A 75-year-old man presented with fatigue, decreased urine output, and lower back pain. Examination found lumbar tenderness and leg swelling. Labs showed anemia, elevated creatinine and calcium, but no blood or protein in the urine. This presentation is most consistent with renal deposition of immunoglobulin light chains from multiple myeloma.

1. 1
A 75-year-old man comes to the physician because of fatigue and decreased urine output
for 1 week. He takes ibuprofen as needed for lower back pain and docusate for
constipation. Physical examination shows tenderness to palpation over the lumbar spine.
There is pedal edema. Laboratory studies show a hemoglobin concentration of 8.7 g/dL, a
serum creatinine concentration of 2.3 mg/dL, and a serum calcium concentration of 12.6
mg/dL. Urine dipstick is negative for blood and protein. Which of the following is the most
likely underlying cause of this patient's symptoms?
A. Antiglomerular basement membrane antibodies
B. Immunoglobulin light chains
C. Renal deposition of AL amyloid
D. Anti-double-stranded DNA antibodies
E. Hypersensitivity reaction

2. Subjective clinical presentation
2
⊡ Patient profile: 75 year old man.
⊡ Chief complaint: fatigue and decreased urine output for 1 week.
⊡ Medications: ibuprofen for lower back pain and docusate for constipation.
⊡ Physical examination: tenderness over the lumbar spine and pedal edema.
⊡ Laboratory studies:
• Hemoglobin concentration is 8.7 g/dL  Decreased  Anemia
• Serum creatinine concentration is 2.3 mg/dL  Elevated  Renal Failure
• Serum calcium concentration is 12.6 mg/dL  Elevated  Constipation
• Urine dipstick is negative for blood and protein.

3. Multiple Myeloma
3
⊡ Malignant monoclonal proliferation of plasma cells in the bone marrow.
⊡ A bone marrow sample composed of 10% of plasma cells at least.
⊡ Disorder of older patients (Median age: 66).
⊡ Highly dependent on high serum IL-6  stimulate plasma cell proliferation and
immunoglobulin production.
⊡ Most symptoms are caused by excess immunoglobulin production by plasma cells 
IgG overproduction in 55% of cases, IgA overproduction in 20% of cases.
⊡ Free light chains only in 15% of cases, building up in different organs and tissues.

4. 4
⊡ Most common clinical features of multiple myeloma: “Old CRAB”.

5. Clinical manifestations
1. Bone pain and hypercalcemia:
⊡ Neoplastic plasma cells produce osteoclast-activating factor that
binds the RANK receptor on osteoclasts leading to bone destruction.
⊡ Characteristic bone lytic lesions ‘punched out’ are seen on x-ray
especially in the vertebra causing back pain, and skull.
⊡ Increased risk for fracture.

6. Figure 1: Characteristic bony lytic lesions on x-ray consistent with multiple myeloma.

7. Clinical manifestations
2. Elevated serum protein.
⊡ Neoplastic plasma cells produce abnormal
monoclonal immunoglobulins with
characteristic M spike on serum protein
electrophoresis resulting in elevated serum
protein
3. Increased risk of infection.
⊡ Since there is monoclonal proliferation of
plasma cells, plasma cells will be producing
monoclonal antibodies which lacks antigenic
diversity.
⊡ Infection is the most common cause of death
in multiple myeloma

8. Clinical manifestations
4. Rouleaux formation of RBC’s.
⊡ The presence of increased positively charged
plasma proteins (serum immunoglobulins in
case of multiple myeloma) decreases charge
between RBC’s allowing them to stick together.
Figure 3: Rouleaux formation of RBC’s on blood smear.

9. Clinical manifestations
5. Primary Al amyloidosis.
⊡ Overproduction of free light chains by neoplastic plasma cells in the serum,
causes them to eventually deposit in tissues and cause amyloidosis.
6. Proteinuria.
⊡ Free light chains can be excreted in the urine as Bence Jones proteins
(Figure 4). The deposition of these proteins in kidney tubules leads to risk of
renal failure.
⊡ Bence Jones protein show negative result on urine dipstick. Confirmed by
electrophoresis.

10. 10
Figure 4: Bence Jones protein cast.

11. Clinical manifestations
7. Normocytic/normochromic Anemia.
⊡ Inadequate production of red blood cells could be due to 3 reasons:
- Erythropoietin deficiency from accompanying renal failure
- Pronounced marrow replacement by myeloma cells which crowd out the
production of healthy cells.
- Cytokine-mediated marrow suppression.

12. Risk Factors
 Age : Myeloma occurs most commonly in people over 60.
 Gender : Male > Female
 Genetic
 Monoclonal gammopathy of undetermined significance (MGUS)
 Obesity

13.  Diagnosis :

14. Treatment
⊡ Immunotherapy
⊡ Chemotherapy
⊡ Corticosteroids
⊡ Bone marrow ( stem cell ) transplant

15. A. Antiglomerular basement membrane antibodies
B.
C.Immunoglobulin light chains
D.Renal deposition of AL amyloid
E. Anti-double-stranded DNA antibodies
F. Hypersensitivity reaction
Immunoglobulin light chains

16. A. Antiglomerular basement membrane antibodies

17. ⊡ A 75-year-old man comes to the physician because of fatigue and decreased urine
output for 1 week. He takes ibuprofen as needed for lower back pain and docusate for
constipation. Physical examination shows tenderness to palpation over the lumbar
spine. There is pedal edema. Laboratory studies show a hemoglobin concentration of
8.7 g/dL, a serum creatinine concentration of 2.3 mg/dL, and a serum calcium
concentration of 12.6 mg/dL. Urine dipstick is negative for blood and protein
NO LUNG SYMPTOMS :
Coughing up blood
Dry cough
Shortness of breath
NO HEMATURIA OR PROTEINURIA

18. C. Renal deposition of AL amyloid

19. Renal deposition of AL amyloid
A 75-year-old man comes to the physician because of fatigue and decreased urine
output for 1 week. He takes ibuprofen as needed for lower back pain and docusate for
constipation. Physical examination shows tenderness to palpation over the lumbar spine.
There is pedal edema. Laboratory studies show a hemoglobin concentration of 8.7 g/dL,
a serum creatinine concentration of 2.3 mg/dL, and a serum calcium concentration of
12.6 mg/dL. Urine dipstick is negative for blood and protein
NO SYMPTOMS FROM OTHER ORGANS :
Cardiac abnormalities
NO PROTEINS IN URINE

20. D. Anti-double-stranded DNA antibodies

21.  FATIGUE
 LOWER BACK PAIN
 RENAL FAILURE
NO other classic findings of underlying SLE:
FEVER
CARDIAC ABNORMALITIES
MALAR RASH
Anti-double-stranded DNA antibodies

22. Hypersensitivity nephropathy:
is an acute interstitial nephritis (AIN) which
may occur in patients with long-term use of
analgesic agents, including ibuprofen
IN OUR CASE :
NO FEVER, FLANK PAIN AND HEMATURIA