1. International Experiences in Standardization Advantages of a National Program 11 th Annual HuQAS Scientific Conference Kenya Institute of Education Nairobi, Kenya September 29 th, 2011

2. Appreciating To-day’s Reality “Laboratories are like boats on a lake – everyone is busy paddling away without talking to each other - and no one knows where the dock is”

4. An International study examining the “trueness” and precision of lipid measurements in 27 countries AnalyteNCEP Performance goal (TE) % Failure Total cholesterol9 %22% Triglycerides15%7% HDL13%48% LDL12%33%

6. TC/HDL Ratio A TC/HDL ratio 5 or greater is associated with an increased risk of premature CVD HDL values reported: 0.7 to 3.44 mmol/L TC/HDL ratios reported for a patient having a total cholesterol value of 6 mmol/L 6 (3 labs)

7. Kidney Disease < 90% of diabetic patients are not screened for kidney disease < 20% of those with kidney disease even know they have it 76% of patients on first referral to nephrologists already have Stage 4 disease

8. Understanding the Problem CKD – a major health problem; growing Consuming a disproportionate amount of healthcare resources Patients identified late in the disease – missing opportunities for prevention Evidence based guidelines recommending treatment Testing of critical analytes triggering expensive treatments Greater appreciation of the costs associated with lab error

9. Clinical Guidelines for Chronic Kidney Disease GFR should be estimated from prediction equations Serum creatinine alone should not be used to assess the level of kidney function Clinical laboratories should report an estimate of GFR Measurement of creatinine clearance using timed urine collections does not improve the estimation of GFR (AM J Kidney Dis 37 (suppl 1):S182-S238, 2002)

11. What is required? Labs to report a new index of renal function (eGFR) for earlier identification of kidney disease Critical analytes for the diagnosis and management of kidney disease need to be standardized Reporting comments from the laboratory should be aligned with evidence based treatment guidelines Reporting comments should be harmonized throughout a healthcare system for unified messaging Communication strategies are needed to increase the public’s awareness of the disease and what they can do to prevent it

12. The Lab View “What will this change mean to me?” “What do I need to know?” “What additional resources will I need?”

13. Is my creatinine method standardized? How do I know? What equation should I use? How will eGFR be calculated on a routine basis? What limitations should I be aware of? Who will program the algorithm into my LIS ? Do we have the budget for this programming? What reference intervals should I use for reporting creatinine and eGFR ?

14. Should we stop providing Crockcroft-Gault calculated GFR? What equation should we use for paediatric patients? This will increase the number of referrals for kidney disease – do we have the clinical resources to deal with this? What should I tell the doctors? Do they even want this? Why should we do it?

15. “Going it alone” Cockcroft-Gault equation was being used for reporting eGFR in adults and children. (C-G should not be used in children – Kid. Int’l 67 (2005)2321-2324) GFR could not be reported in 785 adult patients (8.9%) because the patient’s weight was unavailable. In many cases patient self- reported weights were used for calculating GFR Letter sent to 100 referring physicians asking them to routinely record the patient’s weight on the requisition when ordering creatinine. One physician complied Creatinine results (mg/dL) being reported to one decimal place

16. “Going it alone” Conclusion If the MDRD equation had been used for reporting eGFR in adults – 785 additional adults would have had an eGFR reported and 127 additional patients would have been identified as having stage 3 renal disease

17. Looking at the “bigger picture” The laboratory is at the “hub of information flow” within the healthcare system and if you want to uniformly effect a change you are best to do it through the laboratory The routine reporting of eGFR is more than just producing a test result and plugging it into a formula It is important to understand who will be impacted by this change. ( funders of the healthcare system, the testing facilities themselves, laboratory professionals, specialists, family doctors, pharmacists, patients, and the general public)

18. Looking at the “bigger picture” The laboratory is at the “hub of information flow” within the healthcare system and if you want to uniformly effect a change you are best to do it through the laboratory The routine reporting of eGFR is more than just producing a test result and plugging it into a formula It is important to understand who will be impacted by this change. ( funders of the healthcare system, the testing facilities themselves, laboratory professionals, specialists, family doctors, pharmacists, patients, and the general public)

