SM_205a: Renal Syndromes

Question 1

Describe the classification of renal syndromes

Answer 1

Question 2

Dysmorphic RBCs indicate ______

Answer 2

Dysmorphic RBCs indicate glomerular bleeding

Question 3

In a urine workup, _____, _____, and _____ are abnormal

Answer 3

In a urine workup, hematuria, proteinuria, and casts are abnormal

Question 4

RBC cell casts indicate _______

Answer 4

RBC cell casts indicate glomerular hematuria (nephritic syndrome)

Question 5

Lipid casts / oval body indicate ______

Answer 5

Lipid casts / oval body indicate nephrotic syndrome

Question 6

If asymptomatic hematuria without proteinuria or other renal abnormalities, patient needs _____

Answer 6

If asymptomatic hematuria without proteinuria or other renal abnormalities, patient needs urological workup

Question 7

If proteinuria is alone, first ______. If there is no obvious cause and significant proteinuria, patient needs ______

Answer 7

If proteinuria is alone, first quanitfy. If there is no obvious cause and significant proteinuria, patient needs renal workup

Question 8

If hematuria + proteinuria, casts, or elevated serum creatinine, patient needs ______

Answer 8

If hematuria + proteinuria, casts, or elevated serum creatinine, patient needs renal workup

Question 9

Purpose of a kidney biopsy is to ______ and ______

Answer 9

Purpose of a kidney biopsy is to confirm diagnosis and dictate management

Question 10

Patients with _____, _____, _____, and _____ for which the cause is not obvious require a kidney biopsy

Answer 10

Patients with nephrotic syndrome, nephritic syndrome, AKI and kidney transplant for which the cause is not obvious require a kidney biopsy

• Nephrotic syndrome: lot of proteinuria
• Nephritic syndrome: results from glomerular inflammation and presents with hematuria

Question 11

Describe the different ways of analyzing kidney biopsies

Answer 11

Analyzing kidney biopsies

• Light microscopy: cell proliferation, GBM abnormalities
• Immunofluorescence microscopy: immunocomplement / Ig staining
• Electron microscopy: immune complex deposits, thickness of GBM, foot process effacement of podocytes

Question 12

This is a _____ glomerulus

Answer 12

This is a normal glomerulus

• No proliferation, crescent, or segmental lesions

Question 13

Describe nephrotic syndrome

Answer 13

Nephrotic syndrome

• Constellation of findings: proteinuria >3g/day, hypoalbuminemia, HLD, lipiduria, edema
• Primary causes: minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy
• Secondary causes: diabetes, amyloidosis

Question 14

Describe minimal change disease

Answer 14

Minimal change disease

• Most common cause of nephrotic syndrome in children
• Due to secondary cause in adults (hematologic malignancy, medications)
• Presents with sudden onset edema + other features of nephrotic syndrome sometimes following infection

Question 15

Most common cause of nephrotic syndrome in kids is ______

Answer 15

Most common cause of nephrotic syndrome in kids is minimal change disease

Question 16

Kidney biopsy of minimal change disease reveals _____, _____, and _____

Answer 16

Kidney biopsy of minimal change disease reveals normal-appearing glomeruli on LM, negative IF, and diffuse podocyte foot process effacement on EM

Question 17

Minimal change disease is often responsive to treatment with _____

Answer 17

Minimal change disease is often responsive to treatment with steroids

Question 18

Describe focal segmental glomerulosclerosis

Answer 18

Focal segmental glomerulosclerosis

• Most common cause of primary nephrotic syndrome in African Americans
• Recently linked to APOL1 mutation
• Often primary or idiopathic but can be secondary to other conditions
• HTN, edema
• Proteinuria ± hematuria
• Serum creatinine normal or elevated

Question 19

_____ is most common cause of primary nephrotic syndrome in African Americans

Answer 19

Focal segmental glomerulosclerosis is most common cause of primary nephrotic syndrome in African Americans

