Renal_ Thomas: Acute/subacute Renal Failure: Glomerular Diseases

Front 1

General Rule:
It is easier to rule out _______, so do this first unless your history or clinical suspicion dictates otherwise!

Back 1

pre- or post- renal failure

Front 2

These are epithelial cells on the basement membrane

Back 2

Podocytes

Front 3

These cells support the capillary wall

Back 3

Mesangial Cells

Front 4

Typically Non-inflammatory

Damage to basement membrane/epithelium=↑permeability

-↑ permeability= protein leakage >3.5g/day in urine

Back 4

Nephrotic Syndrome

Front 5

-↓ albumin

-↓ oncotic pressure --> 3rd spacing

-↓ effective circulating volume = activation of RAA

-loss of Antithrombin III -->hypercoaguable -->clots/emboli

-liver stimulated to make cholesterol

Back 5

Nephrotic Syndrome

Front 6

Characterized by:

proteinuria, edema, hyperlipidemia, hypercoaguability

Back 6

Nephrotic Syndrome

Front 7

Typically Inflammatory Process

Immune-mediated Damage

Infiltrates of neutrophils and phagocytes and/or proliferation of mesangium

Back 7

Nephritic Syndrome

Front 8

Infiltrates of neutrophils and phagocytes and/or proliferation of mesangium cause:

– Crescentic lesions

– Plugging up of Bowman‟s space

– Necrosis/Thinning of Glomerular Basement Membrane

– Rupture of GBM

Back 8

Nephritic Syndrome

Front 9

CLINICAL = hematuria, oliguria, HTN

LABS: urinalysis usually with (+) blood, RBC casts, and/or protein <3.5 g/day

Back 9

Nephritic Syndrome

Front 10

Proteinuria: >3.5 g/day

This is usually indicative of

Back 10

Nephrotic Syndrome

Front 11

Proteinuria: <3.5 g/day

This can be associated with _______

Back 11

Nephritic Syndrome

Front 12

You're looking at a urinalysis report and see: (+) blood, RBC casts,
and/or protein <3.5 g/day

Back 12

Nephritic Syndrome

Front 13

What are some typical symptoms of Glomerular Dz?

Back 13

Edema*

weight gain

malaise

oliguria*

hematuria*

worsening HTN*

Front 14

A Family Hx of kidney disease, DM, autoimmune diseases might make you think a patient's symptoms are due to _________

Back 14

Glomerular Dz

Front 15

Physical Exam Findings for Glomerular Dz?

Back 15

– Signs of fluid overload
(edema, JVD, crackles)

– Hypertension

– Conjunctival pallor (anemia)

– Signs of Autoimmune Diseases

–Xanthomas

Front 16

What are some physical exam findings
suggestive of autoimmune diseases?

Back 16

**SLE**- malar rash, alopecia, apthous ulcers, peripheral edema, pallor

**RA**- nodules, joint effusions, ulnar deviation of fingers

Front 17

What tests are used to help rule out
pre- and post-renal ARF?

Back 17

PRE- FeNa, sp gravity, Una, Uosm

POST- bladder scan, Foley, renal US

Front 18

Characterized by:

• Proteinuria > 3.5 g/day
(>50mg/kg/day for kids)

-Cholesterol in 300-400 mg/dL range
• Serum Albumin < 3.5 g/dL

Back 18

Nephrotic Syndrome

**Low Sr Albumin b/c we're losing protein in urine**

Front 19

If you see fatty casts (oval fat bodies) in urinalysis what are you thinking?

