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65-years- old patient with multiple myeloma with AKI with multiple co morbidities

DR KAZI FAZLUR RAHMAN

PHASE B RESIDENT

DEPARTMENT OF HAEMATOLOGY

BSMMU

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  • Mr Solaiman Khan, a 65 –year-old hypertensive male hailing from cumilla presented to BSMMU with the complaints of –

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    • Low back pain for 5 months
    • Generalised weakness for 2 months

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  • According to the statement of the patient, he was relatively well about 5 months back. Then he complained low back pain which was

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      • Gradual in onset .
      • Localised .
      • Aggravated on movement.
      • Partially relieved on taking some analgesics prescribed by local pharmacy.

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  • He also stated loss of appetite but no nausea or vomiting.
  • He aslo had generalized weakness for 2 months which is gradual in onset and progressively increasing having no diurnal variation.
  • This weakness is now making him unable to do his daily activities.

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  • On query he stated about cough which is dry in nature , more marked in the morning.

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  • He also informed about loose watery stool for 10 days . Not blood mixed & not associated with abdominal pain , tenesmus.

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  • He has no history of –
    • Trauma
    • Tuberculosis
    • Malignancy.
    • Drug history.
    • Past family & social history.

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  • On examination he is –

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      • Drowsy.
      • Anaemic.
      • Mildly dehydrated.
      • He has tenderness on 3rd lumber spine .

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Other systemic examination reveals no abnormality.

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  • With all these complaints he consulted with few physicians & gone through with some investigations .

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12th april 2021

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MRI report of lumber spine

  • Degenerative disc disease.
  • Compression fracture of L1,L2,L3,L5
  • Retropulsed body of L1 causing spinal canal stenosis and conus compression.
  • Bilateral neural foraminal narrowing at L4-L5 level due to posterolateral osteophytosis with abutting disc.

XRAY LUMBO SACRAL SPINE

Degenerative change with compression collapse of L1,L2,L3,L5

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CBC

17 th may

Hb 5.2

ESR 37

TC 9400

Platelet 130000

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Serum creatinine

12 th april

5th may

17th may

4.9

6.98

6.58

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USG

17th may

Bilateral chronic parenchymal disease .

Enlarged prostate.

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  • Then the patient was advised to take admission in department of nephrology BSMMU on 20th may 2021.

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17TH MAY

23TH MAY

26TH MAY

31st may

1st june

CBC

HB 5.2

ESR 37

TC 940O

PLATELET 130000

7.5

37

7000

120000

9.7

38

7300

110000

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cratinine

6.58

6.27

eGFR 10

6.5

6.48

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Phosphate

4.2

4.4

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1

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23rd may

10th june

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Serum calcium

10.4

12.1

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Uric acid

10.2

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pTH

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3.9

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S albumin

33

29

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20th may

23rd may

24th may

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Bence jones protein

absent

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Xray skull

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normal

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Xray L/S spine

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Partial collapseof L1 vertebrae

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Xray chest

normal

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1st june

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Serum protein electrophoresis

Monoclonal gammopathy

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  • They consulted with haematology department and advised to do
        • Bone marrow examination.
        • B2 microglobulin.
        • Serum free light chain ratio.
        • S LDH
        • FISH for myeloma.

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Bone marrow examination

Features are suggestive of plasma cell dyscrasia .

B2 microglobulin

9.4

LDH

200

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  • Patient cant do serum free light chain ratio and FISH for myeloma.

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  • On 18th june patient is transferred to haematology department.
  • On admission
    • Patient is drowsy .
    • Anaemic .
    • Dehydrated.
    • Tenderness over the lumber region. Patients attendent complaints about oliguria.

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  • Lower limb examination :
  • Muscle tone normal .
  • Sensory intact.
  • Jerks normal.
  • Planter bilateral flexor.

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On Admission

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Electrolytes

Na 128

K 8.1

Cl 100

Albumin

1.1

SGPT

32

calcium

18.64

Total protein

7.4

creatinine

7.92

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  • On admission our diagnosis is

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Multiple Myeloma with CKD with hypercalcaemia with electrolyte imbalance.

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  • Immediately after admission we follow up the patient and
      • Give management of hyperkalaemia.
      • Give management of hypercalcaemia by giving calcitonin.
      • Assess fluid balance.
      • Urgent referral to nephrology for dialysis.

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  • Patient got his 1st dialysis on 20st june.
  • Till now patient has got 4 dialysis.

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Post dialysis reports shows

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21st june

Electrolyte

Na 136

K 5.5

Cl 103

Urea

85

S creatinine

7

S calcium

2.6

albumin

1.6

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CBC Reports

23rd june

24th june

26th june

1st july

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Hb 7.2

ESR 90

Platelet 40000

WBC 7000

8

85

60000

6000

9

70

50000

5000

7.5

90

150000

5000

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  • We started VTD protocol on 21st june.

