Nephron-Glomerular Disease

Question 1

What are the two ways that glomerular disease presents?

Answer 1

1-Nephrotic syndrome

2-Nephritic syndrome

Question 2

What is nephrotic syndrome?

Answer 2

Urine protein excretion >3500mg/24h or a urine protein-creatinine ratio of >3500 mg/g that may be accompanied by hypoalbuminemia, edema, and HLD

Question 3

What is the most common cause of nephrotic syndrome? What is the most common cause of IDIOPATHIC nephrotic syndrome in adults?

Answer 3

Diabetes mellitus

Idiopathic: Membranous glomerulopathy and FSGS

Question 4

What is nephritic syndrome?

Answer 4

glomerular inflammation with evidence of hematuria, variable proteinuria, and sometimes leukocytes in the urine sediment–edema, hypertension, kidney failure

Question 5

What is the role of serum complement with glomerulonephritis?

Answer 5

It helps differentiate the underlying etiology of GN. Levels are typically normal in anti-glomerular basement membranes disease and pauci-immune GN but are LOW in immune complex GN (with the exception of IgA nephropathy)

Question 6

What race is FSGS most common in?

Answer 6

black persons

Question 7

What is treatment and prognosis for FSGS?

Answer 7

Spontaneous remission only occurs in a small number of patients. Therefore treatment is indicated in most patients.

• Treat with glucocorticoids or calcineurin inhibitors at time of presentation or for relapsing disease.
• If FSGS is due to a drug or disease, then treat disease or remove drug
• Remission on treatment suggests a good clinical course. Some may need a transplant…

Question 8

What diseases is FSGS associated with?

Answer 8

HIV and heroin use

Question 9

In patients with membranous glomerulopathy, what are they at increased risk for?

Answer 9

They are at increased risk for thromboembolic events–particularly renal vein thrombosis. Malignancy can precipitate MG as well!

Question 10

What is the treatment and prognosis for MG?

Answer 10

• Idiopathic MG that does not subside after 6-12 months or someone has a thromboembolic event, treat with steroids, calcineurin inhibitors, cyclophosphamide
• If refractory to this… give MMF, rituximab

Question 11

What are the calcineurin inhibitors

Answer 11

Cyclosporine and tacrolimus

Question 12

What are some secondary causes of MG?

Answer 12

SLE, hep B and C, NSAIDS, TNF-a inhibitors
Malignancies
Thyroid disease

Question 13

Which of the nephrotic syndromes has a higher risk for renal vein thrombosis?

Answer 13

membranous glomeruopathy

Question 14

How are these three diagnosed on renal biopsy and EM:

-

Answer 14

FSGS: Segmental scars in some glomeruli, on EM you see visceral epithelial foot process effacement but NO IMMUNE DEPOSITS

MG: Glomerular capillary loops that appear thickened. EM and IMMUNOFLUORESCENCE show immune deposits and PLA2R antibodies

MCD: normal glomeruli on light and immunofluorescence, on EM the GBM is normal with extensive effacement of epithelial foot processes

Question 15

How is nephrotic syndrome from DM diagnosed?

Answer 15

proteinuria with diagnosis of diabetes

Question 16

How should MCD be treated

Answer 16

Patients usually respond to glucocorticoids, but if relapsing or refractory–cyclophosphamide, calcineurin inhibitors, MMF, rituximab

Question 17

How should diabetic nephropathy be treated?

Answer 17

ACE inhibitors or ARBs

Question 18

What are the most common causes of glomerulonephritis?

Answer 18

Pauci-immune and IgA nephropathy (immune complex mediated)

Question 19

Describe the clinical course and epi of RPGN

Answer 19

–associated with anti-GBM antibodies and pauci-immune small vessel vasculitis

*goes to advanced kidney failure very quickly

Question 20

Diagnosis of RPGN

Answer 20

DEFINITIVE:
*kidney biopsy with glomerular crescents associated with inflammation of glomerular capillaries–specific diagnosis is Ade with immunofluorescence microscopy (immune complexes, linear anti-GBM, pauci-immune)

SUPPORTIVE:
*serology: +ANCA, systemic vasculitis or anti-GBM antibodies

*chest imaging may show diffuse infiltrates in a pt with pulmonary hemorrhage or nodules in the presence of granulomatosis with polyangiitis (Wegeners)

Question 21

Kidney biopsy findings

• RPGN
• Infectious GN
• Anti-GBM
• Pauci Immune
• IgA Nephropathy

Answer 21

• RPGN: glomerular crescents associated with inflammation of glomerular capillaries–specific diagnosis is Ade with immunofluorescence microscopy (immune complexes, linear anti-GBM, pauci-immune)
• Infectious: Kidney biopsy: diffuse endocapillary proliferative and exudative GN, and rarely crescents on light microscopy, immunofluorescence microscopy reveals C3-dominant or C3 codominant glomerular straining
• Anti-GBM: proliferative GN often with many crescents, EM with immunofluoresence for anti-GBM
• Pauci-immune; Kidney biopsy: absent or minimal staining with immunoglobulin (hence pauci-immune)
• *Spectrum of abnormalities range from mild focal and segmental GN to a diffuse necrotizing GN