Back 19

Nephrotic Syndrome

**high cholesterol in plasma**

Front 20

Can see:

↓calcium due to ↓albumin, but also
due to loss of proteins which bind
vitamin D

• Anemia due to loss of transferrin and erythropoietin

• Hypercoaguability due to loss of
Antithrombin III (AT III)

Back 20

Nephrotic Syndrome

Front 21

BUZZWORDS FOR BOARDS:

Proteinuria
Hypoalbuminemia
Edema
Hyperlipidemia

Back 21

Nephrotic Syndrome

Front 22

Treatment usually always includes:

Statins, ACEI/ARBs, fluid and salt restriction

Back 22

Nephrotic Syndrome

Front 23

T/F

Nephrotic Syndrome is associated with 24-hr urine protein >3.5 g/day

Back 23

True

Front 24

Damage due to effacement/flattening of
podocytes

Back 24

Minimal Change Disease

Front 25

Minimal Change Disease is a subtype of __________

Back 25

Nephrotic Syndrome

Front 26

Minimal Change Disease can be associated with what 2 things?

Back 26

Can be associated with:

– Medications (lithium, NSAIDs)

– *Lymphomas*

Front 27

Most common type of nephrotic
syndrome in kids, accounting for 90%
of nephrotic cases < 10 years old

Back 27

Minimal Change Dz

Front 28

Why do you get nephrotic range
proteinuria with minimal change
disease?

**EXAM**

Back 28

Effacement of podocytes
↓
Disruption of filtration slits
↓
proteins leak through "big holes"

Front 29

Si/Sx: edema, massive proteinuria (Pr/Cr up to 9)

Dx: kidney biopsy shows effacement of podocytes

Back 29

Mimimal Change Dz

Front 30

Rx for Minimal Change Dz?

Back 30

Steroids for 8 weeks

Front 31

A previously healthy 32 year old female presents to your office after having swollen legs for the last 3 weeks.
She denies any recent illnesses, history of HIV or Hepatitis B or C, and does not endorse any symptoms of autoimmune diseases.

LABS:
Urinalysis: 3+ protein, no WBCs, RBCs or casts
Serum Albumin: 3.0 g/dL (normal 4.0 g/dL)
Serum Creatinine: 1.0 mg/dL (normal)

You decide to get a kidney biopsy. What would you expect to see?

A.Linear IgG deposition

B. Positive immunofloresence for GBM antibodies

C. Effacement of podocytes

D. No pathologic changes

Back 31

C. Effacement of Podocytes

**Minimal Change Dz**

Front 32

#1 cause of nephrotic syndrome in
African Americans

Back 32

Focal Segmental Glomerulosclerosis
(FSGS)

Front 33

HTN at level of glomerulus causes
hyperfiltration, which leads to
accumulation of extracellular matrix and eventual scarring and tamponade of glomerulus. EPITHELIAL cells are damaged.

Back 33

Focal Segmental Glomerulosclerosis
(FSGS)

**Epithelial Cell (podocyte) damage d/t HTN**

Front 34

What cells are damaged in FSGS?

Back 34

Epithelial Cells are damaged due to HTN
(podocytes)

Front 35

Associated with:
- HIV**
-Ureteral reflux (kids with posterior bladder valves
-Massive obesity
-Obstructive Sleep Apnea
-Chronic pyelonephritis
-Interstitial kidney disease
-IV Heroin**

Back 35

Focal Segmental Glomerulosclerosis
(FSGS)

Front 36

CLINICAL:

-indolent course; usually asymptomatic in early disease

-microscopic hematuria initially

Back 36

Focal Segmental Glomerulosclerosis
(FSGS)

Front 37

Prognosis: *50% progress to ESRD in 5 years*

Back 37

Focal Segmental Glomerulosclerosis
(FSGS)

Front 38

This is the exception to the rule that NEPHROTIC syndromes are not due to antibody problems, but is in keeping with the fact that NEPHROTIC is usually NONINFLAMMATORY

Back 38

Membranous Glomerulonephropathy

**Results from antibody/IC deposition**

Front 39

-Damage to mesangial matrix

• Although there are immune complexes associated with this disease, they can't cross basement membrane and, therefore, DO NOT cause inflammatory changes

Back 39

Membranous Glomerulonephropathy

Front 40

Associated with:

– ***Hepatitis B/C ***

– Syphilis

– Diabetes Mellitus

– **SLE, RA **

– ***Malignancies***
• Breast, colon, stomach, kidney, lung

Back 40

Membranous Glomerulonephropathy

Front 41

Workup:

