CASE STUDIES

 

A previously healthy 35-year old Caucasian female was seen on Jan. 2002 by her GP because of knee pain (right side) and fatigue. Lab analysis showed hypercalcemia, but normal S-creatinine (106 µmol/l), and she was referred to the Dept. of Internal Medicine. Unfortunately, as she canceled her first appointment, she was not seen until Oct. 2002.

It was noticed that she was pale. As she had a cold and signs of sinusitis peroral treatment with amoxicillin 375 mg x 2 was started. Her body temperature was 37.4 C. Lab analysis showed hemoglobin 73 g/l, sedimentation rate 80 mm, S-albumin 46 g/l, S-creatinine 439 µmol/l, and S-Calcium 2.66 µmol/l. A Dipstix showed no sign of albuminuria. She was referred to a Renal Clinic.

On Oct. 16 she was seen by a Nephrologist. She was pale but otherwise unaffected. Body weight was 98.6 kg and her height 173 cm. Her blood pressure was 166/103 mmHg and peroral treatment with enalapril 10 mg x 1 and felodipin 5 mg x 1 was initiated. Evaluation of routine cardiac, abdominal, neurological and pulmonary status were normal. Renal ultrasonography showed two normal-sized kidneys without signs of obstruction. A renal biopsy was performed (Fig. 1).

Fig. 1

Light microscopy showed 22 glomeruli with no signs of sclerosis or crescents. However, a chronic tubulointerstitial nephritis with moderate tubular atrophy and tubulointerstitial lymphocytic interstitial inflammation was present.

Question 1

A 24-hour urinary collection (Fig. 2) was done.

Fig. 2

Result: • U-protein 8.7 g/24h
          • U-albumin 129 mg/24h.

Question 2

Urine electrophoresis was performed and showed marked Bence-Jones proteinuria with excretion of light chains type kappa at a concentration of 8237 mg/24h. Also a plasma electrophoresis showed a M-component of free light chains type kappa. Slightly depressed levels of plasma IgA (0.47 g/l) were also noted.

Question 3

A bone marrow specimen showed a hypercellular bone marrow with 15% pathological plasma cells.
A X-ray of the skull (Fig. 3) showed a number of lytic changes. Lytic changes were also found in the right femur of the patient.

Fig. 3

Immunohistochemical staining (Fig. 4) showed a pathological staining pattern (anti-kappa) in tubular cells.

Fig. 4

Thus, a diagnosis of light-chain multiple myeloma was made.

Question 4

 

The glomerular filtration rate (iohexol clearance) was 15 ml/min/m2. Therefore advanced renal failure was present.

Question 5

Fanconi's syndrome, which was first described by the Swiss Pediatrician Guido Fanconi (1892-1979) (the person to the right in Fig. 5), may occur in many systemic disorders, including multiple myeloma. The classical Fanconi's syndrome includes hyperexcretion of amino acids, ions and proteins with molecular weights under 50 kD in conjunction with renal tubular acidosis and vasopressin-resistant polyuria.

Fig. 5

Question 6

Constantly elevated S-Calcium levels ranging between 2.76-2.86 mmol/l were noted. On the other hand, there were no signs of hyperphosphatemia (1.4 mmol/l), hyperkalemia (4.0 mmol/l), hyponatremia (135 mmol/l) or acidosis.

Question 7

On Oct. 24 the patient was transferred to the Dept. of Hematology for cytostatic treatment. A standard regimen of adriamycin, oncovin and dexamethason was initiated. As S-Calcium remained elevated intravenous zoledroan acid (a biphosphonate) was given, which resulted in a transient hypokalcemia (1.77 mmol/l) and paresthesias. The patient received blood transfusion and rhEPO (4000 E x 2/w) treatment was initiated. Upon dismissal, on Oct. 30, her hemoglobin was 101 g/l whereas S-creatinine had decreased from 473 to 323 µmol/l. As of today the patient is at home with her husband and son and feels better, although she is still tired.

Question 8

Teaching points

1) The present case illustrates the sad fact that, although rare, multiple myeloma can occur even in young adult patients. Thus, all patients with unclear skeletal pain, proteinuria and/or unexplained renal impairment should be evaluated with plasma and urine electrophoresis irrespective of age.

2) A normal Dipstix test does not exclude an abnormal urinary protein excretion.

3) If a marked discrepancy between urinary protein - and albumin excretion is noted urine electrophoresis is mandatory.

4) Intravenous infusion of biphosphonates should not be given too rapidly as it may cause symptomatic hypocalcemia.