(1037 days)
Not Found
Not Found
Yes
The device description explicitly states that the algorithm used to generate the risk assessment score is "artificial intelligence derived" and was "modeled using machine learning (Random Forest)".
No.
This device is an in-vitro diagnostic tool designed to assess the risk of progressive decline in kidney function. It provides a risk assessment score and does not treat or prevent any condition.
Yes
Explanation: The "Intended Use / Indications for Use" section explicitly states "KidneyIntelX.dkd is for in-vitro diagnostic use." It also describes its use as "an aid in assessment of the risk of progressive decline in kidney function," which clearly indicates a diagnostic purpose.
No
The device description explicitly states that the device includes the measurement of biomarkers using a physical instrument (MESO SECTOR® S 600) and assay components, which are hardware and physical reagents, not solely software.
Yes, this device is an IVD (In Vitro Diagnostic).
Here's why:
- Intended Use: The "Intended Use / Indications for Use" section explicitly states "KidneyIntelX.dkd is for in-vitro diagnostic use".
- Sample Type: The device analyzes "human plasma" and "urine albumin creatinine ratio (uACR)", which are biological samples taken from the body.
- Measurement Method: It uses an "electrochemiluminescence immunoassay" to quantitatively measure biomarkers in these samples.
- Purpose: The purpose is to provide an "aid in assessment of the risk of progressive decline in kidney function", which is a diagnostic purpose.
- Device Description: The "Device Description" further clarifies that it measures "circulating biomarkers in human EDTA plasma" using an "in vitro quantitative determination" method.
All of these points align with the definition of an In Vitro Diagnostic device, which is used to examine specimens derived from the human body to provide information for diagnostic purposes.
No
The letter does not explicitly state that the FDA has reviewed, approved, or cleared a PCCP for this specific device.
Intended Use / Indications for Use
KidneyIntelX.dkd is for in-vitro diagnostic use for the determination of a KidneyIntelX.dkd Level using an algorithm to combine clinical variables (blood urea nitrogen (BUN), hemoglobin A 1c (HbAlc) and urine albumin creatinine ratio (uACR)) and the quantitative measurements of tumor necrosis factor receptor-1 (TNFR-1), tumor necrosis factor receptor-2 (TNFR-2) and kidney injury molecule-1 (KIM-1) in human plasma employing a Meso Sector S 600 electrochemiluminescence immunoassay. It is indicated for use as an aid in assessment of the risk of progressive decline in kidney function (sustained decrease in eGFR greater than or equal to 40% lasting more than 3 months) within a period of up to 5 years following KidneyIntelX.dkd Level measurement in adult patients with type 2 diabetes and existing chronic kidney disease (defined for the purposes of this device as patients with an estimated glomerular filtration rate of 30-59 ml/min/1.73m2 or eGFR >= 60 ml/min/1.73m2 with albuminuria (uACR >= 30 mg/g)).
KidneyIntelX.dkd is not intended for screening or as a stand-alone diagnostic test.
Product codes (comma separated list FDA assigned to the subject device)
QWZ
Device Description
KidneyIntelX.dkd provides the KidneyIntelX.dkd level, generated by the KidneyIntelX.dkd algorithm. The algorithm includes inputs from clinical data collected on the patient as well as component analytes measured directly by KidneyIntelX.dkd.
The three component analytes measured by KidneyIntelX.dkd directly are quantitated via a multiplex electrochemiluminescence technology for the in vitro quantitative determination the concentration of three circulating biomarkers in human EDTA plasma:
- i) soluble Tumor Necrosis Factor Receptor 1 (TNFR-1),
- ii) soluble Tumor Necrosis Factor Receptor 2 (TNFR-2),
- iii) and Kidney Injury Molecule (KIM)-1.