19. Looking at the “bigger picture” Each of these impacted groups will have specific questions and educationalrequirements that will have to be tailored to meet their specific needs At a fundamental level, there needs to be an understanding of the factors that will work against implementation and a unified strategy defined that will over come these negative forces Newer, more accurate algorithms will be developed in the future, the strategy needs to be flexible enough to accommodate these changes when they occur

20. Implementing Change A definition of what is expected A system that measures variation from the expected A strategy for effecting and sustaining the desired change A system for measuring and monitoring impact of the change over time

21. A Case Study Population – 4.5 million people Publically funded healthcare system Estimated that 145,000 people may have some degree of CKD There is a need to identify these people – affording an opportunity for prevention All labs asked to implement the routine reporting eGFR

22. “When it comes to measuring creatinine, how good are we?”

23. Performance Assessment (2003) Test samples - human serum Creatinine concentrations – selected to assess performance at decision levels for stage 3 renal disease Target value assigned by ID-GC/MS Record reagent, calibrator lot numbers and reference intervals for creatinine from each laboratory

24. Creatinine – Performance Goals National Kidney Disease Education Program – routine reporting of eGFR by the MDRD formula (NKDEP- eGFR) Recommended Total Error performance goals for the measurement of creatinine as calculated on the basis of biological variation: Minimum11.4 % Desirable 7.6% Optimal 3.8% Clin Chem 52:5-18 (2006)

26. Performance Assessment (2003) TE = 23.9% Bias = 16.5% (+) CV = 3.02 ; SD = 2.24

27. Impact of Standardization Program on Creatinine Results (RV +/- 10%) 50.4% Pass | 49.6% Fail ; 90.3% Pass | 9.7% Fail Impact on eGFR (RV +/- 10%) 58.7% Pass | 41.3% Fail; 86.6% Pass | 13.4% Fail

30. Change Strategy All labs report eGFR + creatinine Oct 03 Jan 04 Jun 04 Oct 04 Dec 04 Creatinine normalization project starts Standardization project results reviewed, adopted policy for standardization; Develop standard comments Standard comments agreed upon Standard comments appear on lab reports Guidelines and educational materials distributed to all doctors

31. Impact of Program (2003) Strategy reduced mean bias for creatinine measurement from 16.5% to 2.7% At a maximum the program theoretically reduced false positives by 84% keeping 449,400 people from being “incorrectly classified” as being “at risk” (2004 statistics) Follow-up testing on these patients would have cost the country’s healthcare system $36 million (J Am Soc Nephrol 19:164-169 (2008)

32. Monitoring Program (2004) 99% participation rate (submitted subscriptions) 3 labs – did not apply assigned normalization factor 4 labs - made a mistake in applying normalization factor 12 labs calculated eGFR incorrectly 7 labs were not routinely reporting eGFR eGFR routinely reported by 93% of the labs

33. Monitoring Program (2008) Participation – 100% 49% of the labs now reporting that their calibration is traceable to IDMS (previous challenge – 26%) Eleven IDMS traceable labs using the wrong formula for calculating eGFR Five IDMS traceable labs reported an incorrect value for eGFR (reason unknown) Some labs confused as to whether or not their system was IDMS traceable

34. Observations Poor understanding of eGFR – how it is calculated and the different formula available Labs uncertain as to why eGFR is better than creatinine alone Standardization of creatinine – difficulty in understanding – total error concepts vs PT peer group assessments Poor understanding of the clinical use of the index – problems answering stake holders questions on its use and limitations Lab personnel hesitant to interact with physicians – out of their depth Resistance barriers – drug dosing all tied to C-G, doctors used to C-G, not sure how MDRD eGFR relates to C-G, and others

35. North America Performance Data Accuracy based PT/EQA program for the measurement of creatinine Creatinine (2010.05) Performance Assessment Criteria RV +/- 7.6% N= 176 IDMS Reference (umoles/L) (mg/dL) 113.5 1.28 97.2 1.10 65.4 0.74 % of labs failing7.4%14.8%38.2%

36. Patient Visits to Nephrology

37. Conclusions Reporting of eGFR was associated with an increase in first nephrologist visits – particularly among patients With more severe kidney dysfunction Women, middle-aged and very elderly patients And those with co-morbidities Hemmelgarn, BR et al. JAMA. 2010;303(12):1151-1158

