FAQs

What is KidneyIntelX™?

KidneyIntelX is a Laboratory Developed Test that employs bioprognosis™ and a proprietary machine learning-enabled algorithm. It starts with a standard blood draw with a lavender top K2EDTA tube and is a quantitative electrochemiluminescence immunoassay using a MESO SECTOR S 600 instrument for measurement of 3 blood-based biomarkers: soluble Tumor Necrosis Factor Receptor-1 (TNFR1), soluble Tumor Necrosis Factor Receptor-2 (TNFR2), and Kidney Injury Molecule-1 (KIM-1), which are closely correlated with subclinical inflammation and kidney tubular injury.

KidneyIntelX combines these three blood-based biomarkers with seven clinical data inputs from a patient’s medical record (eGFR, UACR, serum calcium, HbA1c, systolic blood pressure, platelets, and AST) to generate a custom risk score that indicates whether an adult patient is at low, intermediate, or high risk of rapid progressive decline in kidney function. In addition to the patient’s risk score, each test report provides an actionable, guideline-recommended care path for both the physician and the patient.

What is the indicated use for the KidneyIntelX test?

KidneyIntelX is indicated for use as an aid to further assess the risk of progressive decline in kidney function within a period of up to 5 years in adult patients with type 2 diabetes and existing chronic kidney disease.

Patients with chronic kidney disease will have an estimated Glomerular Filtration Rate [eGFR] of 30-59 ml/min/1.73m2 [G3a, G3b] or an eGFR ≥ 60 with albuminuria [UACR] ≥ 30 mg/g [A2, A3] stages (1-3).

  • Stage 1: eGFR ≥90 ml/min/1.73m2 and a UACR level ≥30 mg/g
  • Stage 2: eGFR ≥60-89 ml/min/1.73m2 and an UACR level ≥ 30 mg/g
  • Stage 3: eGFR between 30-59 ml/min/1.73m2, regardless of the albumin level

What specific prognostic biomarkers are being used for KidneyIntelX testing?

KidneyIntelX is a prognostic test that incorporates inputs from three (3) well studied biomarkers from human plasma:

  • TNFR1: soluble Tumor Necrosis Factor Receptor-1
  • TNFR2: soluble Tumor Necrosis Factor Receptor-2
  • KIM-1: Kidney Injury Molecule-1

The three biomarkers are accurately measured using an analytically validated electrochemiluminescence immunoassay on a Mesoscale Sector S 600 instrument at CLIA certified Renalytix laboratories. The immunoassay is approved by the New York State Department of Health.

What are the clinical data points that are included in the KidneyIntelX test result?

Along with the values of the 3 proprietary biomarkers that we measure in the Renalytix lab, we also incorporate the values for the following clinical inputs:

  • eGFR
  • UACR
  • Serum Calcium
  • HbA1c
  • Systolic Blood Pressure
  • Platelets
  • AST

If there is not a UACR, serum calcium, platelets, or AST value, then the values will be “imputed” to represent the population mean for one or all 4 of these clinical inputs. We have data which demonstrates a non-significant impact on the risk score if this approach is used in the subset of individuals that do not have these clinical inputs.

How is progression of kidney disease defined?

The KidneyIntelX test was validated in an analysis of 1146 adult patients with type 2 diabetes selected from two independent cohorts with chronic kidney disease that are representative of patients in the intended use population (adult patients with type 2 diabetes and chronic kidney disease stages 1-3).

For the KidneyIntelX validation studies , progression was defined by 3 criteria:

  • A rapid decline in kidney function (eGFR slope ≥5 ml/min/1.73m2)
  • A ≥40% decline in kidney function from time zero that is sustained (confirmed at least 3 months later)
  • “Kidney failure” is defined as a sustained level of eGFR < 15 ml/min/1.73m2 (consistent with stage 5 CKD/DKD), the need for long-term dialysis (either hemodialysis or peritoneal dialysis), or the receipt of a kidney transplant.

What is the benefit of ordering a KidneyIntelX test if my patient’s CKD is under control?