Question 20

Describe kidney biopsy findings of focal segmental glomerulosclerosis

Answer 20

Kidney biopsy findings of focal segmental glomerulosclerosis

• Focal: not all glomeruli involved
• Segmental: only a portion of glomerulus involved
• Need ≥ 1 lesions of segmental sclerosis on LM
• Scant or non-specific staining of IgM, C3, or C1q on IF
• Podocyte foot process effacement (focal or diffuse) on EM

Question 21

Describe treatment of focal segmental glomerulosclerosis

Answer 21

Treatment of focal segmental glomerulosclerosis (FSGS)

• Challenging
• Treat secondary cause (HIV, obesity, etc) if possible
• If primary/idiopathic FSGS, start with steroids -> most do not respond -> try Calcineurin inhibitor or Cellcept

Question 22

Describe membranous nephropathy

Answer 22

Membranous nephropathy

• Most common cause of primary nephrotic syndrome in Caucasian adults
• Can be associated with solid tumor cancers, medication exposures (NSAIDs, Gold), infections (Hepatitis B or C), or autoimmune disease (SLE)
• If no secondary cause, called primary
• Onset occurs over days to weeks

Question 23

Describe kidney biopsy findings of membranous nephropathy

Answer 23

Kidney biopsy findings of membranous nephropathy

• Thickened GBM on LM
• “Spikes and holes” on silver stain
• Granular IgG on IF
• Subepithelial immune deposits on EM
• • PLA2R in primary disease

Question 24

Describe treatment of membranous nephropathy

Answer 24

Treatment of membranous nephropathy

• Prompt treatment needed to avoid complications of the disease
• Treatment of an existing secondary cause may cause resolution of membranous nephropathy
• If primary depends on degree of proteinuria: low level treated with RAAS blockade, salt restriction, and diuresis; high level treated with immune modulation (cyclophosphamide, calcineurin inhibitor)

Question 25

Describe nephritic syndrome

Answer 25

Nephritic syndrome * Clinical sequelae of glomerular inflammation * Hematuria * Dysmorphic RBCs and/or RBC casts * Proteinuria (usually \< 3g/day) * Varying degrees of renal insufficiency, HTN, and edema * Rapidly progressive glomerulonephritis (RPGN): glomerular inflammation that causes renal failure in weeks to months, crescentic glomerulonephritis on biopsy

Question 26

Rapidly progressive glomerulonephritis manifests as _____ on biopsy

Answer 26

Rapidly progressive glomerulonephritis manifests as crescentic glomerulonephritis on biopsy

Question 27

Three broad classifications of nephritic syndrome are \_\_\_\_\_, \_\_\_\_\_, and \_\_\_\_\_

Answer 27

Three broad classifications of nephritic syndrome are immune-complex mediated, pauci-immune, and anti-glomerular basement membrane disease * Immune-complex mediated: post-infectious GN, IgA nephropathy, lupus nephritis, membranoproliferative GN * Pauci-immune (ANCA positive): granulomatosis with polyangiitis, microscopic polyangiitis * Ant-glomerular basement membrane disease

Question 28

Describe anti-GBM disease

Answer 28

Anti-GBM disease * Pulmonary-renal syndrome * Auto-antibodies that bind to type IV collagen in the GBM * Goodpasture's when lung involvement * Symptoms: malaise, weight loss, hemoptysis * Labs: hematuria, proteinuria, often rising Cr, + anti-GBM anitbody * Biopsy: diffuse crescentic glomerulonephritis on LM, classic linear IgG staining on IF * Treatment: steroids + cyclophosphamide + plasmapheresis (aggressive)

Question 29

Anti-GBM characteristic lab finding is ______ and characteristic biopsy finding is \_\_\_\_\_\_

Answer 29

Anti-GBM characteristic lab finding is + anti-GBM antibody and characteristic biopsy finding is linear IgG staining on IF