The three measured components of the KidneyIntelX.dkd level are measured using the MESO SECTOR® S 600 instrument, by trained laboratory personnel using the assay components that includes the KidneyIntelX 96-well plate, the detection antibody, calibrator, and controls along with the Meso Scale Diagnostics diluents, blocker, wash buffer and read buffer.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
A software with an artificial intelligence derived algorithm provides a risk assessment score by combining the biomarker results from the assay (TNFR-1, TNFR-2, and KIM-1) and a set of clinical data, which are provided by a patient's physician via a test requisition form (urine albumin creatinine ratio [uACR], hemoglobin A1c [HbA1c], and Blood Urea Nitrogen [BUN]). The algorithm generates a risk level (Low, Moderate, or High) for progressive decline in kidney function, defined as sustained decrease (60 mL/min/1.73 m2 and uACR is >30 mg/g
Specimens were also required to have the externally provided measurements (BUN, uACR, HbA1c) within 12 months prior to enrollment.
Total N=657 patients.
| Enrollment Criterion | Total (N=657) n (%) |
|---|---|
| eGFR value is between 30 to 59.9 mL/min/1.73 m² | 388 (59%) |
| eGFR is ≥60 mL/min/1.73 m² and uACR is ≥30 mg/g | 269 (41%) |
Median Age: 72 (64, 78); Min, Max: 38, 90.
Sex: Male 284 (43.2%), Female 373 (56.8%).
Race: American Indian/Alaskan Native 3 (0.5%), Asian 27 (4.1%), Black/African American 240 (36.5%), Native Hawaiian/Pacific Islander 0 (0%), White 100 (15.2%), Other 284 (43.2%), No Response 3(0.5%).
Ethnicity: Hispanic 264 (40.2%), Non-Hispanic 393 (59.8%).
Clinical History: Hypertension 568 (86.5%), Heart Failure 78 (11.9%), Coronary Artery Disease 138 (21.0%).
The pre-specified event rate for the analysis is time to the first occurrence of a composite end point that was defined as ≥40% sustained decline in eGFR or reaching end stage kidney disease (sustained eGFR =40% sustained decline in eGFR or reaching end-stage kidney disease within 5 years).
Observed Events (40% decline events):
- Low Level (N=374): 17 events (4.6% of patients, 95% CI: 2.7-7.2%)
- Moderate Level (N=228): 38 events (16.7% of patients, 95% CI: 12.1-22.2%)
- High Level (N=55): 23 events (41.8% of patients, 95% CI: 28.7-55.9%)
Follow Up Time (Mean (SD) in days):
- Low Level: 1344.9 (471.68)
- Moderate Level: 1158.6 (555.39)
- High Level: 719.5 (488.52)
- Total: 1227.9 (532.95)
Kaplan-Meier Survival Analysis (Estimated rate at 5-years):
- Low Level: 5.9% (95% CI: 3.6-9.4%)
- Moderate Level: 21.5% (95% CI: 15.9-28.6%)
- High Level: 66.9% (95% CI: 49.3-83.5%)
Subgroup analysis for Starting eGFR:
eGFR 30-59.9 (n=388):
- Low (n=215): 6.5% (3.6-11.7%) estimated rate at 5 years
- Moderate (n=131): 24.2% (16.7-34.3%) estimated rate at 5 years
- High (n=42): 76.9% (55.4-93.1%) estimated rate at 5 years
eGFR >=60 (n=269):
- Low (n=159): 4.9% (2.2-10.8%) estimated rate at 5 years
- Moderate (n=97): 16.9% (9.9-28.0%) estimated rate at 5 years
- High (n=13): 45.5% (19.5-81.6%) estimated rate at 5 years
Subgroup analysis for Race:
Black/African American (n=240):
- Low (n=140): 4.9% (2.2-10.7%) estimated rate at 5 years
- Moderate (n=82): 22.2% (13.7-34.8%) estimated rate at 5 years
- High (n=18): 83.9% (52.4-98.9%) estimated rate at 5 years
Non-Black/African American (n=417):
- Low (n=234): 6.6% (3.6-11.8%) estimated rate at 5 years
- Moderate (n=146): 20.6% (13.8-30.0%) estimated rate at 5 years
- High (n=37): 60.1% (39.1-81.7%) estimated rate at 5 years
End Stage Kidney Disease Events:
- Low Level: 0% of patients
- Moderate Level: 3.1% of patients
- High Level: 18.2% of patients
- Total: 2.6% of patients
Standalone Performance: Not applicable (adjunctive aid).