When doctors combine patient information gathered through KidneyIntelX with newer cardio- and reno-protective therapies, it’s a win-win. They will be able to confirm which patients are at higher to lower risk for rapid kidney disease progression, and therefore, can appropriately continue to target resources, medications, and guideline-recommended treatments to advance kidney health.

Is there an age range?

KidneyIntelX is indicated for use in adult patients 21 years of age and older.

Can I use this test on non-diabetics?

No. KidneyIntelX is an aid to further assess the risk of progressive decline in kidney function for adult patients with type 2 diabetes and early-stage chronic kidney disease.

How will KidneyIntelX benefit my practice and my patients?

After adult patients with type 2 diabetes are screened for kidney disease, you will still need to identify which of those patients will need lower-level maintenance or ongoing monitoring or immediate lifestyle and therapeutic adjustments and referrals to a specialist.

KidneyIntelX yields a clinically validated, simple-to-understand, custom risk score, identifying adult diabetic patients with chronic kidney disease in stages 1-3b who are at low, intermediate, or high risk for rapid kidney disease progression over the next five years.

Our 3-part, proprietary methodology – bioprognosis™ for kidney health – predicts risk and outcomes to promote and preserve kidney health.

With one simple blood test, you will receive your patient’s custom risk score with actionable, guideline-recommended treatment steps.

Why is KidneyIntelX a more advanced measure for risk of CKD progression in adult type 2 diabetes patients than UACR or eGFR alone?

Existing measurements do not predict disease progression for two primary reasons:

1. Biological variability at the patient level.

There is too much fluctuation present when using eGFR and UACR as the core measurements for kidney disease progression. For these to be reliable metrics to ascertain kidney disease staging, the patient results would need to be consistent from week to week. Studies indicate that this is not the case.

2. Hyperfiltration.

Hyperfiltration plays a critical role in chronic kidney disease in diabetes as it puts stress on the filtration barrier and post-filtration mechanisms.

The increased flow increases the delivery and reabsorption of small and large molecular weight solutes resulting in injury to the kidneys.

Despite significant damage to some of the kidney’s tissue, the remaining tissue compensates, trying to preserve kidney function. That’s why, even when testing eGFR and urine albumin, kidney function levels can look normal, which may lead to a false sense of security.

That is why doctors should continue to use current measurements to diagnose chronic kidney disease and add the KidneyIntelX test to predict adult patients with type 2 diabetes and with chronic kidney disease stages 1-3b who are at low, intermediate, or high risk for rapid progressive decline in kidney function.

How will I get the results?

You should receive the KidneyIntelX test report in approximately 5-7 days. For those without electronic health record integration (EHR), results will be delivered through a secure channel.

Who will get my patient’s results?

The ordering physician will receive the KidneyIntelX test report which includes a patient-specific risk assessment score and a guideline-recommended care path.

HOW SHOULD I INTERPRET THE KIDNEYINTELX RISK SCORE?

LOW RISK

What does a low-risk test result mean?

A KidneyIntelX score of ≤45 is classified as low-risk or “green”. In the clinical validation study, the low-risk patient group averaged a 10% probability of progressive decline in kidney function over 5 years compared to the intermediate-risk and high-risk groups that averaged a 22% and 61% probability, respectively. 5-6

What are the clinical recommendations for a low-risk test result?

The clinical pathway recommendation was based on the following guidelines: American Diabetes Association Standards of Medical Care in Diabetes 2022, KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD, VA/DoD Clinical Practice Guidelines- Management of CKD (2019) and KDIGO 2012 Clinical Practice Guidelines for the Evaluation and Management of CKD.

Each health care system will have their own clinical pathway recommendations. Subject matter expert physicians recommend a comprehensive strategy to reduce diabetic kidney disease progression and cardiovascular disease which include:

In additional to lifestyle modifications and metformin, the following pharmacologic strategies are recommended to reduce risk of CKD progression and cardiovascular disease:

The following pharmacologic strategies are recommended to reduce risk of CKD progression and cardiovascular disease:

Frequency of monitoring

Monitor eGFR and UACR at least once annually

INTERMEDIATE RISK

What does an intermediate-test result mean?

