Effectiveness of Haemodiafiltration with Heat Sterilized High-Flux Polyphenylene HF Dialyzer in Reducing Free Light Chains in Patients with Myeloma Cast Nephropathy

Abstract

Introduction: In cases of myeloma cast nephropathy in need of haemodialysis (HD), reduction of free light chains using HD with High-Cut-Off filters (HCO-HD), in combination with chemotherapy, may be associated with better renal recovery. The aim of the present study is to evaluate the effectiveness of haemodiafiltration (HDF) in reducing free light chain levels using a less expensive heat sterilized high-flux polyphenylene HF dialyzer (HF-HDF).

Methods: In a single-centre prospective cohort study, 327 dialysis sessions were performed using a 2.2 m2 heat sterilized high-flux polyphenylene HF dialyzer (Phylther HF22SD), a small (1.1m2) or large (2.1 m2) high-cut-off (HCO) dialyzer (HCOS and HCOL) in a cohort of 16 patients presenting with dialysis-dependent acute cast nephropathy and elevated free light chains (10 kappa, 6 lambda). The outcomes of the study were the mean reduction ratio (RR) of kappa and lambda, the proportion of treatments with an RR of at least 0.65, albumin loss and the description of patient outcomes. Statistical analysis was performed using linear and logistic regression through generalized estimating equation analysis so as to take into account repeated observation within subjects and adjust for session duration.

Results: There were no significant differences in the estimated marginal mean of kappa RR, which were respectively 0.67, 0.69 and 0.70 with HCOL-HD, HCOS-HDF and HF-HDF (P = 0.950). The estimated marginal mean of the proportions of treatments with a kappa RR ≥0.65 were 68%, 63% and 71% with HCOL-HD, HCOS-HDF and HF-HDF, respectively (P = 0.913). The estimated marginal mean of lambda RR were higher with HCOL-HDF (0.78), compared to HCOL-HD and HF-HDF (0.62, and 0.61 respectively). The estimated marginal mean proportion of treatments with a lambda RR ≥0.65 were higher with HCOL-HDF (81%), compared to 57% in HF-HDF (P = 0.042). The median albumin loss were 7, 21 and 63 g/session with HF-HDF, HCOL-HD and HCOL-HDF respectively (P = 0.044). Among survivors, 9 out of 10 episodes of acute kidney injuries became dialysis-independent following a median time of renal replacement therapy of 40 days (range 7-181).

Conclusion: Therefore, in patients with acute dialysis-dependent myeloma cast nephropathy, in addition to chemotherapy, HDF with a heat sterilized high-flux polyphenylene HF dialyzer could offer an alternative to HCO dialysis for extracorporeal kappa reduction with lower albumin loss.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Fig 1. Free light chain reduction ratio by modality of renal replacement therapy.

The left panel shows A) the crude reduction ratio (RR) of kappa free light chain by haemodialysis (HD) or haemodiafiltration (HDF) using large (2.1 m2) high cut-off filters (HCOL), small (1.1 m2) high cut-off filters (HCOS), and the 2.2 m2 heat sterilized high-flux polyphenylene HF (HF). Panel B shows the estimated marginal means of kappa reduction ratio taking into account repeated measurements within individuals and session duration using a GEE model. The percentages of the treatments with a kappa reduction ratio of ≥ 0.65 with each modality is shown in panel C. Panel D shows the percentages of the treatments with a kappa reduction ratio of ≥ 0.65 with each modality taking into account repeated measurements within individuals and session duration using a GEE model. The right panel shows the crude RR of lambda free light chain by renal replacement modality (E), and the estimated marginal means of lambda RR (F) taking into account repeated measures within individuals and session duration using GEE model. The crude and adjusted (within subjects and session duration) percentage of treatments with a lambda RR ≥0.65 are respectively shown in panels G and H. All p-values take into account adjustments for multiple comparisons using Bonferroni method.

Fig 2. Impact of haemodiafiltration method of free light chain reduction ratio.

The impact of haemodiafiltration (HDF) in predilution (Pre), low-efficiency post-dilution (15L post) are performed using large (2.1 m2) high cut-off filters (HCOL), small (1.1 m2) high cut-off filters (HCOS), and the 2.2 m2 heat sterilized high-flux polyphenylene HF (HF). The estimated marginal means of kappa (A) and lambda (B) light chain reduction ratio taking into account repeated measures and duration of each treatment session. P-values reported are adjusted for multiple comparisons using the Bonferroni correction method.* indicates that values are statistically different from other groups (P<0.01), ** indicates that values are statistically not different compared to other groups.

Fig 3. Reduction ratio of molecules of increasing molecular weights.

The figure shows the reduction ratio (RR) of creatinine (113 Da), β-2 microglobulin (β2M, 11.8kDa), kappa (22.5 kDa) and lambda (45 kDa) free light chains, using haemodiafiltration with heat sterilized high-flux polyphenylene HF (HF-HDF), compared to haemodialysis or haemodiafiltration with a large (2.1 m2) high-cut-off dialyzer (HCOL). Estimates are obtained by generalized estimating equation taking into account repeated measures and session duration. * indicates a P-value of <0.05.