AUC, MRMC: Not Found
Key Metrics (Sensitivity, Specificity, PPV, NPV, etc.)
Not Found
Predicate Device(s): If the device was cleared using the 510(k) pathway, identify the Predicate Device(s) K/DEN number used to claim substantial equivalence and list them here in a comma separated list exactly as they appear in the text. List the primary predicate first in the list.
Not Found
Reference Device(s): Identify the Reference Device(s) K/DEN number and list them here in a comma separated list exactly as they appear in the text.
Not Found
Predetermined Change Control Plan (PCCP) - All Relevant Information for the subject device only (e.g. presence / absence, what scope was granted / cleared under the PCCP, any restrictions, etc).
Not Found
N/A
0
EVALUATION OF AUTOMATIC CLASS III DESIGNATION FOR KidneyIntelX.dkd DECISION SUMMARY
I Background Information:
A De Novo Number
B Applicant
Renalytix AI, Inc.
C Proprietary and Established Names
KidneyIntelX.dkd
D Regulatory Information
| Product
Code(s) | Classification | Regulation
Section | Panel |
|--------------------|-----------------------------------|----------------------------------------------------------------------------------------------------|----------------------------------------------|
| QWZ | Class II with
special controls | 21 CFR 862.1223 -
Prognostic test for
assessment of chronic
kidney disease
progression | Clinical Chemistry and
Toxicology Devices |
Submission/Device Overview: II
A Purpose for Submission:
De Novo request for evaluation of automatic class III designation for KidneyIntelX.dkd.
B Measurand:
The device reports a KidneyIntelx.dkd score derived from measurements of Tumor Necrosis Factor Receptor 1 (TNFR-1), Tumor Necrosis Factor Receptor 2 (TNFR-2), Kidney Injury Molecule 1 (KIM-1) and clinical variables (Urine Albumin Creatinine Ratio (uACR), Hemoglobin Alc (HbAlc) and Blood Urea Nitrogen (BUN).
C Type of Test:
Immunofluorescent quantitative assay
1
III Indications for Use:
A Indication(s) for Use:
KidneyIntelX.dkd is for in-vitro diagnostic use for the determination of a KidneyIntelX.dkd Level using an algorithm to combine clinical variables (blood urea nitrogen (BUN), hemoglobin A 1c (HbAlc) and urine albumin creatinine ratio (uACR)) and the quantitative measurements of tumor necrosis factor receptor-1 (TNFR-1), tumor necrosis factor receptor-2 (TNFR-2) and kidney injury molecule-1 (KIM-1) in human plasma employing a Meso Sector S 600 electrochemiluminescence immunoassay. It is indicated for use as an aid in assessment of the risk of progressive decline in kidney function (sustained decrease in eGFR greater than or equal to 40% lasting more than 3 months) within a period of up to 5 years following KidneyIntelX.dkd Level measurement in adult patients with type 2 diabetes and existing chronic kidney disease (defined for the purposes of this device as patients with an estimated glomerular filtration rate of 30-59 ml/min/1.73m2 or eGFR ≥ 60 ml/min/1.73m2 with albuminuria (uACR ≥ 30 mg/g)).
KidneyIntelX.dkd is not intended for screening or as a stand-alone diagnostic test.
B Special Conditions for Use Statement(s):
Rx - For Prescription Use Only
KidneyIntelX.dkd is for In-Vitro Diagnostic Use: Only performed at Renalytix clinical laboratory.
KidneyIntelX.dkd is not intended as a screening or stand-alone diagnostic test.
KidneyIntelX.dkd is not for use in the diagnosing or staging of diabetic kidney disease.
