Abstract
Introduction. Acute renal failure (ARF) develops in 10–15% of patients with multiple myeloma (MM). Typically, complexes of serum free light chains (sFLC) and Tamm-Horsfall protein form casts in the distal tubules that block urine flow. Many patients, subsequently, require long-term hemodialysis (HD) and may have reduced survival. In an attempt to minimise renal damage, plasma exchange (PE) has been used to reduce the pre-renal load of sFLC. Zucchelli et al., (Kidney Int1988; 33:1175–1180) showed that PE reduced HD requirements but subsequent controlled trials showed no benefit (Johnson WJ et al., Arch Intern Med1990; 150:863–869: Clarke WF et al., Haematologica2005; 90(s1) p117). The availability of sFLC immunoassays now allows an informed evaluation of the role of PE and/or HD in treating these patients.
Methods. sFLC were measured in 1: 100 patients with chronic renal failure (CRF), GFR< 15ml/min and not on dialysis; 2: 38 at the beginning and end of HD (dialyzer A) and 3: 25 on chronic ambulatory peritoneal dialysis (CAPD). sFLC hemofiltration efficiency was assessed, in-vitro, for three different dialyzers, using standard pump pressures and flow rates. Sera containing approximately 1,000 mg/L of monoclonal kappa (κ ) (NR < 20mg/L) and lambda (λ ) FLC (NR < 27mg/L) were recycled for ~45 minutes through the dialyzers and clearance rates assessed. A two-compartment, mathematical model was constructed to assess sFLC removal by HD and PE from hypothetical patients. The following parameters were considered:- sFLC concentrations in MM at clinical presentation; monomeric κ or dimeric λ clearance differences; partition of sFLC between vascular and extravascular compartments; flow of FLC between compartments; half-life of sFLC in ARF; sFLC production and tumour killing rates with chemotherapy. The model was interrogated for various dialysis times, different dialyzers and a PE protocol of 3L, x6 over 2 weeks.
Results. Mean sFLC concentrations in severe CRF were: κ 93 mg/L (range 43–207); λ 64 mg/L (range 43–134). Mean sFLC before and after HD: κ 130 mg/L (range 40–567) to 49 (range 20–234); λ 100 mg/L (range 31–225) to 61 (range 24–159). Mean sFLC in CAPD patients: κ 118 mg/L (range 31–266); λ 114 mg/L (range 36–263). Clearances of sFLC by the 3 dialyzers were: A: BBraun high flux polyethersulfone 1.8sqm (HI PeS) (the dialyzer in routine use); κ 46%: λ 39%, B: Idmesa high flux polyethersulphone 2.0sqm (200MHP); κ 67%: λ 59%, C: Asahi high flux polysulphone 2.1sqm (APS 1050); κ 71%: λ 65%. Model calculations showed that sFLC reduced from a starting value of 14g/L (typical of light chain MM) to less than 0.5g/L in 14 days using PE. Membrane A, used for four hours, x3/week, was approximately 20% more efficient than PE and reduced κ sFLC approximately 50% faster than the natural clearance rate of patients in ARF. Dialyzers B and C were approximately twice as efficient. Performing initial, 16-hour dialyses daily for 3 days, with dialyzer C reduced sFLC to less than 0.5g/L in 2–3 days with ~95% of the sFLC being removed. Dimeric λ sFLC were removed ~50% more slowly.
Conclusion. PE was less efficient at removing sFLC than routine HD. Prolonged HD with high-flux dialyzers removed monoclonal sFLC quickly and should be assessed in a clinical trial for patients with acute myeloma kidney. CAPD was inefficient at removing sFLC.
Estimating the Effect of Chirality and Size on the Mechanical Properties of Carbon Nanotubes Through Finite Element Modelling
