Kidney in Systemic Disease II

Question 1

What causes Sickle Cell Pain Crisis?
• what are some key lab values you would expect to see in this disease?

Answer 1

Sickle Cell Crisis:
• Vasoocclusive Phenomenon

Key Labs (outside of peripheral smear):
• Elevated Reticulocytes
•Elevated Lactate Dehydrogenase and Bilirubin

Smear would show:
• Howell Jolly Bodies from Splenic Infarcts and Sickled cells

Question 2

What percentage of Sickle Cell Patients will progress to end stage renal disease?

Answer 2

4-12% - these patients are hard to take care of because you have anemia on top of renal dysfunction

Question 3

What type of Renal Pathology would you expect to see in someone with Sickle Cell Nephropathy at different points in disease progression:
• Early

• Late
• End Stage

Answer 3

EARLY:
• Focal areas of cortical injury, Hemorrhage and Necrosis with Glomerular Hypertrophy
LATE:
• TUBULAR atrophy and Papillary Infarcts
END STAGE:
• Focal Segmental Glomerulosclerosis

***Really you’re just getting infarcts in the cortex (peritubular capillaries) that also progress through the vasa recta causing ischemia and decreased absorption, eventually tubular dysfunction leads to a decreased GFR.

Question 4

T or F: what is shown here is Chronic Injury due to Sickle Cell.
• KEY FEATURES?

Answer 4

FALSE, this is acute injury, all you see is CONGESTION of peritubular capillaries and ACUTE TUBULAR NECROSIS (notice nuclear fallout on both of these images)

note front and back are both Acute Sickle Cell Nephropathies

Question 5

What immune complexes will stain positive in Sickle Cell Nephropathy?
• Key features on silver staining?

Answer 5

• NONE, sickle cell nephropathy is not associated with immune complex deposition
• Silver Staining Key Features - Duplication of the Basement membrane

Question 6

How do you differentiate this silver staining from Membranoproliferative Glomerulonephritis type I based on the image below?
• Serological studies?

Answer 6

Shown here is Sickle Cell disease you can see sickeled cells inside the glomerular capillaries

Serological Studies:
• Immunoglobulins/ Low C3 levels will be present in MPGN type I, this is not the case in sickle cell

Question 7

Is the image shown below more indicative of acute or chronic sickle cell disease?

Answer 7

CHRONIC - you can see severe sclerosis of the glomeruli here

Question 8

What are the key features seen in this EM from a sickle cell patient?

Answer 8

Podocyte Food Process Effacement
• Impacted cell also suggest an abnormal amount of clotting within the glomerulus

Question 9

What cancer of the Kidney is EXCLUSIVELY associated with sickle cell patients?

• Prognosis?
• Location?

Answer 9

MEDULLARY CARCINOMA OF THE KIDNEY

Prognosis:
• VERY POOR these pts. typically present with Metastatic cancer and die in 4-6 months

Location:
• Cancer is typically localized to the RIGHT kidney

Question 10

What 3 chronic kidney diseases actually cause ENLARGMENT of the kidney?
• why is this unusual?

Answer 10

ENLARGMENT of the kidney:
• Renal Amyloidosis
• Diabetic Nephropathy
• HIV associated Nephropathy

Question 11

What Disease is shown here?
• how does kidney disease progress in a patient who shows thiss?

Answer 11

RENAL AMYLOIDOSIS - any type

Progression: Tubular and Interstitial Deposits may lead to TUBULAR atrophy and INTERSTITIAL fibrosis

Question 12

What type of Amyloidosis should you suspect in someone who has Rheumatoid Arthritis and nephrotic syndrome?

Answer 12

AA amyloid, it associated with diseases of chronic inflammation

Question 13

What type of amyloidosis should you suspect in a person who has polyneuropathy and family history of amyloidosis?

Answer 13

ATTR - transthyretin type of amyloidosis runs in families

Question 14

What type of amyloid should you suspect in a patient with ‘shoulder pads’ and glossomegaly?

