any which way; should always been on the differential.

Pathology: Classically, immunofluorescence shows a “lumpy-bumpy” pattern due to deposition of IgG, IgA, C3, IgM, and C1q. “Full house” on IF (everything present).

Question 8

Cryoglobulinemia

Answer 8

Classically associated with Hepatitis C infection. Etiology is IgM immune deposition in the small vessels, in this case often assx with Rheumatoid factor. Also seen with lymphoproliferative disorders, infection, and autoimmune disease (Sjogren). Most patients develop palpable purpura, arthralgias, and weakness. Low C4 levels and rheumatoid factor activity is indicative of cryoglobulinemia. Tx for Hep C positive patients is antiviral (peginterferon alpha, ribavirin). Plasmapheresis for severe disease, rituxumab if B cell mediated.

Question 9

Henoch-Schonlein Purpura

Answer 9

The classic clinical manifestations of HSP in children include skin lesions (palpable purpura), arthritis, GI involvement (colic and bleeding) and glomerulonephritis. In adults renal involvement is often more severe and systemic disease less obvious. The renal lesion is similar to IgA nephropathy but more severe with a focal proliferative necrotizing glomerulonephritis, often with crescent formation, accompanied by mesangial and capillary wall deposits of IgA. IgA nephropathy and HSP are believed to be caused by similar mechanisms involving IgA immune complexes. “Systemic IgA disease.”

Question 10

Crescents are seen in what three disease categories?

Answer 10

Lupus
Anti-GBM
ANCA associated vasculitis

OR 4 categories (immune complex, anti-GBM, systemic disease, idiopathic) –from Lucia lecture

*clinically present as RPGN

Question 11

Pulmonary renal syndrome is seen in what three disease categories?

Answer 11

Lupus
Anti-GBM
ANCA associated vasculitis

Question 12

Syndromes associated with more aggressive disease (3)?

Answer 12

Pulmonary renal syndrome
Crescent formation
Rapidly progressive Glomerulonephritis

Question 13

RPGN assx with what three disease categoreis?

Answer 13

Lupus
Anti-GBM
ANCA assx vasculitis

Question 14

What are the 5 primary characteristics of nephritic syndrome?

Answer 14

Reduction in GFR (an elevated serum creatinine)
Active urine sediment (RBC’s, WBC’s, and RBC casts)
Proteinuria (usually sub-nephrotic)
Edema
Hypertension

Question 15

Name 6 Nephritic diseases

Answer 15

Benign Familial Hematuria (Thin BM disease)
Alport Disease
IgA nephropathy
Postinfectious GN
Focal necrotizing/crescentic GN
Lupus Gn

Question 16

What is the deal with Benign Familial Hematuria.

Answer 16

Estimated that 1% of the population is affected by this SNP in genes encoding collagen IV. Basement membrane is thinner than usual, and leads to occasional hematuria after stress (eg excercise, work, illness). Not truly a disease, as mortality is not increased and there is no assx morbidity. EM is diagnostic.

Question 17

What’s up with Alport disease.

Answer 17

Triad of nephritis, deafness, and ocular lesions. Cannot form normal basement membranes. X linked malformation in alpha-5 chain of collagen IV, so males more affected. Females can be affected. “Basket weaving” of lamina densa is pathognomonic (EM). Usually progress to end stage renal disease.

Question 18

What are the morphologic patterns of Glomerular disease to run through when looking at pathology?

Answer 18

1) Cell proliferation (Mesangial, Endocapillary, Epithelial (podocyte) - crescents)
2) Leukocytic infiltration
3) GBM Thickening
4) Sclerosis

Question 19

What are the terms that distinguish pathology of all glomeruli vs some?

Answer 19

Focal (some glomeruli affected) vs diffuse (many/all affected)

Question 20

What are the terms that distinguish whether the a single glomerulus is affected by pathology or only part?

Answer 20

Segmental vs Global

Question 21

How many nuclei per mesangial region in a healthy glomerulus?

Answer 21

2-3

Question 22

Crescentic GN. Talk about it, name 3 disease categories and the diseases that fall into them.

Answer 22

Proliferation of epithelial cells within Bowmans space. Don’t see proliferation of mesangial cells or endothelial cells in the capillary loops. Many disease processes, but they present as a RPGN. Prognosis is poor because crescentic disease heals with a scar, so you generally lose the affected nephrons.

Immunofluorescene is the most important way to differentiate the etiology, since this is a diverse disease category and treatments will vary. 3 categories:

1) Linear staining (Goodpasture, Anti-GBM)
2) Granular staining (IgA, SLE, Endocarditis, Idiopathic)
3) No staining (Wegeners [GPA], microscopic PAN, Churg-Strauss, Idiopathic) –> so called “pauci-immune”