Nephron-Glomerular Disease Flashcards
What are the two ways that glomerular disease presents?
1-Nephrotic syndrome
2-Nephritic syndrome
What is nephrotic syndrome?
Urine protein excretion >3500mg/24h or a urine protein-creatinine ratio of >3500 mg/g that may be accompanied by hypoalbuminemia, edema, and HLD
What is the most common cause of nephrotic syndrome? What is the most common cause of IDIOPATHIC nephrotic syndrome in adults?
Diabetes mellitus
Idiopathic: Membranous glomerulopathy and FSGS
What is nephritic syndrome?
glomerular inflammation with evidence of hematuria, variable proteinuria, and sometimes leukocytes in the urine sediment–edema, hypertension, kidney failure
What is the role of serum complement with glomerulonephritis?
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)
What race is FSGS most common in?
black persons
What is treatment and prognosis for FSGS?
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…
What diseases is FSGS associated with?
HIV and heroin use
In patients with membranous glomerulopathy, what are they at increased risk for?
They are at increased risk for thromboembolic events–particularly renal vein thrombosis. Malignancy can precipitate MG as well!
What is the treatment and prognosis for MG?
- 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
What are the calcineurin inhibitors
Cyclosporine and tacrolimus
What are some secondary causes of MG?
SLE, hep B and C, NSAIDS, TNF-a inhibitors
Malignancies
Thyroid disease
Which of the nephrotic syndromes has a higher risk for renal vein thrombosis?
membranous glomeruopathy
How are these three diagnosed on renal biopsy and EM:
-
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
How is nephrotic syndrome from DM diagnosed?
proteinuria with diagnosis of diabetes
How should MCD be treated
Patients usually respond to glucocorticoids, but if relapsing or refractory–cyclophosphamide, calcineurin inhibitors, MMF, rituximab
How should diabetic nephropathy be treated?
ACE inhibitors or ARBs
What are the most common causes of glomerulonephritis?
Pauci-immune and IgA nephropathy (immune complex mediated)
Describe the clinical course and epi of RPGN
–associated with anti-GBM antibodies and pauci-immune small vessel vasculitis
*goes to advanced kidney failure very quickly
Diagnosis of RPGN
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)
Kidney biopsy findings
- RPGN
- Infectious GN
- Anti-GBM
- Pauci Immune
- IgA Nephropathy
- 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
Clinical manifestations of Anti-GBM antibody disease
kidney function deteriorates over days to weeks, pts with pulmonary hemorrhage may have life threatening respiratory failure with diffuse alveolar infiltrates on chest radiograph
Diagnosis of anti-GBM disease
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
Treatment of RPGN
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
Treatment of anti-GBM disease
Steroids, cyclophosphamide and daily plasmapheresis to remove circulating anti-GBM
Clinical manifestations of PAUCI-immune GN
- 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
Diagnosis of Pauci-Immune GN
- 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
Treatment and prognosis of Pauci-Immune
ACUTE: glucocorticoids with cyclophosphamide with or without plasmapheresis
MAINTENANCE: azathioprine, MMF, or MTX
Ig A vasculitis–Diagnosis
Leukocytoclastic vasculitis or kidney biopsy shows mesangial proliferation with IgA deposits
Lupus nephritis–clinical symptoms
Extrarenal symptoms of SLE with active lupus serologies (ANA antibodies, ds-DNA antibodies) and low complement levels
Lupus nephritis–treatment and prognosis
Treatment is primarily directed at treating the class of lupus. Class I and II LN require aggressive combination immunosuppressive therapy
Diagnosis of lupus nephritis
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
Classification of Lupus nephritis: I-VI
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
Infection-related GN–clinical manifestations
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
Diagnosis of infectious GN
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
What are cryoglobulins?
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
Describe amyloid
Amyloid consists of randomly oriented fibrils composed of various proteins that form organized beta-pleated sheets within tissues
How is amyloid seen on biopsy?
Stains with apple green or Congo red under a polarizing microscope or EM
Describe the overall picture with cryoglobulinemia? What disease processes does it lead to? How diagnosed?
Waldenstrom’s macroglobulinemia
Myeloma
Hepatitis C
Connective tissue disease
Range of clinical spectrum from mild proteinuria and hematuria to RPGN, low complement, positive RF