Answer 14

AL amyloid - deposition of restricted immuno light chains

Question 15

What disease associations should you make with AL amyloid?

Answer 15

• Multiple Myeloma
• Lymphoma
• Waldenstrom’s Macroglobulinemia

Question 16

What disease associations should you make with AA amyloid?

Answer 16

Any disease that causes chronic Inflammation or Infection

Question 17

Who gets ß2-microglobulin amyloidosis?
• typical sight of deposition?

Answer 17

• People with CHRONIC KIDNEY DISEASE/ PEOPLE on DIALYSIS
• Tends to deposit in the Joints

Question 18

After seeing apple green birefringence on Congo Red Staining of Biopsy, how can you confirm the type of amyloid you’re dealing with?
• AA?
• AL?
• ATTR?

Answer 18

AA:
• Immunohistochemistry is typically enough

AL:
• Need to show MONOCLONAL proliferation in the Bone or Kappa or Lamba restricted light chains in the tissue biopsy

ATTR:
• Need to do a DNA test

Question 19

AL Amyloidosis Nephropathy:
• who are you most likely to see it in?
• Kidney size? HTN? Other problems?

Answer 19

• Mean age is 64 y/o - these pts. probably have cancer/pre-cancer
• Kidney is enlarged in this condition (b/c its an amyloidosis)
• NO hypertension associated with this disease

**Restrictive Cardiomyopathy and GI immotility may also be issues for these patients

Question 20

What is the prognosis after getting diagnosed with PRIMARY AL amyloid?
• What are your treatment options?

Answer 20

Px: BAD, most pts. only live 10 months after diagnosis

Patients under 50:
• Melphalan and get a Stem Cell transplant

Patients over 50:
• Melphalan + Dexamethasone

Question 21

Patients with what type of AL amyloidosis have the greatest chance of developing Multiple Myeloma?

Answer 21

• I Chain AL amyloidosis is most associated with this

Question 22

What is shown here?

Answer 22

Bence Jones proteins can precipitate in the urine or in the tubules and the tubular epithelial cells can coalesce into a syncytium around them:

Shown Below is a Bone Marrow Biopsy of a Patient with amyloidosis

Question 23

What is the main target organ for AA amyloidosis?
• What is the newest treatment option?
• what typically causes death in these patients?

Answer 23

Main Target Organ:
1st = Kidney
2nd = GI

(compare to AL that also targets the hrt)

Newest Tx:
Eprodisate - Prevents interaction between GAGs needed to form amyloid sheets (does not improve survival)

Death:
• Typically related to infection from dialysis

Question 24

What is this patients’ biggest risk factor for experiencing this injury?

Answer 24

This is a ß2 microglobulin defect that deposits in BONE leading to destruction

DIALYSIS patients are the people most often seen with this

Below you can see an H and E of this disease

Question 25

What is Light Chain Deposition Disease? •what is it associated with? • Amyloid Staining? explain.

Answer 25

**Light Chain Deposition Disease**: • Associated with: **MULTIPLE MYELOMA** This **DOES NOT complex** to form chains that are characteristic of amyloid this means it also **WILL NOT STAIN WITH THE CONGO RED DYE**

Question 26

How might someone with light chain syndrome present?

Answer 26

* Proteinuria and renal failure * May have non-nephrotic range proteinuria with a tubulointerstitial syndrome * May present with rapidly declining renal function * May have hepatomegaly * Cardiomegaly, CHF, conduction disturbances * Peripheral neuropathy, GI disturbances, pulmonary nodules, arthropathy, sicca syndrome

Question 27

What are the Key Features of the Image seen here? • what should be in your differential for this image?

Answer 27

* **NODULAR Glomerulosclerosis** * **Deposition along the outside of the Tubular Membrane** * **Expansion of the Mesangial Matrix** **Differential: • Light Chain Deposition Disease • Diabetic Nephropathy**

Question 28

Shown here is a Kappa light chain stain. • Key features? • Dx?