*IgA Nephropathy: kidney biopsy shows mesangial proliferation with IgA deposits

Question 22

Clinical manifestations of Anti-GBM antibody disease

Answer 22

kidney function deteriorates over days to weeks, pts with pulmonary hemorrhage may have life threatening respiratory failure with diffuse alveolar infiltrates on chest radiograph

Question 23

Diagnosis of anti-GBM disease

Answer 23

Nephritic syndrome

• Serology: normal complement and elevated anti-GBM antibody
• Kidney bx: proliferative GN often with many crescents
• EM: There are linear deposits along the GBM by immunofluorescence

Question 24

Treatment of RPGN

Answer 24

1st: IV pulse steroids followed by oral glucocorticoids
2nd: cyclophosphamide or rituximab may be needed
3rd: Plasmapheresis may be indicated in the presence of pulmonary hemorrhage or severe kidney failure to remove circulating antibody

Question 25

Treatment of anti-GBM disease

Answer 25

Steroids, cyclophosphamide and daily plasmapheresis to remove circulating anti-GBM

Question 26

Clinical manifestations of PAUCI-immune GN

Answer 26

* Most people have circulating ANCA * Associated with granulomatosis with polyangiitis, granulomas associated with necrotizing vasculitis, microscopic polyangiitis * wide range of minimal symptoms with hematuria to RPGN * leukocytoclastic vasculitis resulting palpable purpura, as well as pulmonary disease * Granulomatous lesions on biopsy, particularly for GPA: saddle nose tissue destruction, tracheal stenosis, hearing loss * If eosinophilic granulomatosis wit polyangiitis, then patients have a history of asthma, pulmonary infiltrates, and eosinophilia

Question 27

Diagnosis of Pauci-Immune GN

Answer 27

* most positive for ANCA * specifically, GPA is pr3-ANCA * specifically, MPA is myeloperoxidase-ANCA * *Kidney biopsy: absent or minimal staining with immunoglobulin (hence pauci-immune) * *Spectrum of abnormalities range from mild focal and segmental GN to a diffuse necrotizing GN

Question 28

Treatment and prognosis of Pauci-Immune

Answer 28

ACUTE: glucocorticoids with cyclophosphamide with or without plasmapheresis MAINTENANCE: azathioprine, MMF, or MTX

Question 29

Ig A vasculitis--Diagnosis

Answer 29

Leukocytoclastic vasculitis or kidney biopsy shows mesangial proliferation with IgA deposits

Question 30

Lupus nephritis--clinical symptoms

Answer 30

Extrarenal symptoms of SLE with active lupus serologies (ANA antibodies, ds-DNA antibodies) and low complement levels

Question 31

Lupus nephritis--treatment and prognosis

Answer 31

Treatment is primarily directed at treating the class of lupus. Class I and II LN require aggressive combination immunosuppressive therapy

Question 32

Diagnosis of lupus nephritis

Answer 32

ANA antibodies, anti-DS DNA antibodies usually positie C3 and C4 is usually depressed Kidney biopsy required to make the diagnosis and classify the lesions of LN to guide treatment

Question 33

Classification of Lupus nephritis: I-VI

Answer 33

I-no renal findings II-mild clinical kidney disease, minimally active urine sediment, mild to moderate proteinuria, active serology III-focal proliferative LN with <50% glomeruli involvement, increased proteinuria, may have hypertension and some active lesions may require treatment IV- Diffuse proliferative LN >50% glomeruli involvement--active urine sediment, HTN, heavy proteinuria reduced GFR, active serology, active lesions requiring treatment V-membranous LN GN-significant proteinuria (often nephrotic) with less active serology VI-Advanced sclerosing LN-more than 90% glomerulosclerosis; no treatment prevents kidney failure

Question 34

Infection-related GN--clinical manifestations

Answer 34

Acute nephritis syndrome, occurs after infection/illness after a latent period of 1-6 weeks Staphylococcus GN usually is associated with ongoing infection at the time of development of nephritis

Question 35

Diagnosis of infectious GN

Answer 35

Patients are nephritic and have an ongoing or preceding infection Search for infection using microbiologic cultures usually shows the inciting organism in nonstreptococcal GN * Depressed complement * Post-strep GN, depressed complement levels, usually C3, signifying activation of the complement pathway.... in PSGN antibodies to streptococcal antigens (antistreptolysin-O, anti-DNAse B) are detected in almost all cases *Kidney biopsy: diffuse endocapillary proliferative and exudative GN, and rarely crescents on light microscopy, immunofluorescence microscopy reveals C3-dominant or C3 codominant glomerular straining

Question 36

What are cryoglobulins?

Answer 36

Cryoglobulins are immune-related proteins that precipitate at temps below 37C in vitro and may be associated with a systemic inflammatory syndrome involving small to medium vessel vasculitis

Question 37

Describe amyloid

Answer 37

Amyloid consists of randomly oriented fibrils composed of various proteins that form organized beta-pleated sheets within tissues

Question 38

How is amyloid seen on biopsy?

Answer 38

Stains with apple green or Congo red under a polarizing microscope or EM

Question 39

Describe the overall picture with cryoglobulinemia? What disease processes does it lead to? How diagnosed?

Answer 39

Waldenstrom's macroglobulinemia Myeloma Hepatitis C Connective tissue disease Range of clinical spectrum from mild proteinuria and hematuria to RPGN, low complement, positive RF