KidneyIntelX.dkd test results are intended to be used in conjunction with other clinical and diagnostic findings, consistent with professional standards of practice, including information obtained by alternative methods, and clinical evaluation and physician assessment as appropriate.
Always interpret KidneyIntelX.dkd test results in conjunction with the patient's medical history, clinical presentation, physician assessment and other findings.
A KidneyIntelX.dkd Low Level is associated with a lower prognostic risk, but disease progression will occur in some patients with a KidneyIntelX.dkd Low Level test result.
A KidneyIntelX.dkd High Level is associated with a higher prognostic risk, but disease progression does not occur in some patients with a KidneyIntelX.dkd High Level test result.
Only K2EDTA plasma samples can be analyzed for the measurement of KIM-1, TNFR-1 and TNFR-2 used to generate the KidneyIntelX.dkd test results.
Only measurements of uACR, HbA1c, and BUN within measuring intervals and eGFR and serum creatinine detailed in the Test Requisition Form taken within 12 months prior to sample collection should be used with the KidneyIntelX.dkd test.
2
All inputs to the KidneyIntelX.dkd algorithm are subject to measurement and intra-individual variability resulting in some subjects being reported at different KidneyIntelX.dkd Levels on repeat testing.
C Special Instrument Requirements:
Plate imager instrument
IV Device/System Characteristics:
A Device Description:
KidneyIntelX.dkd provides the KidneyIntelX.dkd level, generated by the KidneyIntelX.dkd algorithm. The algorithm includes inputs from clinical data collected on the patient as well as component analytes measured directly by KidneyIntelX.dkd.
The three component analytes measured by KidneyIntelX.dkd directly are quantitated via a multiplex electrochemiluminescence technology for the in vitro quantitative determination the concentration of three circulating biomarkers in human EDTA plasma:
- i) soluble Tumor Necrosis Factor Receptor 1 (TNFR-1),
- ii) soluble Tumor Necrosis Factor Receptor 2 (TNFR-2),
- iii) and Kidney Injury Molecule (KIM)-1.
The three measured components of the KidneyIntelX.dkd level are measured using the MESO SECTOR® S 600 instrument, by trained laboratory personnel using the assay components that includes the KidneyIntelX 96-well plate, the detection antibody, calibrator, and controls along with the Meso Scale Diagnostics diluents, blocker, wash buffer and read buffer.
Principle of Operation B
A sandwich immunoassay is used to measure KIM-1, TNFR-1, and TNFR-2. The plate wells are precoated with goat polyclonal antibodies to KIM-1, and mouse monoclonal antibodies specific to TNFR-1 and TNFR-2. After treating the wells with a blocking solution, the specimens and controls are incubated in the wells then washed. The analytes are quantified via electrochemiluminescence, with secondary detection antibodies (goat polyclonal antibodies to KIM-1, and mouse monoclonal antibodies specific to TNFR-1 and TNFR-2) covalently linked to electrochemiluminescent labels. The MESO SECTOR® S 600A instrument measures the light emitted via charged-coupled device (CCD) camera.
A software with an artificial intelligence derived algorithm provides a risk assessment score by combining the biomarker results from the assay (TNFR-1, TNFR-2, and KIM-1) and a set of clinical data, which are provided by a patient's physician via a test requisition form (urine
3
albumin creatinine ratio [uACR], hemoglobin A1c [HbA1c], and Blood Urea Nitrogen [BUN]). The algorithm generates a risk level (Low, Moderate, or High) for progressive decline in kidney function, defined as sustained decrease ( ±10% was observed for the measurements of KIM-1, TNFR-1 and TNFR-2 at the concentrations shown below for the following substances:
| Interfering Substance | Interference
Level | % Observed
Interference |
|------------------------|-----------------------|----------------------------|
| Total Protein | 13 g/dL | 23% |
| Rheumatoid Factor (RF) | 997 IU/mL | -11% |
The sponsor included the following limitations in the labeling:
- . The KidneyIntelX.dkd test should not be used in patients with known elevation of RF above 665 IU/mL.