Answer 28

1. **Kappa Restriction** suggests pathology 2. Can see **NODULAR Glomerulosclerotic** appearance Dx: **Light Chain Disease**

Question 29

What should raise suspicion of a patient having Light Chain Disease?

Answer 29

•Increased index of suspicion with nephrotic syndrome or rapidly progressive tubulointerstitial nephritis, **cardiac diastolic dysfunction**, and **presence of monoclonal immunoglobulin in the urine or serum**

Question 30

HIV-associated Nephropathy • Type of Neuropathy? **What distinguishes it from others of this type?** • Who does this occur in most often?

Answer 30

HIVAN **COLLAPSING Focal Segmental Glomerulosclerosis** mostly occurs in **AFRICAN AMERICANS** **\*\*MYCROCYSTIC DILATED TUBULES with PODOCYTE PROLIFERATION and Interstitial inflammation** distinguish this from other FSGS types

Question 31

Besides HIVAN, what else can cause Microcystic Tubular Dilation and podocyte proliferation in FSGS?

Answer 31

**Bisphosphonate Pamidronate**

Question 32

What viral Genes are believed to be key in causing HIVAN? • genes that make African Americans Susceptible?

Answer 32

Viral Genes: • **Nef and Vpr - cause DE-differentiation of podocytes** African American Susceptibility: • **APOL1** related

Question 33

What should you be thinking when you see the following clinical features? ## Footnote **•Black race** **•Advanced HIV disease** **•Heavy proteinuria** **•Rapid decline in kidney function**

Answer 33

**HIVAN - behind sickle cell, this is the most common cause of End Stage Renal Disease in young African Americans**

Question 34

What cause glomerular collapse in HIVAN?

Answer 34

FSGS leads to collapse because of **PODOCYTE** (visceral epithelial) overgrowth

Question 35

What is shown here? • KEYYYY terms?

Answer 35

**Collapsing FSGS from HIVAN** * This shows the **MICROCYTIC\*\*\*\* tubular interstitial** appearance (lots of little holes to the left) * On the far right in the middle you can see collapsed glomeruli

Question 36

What triad is associated with Cryoglobulinemia? * markers found in serum? * Disease association? * Persistence of the disease?

Answer 36

* **Palpable Purpura * Asthenia * Arthralgia** **Rh factor and Cryoglobulins are key** Disease Association: • **90% of cases are associated with Hepatitis C** Persistence: • **Described as Waxing and Waning**

Question 37

Cryglobulinemia * Immune Complex Disease? * Kidney Pathology? * Presence of Proteinuria or Hematuria? * Px?

Answer 37

* Renal disease usually due to immune complex disease * Was the cause of biopsy proven **glomerulonephritis** * **Membranoproliferative glomerulonephritis** is the typical renal biopsy finding * I**solated proteinuria or hematuria** occurs much more frequently than nephrotic or nephritic syndromes or acute renal failure. * Most patients declare a **chronic or rapidly progressive disease course within three to five years of diagnosis**

Question 38

Where does Cryglobulinemia tend to affect the kidney?

Answer 38

**Intralobular Arteries and Afferent Arterioles** **See Below:** deeply acidophilic material in the vessel probably is a **mixture of thrombus, fibrinoid necrosis, and aggregated cryoglobulins**. The vessel wall and adjacent tissue are i**nfiltrated by leukocytes** with leukocytoclasia.

Question 39

Cryglobulinemia In acute cases, the deposits produce the appearance of **thrombi** or **wire loops** comparable to what is seen in lupus glomerulonephritis.

Question 40

What do you expect to see on immunofluorescence of Cryoglobulinemia? • what immuno stain should you probably use?

Answer 40

**GLOBULAR APPEARANCE** of Cryogloblulins most often is **C3**

Question 41

What key Feature on this EM lets you know that its Cryoglobulinemia?

Answer 41

**Fibrillary** Appearance in the **SUBEPITHELIUM**

Question 42