-exclude SLE, RA

-Hepatitis serologies

***age appropriate cancer screenings***

Rx: steroids and cytotoxic agents

Back 41

Membranous Glomerulonephropathy

Front 42

A 45 year old male presents to the ED
because he has noted foamy urine for the
last several months. He also has gained
about 20 pounds in the last 3 months, which he says “must be water weight” because he has noted that his shoes are too tight from being swollen.
Pertinent past medical history is significant
for only osteoarthritis of his lower back.
Family history is significant for coronary artery disease, diabetes, and colon cancer in his father and paternal uncle at ages 50 and 48, respectively. Patient is a nonsmoker, and results of a recent HIV test were negative.

LABS
-Serum creatinine: 1.2 mg/dL
-Serum Albumin: 3.2 g/dL
-Urinalysis: 3+ protein; oval bodies, no RBCs
-Serum Cholesterol: 355 mg/dL
-Random Glucose: 126

Before proceeding to a kidney biopsy,what other tests would you like to order?

Back 42

**Membranous Glomerulonephropathy**

ANA --> SLE, RA

Hepatitis B and C

**colonoscopy**

RPR --> Syphilis

Front 43

Increased Prevalence in smokers, nonwhites, those with poor glycemic and/or BP control

Back 43

Diabetic Glomerulosclerosis

Front 44

Dx:
-urine microalbumin test: microalb/cr >30

-nodular sclerosis on biopsy (Kimmelstiel-Wilson nodules)

Back 44

Diabetic Glomerulosclerosis

Front 45

You are looking at a kidney biopsy and see nodular sclerosis.

(Kimmelstiel-Wilson nodules)

Back 45

Diabetic Glomerulosclerosis

Front 46

A urine microalbumin test reveals:

microalbumin/Cr > 30

Back 46

Diabetic Glomerulosclerosis

**microalbuminuria**

Front 47

Rx for Diabetic Glomerulosclerosis?

Back 47

-Glycemic Control

-***ACEi/ARBs*** (even if there's no HTN)

-Intensive Cholesterol Control (LDL<100)

Front 48

BUZZWORDS:

CLINICAL:
Hematuria
Oliguria
HTN

LAB:
Urinalysis: (+) blood, RBC casts

Urine protein < 3.5 g/day

Back 48

Nephritic Syndrome

Front 49

T/F

Protein on UA rules out nephritic glomerular diseases.

Back 49

False

Front 50

Which Immunoglobulin plays a critical role in mucosal immunity? (i.e. More is produced in mucosal linings than all other type of antibody combined)

Back 50

IgA

Front 51

#1 cause of glomerulonephropathy
worldwide

• 2-3 days post infection (URI, GI)

• IgA Deposition associated with
–Henoch-Schönlein Purpura

Back 51

IgA Nephropathy

Front 52

Upper respiratory tract or GI infection
↓
Defective mucosal immunity
↓
Overproduction and hence increased serum levels of partially degalactosylated polymeric IgA1 and IgA-immune complexes
(Pathogenic IgA)

Back 52

IgA Nephropathy

Front 53

IgA Symptoms due to inflammation:

-Focal, mesangial proliferative glomerular inflammation

Back 53

Asymptomatic, MICROSCOPIC hematuria

Front 54

IgA Symptoms due to inflammation:

-Diffuse, mesangial proliferative
glomerular inflammation

Back 54

More acute nephritis with MACROSCOPIC hematuria

Front 55

What type of hematuria is associated with IgA nephropathy in patients with a recent GI or UR infection?

Back 55

Macroscopic hematuria (bloody urine)

Front 56

Dx:
history, microscopic/macroscopic hematuria, normal C3, normal C4

Dx: ACEi/ARB2, steroids if pr/cr ratio >1

Back 56

IgA Nephropathy

Front 57

What are the levels of C3 and C4 like in IgA nephropathy?

