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Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment.

Sugihara H, Chihara D, Seike K, Fukumoto K, Fujisawaa M, Suehara Y, Nishida Y, Takeuchi M, Matsue K - Blood Cancer J (2014)

Bottom Line: There is no reliable test for predicting reversibility of RI in MM patients.We postulated that MM with high albuminuria may reflect glomerular disease that is difficult to reverse.Here, we examined the impact of urinary albumin excretion.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Medicine, Kameda Medical Center, Kamogawa-shi, Chiba, Japan.

ABSTRACT
Reversal of renal dysfunction significantly affects the prognosis of multiple myeloma (MM) with renal impairment (RI). There is no reliable test for predicting reversibility of RI in MM patients. We postulated that MM with high albuminuria may reflect glomerular disease that is difficult to reverse. Here, we examined the impact of urinary albumin excretion. We retrospectively analyzed 279 patients admitted to our hospital from April 2000 to December 2013. Clinical variables and laboratory data that may affect myeloma treatment response were extracted. The results were examined for relationship to renal response by univariate and multivariate analysis. RI (estimated glomerular filtration rate ≦50 ml/min per 1.73 m(2)) was observed in 116 patients (46%) and renal responses of renal complete response, renal partial response, renal minor response and no response were obtained in 46 (40%), 15 (13%), 13 (11%) and 42 (36%) patients, respectively. Although renal recovery was significantly associated with Durie-Salmon 1 or 2 (P=0.02), myeloma response better than very good partial response (P=0.03), involved free light-chain (iFLC) reduction from baseline 80% at day 12 (P=0.005), ≧95% at day 21 (P<0.001) and urinary albumin ≦25% on admission (P<0.001) on univariate analysis, only reduction of iFLC 95% at day 21 (P=0.015) and urinary albumin ≦25% (P=0.007) remained significant for any renal response. Our observation indicates that increased urinary albumin excretion >25% and reduction of iFLC ≦95% on day 21 were associated with favorable renal recovery in MM patients with RI, and were considered as negative predictors for renal response.

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ROC analysis of % of iFLC reduction for obtaining any renal response in patients with RI. (a) ROC analysis of FLC reduction at day 12 from the baseline. The highest sensitivity point of % of iFLC reduction at day 12 was identified as 81.7% with sensitivity 0.931, specificity 0.500 and AUC 0.740 with 95% CI of 0.633–0.850. (b) ROC analysis of FLC reduction at day 21 from the baseline. The highest sensitivity point of % of iFLC reduction at day 12 was identified as 95.5% with sensitivity 0.931, specificity 0.500 and AUC 0.742 with 95% CI of 0.635–0.850.
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fig1: ROC analysis of % of iFLC reduction for obtaining any renal response in patients with RI. (a) ROC analysis of FLC reduction at day 12 from the baseline. The highest sensitivity point of % of iFLC reduction at day 12 was identified as 81.7% with sensitivity 0.931, specificity 0.500 and AUC 0.740 with 95% CI of 0.633–0.850. (b) ROC analysis of FLC reduction at day 21 from the baseline. The highest sensitivity point of % of iFLC reduction at day 12 was identified as 95.5% with sensitivity 0.931, specificity 0.500 and AUC 0.742 with 95% CI of 0.635–0.850.

