CHANGES TO KIDNEY FUNCTION TESTING – Supporting Clinicians in Improving Care for Patients with Chronic Kidney Disease

Dear Health Care Providers,

Effective 22 April 2024, LifeLabs is introducing changes to the reporting of kidney function tests, including:

Estimated glomerular filtration rate (eGFR)
Urine albumin-creatinine ratio (ACR)
Kidney Failure Risk Equation (KFRE)

This communication outlines the changes, developed by the Ontario Renal Network (ORN) in consultation with Ontario community laboratories and endorsed by Ontario Health (OH), with a goal to improve the diagnosis, follow-up, and monitoring of chronic kidney disease (CKD). More detailed information, including background, rationale for changes, and new annotations on the detection of kidney disease, will be posted in a revised Ontario Association of Medical Laboratories (OAML) Guideline entitled “Guideline for the Transition from the CKD-EPI 2009 to the CKD-EPI 2021 for the Calculation of Estimated Glomerular Filtration Rate (eGFR), and its Interpretation in Concert with the Urine Albumin/Creatinine Ratio (ACR) and the Kidney Failure Risk Equation (KFRE)”. This Guideline will be available on the OAML website (www.oaml.com) in April 2024.

eGFR:

The calculation for eGFR is changing from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2009 equation to the CKD-EPI 2021 equation.¹ The CKD-EPI 2021 equation is consistent with best clinical practice. It includes diversity in its development and does not include race in the calculation and reporting. The new equation has been endorsed by the Canadian Society of Nephrology² and the United States National Kidney Foundation and the American Society of Nephrology.³ The new eGFR calculation is an important step in alignment of efforts to end race disparities in kidney care in Ontario.

The new eGFR equation has similar overall performance characteristics to the previous and has been assessed externally to not have potential consequences that disproportionately affect any one group of individuals. Internal assessment, using LifeLabs patient data, suggests no significant change for patients with eGFR ≥60 mL/min/1.73m², and an average increase of 6% for patients with eGFR <60 mL/min/1.73m². Individual eGFR results may vary between -3% and +10%.

Once the new equation is implemented, eGFR results for all patients will be accompanied by an annotation indicating that the eGFR is calculated using the CKD-EPI 2021 equation which does not use a race-based adjustment. Please note that the results using the new eGFR equation will not trend with those using the previous equation. Limitations/considerations with the use of CKD-EPI 2021 eGFR are the same as with CKD-EPI 2009.

Important to note:

The CKD-EPI 2021 eGFR, which does not use race-based adjustment in calculation, will be provided with all creatinine results for patients ≥ 18 years of age.
The CKD-EPI 2021 eGFR equation has not been validated for patients who are pregnant or those less than 18 years of age.
eGFR is an estimate of the patient’s GFR, with 80-90% of values within 30% of measured GFR. eGFR values need to be interpreted based on clinical context, and in concert with the ACR values (please see below).
True GFR is not reliably predicted by eGFR in vegetarians, amputees, in those at extremes of weight, muscle mass, and age, and in those with a sudden change in GFR.
Some medications, including trimethoprim, ciprofloxacin, and fenofibrate can increase serum creatinine, causing eGFR to underestimate true GFR.
Recent research has indicated that de-indexed eGFR using equations such as CKD-EPI performed better at predicting measured GFR than did the Cockroft Gault equation for medication dosing in patients with impaired renal function.⁴

ACR, KFRE and clinical decision support for primary care providers:

Clinical practice recommendations suggest ordering ACR with serum creatinine to facilitate appropriate classification of patients with CKD, to assess risk for progression and to monitor patients at risk to develop CKD.^5,6 Analyses by ORN and the Institute for Clinical Evaluative Sciences have indicated many patients in Ontario are either not receiving an ACR test as part of CKD screening or meet the criteria for referral to nephrology based on their serum creatinine and/or urine ACR value but are not seeing a nephrologist.

A new set of annotations will be provided on lab reports when eGFR and/or ACR are ordered as a clinical decision support for the primary care providers, with goals to encourage use of both tests to diagnose CKD, to encourage referral to nephrology in accordance with the KidneyWise toolkit criteria, and to promote the use of KidneyWise clinical toolkit.⁷ KidneyWise toolkit was developed by ORN to provide advice to primary care providers on identification and management of CKD. These annotations will replace the previous interpretive comments, and each annotation will include an estimation of the severity of CKD and recommendations for follow up testing of eGFR and/or ACR, and referral to nephrology when required. The detailed annotations are listed as an appendix to the online version of this bulletin.