Back 57

Normal

Front 58

Disease of Children

• Usually follows URI

• Abnormal IgA deposition in:
– Skin
– GI tract
– Kidney
– Joints

Back 58

Henoch-Schönlein Purpura

Front 59

CLINICAL FINDINGS:

• Lower extremity bruising (“palpable purpura”)

• Bloody diarrhea

• Hematuria and Hypertension

• Arthralgias (bleeding into joints)

Rx: Supportive

Back 59

Henoch-Schönlein Purpura

Front 60

You see a patient with:
Subendothelial antigen deposition

• 2-3 weeks post infection (strep
pharyngitis or cellulitis)

• Low C3, Low C4

Back 60

Post-Infectious GN

Front 61

T/F

Prompt treatment of strep infection
does not guarantee that post-infectious
GN will not develop

Back 61

True

Front 62

A 32 year old female with no PMH
presents to your office due to general malaise, runny nose and sore throat. She is also concerned because her urine has been dark. Her symptoms have been going on for about 3 days.
She has a slightly elevated BP at 146/88. The result of her rapid strep test is positive, urine pregancy test is negative, and moderate blood is noted on urine dipstick.

Based on what you know, what is the most likely diagnosis?

A. IgA Nephropathy
B. Post-Infectious GN

Back 62

IgA Nephropathy

Front 63

T/F

Prompt treatment of strep infection
does not guarantee that post-infectious
GN will not develop

Back 63

True

Front 64

A 32 year old female with no PMH
presents to your office due to general malaise, runny nose and sore throat. She is also concerned because her urine has been dark. Her symptoms have been going on for about 3 days.
She has a slightly elevated BP at 146/88. The result of her rapid strep test is positive, urine pregancy test is negative, and moderate blood is noted on urine dipstick.

Based on what you know, what is the most likely diagnosis?

A. IgA Nephropathy
B. Post-Infectious GN

Back 64

IgA Nephropathy

**Timeframe is 2-3 days here.. Not 2-3 weeks which would make you think Post-Infectious GN**

Front 65

What pattern of complement would you expect for IgA nephropathy?

A. Low C3, low C4
B. Low C3, normal C4
C. Normal C3, normal C4
D. Normal C3, low C4

Back 65

Normal C3, Normal C4

Front 66

Usually secondary to other diseases

• Associated with:
– Sjogren‟s Syndrome
– Systemic Lupus Erythematosis
– Hep B/C with cryoglobulinemia
– Infective endocarditis

Back 66

Membranoproliferative GN

Front 67

What are the two characteristic complaints in Sjogren's Disease?

What antibodies are positive in Sjogren's Disease?

Back 67

Dry Mouth, Dry Eyes

Positive Anti-Ro, Anti-La

(Membranoproliferative GN)

Front 68

LABS: UA with dysmorphic RBCs,
erythrocyte casts, LOW C3, NORMAL C4

• Rx: treat underlying cause, steroids,
antiplatelets

Back 68

Membranoproliferative GN

Front 69

C3 and C4 levels in Membranoproliferative GN?

Back 69

C3=LOW

C4=NORMAL

Front 70

• 10-20% of cases of Rapidly
Progressive GN

• Can be ANCA +

• Antibodies to type IV collagen

Back 70

Anti-GBM/Goodpasture's Syndrome

Front 71

CLINICAL
• Rapid Onset of HTN, oliguria
• Fatal if not treated promptly

Kidney only: more common in older women (anti-GBM syndrome)

– Kidney/Lung: more common in young men (Goodpasture‟s syndrome); 70% will have alveolar hemorrhage

Back 71

Anti-GBM/Goodpasture's Syndrome

Front 72

Can have isolated kidney involvement or kidney and lung involvement

Back 72

Anti-GBM/Goodpasture's Syndrome

– Kidney only: more common in older women (anti-GBM syndrome)

– Kidney/Lung: more common in young men (Goodpasture‟s syndrome); 70% will have alveolar hemorrhage

Front 73

Dx: anti-GBM antibodies, biopsy

• Rx: cyclophosphamide + steroids;
plasmapheresis if pulmonary
hemorrhage

Back 73

Anti-GBM/Goodpasture's Syndrome

Front 74

Tx for Goodpasture's patient with pulmonary hemorrhage?

