RESEARCH PROTOCOL
Estimating the comparative risk of kidney failure associated with intravitreal anti-vascular endothelial growth factor exposure in patients with blinding diseases
Estimating the comparative risk of kidney failure associated with intravitreal anti-vascular endothelial growth factor exposure in patients with blinding diseases
Version: 0.0.2
1 List of Abbreviations
| Anti-VEGF | anti-vascular endothelial growth factor |
| DME | diabetic macular edema |
| DR | diabetic retinopathy |
| AMD | age-related macular degeneration |
| VO | vein occlusion |
| CKD | chronic kidney disease |
| ICD | International Classification of Diseases |
| CPT | Current Procedural Terminology |
| OHDSI | Observational Health Data Sciences and Informatics |
| OMOP | Observational Medical Outcomes Partnership |
| CDM | common data model |
| PS | propensity score |
| EHR | electronic health record |
| IRB | Institutional Review Board |
| JHM | Johns Hopkins Medicine |
| ARVO | The Association for Research in Vision and Ophthalmology |
2 Responsible Parties
2.1 Investigators
| Investigator | Institution/Affiliation |
|---|---|
| Cindy Cai, MD * | Wilmer Eye Institute, Johns Hopkins Hospital, Baltimore, MD, USA |
| * Principal Investigator |
2.2 Disclosures
This study is undertaken within Observational Health Data Sciences and Informatics (OHDSI), an open collaboration.
3 Abstract
Background: The potential adverse kidney effects of the commonly used intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications are poorly understood.
Purpose: To estimate the risk of kidney failure after intravitreal anti-VEGF medications across the Observational Health Data Sciences and Informatics (OHDSI) network, comparing ranibizumab, aflibercept, and bevacizumab.
Design: Retrospective comparative cohort analysis of administrative claims and electronic health record (EHR) data in the OHDSI network.
Subjects: Patients with blinding diseases including diabetic macular edema (DME), diabetic retinopathy (DR), age-related macular degeneration (AMD), and vein occlusion (VO) who receive ≥3 monthly anti-VEGF will be included. Patients with pre-existing kidney failure will be excluded.
Methods: Patients receiving ranibizumab will be compared to propensity score matched patients receiving aflibercept, and patients receiving bevacizumab. We will deploy the large-scale propensity score method that adjust for a comprehensive range of baseline characteristics. Cox models will be used to compare the time to kidney failure between patients who receive ranibizumab with patients who receive aflibercept, ranibizumab with bevacizumab, and bevacizumab with aflibercept.
Conclusions: Knowing the relative risk for kidney failure between the three commonly used anti-VEGF medications will allow ophthalmologists to select safer treatments.
4 Amendments and Updates
| Number | Date | Section of study protocol | Amendment or update | Reason |
|---|---|---|---|---|
5 Milestones
| • Identify data partners |
|---|
| • Data partners to share data diagnostics results |
| • Complete candidate phenotypes |
| • Data partners to share phenotype diagnostics results |
| • Finalize analytic package |
| • Data partners to run analytic package |
| • Data partners to share study diagnostic results |
| • Finalize results from data partners |
| • Manuscript drafting and writing |
| • Submit abstract: OHDSI Global Symposium (May 2023), ARVO (Jan 2024) |
6 Rationale and Background
Intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications have revolutionized the treatment of blinding diseases.1,2 Nearly 20 million intravitreal injections were given globally in 2016 to treat conditions such as diabetic macular edema (DME), diabetic retinopathy (DR), age-related macular degeneration (AMD), and vein occlusion (VO).1 When given systemically, anti-VEGF medications have adverse kidney effects (e.g., proteinuria, acute kidney injury).3–5 Patients at high risk for chronic kidney disease (CKD), for example, those ≥60 years and those with diabetes, may be more likely harmed by the adverse kidney effects of intravitreal anti-VEGF.6 CKD can progress to kidney failure, or end stage kidney disease, which is a major source of morbidity and mortality and is a financial burden to society.6,7
