Renal Failure in Multiple Myeloma: Incidence, Correlations and Prognostic Significance.

Introduction: Renal failure (RF) is a common and severe complication of patients with multiple myeloma (MM). The purpose of our study was to assess the incidence of RF in a contemporary series of newly diagnosed patients with MM, its association with specific clinical and laboratory features and its impact on early death rate, on myeloma response and on patients survival.

Patients and Methods: Between January 1995 and December 2004, 756 newly diagnosed symptomatic patients with MM were included in the database of the GMSG. Renal failure, was defined as a serum creatinine ≥2mg/dL at the time of diagnosis. The incidence of RF was correlated with multiple clinical and laboratory variables by univariate and Cox regression analysis.

Results: The incidence of RF in this series of patients was 21%. This figure was similar to the incidence of RF (19%) in patients diagnosed during the preceding decade. Severe RF (serum creatinine ≥6mg/dL) occurred in 4% of patients. There was a significant association of renal failure with poor performance status (p=0.001), increased ISS stage (p<0.001), elevated serum β₂microglobulin (p<0.001), hypercalcemia (p<0.001), increased Bence Jones proteinuria (p<0.001), high serum LDH (p<0.002), low platelet count (p=0.004), low albumin (p=0.036) and light chain only on IgD myeloma (p<0.001). Multivariate analysis showed that RF was independently associated only with ISS and Bence Jones proteinuria. Early death, within 2 months from treatment initiation, was observed in 10% of patients with RF and in 4% of patients without RF (p=0.2). At least partial response (EBMT criteria) was documented in 61% of patients without RF and in 55% of patients with RF (p=0.2). The median survival of patients with RF was 19.5 months versus 40.4 months for patients without RF (p<0.001). Other variables associated with impaired survival by univariate analysis included poor performance status, thrombocytopenia, hypercalcemia, high serum LDH, advanced age and elevated serum β2 microglobulin. However, when multivariate analysis was performed the independent variables were poor performance status, thrombocytopenia, advanced age, high LDH and elevated serum β2 microglobulin but not high creatinine. The median survival of patients with ISS stage 2 and 3 without RF was 36 months and 22 months respectively compared to 19 months and 20 months for patients with RF (p=0.1 and 0.5 respectively).

Conclusions: The incidence of RF remains significant and essentially unchanged in patients with MM diagnosed over the last 20 years. The presence of RF is associated with a trend for higher early death rate but with a similar response to primary therapy. Patients with RF have lower survival compared to patients without RF. The prognostic significance of RF is mainly attributed to its association with higher β₂;microglobulin and Bence Jones proteinuria.