Kidneys in systemic disease

Question 1

What are some systemic causes of CKD?

Answer 1

Myeloma
Amyloidosis
Vasculitis
SLE

Question 2

What is myeloma?

Answer 2

A haematological cancer in which there is clonal expansion of plasma cells causing production of clinical immunoglobulins (M-proteins)

Question 3

What are some symptoms of myeloma?

Answer 3

• Bone pain
• Weakness
• Fatigue
• Weight loss
• Recurrent infections

Question 4

What are some signs of myeloma?

Answer 4

• Anaemia
• Hypercalcaemia
• Renal failure
• Lytic bone lesions

Question 5

What causes renal impairment in myeloma (20-40%)?

Answer 5

• Glomerular - Monoclonal immunoglobulin deposition
• Tubular - Light chain cast nephropathy
• Misc. - Dehydration, hypercalcaemia, contract, bisphosphonates and NSAIDs

Question 6

What investigations are required in myeloma?

Answer 6

Bloods
Urine
Bone marrow biopsy
Skeletal survey
Renal biopsy

Question 7

What blood tests in particular are required in myeloma?

Answer 7

Serum protein electrophoresis
Serum free light chains

Question 8

What will be seen in urine in myeloma?

Answer 8

Bence-Jones proteins (Clonal light chains)

Question 9

What are some management options of renal impairment in myeloma?

Answer 9

Stop nephrotoxic drugs
Manage hypercalcaemia
Chemotherapy or stem-cell transplant
Dialysis

Question 10

What is amyloidosis?

Answer 10

This is the deposition of extracellular amyloid (Insoluble protein fibrils) in the tissues or organs

Question 11

Describe the pathophysiology of amyloidosis

Answer 11

Abnormal folding of proteins which then aggregate and become insoluble

Breakdown of usual degredation pathways for abnormally folded proteins

Question 12

What re the 4 most common forms of amyloidosis?

Answer 12

• Primary / Light chain (AL)
• Secondary / Systemic / Inflammatory (AA)
• Dialysis (Aß2M)
• Hereditary and old age (ATTR)

Question 13

Describe the pathway of primary (Light chain) amyloidosis (AL)

Answer 13

Unknown factor causes monoclonal B-lymphocyte proliferation
This causes monoclonal plasma cell formation
This causes release of immunoglobulin light chains (Bence-Jones) which is deposited in the kidneys causing damage

Question 14

Describe the pathway of secondary/systemic/inflammatory amyloidosis (AA)

Answer 14

Chronic inflammation causes macrophage activation
Macrophages release IL-1 and IL-6
This causes liver cells to release SAA protein which build up in the kidneys causing damage

Question 15

Renal presentation of amyloidosis

Answer 15

Nephrotic proteinuria +/- Impaired renal function

Question 16

Cardiac presentation of amyloidosis

Answer 16

cardiomyopathy

Question 17

Nervous presentation of amyloidosis

Answer 17

Peripheral or autonomic neuropathy

Question 18

Gastrointestinal presentation of amyloidosis

Answer 18

• Hepatomegaly/Splenomegaly
• Malabsorption

Question 19

What investigations are required in amyloidosis?

Answer 19

Urinalysis + PCR
Blood tests - RFT, Inf markers, protein electrophoresis
Renal biopsy
SAP scan

Question 20

What test is performed on renal biopsy in amyloidosis?

Answer 20

Congo red staining → Apple green under polarised light

Question 21

What is a SAP scan?

Answer 21

Scintigraphy with radiolabelled serum amyloid to show extent of the disease

Question 22

How is AA amyloidosis managed?

Answer 22

Treat underlying condition

Question 23

How is AL amyloidosis managed?

Answer 23

Immunosuppression - Steroids, chemotherapy, stem cell transplant

Question 24

What is systemic lupus erythematosus (SLE)?

Answer 24

This is a chronic auto-immune inflammatory disease of unknown origin

Question 25

What systems can be affected by SLE?

Answer 25

skin, joints, kidneys, lungs, nervous system and serous membranes

Question 26

Who is most at risk of SLE?

Answer 26

Most commonly affects women aged 20-30 and African Americans and Hispanics

Question 27

What tests are required in SLE?

Answer 27

- Blood tests - Raised inflammatory markers, immunology (Anti-dsDNA) , complement system markers - Urinalysis - Proteinuria +/- microscopic haematuria

Question 28

What percentage of SLE patients have renal involvement?

Answer 28

50%

Question 29

What is renal impairment due to SLE called?

Answer 29

Lupus nephritis

Question 30

What are the 6 ISN classes of lupus nephritis?

Answer 30

- Class I - Minimal mesangial - Class II - Mesangial proliferative - Class III - Focal proliferative - Class IV - Diffuse proliferative - Class V - Membranous - Class VI - Advanced sclerosing

Question 31

How is lupus nephritis managed?

Answer 31

Immunosuppression