When anti-VEGF medications are given intravitreally, there is systemic absorption of the drug that is greatest with bevacizumab and aflibercept and lowest with ranibizumab.8,9 However, evidence about the subsequent kidney effect is conflicting. Several case reports document kidney damage after intravitreal anti-VEGF.10–12 On the other hand, retrospective cohort studies have not identified treatment-associated declines in kidney function, or estimated glomerular filtration rate (eGFR).13,14 A secondary analysis from a randomized trial also did not show differences in rates of kidney damage.15 However, these studies were limited to a single institution, had small sample sizes (<600 patients), only included patients without CKD, or did not evaluate the severe phenotype of kidney failure. To resolve this controversy, a comprehensive study is needed to evaluate the kidney effects of intravitreal anti-VEGF. In populations at high risk for CKD, the treating ophthalmologist can choose alternate forms of therapy (e.g., focal laser for DME), or the intravitreal anti-VEGF with the least systemic absorption (e.g., ranibizumab).16–18
7 Study Objectives
The overall objective of the study is to estimate the comparative risk of kidney failure associated with intravitreal anti-VEGF exposure in patients with blinding diseases. The rationale is that knowing the comparative risk for kidney failure among the three commonly used anti-VEGF medications will allow the ophthalmologist to select the safest treatments, particularly for populations at high risk for adverse kidney effects. To address our hypothesis, we propose the following questions.
Amongst people with blinding diseases (DR/DME, AMD, and VO), does exposure to aflibercept increase the risk of kidney failure, relative to ranibizumab?
Amongst people with blinding diseases (DR/DME, AMD, and VO), does exposure to bevavizumab increase the risk of kidney failure, relative to ranibizumab?
Amongst people with blinding diseases (DR/DME, AMD, and VO), does exposure to bevacizumab increase the risk of kidney failure, relative to aflibercept?
8 Research Methods
8.1 Study Design/Data Sources
This will be a retrospective cohort study of patients with blinding diseases (DR/DME, AMD, and VO) comparing the risk of kidney failure after exposure to aflibercept relative to ranibizumab, bevacizumab to ranibizumab, and bevacizumab to aflibercept. Data sources will be administrative claims or electronic health record (EHR) data across the OHDSI network.
8.2 Study Population
Patients ≥18 years who have received ≥3 monthly intravitreal anti-VEGF injections with ranibizumab, aflibercept, or bevacizumab with a diagnosis of DME/DR, AMD, and VO with at least 365 days of prior observation will be included in the study.16,17,19–22 Cohort entry will begin with the third anti-VEGF medication. Patients with pre-existing kidney failure will be excluded. Patients with pre-existing diagnosis of malignancies will be excluded. (Figure 1) Patients will exit the cohort if they switch to another anti-VEGF medication (e.g., bevacizumab to ranibizumab).
Figure 1: Exposure cohort definition using bevacizumab as the example.
8.3 Exposure Comparators
The exposure is receipt of ≥3 monthly intravitreal anti-VEGF medications (whether ranibizumab, aflibercept, or bevacizumab).
8.4 Outcomes
The outcome is time from the third anti-VEGF to kidney failure, as defined by previously validated OMOP phenotypes, during the observation window after cohort entry.23,24
8.5 Covariates
We will deploy the large-scale propensity score method that adjust for a comprehensive range of baseline characteristics.25
8.6 Negative controls
Negative controls will be picked to represent exposure-outcome pairs where no causal effect is expected to exist.