- The KidneyIntelX.dkd test should not be used in patients with known elevation of total . protein above 8.5 g/dL.
- Specimens with selenium levels above 226 ng/mL may have falsely elevated results. .
4. Assay Reportable Range:
In summary, considering LoB/LoD/LoQ, linearity and precision studies, the sponsor provided data to support the following measuring intervals for the three inputs:
KIM-1 measurement interval: 12 pg/mL to 3,915 pg/mL TNFR-1 measurement interval: 1,057 pg/mL to 14,322 pg/mL TNFR-2 measurement interval: 4,270 pg/mL to 43,291 pg/mL
8
5. Traceability, Stability, Expected Values (Controls, Calibrators, or Methods):
The KIM-1, TNFR-1 and TNFR-2 methodologies used in the KidneyIntelX.dkd laboratory are traceable to internal standards.
The sponsor provided data to support that the KIM-1, TNFR-1 and TNFR-2 are stable for 3 days at up to 37℃, consistent with the instructions for handling samples for shipping to the KidneyIntelX.dkd laboratory.
6. Detection Limit:
Limit of blank (LoB):
Limit of blank was determined for KIM-1. TNFR-1 and TNFR-2 when measured in the KidneyIntelX.dkd laboratory using 2 lots of reagents on 1 instrument. 160 determinations per lot were obtained by testing 8 blank serum samples in 2 replicates during 10 runs.
The LoB was calculated non-parametrically according to the CLSI EP17-A2 as the value at the ranked position (152.5 in this study) using the following equation:
(DR. 0)
where B = total number of blank sample measurements.
Limit of Detection (LoD):
Limit of detection was determined for the for KIM-1, TNFR-1 and TNFR-2 when measured in the KidneyIntelX.dkd laboratory using 2 lots of reagents and 1 instrument. A total of 80 determinations per lot were obtained by testing 4 low analyte serum samples in 2 replicates during 10 runs.
The limit of detection was determined using the precision profile approach as described in the CLSI document EP17-A2
Limit of Quantitation (LoO):
The LoQ was derived using a precision profile approach using data from the low-end region of the measuring interval for KIM-1, TNFR-1, and TNFR-2 when measured in the KidneyIntelX.dkd laboratory. Results from testing of the 13 samples were used for calculation of the LoQ. The LoQ for each reagent lot was determined as the analyte concentration corresponding to the intersection of the acceptance criterion goal with the precision profile. The LoQ was defined as the lowest concentration with total within-laboratory precision of %CV60 mL/min/1.73 m2 and uACR is >30 mg/g
Specimens were also required to have the externally provided measurements (BUN, uACR, HbA1c) within 12 months prior to enrollment.
10
Patient Population
| Enrollment Criterion | Total (N=657)
n (%) |
|-------------------------------------------------|------------------------|
| eGFR value is between 30 to 59.9 mL/min/1.73 m² | 388 (59%) |
| eGFR is ≥60 mL/min/1.73 m² and uACR is ≥30 mg/g | 269 (41%) |
| Age | Median (IQR) | 72 (64, 78) | |
|---|---|---|---|
| Min, Max | 38,90 | ||
| Sex | n (%) | Male 284 (43.2%) | |
| Female 373 (56.8%) | |||
| Race | n (%) | American Indian/Alaskan Native 3 (0.5%) | |
| Asian 27 (4.1%) | |||
| Black/African American 240 (36.5%) | |||
| Native Hawaiian/Pacific Islander 0 (0%) | |||
| White 100 (15.2%) | |||
| Other 284 (43.2%) | |||
| No Response 3(0.5%) | |||
| Ethnicity | n (%) | Hispanic 264 (40.2%) | |
| Non-Hispanic 393 (59.8%) | |||
| Clinical History | n (%) | Hypertension 568 (86.5%) | |
| Heart Failure 78 (11.9%) | |||
| Coronary Artery Disease 138 (21.0%) |
Demographics and Medical History:
