Multiple myeloma, nephrotic syndrome and crystalloid inclusions in podocytes

A 54-year-old white female with a past history of hypothyroidism and smoldering multiple myeloma (MM) presented with the new onset of severe nephrotic syndrome and acute renal failure. She had been diagnosed 2 years earlier with stage IA MM following traumatic fractures of the pelvis and right hip. At that time, she was found to have an immunoglobulin G (IgG)-kappa serum monoclonal ('M') spike of 4.02 g/dl, bone marrow biopsy showed 60-70% plasmacytosis and skeletal survey was negative for lytic lesions. Blood urea nitrogen was 20 mg/dl (7.1 mmol/l) (normal range, 7-25 mg/dl (2.5-8.9 mmol/l)), serum creatinine was 1.0 mg/dl (88 mu mol/l), serum calcium was normal and 24 h urinary protein was 279 mg/day. Following evaluation at two major myeloma treatment centers, it was decided that no specific therapy was needed. Five months after diagnosis, urine protein excretion was 467 mg/day. Osteopenia of the lumbar spine was noted 7 months after the diagnosis of myeloma and she was started on pamidronate 90 mg intravenous monthly. Three months after the initiation of pamidronate therapy, the patient's serum creatinine rose progressively to 1.5-1.6 mg/dl (133-141 mu mol/l) with a decline in serum albumin from 3.5 to 2.5 g/dl (35-25 g/l) (normal range, 4.1-5.3 g/dl (41-53 g/l)). She developed periorbital and lower extremity edema accompanied by the new appearance of nephrotic range proteinuria 14 g/day). Serum creatinine continued to increase to 3.9 mg/dl (345 mu mol/l) 1 month later. At this time, she was found to have a rising serum monoclonal 'M' spike and was started on cyclic dexamethasone (40 mg daily for 4 days every 3 weeks for six cycles), cyclophosphamide, thalidomide 100 mg daily and bortezomib. She was referred for nephrologic evaluation of severe nephrotic syndrome and acute renal failure. Physical examination revealed a well-developed, well-nourished female with a blood pressure of 180/90 mmHg, pulse 68/min and no jugular venous distention. The heart was regular in rate and rhythm and a II/VI systolic ejection murmur was detected at the left sternal border. The lungs were clear to auscultation. The abdomen was soft and non-tender. There was no organomegaly. There was 3+ pitting edema in the lower extremities. Laboratory data on presentation were as follows: hematocrit, 35.6% (normal range, 35-47%); blood urea nitrogen 30 mg/dl (10 mmol/l); serum creatinine, 3.9 mg/dl (345 mu mol/l); creatinine clearance 18 cm(3)/min; 24-h urine protein, 14400mg; total serum protein, 8.2 g/dl (82 g/l) (normal range, 6.3-8.2 g/dl (63-82 g/l)); serum albumin, 2.9 g/dl (29 g/l); and serum bicarbonate 29 mM/l (normal range, 25-32 mM/l). Urinalysis revealed 4+ protein and 3+ heme, with normal pH and negative glucose. Serum sodium, potassium, chloride, calcium, phosphorus and uric acid were normal. Quantitated serum immunoglobulins (Ig) included reduced serum IgA < 7mg/dl (< 0.07 g/l) (normal range, 70-350 mg/dl (0.7-3.5 g/l)); reduced serum IgM 9.6 mg/dl (0.096 g/l) ( normal range, 50-300 mg/dl (0.5-3 g/l)); and markedly elevated serum IgG 3540 mg/dl (35.4 g/l) (normal range, 700-1700 mg/dl (7-17 g/l)). Serum immunofixation revealed an IgG-kappa 'M' spike. A renal biopsy was performed.