9 Data Analysis Plan
9.1 General
Although the primary aim of this study is a comparative safety study, various standardized analytics available in the OHDSI community will be applied. The Strategus pipeline will be used to call various packages in the HADES library for A) data characterization (A1-cohort diagnostics, A2-cohort features, A3-incidence rates, A4-time-to-event), B) patient-level prediction, and C) population-level effect estimation (C1-comparative cohort, C2-self-controlled case-series).26,27
9.2 A) Data Characterization
9.2.1 A1) Cohort Diagnostics
The R package CohortDiagnostics will be executed for all target, comparator, indication, and outcome cohorts to evaluate measurement error in the phenotype development and evaluation process.28
9.2.2 A2) Cohort Features
The Characterization and FeatureExtraction packages in HADES will be used to identify features of patients in each exposure group who had the outcome and those who did not have the outcome.27 Features will be extracted from the 365 day observation prior to cohort entry and will include variables such as demographic data (sex, age group, race, ethnicity), prior conditions/drug exposures/procedures/measurements/devices/observations, and risk scors (e.g., Charlson comorbidity index, DCSI, CHADS2VASC score).
9.2.3 A3) Incidence Rates
The Characterization package in HADES will be used to calculate the incidence rates of the outcome for each exposure cohort and indication cohort. The rate is calculated as the number of outcomes during the time-at-risk divided by the number of total person days.
9.2.3.1 Calculation of time-at risk
The time-at-risk for patients who undergo anti-VEGF starts after the third anti-VEGF injection until the end of the continuous drug exposure, defined as a gap in exposure of >180 days, end of continuous observation period, or study period. Anti-VEGF need typically decreases over time; however, some patients require lifelong VEGF suppression and the proportion of patients who require lifelong VEGF is likely different depending on the disease indication (e.g., DME/DR, versus AMD, versus VO).29–33
Incidence rates will be stratified by gender, age deciles, index year subgroups, and disease indication (DME/DR, AMD, VO).
9.2.4 A4) Time-to-Event
Time to the outcome of kidney failure will be calculated for each exposure cohorts and indication cohort.
9.3 B) Patient-Level Prediction
The PatientLevelPrediction and Cyclops packages in HADES will be used to construct logistic regression models with LASSO regularization to predict the risk of kidney failure 6 months to 2 years after the initial 3 monthly intravitreal anti-VEGF medications.34 The model will be developed on 75% of the data and internally validated on the remaining 25%.
9.4 C) Population-Level Effect Estimation
9.4.1 C1) Comparative Cohort Study
The CohortMethod and Cyclops packages in Hades will be used.27 Large-scale propensity score method will be used to match the targe exposure cohort with the comparator export cohort (e.g., aflibercept versus ranibizumab, bevacizumab versus ranibizumab, and bevacizumab versus aflibercept) using 1:1 propensity score matching. Cox proportional hazards models will be used to estimate the risk of kidney failure while on treatment.35 Negative controls will be used to assess residual bias.
9.4.2 C2) Self-Controlled Case-Series
The SelfControlledCaseSeries and Cyclops packages in Hades will be used to estimate the relative incidence of kidney failure using a self-controlled case-series design.27 Diagnostics will be run to evaluate whether this was an appropriate analysis.
10 Study Diagnostics
- Preference score distributions to evaluate empirical equipoise and population generalizability
- Extensive patient characteristics to evaluate cohort balance before and after PS-adjustment
- Negative control calibration plots to assess residual bias
- Kaplan-Meier plots to examine hazard ratio proportionality assumptions
Study diagnostics to evaluate each databases’ fitness for use to estimate comparative risk of kidney failure between exposure groups.
Study Diagnostic; Brief Description; Threshold Minimum detectable relative risk (MDRR); Evaluates the effect size that the analysis would be able to detect given the available data; <10 Empirical Equipoise; Estimated using preference score, a transformation of propensity score; >0.20 Attrition Fraction; Fraction of the initial cohort that remains in the analytic cohort after propensity score matching and is a measure of generalizability; ≤1 Covariate Balance; Covariate balance of baseline characteristics between target and comparator groups was measured using the standardized mean difference; <0.10 Expected absolute systematic error (EASE); Calculated using a set of negative control outcomes to assess residual bias; <0.25
11 Strengths and Limitations
When executed, this will be the largest study examining the association between intravitreal anti-VEGF medications and kidney failure. Other strengths of this study include the diversity of the sample (from multiple institutions, multiple countries, and a range of underlying kidney impairment at baseline).