The sponsor performed an analysis to identify the ability of the KidneyIntelX.dkd test to predict progressive decline in kidney function by quantifying the event rates for patients in each of the three KidneyIntelX.dkd levels. The pre-specified event rate for the analysis is time to the first occurrence of a composite end point that was defined as ≥40% sustained decline in eGFR or reaching end stage kidney disease (sustained eGFR 60
(n = 269) | Low | 159 | 6 | 153 | 4.9%
(2.2-10.8%) |
| Starting
eGFR > 60
(n = 269) | Moderate | 97 | 13 | 84 | 16.9%
(9.9-28.0%) |
| Starting
eGFR > 60
(n = 269) | High | 13 | 4 | 9 | 45.5%
(19.5-81.6%) |
Kaplan-Meier curves were plotted to show performance of KidneyIntelX.dkd in sub-populations represented in the clinical performance study as defined by race:
14
Image /page/14/Figure/0 description: The image shows product-limit failure curves with 95% confidence limits. The x-axis represents years, ranging from 0 to 5, while the y-axis represents failure probability, ranging from 0.0 to 1.0. There are three curves representing low, moderate, and high failure probabilities over time. The high curve shows the highest failure probability, reaching over 0.8 by year 5, while the low curve shows the lowest failure probability, remaining below 0.1.
Kaplan-Meier curve for progressive decline in kidney function over time up to a maximum follow-up of 5 years of individuals self-identified as Black or African American ancestry.
Image /page/14/Figure/2 description: The image shows product-limit failure curves with 95% confidence limits. The x-axis represents years, ranging from 0 to 5, while the y-axis represents failure probability, ranging from 0.0 to 1.0. There are three curves representing low, moderate, and high failure probabilities. The high failure probability curve reaches approximately 0.6 at 5 years, while the moderate curve reaches approximately 0.2, and the low curve reaches approximately 0.1.
Kaplan-Meier curve for progressive decline in kidney function over time up to a maximum follow-up of 5 years of individuals self-identified of Non-Black or Non-African ancestry.
15
| Subgroup | KidneyIntelX.dkd
Level | Number
of
subjects | Progressive Decline
in Kidney Function | | Estimated rate at
5 years (95%
confidence
intervals) |
|------------------------------------------------|---------------------------|--------------------------|-------------------------------------------|-----|---------------------------------------------------------------|
| | | | Yes | No | |
| Black/African
American
(n = 240) | Low | 140 | 6 | 134 | 4.9%
(2.2-10.7%) |
| | Moderate | 82 | 15 | 67 | 22.2%
(13.7-34.8%) |
| | High | 18 | 9 | 9 | 83.9%
(52.4-98.9%) |
| Non-
Black/African
American
(n = 417) | Low | 234 | 11 | 223 | 6.6%
(3.6-11.8%) |
| | Moderate | 146 | 22 | 124 | 20.6%
(13.8-30.0%) |
| | High | 37 | 14 | 23 | 60.1%
(39.1-81.7%) |
Although the study was not powered to detect statistically significant differences in the rates of end stage kidney disease between groups, the sponsor also provided information on the number of patients who experienced end-stage kidney disease by each risk group:
| | KidneyIntelX.dkd
Level Low
N=374 | KidneyIntelX.dkd
Level Moderate
N=228 | KidneyIntelX.dkd
Level High
N=55 | Total
N=657 |
|--------------------------------------------------------------|----------------------------------------|---------------------------------------------|----------------------------------------|----------------|
| % of patients
experiencing
End Stage
Kidney Disease | 0 | 3.1% | 18.2% | 2.6% |
D Clinical Cut-Off:
Not Applicable.
E Expected Values/Reference Range:
Expected values for apparently healthy subjects and for patients with type 2 diabetes but without CKD were established in accordance with CLS1 guideline EP28-A3c. Study subjects were selected to be representative of the U.S. population. The absence of chronic kidney disease (CKD) was defined as those subjects with eGFR ≥60 mL/min/1.73m2 and uACR