Real World Evidence and Clinical Utility of KidneyIntelX on Patients With Early-Stage Diabetic Kidney Disease: Interim Results on Decision Impact and Outcomes

Abstract

Introduction and Objective: The lack of precision to identify patients with early-stage diabetic kidney disease (DKD) at near-term risk for progressive decline in kidney function results in poor disease management often leading to kidney failure requiring unplanned dialysis. The KidneyIntelX is a multiplex, bioprognostic, immunoassay consisting of 3 plasma biomarkers and clinical variables that uses machine learning to generate a risk score for progressive decline in kidney function over 5-year in adults with early-stage DKD. Our objective was to assess the impact of KidneyIntelX on management and outcomes in a Health System in the real-world evidence (RWE) study. Methods: KidneyIntelX was introduced into a large metropolitan Health System via a population health-defined approved care pathway for patients with stages 1 to 3 DKD between [November 2020 to March 2022]. Decision impact on visit frequency, medication management, specialist referral, and selected lab values was assessed. We performed an interim analysis in patients through 6-months post-test date to evaluate the impact of risk level with clinical decision-making and outcomes. Results: A total of 1686 patients were enrolled in the RWE study and underwent KidneyIntelX testing and subsequent care pathway management. The median age was 68 years, 52% were female, 26% self-identified as Black, and 94% had hypertension. The median baseline eGFR was 59 ml/minute/1.73 m2, urine albumin-creatinine ratio was 69 mg/g, and HbA1c was 7.7%. After testing, a clinical encounter in the first month occurred in 13%, 43%, and 53% of low-risk, intermediate-risk, and high-risk patients, respectively and 46%, 61%, and 71% had at least 1 action taken within the first 6 months. High-risk patients were more likely to be placed on SGLT2 inhibitors (OR = 4.56; 95% CI 3.00-6.91 vs low-risk), and more likely to be referred to a specialist such as a nephrologist, endocrinologist, or dietician (OR = 2.49; 95% CI 1.53-4.01) compared to low-risk patients. Conclusions: The combination of KidneyIntelX, clinical guidelines and educational support resulted in changes in clinical management by clinicians. After testing, there was an increase in visit frequency, referrals for disease management, and introduction to guideline-recommended medications. These differed by risk category, indicating an impact of KidneyIntelX risk stratification on clinical care.

A Real-World Precision Medicine Program Including the KidneyIntelX Test Effectively Changes Management Decisions and Outcomes for Patients With Early-Stage Diabetic Kidney Disease

“…6, 8 - 10 The reasons for this are multifactorial, but a lack of early and accurate risk stratification to identify those most at risk for DKD progression is a key problem. 8 , 11 Therapeutic inertia is common in kidney disease, due to inadequate ability to determine who will derive the most (absolute) benefit from new treatments for a silent condition that takes years to realize the gains of therapy on a patient-level basis.…”

“…We have previously reported on the 6-month interim results of a real-world evidence (RWE) study using the KidneyIntelX test, which demonstrated changes in clinical management of patients with T2D and early-stage (Grade (G)1-G3) DKD. 11 Here, we sought to ascertain the 1-year data from the RWE KidneyIntelX program at MSHS. Our focus was on sustainability of the KidneyIntelX testing platform as a program of personalized risk assessment with an emphasis on treatment with cardio-renal protective agents, utilization of consult services, advanced practice provider driven protocols post-testing, and impact on A1C, UACR, and the eGFR slope as drivers of patient-provider compliance and improved outcomes.…”

Derivation and independent validation of kidneyintelX.dkd: A prognostic test for the assessment of diabetic kidney disease progression

“…All patients had T2D and established DKD at baseline, with an eGFR of 30 to 59 mL/min/1.73 m 2 or an eGFR ≥60 mL/min/1.73 m 2 with albuminuria (uACR ≥30 mg/g). 17,20,21 2.1 | Study populations…”

“…The laboratory assay of the kidneyintelX.dkd test quantitatively measures K2EDTA plasma TNFR1, TNFR2 and KIM‐1, and combines these measurements with clinical data to produce a level of risk (low, moderate or high) associated with PDKF for adult patients with T2D and CKD (ie, DKD). All patients had T2D and established DKD at baseline, with an eGFR of 30 to 59 mL/min/1.73 m 2 or an eGFR ≥60 mL/min/1.73 m 2 with albuminuria (uACR ≥30 mg/g) 17,20,21 …”

“…years and 43% were women. The mean (SD) eGFR was 58(20) mL/min/1.73 m 2 and the median (interquartile range [IQR]) uACR was 54 (14-221) mg/g. In the BioMe cohort, 657 participants were included in the analysis based on prespecified inclusion/exclusion criteria; the mean (SD) age was 70(11) years and 57% were women.…”