A KidneyIntelX score ≥50 and ≤85 is classified as intermediate-risk or “orange”. In the clinical validation study, the intermediate-risk patient group averaged a 22% probability of progressive decline in kidney function over 5 years compared to the low-risk and high-risk groups that averaged a 10% and 61% probability, respectively.5,6

What are the clinical recommendations for an intermediate-risk test result?

The clinical pathway recommendation was based on the following guidelines: American Diabetes Association Standards of Medical Care in Diabetes 2022, KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD, VA/DoD Clinical Practice Guidelines- Management of CKD (2019) and KDIGO 2012 Clinical Practice Guidelines for the Evaluation and Management of CKD.

Each health care system will have their own clinical pathway recommendations. Studies are being conducted to determine the optimal treatment regimen for patients with intermediate-risk scores. Subject matter expert physicians recommend a comprehensive strategy to reduce diabetic kidney disease progression and cardiovascular disease which include:

In addition to lifestyle modifications and metformin, the following pharmacologic strategies are recommended to reduce risks of CKD progression and cardiovascular disease

  • Titrate ACEi or ARB to the maximum tolerated dose
  • SGLT2i (or GLP-1 RA if SGLT2i not tolerated or contraindicated)
  • Consider non-steroidal MRA, if clinically indicated

Frequency of monitoring

  • Monitor eGFR and UACR up to 2 times per year

HIGH RISK

What does a high-risk test result mean?

A KidneyIntelX score >85 is classified as high-risk or “red”. In the clinical validation study, the high-risk patient group averaged a 61% probability of progressive decline in kidney function over 5 years compared to the low-risk and intermediate-risk groups that averaged a 10% and 22% probability, respectively.5,6

What are the clinical recommendations for a high-risk test result?

The clinical pathway recommendation was based on the following guidelines: American Diabetes Association Standards of Medical Care in Diabetes 2022, KDIGO 2020 Clinical Practice Guideline for Diabetes Management in CKD, VA/DoD Clinical Practice Guidelines- Management of CKD (2019) and KDIGO 2012 Clinical Practice Guidelines for the Evaluation and Management of CKD.

Each health care system will have their own clinical pathway recommendations. Studies are being conducted to determine the optimal treatment regimen for patients with high-risk scores. Subject matter expert physicians recommend a comprehensive strategy to maximize protection for diabetic kidney disease progression and cardiovascular disease which includes:

In addition to lifestyle modifications and metformin, the following pharmacologic strategies are recommended to reduce risks of CKD progression and cardiovascular disease

  • Titrate ACEi or ARB to the maximum tolerated dose

Strongly consider the following therapies:

  • SGLT2i (or GLP-1 RA if SGLT2i not tolerated or contraindicated)
  • Non-steroidal MRA

Frequency of monitoring

  • Monitor eGFR and UACR up to 3 times per year
  • Specialist consultation, if clinically indicated

Can my patient’s risk score change over time?

Studies are being conducted on the timing and degree that a risk score changes over time. Preliminary data suggests that better cardiometabolic risk factor control results in improvements in your patient’s KidneyIntelX risk score over time. For example, better blood pressure control, glucose control, and decreases in UACR along with the use of agents that reduce cardiovascular and kidney risk in patients with diabetes (such as SGLT2 inhibitors, non-steroidal MRAs, or GLP1 receptor agonists), may improve (lower) a patient’s risk score.

When should I retest my patient?

Retesting is not available at this time. The current model has been developed using a one-time assessment of the risk score in our validation studies.5,6 However, we are in the process of conducting studies that assess the value of retesting at increments of 12 months.

Is KidneyIntelX precision limited by race like eGFR?

No. KidneyIntelX does not use race as an input to the algorithm. KidneyIntelX uses 3 proprietary prognostic biomarkers, 7 clinical data points, and a validated algorithm to generate a simple-to-understand patient-specific risk score.

Why is the KidneyIntelX risk score high when serum creatinine is normal?

Hyperfiltration precedes CKD progression and masks CKD while kidney injury continues. Hyperfiltration provides a false sense of security. There can be a 50% loss of nephron mass before a decline in eGFR.3

Should chronic kidney disease (CKD) patients on a SGLT2i be tested with KidneyIntelX?