38. Mexico Symposium on CKD held in Guadalajara in November 2010 Meeting was organized by laboratory professionals for laboratory professionals (FeMPaC) – supported by WASPaLM and IFCC By chance a nephrologist who had heard of the symposium at the last moment decided to attend the symposium Discussions from the floor lead to a post-symposium meeting and the formation of a task force on kidney disease

39. “Laboratory Task force on the prevention of chronic kidney disease in Mexico” Federación Mexicana de Patología Clínica (FeMPaC/WASPaLM) Asociación Mexicana de Bioquímica Clínica (AMBC/IFCC) Confederación Nacional de Químicos Clínicos Colegio de Nefrólogos de México (CNM) Asociación Nacional de Nefrólogos de México (ANNM) Instituto Mexicano de Investigaciones Nefrológicas (IMIN)

40. State/laboratories agreeing to participate in the eGFR/kidney disease pilot program in Mexico 1.AGUASCALIENTES A GUASCALIENTES (1) 2.BAJA CALIFORNIAT IJUANA (5) 3.COAHUILA T ORREÓN (2) 4.COLIMA T ECOMÁN (1) 5.DISTRITO FEDERAL DF (14) 6.DURANGO G ÓMEZ P ALACIO (1) 7.ESTADO DE MÉXICO H UIXQUILUCAN (1) 8.GUANAJUATO L EÓN (2), I RAPUATO (1) 9.JALISCO G UADALAJARA (15) 10.MICHOACÁN M ORELIA (1), L A P IEDAD (1) 11.NUEVO LEÓN M ONTERREY (1), S N N ICOLÁS DE LOS 6 (2) 12.OAXACA O AXACA (2) 13.PUEBLA P UEBLA (7) 14.QUINTANA ROO C ANCÚN (1) 15.QUERÉTARO Q UERÉTARO (4) 16.SAN LUIS POTOSÍ S AN L UIS P OTOSÍ (3) 17.SINALOA C ULIACÁN (1) 18.TABASCO V ILLA H ERMOSA (1), C OMALCALCO (1) 19.TLAXCALA A PIZACO (1) 20.VERACRUZ X ALAPA (1), V ERACRUZ (2), C ÓRDOBA (1) 21.YUCATÁNM ÉRIDA (4) 1.BAJA CALIFORNIA SUR 2.CAMPECHE 3.CHIAPAS 4.CHIHUAHUA 5.GUERRERO 6.HIDALGO 7.MORELOS 8.NAYARIT 9.SONORA 10.TAMAULIPAS 11.ZACATECAS States/laboratories recruited States/laboratories yet to be recruited

41. Nuevo León 3 Colima: 1 Michoacán 2 Jalisco 22 Guanajuato: 3 Edo. de México: 1 Durango Distrito Federal: 14 Coahuila Baja California Norte Aguascalientes: 1 Veracruz: 4 Tlaxcala:1 Tabasco 1 Sinaloa 1 San Luis Potosí 3 Querétaro: 5 Quintana Roo 1 Puebla 7 Oaxaca 2 Yucatán 4 6 2 1 Sonora Chihuahua Baja California Sur Nayarit Zacatecas Tamaulipas Guerrero Hidalgo Chiapas Campeche Morelos Location of recruited laboratories for the eGFR/kidney disease pilot program in Mexico

42. Creatinine testing in the Caribbean

44. Guyana Population – 770,794 Life expectancy – 66 years GDP per capita - $3,700 Kidney disease – a growing problem Dialysis available to only a few Three months ago – Kidney Foundation of Guyana formed Strategic plan being developed at the national level for the standardization of creatinine and the routine reporting of eGFR

45. “ What about a National Program for Kenya?”

46. “Travelling to the future is like any other trip, it is hard to know about the destination until you arrive” (Frank Ogden)

47. Thank You David W Seccombe MD, PhD, FRCPC Department of Pathology and Laboratory Medicine University of British Columbia, Vancouver CANADA Canadian External Quality Assessment Laboratory (CEQAL) dseccombe@ceqal.com