Freelite SFLC in CKD why use a different reference range? Dr Colin Hutchison Nephrologist Hawke s Bay DHB

Transcription

1 Freelite SFLC in CKD why use a different reference range? Dr Colin Hutchison Nephrologist Hawke s Bay DHB

2 Disclosures I have only really worked with the Freelite assays Previous research funding, technical support and brief employment with The Binding Site

3 Freelite sflc in CKD why use a different reference range?

4 Freelite SFLC in CKD why use a different reference range? CKD or Renal (impairment) Reference range???

5 Freelite SFLC in CKD why use a different reference range? Why do we have a Renal reference range Biology there of Does it matter? Clinically important or a lab variable? Assay issue? Freelite vs N-latex (Siemens)

6 Free light chains (FLCs) - bi-products of intact immunoglobulin synthesis Kappa Monomeric (22.5kDa) Lambda Dimeric (45kDa)

7 FLC renal metabolism + sites of injury

8 Kinetic model of FLCs in renal failure P(t) k k 1e k d k re k 21 k re Department of engineering, University of Warwick. Hutchison et al. J Am Soc Neph 2007

9 Serum polyclonal FLC concentrations increase as GFR decreases Kappa (shaded) Lambda (clear) Both: P<0.01 cjasn

10 Serum FLC ratio increases through the CKD stages P<0.001 cjasn

11 Why FLC ratio changes? When kidneys are working well: k>l clearance When kidneys are not working: RE clearance dominates no difference (k or l) Therefore no kidneys serum ratio represents the underlying production rate k/l of 1.8

12 The advent of the Renal FLC Range Mayo normal: (in this group there will be some with renal impairment) Renal range:

13 The advent of the Renal FLC Range Mayo normal: Renal range: Abadie et al. Renal range: up to 3.1 Marshall et al. Renal range: up to 3.2 Abadie JM, Am J Clin Path Marshall G, Am J Clin Path 2009

14 The advent of the Freelite Renal FLC Range Mayo normal: Renal range: Clinically relevant???

15 Evaluated serum FLC immunoassays as a diagnostic tool in patients with severe renal failure 142 patients with new dialysis dependent renal failure Serum was screened by SPE and FLCs (IFE) Urine was analysed where available 41 patients had a clinical diagnosis of multiple myeloma BMC Nephrology

16 Serum lambda FLC (mg/l) Serum kappa FLC (mg/l) BMC Nephrology

17 ROC Normal vs Renal for Myeloma Kidney Standard (Green) New range (Blue) BMC Nephrology

18 So.. Renal reference range decreases false +ves Reduced phone calls to haematologist or the laboratory: What does a FLC ratio of 2.76 mean.. But does it change the way we practice?

19 What is the role of the FLC assay?

20 What is the role of the FLC assay? It is only ever a part of the patient work-up for?myeloma Tissue (Kidney or Marrow or both ) SPE/IFE Urine analysis Skeletal surveys etc

21 Renal range in the Real Renal World Review of the last 50 new outpatients in the renal clinic i.e. not AKI Mostly advancing CKD or proteinuria

22 FLC normal range

23 FLC ranges in clinic

24 Renal ranges.. In clinic.

25 Hawke s Bay New Patients 50 patients: egfr 31 (range 6-95) mls/min/1.73m2 Kappa 38.1 ( ) mg/l Lambda 36.1 ( ) mg/l Ratio 0.98 ( ) all polyclonals Excluded: 2 with plasma cell dyscrasias

26 Hawke s Bay New Patients Excluded: 2 with plasma cell dyscrasias Myeloma kidney: egfr 18mls/min Kappa 11,000mg/L Lambda 3.71mg/L ratio 2964 AL-amyloid: egfr 30mls/min Kappa 700mg/L Lambda 8.8mg/L ratio 80

27 Hawke s Bay New Patients 100% FLC ratio range: (polyclonals) Birmingham renal patients with plasma cell dyscrasias 2 patients with ratios outside of normal 1.76 and 1.77 so 4% of patients false +ve

28 Ratio changes with egfr

29 An assay issue Freelite vs N-latex N Latex FLC serum FLC assays in patients with renal impairment. Jacobs JF et al, Clin Chem Lab Med 2014; 52:853-9 All patients with CKD had FLC within normal ratio with N-latex But not with Freelite

30 An assay issue Freelite vs N-latex Berlanga et al Clin Chem Lab Med 2014

31 Summary of diagnostics: With Freelite the normal range does change with impaired renal function Reduced clearance better representation of underlying synthesis Unresolved differences between Freelite and N-latex