Question 30

Describe post-infectious glomerulonephritis

Answer 30

Post-infectious glomerulonephritis * Onset of nephritic syndrome 10-14 days after Strep pharyngitis or skin infection * Symptoms: gross hematuria, fever, malaise, HTN * Labs: elevated Cr, hematuria, proteinuria, low C3/C4, possibly +ASO titer * Biopsy: hypercellularity on LM, "starry sky" on IF, subepithelial humps on EM * Treatment: supportive (antibiotics for infection), steroids if severe to reduce inflammation

Question 31

Post-infectious glomerulonephritis manifests as _____ on IF and ______ on EM

Answer 31

Post-infectious glomerulonephritis manifests as starry sky on IF and epithelial humps on EM

Question 32

Describe lupus nephritis

Answer 32

Lupus nephritis * Prototypical immune-complex GN * Usually younger woman with known lupus * Symptoms: malaise, joint pain, rash, oral ulcers, serositis, edema * Labs: + ANA, + anti-dsDNA, low C3/C4, anemia * Urine: hematuria and/or proteinuria * Kidney biopsy required for diagnosis * Treatment: supportive for minimal inflammation, high dose steroids + immune-modulating drugs (cyclophosphamide + Cellcept) for active inflammation

Question 33

\_\_\_\_ is required for diagnosis of lupus nephritis

Answer 33

Kidney biopsy is required for diagnosis of lupus nephritis (6 classes)

Question 34

Describe IgA nephropathy

Answer 34

IgA nephropathy * Most common GN worldwide * Can be secondary to inflammatory bowel disease or cirrhosis * Symptoms: hematuria at the same time or 1-2 days after upper respiratory infection (or diarrheal illness) * Labs: Cr normal or elevated, C3/C4 normal, variable proteinuria * Biopsy: mesangial proliferation on LM and + IgA on IF * Treatment: ACE-i/ARB if mild, steroids or immunosuppressive therapy if high risk

Question 35

Kidney biopsy in IgA nephropathy shows _____ on LM and _____ on IF

Answer 35

Kidney biopsy in IgA nephropathy shows mesangial proliferation on LM and +IgA on IF

Question 36

Describe membranoproliferative glomerulonephritis

Answer 36

Membranoproliferative glomerulonephritis * Often associated with underlying infection (Hepatitis C) * Can also be related to genetic mutation (C3 nephritic factor) or be idiopathic * Presentation: nephritic or nephrotic features * Labs: Cr usually elevated, C3 may be low * Biopsy: lobular glomeruli on LM, tram-track appearance on Jones/silver stain, IF often shows C3 and IgG staining, various types of immune complex deposits on EM * Treatment: for infection of Hep-C associated, otherwise difficult

Question 37

Membranoproliferative glomerulonephritis manifests as _____ on LM and has a _____ appearance on Jones/silver stain

Answer 37

Membranoproliferative glomerulonephritis manifests as lobular glomeruli on LM and has a tram-track appearance on Jones/silver stain (IF often shows C3 and IgG staining, various types of immune complex deposits on EM)

Question 38

Describe granulomatosis with polyangiitis (Wegener's granulomatosis)

Answer 38

Granulomatosis with polyangiitis (Wegener's granulomatosis) * Pulmonary-renal syndrome * Middle age or older individuals * Symptoms: constitutional, nasal or sinus (saddle nose deformity), palpable purpura * Labs: hematuria, proteinuria, elevated Cr, + c-ANCA, PR-3 * Biopsy: necrotizing crescentic GN * Treatment depends on level of organ involvement/damage, often high-dose steroids + cyclophosphamide

Question 39

Describe microscopic polyangiitis

Answer 39

Microscopic polyangiitis * Pulmonary-renal syndrome * Middle-aged individuals * Symptoms: constitutional, lower respiratory tract (hemoptysis), palpable purpura * Labs: hematuria, proteinuria, elevated CR, + p-ANCA, MPO * Biopsy: necrotizing crescentic GN * Treatment: depends on level of organ involvement/damage, often high-dose steroids + cyclophosphamide

Question 40

Nephritic syndrome is the result of \_\_\_\_\_\_

Answer 40

Nephritic syndrome is the result of glomerular inflammation