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  • Inj bortezimib 2 mg
  • Tab Thallidomide 100 mg
  • Inj Dexamethasone

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28th may

30th may

1st june

5th june

CBC

HB

WBC

PLATELET

8.6

8000

100000

7.5

5000

105000

7.5

5000

150000

6.7

5000

90000

S CREATININE

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5.12

6

5.98

Urea

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34.9

130.8

Iron

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88 ug /l

Vitamin B12

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410 ng/ml

Folate

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6.08 ng/ml

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  • Now patient complaints –
  • severe back pain that he can not move .
  • Weakness .

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Problems

  • Management of Multiple Myeloma in renal impairment patient.
  • What can we do for bony protection of this patient?
  • Management of anaemia
  • Pain management

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  • Multiple myeloma

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  • Both criteria must be met:
  • − Clonal bone marrow plasma cells 10% or biopsy-proven bony or extramedullary plasmacytoma

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  • − Any one or more of the following myeloma defining events: Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically:

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  • • Hypercalcemia: serum calcium >025 mmol/L (>1 mg/dL) higher than the upper limit of normal or >275 mmol/L (>11 mg/dL)
  • • Renal insufficiency: creatinine clearance 177 μmol/L (>2 mg/dL)

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  • • Anemia: hemoglobin value of >2 g/dL below the lower limit of normal, or a hemoglobin value <10 g/dL
  • • Bone lesions: one or more osteolytic lesions on skeletal radiography, computed tomography (CT), or positron emission tomography-CT (PET-CT) • Clonal bone marrow plasma cell percentage 60%

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  • • Involved : Uninvolved serum free light chain (FLC) ratio-100 (involved free light chain level must be 100 mg/L)
  • • >1 focal lesions on magnetic resonance imaging (MRI) studies (at least 5 mm in size

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Kidney disease in multiple myeloma

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  • Approximately 50 percent of patients with multiple myeloma experience acute kidney injury (AKI) or chronic kidney disease (CKD)

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  • Severe kidney failure, acute or chronic requiring dialysis generally occurs in 1 to 3 percent of patient with multiple myeloma

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Fig: Mechanisms of FLC-induced cast nephropathy and its clinical correlation. THP/THPM - Tamm Horsafall glycoprotein/mucoprotein UROMODULIN

Ref :- Clinical Kidney Journal, 2018, vol. 11, no. 6, 777–785

Fanconi’s Syndorme

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I. AL amyloidosis

  • Nephrotic syndrome

II. LCDD:

  • Proteinuria
  • Microhematuria
  • Varying degrees of renal insufficiency

Proteinuria

With albuminuria

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    • Beta-shaped arranged fibrils interacting serum amyloid call light chain amyloidosis (AL)

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    • FLCs are deposited themselves without any organization (LCDD)

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Fig: FLC can deposit glomerular basement membrane and mesangium and disruption of the filtration barrier.

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Three different condition seen in a myeloma patient with renal impairment

  • Functional renal insufficiency –Rapidly improve after appropriate supportive care

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  • Acute Kidney Injury – Due to cast nephropathy

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  • Chronic kidney diseases – Myeloma may not be the main cause

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Myeloma and Acute Kidney injury

Looking for a trigger (dehydration, hypercalcemia)

Detection serum monoclonal proteins (SPE, IFE)

FLC quantification (nephelometric immunoassays)

Urinary Albumin/Protein ratio

Mainly Albumin (serum FLCs high < 500 mg/L)

Clinical indication for HD?

Candidate for Chamotherapy?

Early HCO HD availability?

Al Amyloid?

Light Chain deposition disease?

Others?

NO

Supportive treatment

YES

Biopsy

NO MCN

Early Chemotherapy + Conventional HD

Early Chemotherapy + HCO HD

FLC monitoring

Biopsy?

Biopsy

Ref :- Clinical Kidney Journal, 2018, vol. 11, no. 6, 777–785

Fig: Proposed algorithm for AKI management and use of HCO-HD in MM patients.

Mainly FLC

(serum FLCs high > 500 mg/L)

Clinical indication for HD?

Candidate for Chemotherapy?

Early HCO HD availability?

Biopsy

MCN

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Bortezomib

  • Safe for patient on dialysis
  • Very effective and act rapidly
  • No dose modification is required
  • 20-50% become dialysis independent
  • Bortezomib-based regimens, especially triplet combinations, should be considered the gold standard in the management of patients with MM-related RI
  • High dose dexamethasone Improve renal function 50% of myeloma patient
  • Shorter time of renal recovery

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High dose dexamethasone

Anti myeloma therapy

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Thalidomide

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  • 1st IMiD use for treatment of myeloma
  • Not secreted by kidney
  • No dose adjustment is required

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Lenalidomide

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  • Renaly excreted and dose adjustments are required
  • Increase toxicity (Thrombocytopenia)

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Anti myeloma therapy

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Thank you