Limitations are mainly due to the retrospective nature of the study which might have confounding despite propensity score matching and stratified analyses.
12 Protection of Human Subjects
The JHM IRB has already approved this project (IRB00356149). Each participating institution will seek IRB approval for this study.
13 Management and Reporting of Adverse Events and Adverse Reactions
JHM will serve as the coordinating center for this OHDSI network study. All findings and adverse events/reactions will be reported to them.
14 Plans for Disseminating and Communicating Study Results
The results will be shared and discussed among the study participants and broader OHDSI community during the weekly Tuesday community calls throughout the SOS Challenge. This work will be presented at conferences (OHDSI Global Symposium and/or ARVO) and published as a manuscript.
References
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Appendix
A Exposure Cohort Definitions
A.1 Ranibizumab exposures after new use with 3 exposures in 21-70d windows
A.1.1 Cohort Entry Events
People may enter the cohort when observing any of the following:
- drug exposures of ‘[SOS] ranibizumab’.
A.1.2 Additional Inclusion Criteria
I. has at least 1 prior exposure with 2 or more prior exposures in 21-70d with blinding disease and no other cancer and 365d before first
Entry events having at least 1 drug exposure of ‘[SOS] ranibizumab’, starting anytime on or before cohort entry start date; having at least 1 drug exposure of ‘[SOS] ranibizumab’, starting between 70 days before and 21 days before ‘[SOS] ranibizumab’ start date; having at least 1 drug exposure of ‘[SOS] ranibizumab’ for the first time in the person’s history, starting between 70 days before and 21 days before ‘[SOS] ranibizumab’ start date; with all of the following criteria:
having at least 1 observation period, starting anytime up to 365 days before ‘[SOS] ranibizumab’ start date and ending between 0 days after and all days after ‘[SOS] ranibizumab’ start date.
having no drug exposures of ‘[SOS] aflibercept ranibizumab and bevacizumab’, starting anytime prior to ‘[SOS] ranibizumab’ start date; allow events outside observation period.
having no condition occurrences of ‘[SOS] Malignant neoplasms excluding non-melanoma skin cancer’, starting anytime on or before ‘[SOS] ranibizumab’ start date; allow events outside observation period.
with any of the following criteria:
- having at least 1 condition occurrence of ‘[SOS] Retinal Vein Occlusion’, starting anytime on or before ‘[SOS] ranibizumab’ start date.
- having at least 1 condition occurrence of ‘[SOS] Age related Macular Degeneration’, starting anytime on or before ‘[SOS] ranibizumab’ start date.
- having at least 1 condition occurrence of ‘[SOS] Diabetic retinopathy’, starting anytime on or before ‘[SOS] ranibizumab’ start date.
- having at least 1 condition occurrence of ‘[SOS] Macular edema’, starting anytime on or before ‘[SOS] ranibizumab’ start date.
A.1.3 Cohort Exit
The cohort end date will be based on a continuous exposure to ‘[SOS] ranibizumab’: allowing 180 days between exposures, adding 0 days after exposure ends, and using days supply and exposure end date for exposure duration.
The person also exists the cohort when encountering any of the following events:
- drug exposures of ‘[SOS] aflibercept’.
- drug exposures of ‘[SOS] bevacizumab’.
A.1.4 Cohort Eras
Entry events will be combined into cohort eras if they are within 0 days of each other.