Yes. One of the guideline recommendations, especially for high- and intermediate-risk patients is to start SGLT2i. If the risk score is low, this is a good indication that the therapy is working. If the risk score is high, then other factors need to be considered including glycemic control, blood pressure (dosing of ACEi/ARB) and lifestyle changes.5,6

Can my patient’s eGFR decrease after I start them on an SGLT2i? Does this mean my patients risk is worsening?

Yes. Studies have shown that an immediate decline in eGFR (<30%) can be expected after initiation of an SGLT2i and may be attributed to a hemodynamic effect on intraglomerular pressures. Clinical studies have shown that, on average, eGFR in the treatment group will cross-over the eGFR in the placebo group at around 12 months after initiation of treatment, with a slower rate of decline vs. placebo over time. This immediate drop in eGFR does not mean that the risk has increased.2

Why are patients on Enbrel contraindicated for KidneyIntelX?

Enbrel interferes with the ability to accurately measure the TNFR2 biomarker.

Who do I contact if I have questions?

If you have questions about KidneyIntelX results, please email medicalaffairs@renalytix.com.

If you have questions about billing, please contact client services at 888-203-2725 or email billing billing@renalytix.com.

REFERENCES:

  1. Chan, L. et al. Derivation and validation of a machine learning risk score using biomarker and electronic patient data to predict progression of diabetic kidney disease. Diabetologia 64, 1504-1515, doi:10.1007/s00125-021-05444-0 (2021).
  2. Chauhan, K. et al. Initial Validation of a Machine Learning-Derived Prognostic Test (KidneyIntelX) Integrating Biomarkers and Electronic Health Record Data to Predict Longitudinal Kidney Outcomes. Kidney360 1, 731-739, doi:10.34067/kid.0002252020 (2020).
  3. Krolewski, A. S. et al. Early progressive renal decline precedes the onset of microalbuminuria and its progression to macroalbuminuria. Diabetes Care 37, 226-234, doi:10.2337/dc13-0985 (2014).
  4. Coca, S. G. et al. Plasma Biomarkers and Kidney Function Decline in Early and Established Diabetic Kidney Disease. J Am Soc Nephrol 28, 2786-2793, doi:10.1681/ASN.2016101101 (2017).
  5. Sen, T. et al. Effects of the SGLT2 Inhibitor Canagliflozin on Plasma Biomarkers TNFR1, TNFR2, and KIM-1 in the CANVAS Trial. Diabetologia (2021 (in press)).
  6. Bhatraju, P. K., Zelnick, L. R., Shlipak, M., Katz, R. & Kestenbaum, B. Association of Soluble TNFR1 Concentrations with Long-Term Decline in Kidney Function: The Multi-Ethnic Study of Atherosclerosis. J Am Soc Nephrol 29, 2713-2721, doi:10.1681/ASN.2018070719 (2018).
  7. Kidney Disease: Improving Global Outcomes Diabetes Work, G. KDIGO 2020 Clinical Practice Guideline for Diabetes Management in Chronic Kidney Disease. Kidney Int 98, S1-S115, doi:10.1016/j.kint.2020.06.019 (2020).
  8. Neuen, B. L. et al. Relative and Absolute Risk Reductions in Cardiovascular and Kidney Outcomes With Canagliflozin Across KDIGO Risk Categories: Findings From the CANVAS Program. Am J Kidney Dis 77, 23-34 e21, doi:10.1053/j.ajkd.2020.06.018 (2021).
  9. Neuen, B. L. et al. Cardiovascular and Renal Outcomes With Canagliflozin According to Baseline Kidney Function. Circulation 138, 1537-1550, doi:10.1161/CIRCULATIONAHA.118.035901 (2018).
  10. Neuen, B. L. et al. SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis. Lancet Diabetes Endocrinol 7, 845-854, doi:10.1016/S2213-8587(19)30256-6 (2019).
  11. Bakris, G. L. et al. Effect of Finerenone on Chronic Kidney Disease Outcomes in Type 2 Diabetes. N Engl J Med 383, 2219-2229, doi:10.1056/NEJMoa2025845 (2020).
  12. Pitt, B. et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes. N Engl J Med, doi:10.1056/NEJMoa2110956 (2021).
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