Mentions: We retrospectively reviewed the medical records of the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa-shi, Japan, from April 2000 to December 2013. Patients diagnosed as MM complicated with RI were included in the study. Diagnosis of myeloma and evaluation of treatment response were performed according to the International Myeloma Foundation criteria and the treatment response criteria.15 Patients with primary systemic amyloid light-chain (AL) amyloidosis were excluded from this study. RI was defined as an estimated glomerular filtration rate (eGFR) that was measured before treatment ≦50 ml/min per 1.73 m2 by the simplified Modification of Diet in Renal Disease formula.16, 17, 18 Maximal renal response was evaluated during the course of disease according to the recently proposed ‘Criteria for the Definition of Renal Response to Antimyeloma Therapy' from the International Myeloma Working Group.2 Briefly, renal complete response (CRenal) was defined as a sustained (i.e., lasting for at least 2 months) increase in baseline eGFR to 60 ml/min per 1.73 m2. Renal partial response (PRenal) was defined as an increase of eGFR from 15 to 30–59 ml/min per 1.73 m2 and renal minor response (MRenal) as sustained improvement of baseline eGFR of <15 to 15–29 ml/min per 1.73 m2 or, if baseline eGFR was 15–29 ml/min per 1.73 m2, improvement to 30–59 ml/min per 1.73 m2. If the patient was dependent on dialysis, achievement of dialysis independency was regarded as at least MRenal depending on the recovery of eGFR. Demographic and laboratory data were obtained from electronic records. Patients with pre-existing severe RI (creatinine ≧2.0 mg/dl) owing to causes other than MM were excluded from the study. Extracted clinical data related to myeloma and RI included age, sex, complete blood count, urinalysis, serum protein electrophoresis, serum FLCs, serum albumin, β2-microglobulin, serum creatinine, total urinary protein and urine protein electrophoresis. The percentage of urinary albumin excretion was calculated by protein electrophoresis pattern on admission, and it was considered zero if the protein electrophoresis could not detect any albumin (5 mg/dl). Typical measurement of urine albumin by urine protein electrophoresis was shown in Figure 1. Serum FLCs were measured by nephelometry using the BN II nephelometer (Dade Behring, Deerfield, IL, USA) and Freelite Serum Free Light Chain Kit (The Binding Site, San Diego, CA, USA). Reduction of serum FLC was checked at day 12 and at day 21 after the start of antimyeloma therapy. Baseline serum FLC data were available for 90 patients with RI, as the Freelite assay was not available at our institution until September 2007.


Percentage of urinary albumin excretion and serum-free light-chain reduction are important determinants of renal response in myeloma patients with moderate to severe renal impairment.

Sugihara H, Chihara D, Seike K, Fukumoto K, Fujisawaa M, Suehara Y, Nishida Y, Takeuchi M, Matsue K - Blood Cancer J (2014)

