Renal failure is present in about 20% of patients with multiple myeloma (MM) at diagnosis. Renal function impairment is usually caused by the so-called "Myeloma Kidney" and is associated with shortened survival. Renal failure is reversible in up to 50% of patients, particularly when its degree is moderate and related to precipitation factors such as hypercalcemia. However, in our experience, approximately 10% of patients diagnosed with MM in a general hospital have renal failure severe enough to require dialysis. Despite its frequency and poor prognostic significance, there are few reports dealing with MM and renal failure. In this short report, the following issues are summarized:
Results from a Single Institution Series
During a 25-year period, 94 of a series of 423 (22%) patients with MM had serum creatinine level equal or higher than 2mg/dL (44 patients had a serum creatinine level from 2 to 3.9mg/dL while the remaining 50 patients had a serum creatinine equal or higher than 4mg/dL. The response to chemotherapy was 39% (24% in patients treated with a single alkylating agent and prednisone vs. 50% in patients given combination chemotherapy; p=0.031). Complete renal function recovery was achieved in 26% of patients (48% of patients with serum creatinine between 2 and 3.9mg/dL and 8% of patients with serum creatinine equal or higher than 4mg/dL; p=0.001). Using logistic regression analysis, the factors independently associated with renal function recovery were: serum creatinine <4mg/dL, serum calcium >11.5mg/dL, urine protein excretion <1g/24 hours. The median survival of the 94 patients with renal failure was 9 months vs. 33 months for those with normal renal function. Of interest, patients who recovered from renal failure had a survival similar to that of those with normal renal function at diagnosis. Using multivariate analysis, the factors significantly influencing survival were serum creatinine and response to chemotherapy.
Long-term Dialysis in Multiple Myeloma
During a 12-year period, 30 patients with MM required hemodialysis (HD) at our institution. The results observed in 20 patients who survived more than 2 months on HD are summarized. 85% of the patients were in stage III. Renal biopsy was consistent with myeloma kidney in all 10 patients in whom a biopsy was carried out. The response rate to chemotherapy was 40%. HD was discontinued in only 2 patients (one received a kidney graft and one had a late partial recovery). The median survival was 20 months and six patients survived for more than 3 years. There were a total of 42 hospital admissions. The mean hospitalization was 19 days per year. However, the subgroup of patients who survived less than 1 year spent 38 days in the hospital whereas the mean hospitalization days for those who survived more than 1 year was only 9 days. This was the same as for patients on HD program because of diabetic nephropathy.
Role of Plasma Exchange
It has been suggested that a rapid removal of light chains with chemotherapy and plasma-exchange could prevent or improve renal failure. However, at the Mayo Clinic, a trial comparing forced diuresis and chemotherapy vs. forced diuresis, chemotherapy and plasma-exchange was carried out. There was a trend in favor of plasma-exchange, but the difference was not statistically significant. In our experience, patients with renal failure severe enough to require dialysis are very unlikely to respond to plasma exchange. In contrast, patients with severe, non-oliguric, renal failure are more likely to benefit from this procedure.
High-dose Therapy/Autotransplantation in Patients with MM and Renal Failure
The experience of the Spanish Registry for Transplant in MM was analyzed. A total of 566 evaluable patients were included and analyzed in the three following groups:
- Patients with normal renal function at diagnosis and transplant (n=476),
- Patients with abnormal renal function at diagnosis, but normal at the time of transplant (n=73),
- Patients with renal failure at the time of diagnosis and at the time of trans-plantation (n=14).
The transplant related mortality (TRM) was significantly higher in the group with renal failure at transplantation (29% vs. 3.3% and 4.2%). However, in evaluable patients the response rate after transplant was similar in the three groups (90% vs. 91% vs. 92%). In addition, the 3-year survival from transplant was similar in the three groups. Using multivariate analysis on TRM, three variables showed independent influence: performance status 3 or 4, hemaglobin level <9g/dL and serum creatinine higher than 5mg/dL. According to these results, patients with poor performance status and a serum creatinine higher than 5mg/dL should be excluded from transplant programs.
Treatment proposal for Patients with Severe Non-oliguric Renal Failure
Considering the crucial importance of the serum creatinine level in the reversibility of renal failure, our proposal for patients with a serum creatinine higher than 4mg/dL and still with no need for dialysis is chemotherapy with VAD or cyclophosphamide/dexamethasone (in those with cardiac disorders) along with early plasma-exchange with serial measurements of light chains in serum and urine before and after each plasma exchange in order to investigate the efficacy and optimal timing of this procedure.
- Bladé, J, Fernandez-Llama P, Bosch F, et al. Renal failure in multiple myeloma. Presenting features and predictors of outcome in 94 patients from a single institution. Arch Intern Med 1998; 158: 1889-1893
- Torra R, Bladé J, Cases A, et al. Patients with multiple myeloma requiring long-term dialysis: presenting features, response to therapy, and outcome in a series of 20 cases. Br J Haematol 1995; 91: 854-859.
- San Miguel JF, Lahuerta JJ, Garcia-Sanz R, et al. Are myeloma patients with renal failure candidates for autologous stem cell transplantation? The Haematology Journal 2000; 1: 28-36