A.1.6 Concept: [SOS] Diabetic retinopathy
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4174977 | Retinopathy due to diabetes mellitus | 4855003 | SNOMED | NO | YES | NO |
A.1.7 Concept: [SOS] Macular edema
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4290333 | Macular retinal edema | 37231002 | SNOMED | NO | YES | NO |
| 4208200 | Postoperative cystoid macular edema | 312920004 | SNOMED | YES | YES | NO |
A.1.8 Concept: [SOS] Retinal Vein Occlusion
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 440392 | Retinal vascular occlusion | 73757007 | SNOMED | NO | YES | NO |
| 4334245 | Retinal artery occlusion | 232035005 | SNOMED | YES | YES | NO |
| 437544 | Arterial retinal branch occlusion | 50821009 | SNOMED | YES | YES | NO |
| 4338905 | Cilioretinal artery occlusion | 232036006 | SNOMED | YES | YES | NO |
A.1.9 Concept: [SOS] aflibercept ranibizumab and bevacizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 40244266 | aflibercept | 1232150 | RxNorm | NO | YES | NO |
| 1397141 | bevacizumab | 253337 | RxNorm | NO | YES | NO |
| 19080982 | ranibizumab | 595060 | RxNorm | NO | YES | NO |
A.1.10 Concept: [SOS] Malignant neoplasms excluding non-melanoma skin cancer
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4112752 | Basal cell carcinoma of skin | 254701007 | SNOMED | YES | YES | NO |
| 4111921 | Squamous cell carcinoma of skin | 254651007 | SNOMED | YES | YES | NO |
| 443392 | Malignant neoplastic disease | 363346000 | SNOMED | NO | YES | NO |
A.1.11 Concept: [SOS] ranibizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 19080982 | ranibizumab | 595060 | RxNorm | NO | YES | NO |
A.1.12 Concept: [SOS] aflibercept
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 40244266 | aflibercept | 1232150 | RxNorm | NO | YES | NO |
A.1.13 Concept: [SOS] bevacizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 1397141 | bevacizumab | 253337 | RxNorm | NO | YES | NO |
A.2 Bevacizumab exposures after new use with 3 exposures in 21-70d windows
A.2.1 Cohort Entry Events
People may enter the cohort when observing any of the following:
- drug exposures of ‘[SOS] bevacizumab’.
A.2.2 Additional Inclusion Criteria
I. has at least 1 prior exposure with 2 or more prior exposures in 21-70d with blinding disease and no other cancer and 365d before first
Entry events having at least 1 drug exposure of ‘[SOS] bevacizumab’, starting anytime on or before cohort entry start date; having at least 1 drug exposure of ‘[SOS] bevacizumab’, starting between 70 days before and 21 days before ‘[SOS] bevacizumab’ start date; having at least 1 drug exposure of ‘[SOS] bevacizumab’ for the first time in the person’s history, starting between 70 days before and 21 days before ‘[SOS] bevacizumab’ start date; with all of the following criteria:
having at least 1 observation period, starting anytime up to 365 days before ‘[SOS] bevacizumab’ start date and ending between 0 days after and all days after ‘[SOS] bevacizumab’ start date.
having no drug exposures of ‘[SOS] aflibercept ranibizumab and bevacizumab’, starting anytime prior to ‘[SOS] bevacizumab’ start date; allow events outside observation period.
having no condition occurrences of ‘[SOS] Malignant neoplasms excluding non-melanoma skin cancer’, starting anytime on or before ‘[SOS] bevacizumab’ start date; allow events outside observation period.
with any of the following criteria:
- having at least 1 condition occurrence of ‘[SOS] Retinal Vein Occlusion’, starting anytime on or before ‘[SOS] bevacizumab’ start date.
- having at least 1 condition occurrence of ‘[SOS] Age related Macular Degeneration’, starting anytime on or before ‘[SOS] bevacizumab’ start date.
- having at least 1 condition occurrence of ‘[SOS] Diabetic retinopathy’, starting anytime on or before ‘[SOS] bevacizumab’ start date.
- having at least 1 condition occurrence of ‘[SOS] Macular edema’, starting anytime on or before ‘[SOS] bevacizumab’ start date.