ROC analysis of % of iFLC reduction for obtaining any renal response in patients with RI. (a) ROC analysis of FLC reduction at day 12 from the baseline. The highest sensitivity point of % of iFLC reduction at day 12 was identified as 81.7% with sensitivity 0.931, specificity 0.500 and AUC 0.740 with 95% CI of 0.633–0.850. (b) ROC analysis of FLC reduction at day 21 from the baseline. The highest sensitivity point of % of iFLC reduction at day 12 was identified as 95.5% with sensitivity 0.931, specificity 0.500 and AUC 0.742 with 95% CI of 0.635–0.850.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
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fig1: ROC analysis of % of iFLC reduction for obtaining any renal response in patients with RI. (a) ROC analysis of FLC reduction at day 12 from the baseline. The highest sensitivity point of % of iFLC reduction at day 12 was identified as 81.7% with sensitivity 0.931, specificity 0.500 and AUC 0.740 with 95% CI of 0.633–0.850. (b) ROC analysis of FLC reduction at day 21 from the baseline. The highest sensitivity point of % of iFLC reduction at day 12 was identified as 95.5% with sensitivity 0.931, specificity 0.500 and AUC 0.742 with 95% CI of 0.635–0.850.
Mentions: We retrospectively reviewed the medical records of the Department of Hematology/Oncology at Kameda Medical Center, Kamogawa-shi, Japan, from April 2000 to December 2013. Patients diagnosed as MM complicated with RI were included in the study. Diagnosis of myeloma and evaluation of treatment response were performed according to the International Myeloma Foundation criteria and the treatment response criteria.15 Patients with primary systemic amyloid light-chain (AL) amyloidosis were excluded from this study. RI was defined as an estimated glomerular filtration rate (eGFR) that was measured before treatment ≦50 ml/min per 1.73 m2 by the simplified Modification of Diet in Renal Disease formula.16, 17, 18 Maximal renal response was evaluated during the course of disease according to the recently proposed ‘Criteria for the Definition of Renal Response to Antimyeloma Therapy' from the International Myeloma Working Group.2 Briefly, renal complete response (CRenal) was defined as a sustained (i.e., lasting for at least 2 months) increase in baseline eGFR to 60 ml/min per 1.73 m2. Renal partial response (PRenal) was defined as an increase of eGFR from 15 to 30–59 ml/min per 1.73 m2 and renal minor response (MRenal) as sustained improvement of baseline eGFR of <15 to 15–29 ml/min per 1.73 m2 or, if baseline eGFR was 15–29 ml/min per 1.73 m2, improvement to 30–59 ml/min per 1.73 m2. If the patient was dependent on dialysis, achievement of dialysis independency was regarded as at least MRenal depending on the recovery of eGFR. Demographic and laboratory data were obtained from electronic records. Patients with pre-existing severe RI (creatinine ≧2.0 mg/dl) owing to causes other than MM were excluded from the study. Extracted clinical data related to myeloma and RI included age, sex, complete blood count, urinalysis, serum protein electrophoresis, serum FLCs, serum albumin, β2-microglobulin, serum creatinine, total urinary protein and urine protein electrophoresis. The percentage of urinary albumin excretion was calculated by protein electrophoresis pattern on admission, and it was considered zero if the protein electrophoresis could not detect any albumin (5 mg/dl). Typical measurement of urine albumin by urine protein electrophoresis was shown in Figure 1. Serum FLCs were measured by nephelometry using the BN II nephelometer (Dade Behring, Deerfield, IL, USA) and Freelite Serum Free Light Chain Kit (The Binding Site, San Diego, CA, USA). Reduction of serum FLC was checked at day 12 and at day 21 after the start of antimyeloma therapy. Baseline serum FLC data were available for 90 patients with RI, as the Freelite assay was not available at our institution until September 2007.

Bottom Line: There is no reliable test for predicting reversibility of RI in MM patients.We postulated that MM with high albuminuria may reflect glomerular disease that is difficult to reverse.Here, we examined the impact of urinary albumin excretion.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology/Oncology, Department of Medicine, Kameda Medical Center, Kamogawa-shi, Chiba, Japan.

ABSTRACT
Reversal of renal dysfunction significantly affects the prognosis of multiple myeloma (MM) with renal impairment (RI). There is no reliable test for predicting reversibility of RI in MM patients. We postulated that MM with high albuminuria may reflect glomerular disease that is difficult to reverse. Here, we examined the impact of urinary albumin excretion. We retrospectively analyzed 279 patients admitted to our hospital from April 2000 to December 2013. Clinical variables and laboratory data that may affect myeloma treatment response were extracted. The results were examined for relationship to renal response by univariate and multivariate analysis. RI (estimated glomerular filtration rate ≦50 ml/min per 1.73 m(2)) was observed in 116 patients (46%) and renal responses of renal complete response, renal partial response, renal minor response and no response were obtained in 46 (40%), 15 (13%), 13 (11%) and 42 (36%) patients, respectively. Although renal recovery was significantly associated with Durie-Salmon 1 or 2 (P=0.02), myeloma response better than very good partial response (P=0.03), involved free light-chain (iFLC) reduction from baseline 80% at day 12 (P=0.005), ≧95% at day 21 (P<0.001) and urinary albumin ≦25% on admission (P<0.001) on univariate analysis, only reduction of iFLC 95% at day 21 (P=0.015) and urinary albumin ≦25% (P=0.007) remained significant for any renal response. Our observation indicates that increased urinary albumin excretion >25% and reduction of iFLC ≦95% on day 21 were associated with favorable renal recovery in MM patients with RI, and were considered as negative predictors for renal response.

Show MeSH
Related in: MedlinePlus