Back 74

PLASMAPHERESIS

Front 75

• Prognosis depends on:

–promptness of diagnosis and
treatment

–Degree of kidney involvement (if Cr
> 5 or dialysis required, prognosis
poor)

Back 75

Anti-GBM/Goodpasture's

Front 76

2 Types of Small Vessel Vasculitis?

Back 76

1. Wegener's Granulomatosis
-lung, kidney and sinus involvement

2. Microscopic Polyangiitis

Front 77

Patient has a Small vessel vasculitis with:
-lung, kidney and sinus involvement

Back 77

Wegener's Granulomatosis

Front 78

CLINICAL: (non-specific)
-decreased appetite
-weight loss
-hematuria and/or proteinuria
-polymyalgia

Back 78

Small Vessel Vasculitis

Front 79

c-ANCA +

anti-PR3– Wegener's

anti-MPO– Microscopic Polyangiitis

Back 79

Small Vessel Vasculitis

Front 80

anti-PR3– ?

Back 80

Wegener's

Front 81

anti-MPO– ?

Back 81

Microscopic Polyangiitis

Front 82

A 50 year old female presents to the office with a chief complaint of coughing up blood. She has no significant past medical history and has not had any recent respiratory illnesses. A PPD placed 6 months ago was negative. She is a lifelong nonsmoker. Routine labs reveal an increase in serum creatinine from 0.8 to 3.2 mg/dL in 3 months.

Vital Signs are unremarkable except for a
BP of 150/80.
You are concerned that the hemoptysis may be part of a pulmonary-renal syndrome like Goodpasture‟s or Wegener‟s.

What one question about associatedsymptoms could help you differentiate between Goodpasture‟s Syndrome and Wegener‟s Granulomatosis?

Back 82

History of recurrent sinusitis = Wegener's

*****

Front 83

What labs could you order to help you differentiate between Goodpasture's Syndrome and Wegener's Granulomatosis?

Back 83

c-ANCA (positive in Wegener's)

anti-PR3 (Wegener's)

anti-GBM (Goodpastures)

Front 84

What is the treatment for pulmonary
hemorrhage in either Wegener's or
Goodpasture's?

Back 84

Plasmapheresis

Front 85

CLINICAL:
acute onset of hematuria, proteinuria and edema; can also see pancytopenia

• Diagnosis: anti-Sm, anti-DS DNA**

Back 85

Lupus Nephritis

Front 86

– III focal nephritis

– IV diffuse nephritis

– V membrane formation, nephrotic range proteinuria

– VI >90% of glomeruli sclerotic, chronic

Back 86

Lupus Nephritis

Front 87

This disease is *associated with both membranous and membranoproliferative GNs*

Back 87

Lupus Nephritis

Nephrotic/Nephritic Syndrome

Front 88

Rx: Class III and above: cyclophosphamide +/- steroids

• Px: Depends on
– Kidney function on presentation
– Histologic type
– Crescents (aggressive disease)

Back 88

Lupus Nephritis

Front 89

Know this summary slide

Back 89

Front 90

Know this algorithim

Back 90

Front 91

Nephritic or Nephrotic Diseases? :

-IgA Nephropathy

• Henoch Schönlein Purpura

• Post-Infectious Glomerulonephritis

• Membranoproliferative GN

• Anti-GBM/Goodpasture‟s Syndrome

• Small Vessel Vasculitis

• Lupus Nephritis

Back 91

Nephritic

Front 92

Nephritic or Nephrotic Diseases? :

-Minimal Change Disease

• Focal Segmental Glomerulosclerosis

• Membranous Glomerulonephropathy

• Diabetic Glomerulosclerosis
(aka Diabetic Nephropathy)

• Amyloid

Back 92

Nephrotic