A.2.3 Cohort Exit
The cohort end date will be based on a continuous exposure to ‘[SOS] bevacizumab’: allowing 180 days between exposures, adding 0 days after exposure ends, and using days supply and exposure end date for exposure duration.
The person also exists the cohort when encountering any of the following events:
- drug exposures of ‘[SOS] aflibercept’.
- drug exposures of ‘[SOS] ranibizumab’.
A.2.4 Cohort Eras
Entry events will be combined into cohort eras if they are within 0 days of each other.
A.2.6 Concept: [SOS] Diabetic retinopathy
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4174977 | Retinopathy due to diabetes mellitus | 4855003 | SNOMED | NO | YES | NO |
A.2.7 Concept: [SOS] Macular edema
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4290333 | Macular retinal edema | 37231002 | SNOMED | NO | YES | NO |
| 4208200 | Postoperative cystoid macular edema | 312920004 | SNOMED | YES | YES | NO |
A.2.8 Concept: [SOS] Retinal Vein Occlusion
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 440392 | Retinal vascular occlusion | 73757007 | SNOMED | NO | YES | NO |
| 4334245 | Retinal artery occlusion | 232035005 | SNOMED | YES | YES | NO |
| 437544 | Arterial retinal branch occlusion | 50821009 | SNOMED | YES | YES | NO |
| 4338905 | Cilioretinal artery occlusion | 232036006 | SNOMED | YES | YES | NO |
A.2.9 Concept: [SOS] aflibercept ranibizumab and bevacizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 40244266 | aflibercept | 1232150 | RxNorm | NO | YES | NO |
| 1397141 | bevacizumab | 253337 | RxNorm | NO | YES | NO |
| 19080982 | ranibizumab | 595060 | RxNorm | NO | YES | NO |
A.2.10 Concept: [SOS] Malignant neoplasms excluding non-melanoma skin cancer
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4112752 | Basal cell carcinoma of skin | 254701007 | SNOMED | YES | YES | NO |
| 4111921 | Squamous cell carcinoma of skin | 254651007 | SNOMED | YES | YES | NO |
| 443392 | Malignant neoplastic disease | 363346000 | SNOMED | NO | YES | NO |
A.2.11 Concept: [SOS] bevacizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 1397141 | bevacizumab | 253337 | RxNorm | NO | YES | NO |
A.2.12 Concept: [SOS] aflibercept
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 40244266 | aflibercept | 1232150 | RxNorm | NO | YES | NO |
A.2.13 Concept: [SOS] ranibizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 19080982 | ranibizumab | 595060 | RxNorm | NO | YES | NO |
A.3 Aflibercept exposures after new use with 3 exposures in 21-70d windows
A.3.1 Cohort Entry Events
People may enter the cohort when observing any of the following:
- drug exposures of ‘[SOS] aflibercept’.
A.3.2 Additional Inclusion Criteria
I. has at least 1 prior exposure with 2 or more prior exposures in 21-70d with blinding disease and no other cancer and 365d before first
Entry events having at least 1 drug exposure of ‘[SOS] aflibercept’, starting anytime on or before cohort entry start date; having at least 1 drug exposure of ‘[SOS] aflibercept’, starting between 70 days before and 21 days before ‘[SOS] aflibercept’ start date; having at least 1 drug exposure of ‘[SOS] aflibercept’ for the first time in the person’s history, starting between 70 days before and 21 days before ‘[SOS] aflibercept’ start date; with all of the following criteria:
having at least 1 observation period, starting anytime up to 365 days before ‘[SOS] aflibercept’ start date and ending between 0 days after and all days after ‘[SOS] aflibercept’ start date.
having no drug exposures of ‘[SOS] aflibercept ranibizumab and bevacizumab’, starting anytime prior to ‘[SOS] aflibercept’ start date; allow events outside observation period.
having no condition occurrences of ‘[SOS] Malignant neoplasms excluding non-melanoma skin cancer’, starting anytime on or before ‘[SOS] aflibercept’ start date; allow events outside observation period.
with any of the following criteria:
- having at least 1 condition occurrence of ‘[SOS] Retinal Vein Occlusion’, starting anytime on or before ‘[SOS] aflibercept’ start date.