In addition, when ACR and creatinine/eGFR are ordered on the same requisition, KFRE will be provided on the report. KFRE is a risk prediction model that estimates the risk of renal failure, as defined by requirement for renal replacement therapy, in people with CKD stages 3 – 5 (eGFR <60 mL/min/1.73m²).^5,8 KFRE was developed and validated in Canadian patient cohorts.^8,9 It is a more effective predictor of renal failure then eGFR alone and can be used to better tailor advice and treatment of an individual patient, improve patient understanding, ensure the patient’s care needs are met, and reduce the risk of progression to renal failure. The risk estimation by KFRE has replaced the previous estimation of CKD prognosis by eGFR and albuminuria as recommended by the Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for the evaluation and management of chronic kidney disease.⁵ The KDIGO prognostic tool categorized patients as low risk, moderately increased risk, high risk or very high risk. With the implementation of KFRE, estimation of kidney disease progression has been improved as a quantitative value, reported in %. Patients with 5-year KFRE ≥5% have increased risk of progression to renal failure within the next 5 years and should be referred to nephrology.

Important to note:

KFRE will be provided on laboratory reports when both eGFR and ACR are on the same laboratory requisition, and eGFR is <60 mL/min/1.73m².
Four-parameter (age, sex, eGFR, ACR) 5-year KFRE will be calculated, and KFRE results ≥5% will be flagged as an increased risk of progression to renal failure in the next 5 years.
The appropriate annotation will be appended to the renal assessment results suggesting referral to nephrology when any of the following are observed:

- eGFR <30 mL/min/1.73m², confirmed with repeated eGFR at least 3 months later
- eGFR 30-59 mL/min/1.73m² which declines >5 mL/min/1.73m²over a 6-month period
- ACR >60.0 mg/mmol, confirmed with at least 2 of 3 elevated results within 3 months
- ACR 3.0-60.0 mg/mmol, confirmed with at least 2 of 3 elevated results within 3 months, in the presence of hematuria (>20 rbc/hpf on urine microscopy)
- 5-year KFRE ≥5%

With the adoption of the new reporting, the reference cut-off for ACR will change from <2.0 mg/mmol⁵ to <3.0 mg/mmol⁶. A comment will be provided with results 2.0 – 2.9 mg/mmol, to indicate different cut-off recommended by Diabetes Canada.⁵
To improve clinical utility of urine albumin test in calculation of ACR and KFRE, LifeLabs will be lowering the clinical reporting limit for urine albumin from 5 mg/L to 1 mg/L, based on the internal validation of the current Abbott urine albumin assay.

Please also note: To support discussions about ending race-correction in kidney care and the implementation of the CKD-EPI 2021 equation, Ontario Health has developed a patient resource (also available in French) and a health care provider resource.

For any questions, please contact LifeLabs Customer Care Center 1-877-849-3637.

Thank you,

Kika Veljkovic PhD FCACB

Clinical Biochemist and Discipline Head, High Volume Chemistry

Medical-Scientific Department – Ontario

LifeLabs | 100 International Blvd. | Toronto, ON M9W 6J6

E Kika.Veljkovic@LifeLabs.com

Catherine Ross MD MSc FRCPC

Vice President, Medical and Quality Affairs

LifeLabs | 100 International Blvd. | Toronto, ON M9W 6J6

E Catherine.Ross@lifelabs.com

References:

Inker LA, Eneanya ND, MCorsh J, et al. New Creatinine- and Cystatin C–Based Equations to Estimate GFR without Race. New England J Med. 2021: 385:1737-49.
Auguste et al. A Canadian Commentary on the NKF-ASN Task Force Recommendations on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Kidney Med 2023: 6:100746.
Delgado C, Baweja M, Crews DC, et al. A Unifying Approach for GFR Estimation: Recommendations of the NKF-ASN Task Force on Reassessing the Inclusion of Race in Diagnosing Kidney Disease. Am J Kidney Dis. 2021; 79: 268-88.
Stevens LA, Nolin TD, Richardson MM, et al. Comparison of drug dosing recommendations based on measured GFR and kidney function estimating equations. Am J Kidney Dis. 2009;54(1):33-42.
Kidney Disease: Improving Global Outcomes (KDIGO) Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int 2024; 105 (Suppl 4S): S117-S314.
Diabetes Canada Clinical Practice Guidelines Expert Committee. Diabetes Canada 2018 Clinical Practice Guidelines for the Prevention and Management of Diabetes in Canada. Can J Diabetes 2018;42(Suppl 1):S1-S325.
KidneyWise clinical toolkit: kidneywise.ca
Tangri N, Stevens LA, Griffith J, et al. A predictive model for progression of chronic kidney disease to kidney failure. JAMA. 2011;305(15):1553-59.
Whitlock RH, Chartier M, Komenda P, et al. Validation of the Kidney Failure Risk Equation in Manitoba. Can J Kidney Health Dis. 2017;4:1-9.