Diagnostic Pathway In Patients Presenting With Acute Kidney Injury - PowerPoint PPT Presentation

Diagnostic Pathway In Patients Presenting With Acute Kidney Injury Secondary To de novo Multiple Myeloma: A Two Centre Experience. Dr Ritika Rana Renal Research Registrar

Disclosure of Conflict of Interest Professor Mark Drayson I have a relationship with a for-profit and/or a not-for-profit organization to disclose Name of for-profit or not-for-profit Description of relationship(s) Nature of relationship(s) organization(s) Any direct financial payments including receipt of honoraria Abingdon Health Medical Advisor Membership on advisory boards or speakers’ bureaus Funded grants or clinical trials Patents on a drug, product or device Abingdon Health Shares All other investments or relationships that could be seen by a reasonable, well- informed participant as having the potential to influence the content of the educational activity

Disclosure of Conflict of Interest Dr Ritika Rana I do not have a relationship with a for-profit and/or a not-for-profit organization to disclose Name of for-profit or not-for-profit Description of relationship(s) Nature of relationship(s) organization(s) Any direct financial payments including receipt of honoraria Membership on advisory boards or speakers’ bureaus Funded grants or clinical trials Patents on a drug, product or device All other investments or relationships that could be seen by a reasonable, well- informed participant as having the potential to influence the content of the educational activity

BACKGROUND ❖ Myeloma has one of the longest pathways to diagnosis of any cancer in the UK. ❖ The median time to diagnosis is unusually prolonged at 163 days (IQR 84-306). ❖ The average patient interval is considerably shorter than the diagnostic interval.

RENAL IMPAIRMENT ❖ Associated with worse outcomes. ❖ Prompt diagnosis and treatment is required to prevent long term kidney dysfunction and improve outcomes. ❖ Patients with very high light chains (>500 mg/L) are more likely to develop cast nephropathy. Hutchison CA, Plant T, Drayson M, et al. Serum free light chain measurement aids the diagnosis of myeloma in patients with severe renal failure. BMC nephrology. 2008;9(1):11. Yadav P, Leung N, Sanders PW, Cockwell P. The use of immunoglobulin light chain assays in the diagnosis of paraprotein-related kidney disease. Kidney international. 2015;87(4):692-697.

DIAGNOSING MYELOMA: A CHALLENGE ❖ Non specific nature of symptoms, low predictive value. ❖ Nearly 50% of patients diagnosed with myeloma have three or more pre-referral consultations. ❖ Nearly 1/3 patients present as emergencies and have lower survival compared to other routes.

EARLY DIAGNOSIS IS VITAL ❖ Favourable outcomes, fewer complications, reduced mortality, and better quality of life. ❖ Stage at diagnosis is a strong predictor of survival and prolonged interval could lead to stage progression and poor clinical outcomes. Richards M, Westcombe A, Love S, Littlejohns P, Ramirez A. Influence of delay on survival in patients with breast cancer: a systematic review. The Lancet. 1999;353(9159):1119-26. Tørring ML, Frydenberg M, Hamilton W, Hansen RP, Lautrup MD, Vedsted P. Diagnostic interval and mortality in colorectal cancer: U-shaped association demonstrated for three different datasets. Journal of clinical epidemiology. 2012;65(6):669-78.

❖ The Myeloma Early Diagnosis Working Group established late 2016. IMPROVING THE TIMELINE ❖ Point of care test which detects immunoglobulin free light chains.

UHB GUIDELINES ❖ Samples should be sent for serum electrophoresis and serum free light chains for same day light chain tests. ❖ Bone marrow should be performed within 24 hours of presentation to confirm the diagnosis. ❖ Patients should be started on dexamethasone once samples taken, do not wait for results.

❖ AIMS AND OBJECTIVES To review the referral and diagnostic pathway in the newly diagnosed myeloma patients with AKI at two tertiary centres in the U.K. To establish the time to diagnosis in the new myeloma patients. To identify areas where delays occur.

METHODS INCLUSION AND EXCLUSION CRITERIA Patients with AKI and sFLC >= 500 mg/L (1 April 2015 to 31 December 2017). Both centres identified 28 patients with new myeloma. Patients known to have myeloma were excluded.

First Centre Second Centre Referral pathway (number of patients) GP 12 (43%) GP 11 (40%) A and E 10 (36%) Medics 9 (32%) Other 6 (21%) A and E 2 (7%) Other 6 (21%) Median time to first treatment with dexamethasone (days) 5 (0-55) 5 (0-63) Median time to sFLC test request (days) 1 ( 0-33) 1 ( -8-35) Median time from sFLC request to dexamethasone (days) 4.5 (0-30) 4 (0-28) Median time to bone marrow (days) 6 (2-41) 6 (0-49) THE PATHWAY OF Dexamethasone prior to bone marrow INVESTIGATIONS (number of patients) 6 (21%) 10 (36%) Median time (days) 2 days (1-8) 4 days (2-11) Dexamethasone same day as bone marrow (number of patients) 10 (36%) 4 (14%) Dexamethasone post bone marrow (number of patients) Median time (days) 9 (32%) 7 (25%) 8 days (1-15) 7 days (1-21) Renal biopsy (patients) 6 (21%) 5 (18%) Median time (days) 2 days (1-10) 4 days (2-11)

INTERVENTION ❖ System of reporting new sFLC result >=500 mg/L to the requesting consultant. ❖ Biomedical scientist authorising sFLC results would call/email results to requesting consultant.

RE AUDIT AKI+sFLC>=500 mg/l WM New +kidney myeloma ❖ February 2018 to March 2019. disease 12% 13% Dialysis ❖ Patients with AKI and sFLC >= 500 mg/l. 19% ❖ 16 patients who met the criteria. Old myeloma 56% ❖ 2 new myeloma patients. New myeloma Old myeloma Dialysis WM +kidney disease

RESULTS ❖ Median time to sFLC test request 1 day ❖ Median time to bone marrow 2 days. ❖ Median time to dexamethasone 2 days. ❖ Patients had dexamethasone same day as bone marrow .

NEW sFLC RESULT >=500mg/L: PHONED/EMAILED New sFLC>=500 mg/L ❖ 28 patients whose results were phoned from February 2018 to January 2019. New Previous myeloma myeloma 32% ❖ 9 new diagnosis of myeloma. 36% ➢ 5 were outpatient diagnosis ➢ 4 were in patient diagnosis MGUS Dialysis 4% 3% Amyloid 7% Previous Palliated New lymphoma 4% lymphoma 3% 11%

RESULTS 4 Inpatients sFLC request sFLC collection to call 1 day (-15-1) 2.5 days (1-5) Dexamethasone Bone marrow 2.5 days (1-7) 3 days (1-7) 5 Outpatients Bone marrow sFLC collection to call Dexamethasone 15 days (3-36) 4 days (4-14) 26.5 days (4-49)

CONCLUSIONS ❖ The results from the two centres are similar and representative of the investigation and management pathways in large hospital trusts. ❖ Smaller hospitals may well incur an even longer time to diagnosis. ❖ Delays occur throughout the pathway; from requesting sFLC to delay in anti-myeloma therapy. ❖ Early data showing low cost intervention can improve the diagnostic pathway.

❖ Professor Mark Drayson ❖ Professor Paul Cockwell ❖ Dr Jennifer Pinney ACKNOWLEDGEMENTS ❖ Dr Mark Cook ❖ Dr Guy Pratt ❖ Team at Oxford University Hospitals.

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