- having at least 1 condition occurrence of ‘[SOS] Age related Macular Degeneration’, starting anytime on or before ‘[SOS] aflibercept’ start date.
- having at least 1 condition occurrence of ‘[SOS] Diabetic retinopathy’, starting anytime on or before ‘[SOS] aflibercept’ start date.
- having at least 1 condition occurrence of ‘[SOS] Macular edema’, starting anytime on or before ‘[SOS] aflibercept’ start date.
A.3.3 Cohort Exit
The cohort end date will be based on a continuous exposure to ‘[SOS] aflibercept’: allowing 180 days between exposures, adding 0 days after exposure ends, and using days supply and exposure end date for exposure duration.
The person also exists the cohort when encountering any of the following events:
- drug exposures of ‘[SOS] bevacizumab’.
- drug exposures of ‘[SOS] ranibizumab’.
A.3.4 Cohort Eras
Entry events will be combined into cohort eras if they are within 0 days of each other.
A.3.5 Concept: [SOS] aflibercept
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 40244266 | aflibercept | 1232150 | RxNorm | NO | YES | NO |
A.3.7 Concept: [SOS] Diabetic retinopathy
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4174977 | Retinopathy due to diabetes mellitus | 4855003 | SNOMED | NO | YES | NO |
A.3.8 Concept: [SOS] Macular edema
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4290333 | Macular retinal edema | 37231002 | SNOMED | NO | YES | NO |
| 4208200 | Postoperative cystoid macular edema | 312920004 | SNOMED | YES | YES | NO |
A.3.9 Concept: [SOS] Retinal Vein Occlusion
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 440392 | Retinal vascular occlusion | 73757007 | SNOMED | NO | YES | NO |
| 4334245 | Retinal artery occlusion | 232035005 | SNOMED | YES | YES | NO |
| 437544 | Arterial retinal branch occlusion | 50821009 | SNOMED | YES | YES | NO |
| 4338905 | Cilioretinal artery occlusion | 232036006 | SNOMED | YES | YES | NO |
A.3.10 Concept: [SOS] aflibercept ranibizumab and bevacizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 40244266 | aflibercept | 1232150 | RxNorm | NO | YES | NO |
| 1397141 | bevacizumab | 253337 | RxNorm | NO | YES | NO |
| 19080982 | ranibizumab | 595060 | RxNorm | NO | YES | NO |
A.3.11 Concept: [SOS] Malignant neoplasms excluding non-melanoma skin cancer
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4112752 | Basal cell carcinoma of skin | 254701007 | SNOMED | YES | YES | NO |
| 4111921 | Squamous cell carcinoma of skin | 254651007 | SNOMED | YES | YES | NO |
| 443392 | Malignant neoplastic disease | 363346000 | SNOMED | NO | YES | NO |
A.3.12 Concept: [SOS] bevacizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 1397141 | bevacizumab | 253337 | RxNorm | NO | YES | NO |
A.3.13 Concept: [SOS] ranibizumab
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 19080982 | ranibizumab | 595060 | RxNorm | NO | YES | NO |
A.4 Persons with blinding diseases (DR, AMD, ME, RVO)
A.4.1 Cohort Entry Events
People enter the cohort when observing any of the following:
condition occurrences of ‘[SOS] Diabetic retinopathy’.
condition occurrences of ‘[SOS] Age related Macular Degeneration’.
condition occurrences of ‘[SOS] Macular edema’.
condition occurrences of ‘[SOS] Retinal Vein Occlusion’.
Limit cohort entry events to the earliest event per person.
A.4.2 Cohort Exit
The person also exists the cohort at the end of continuous observation.
A.4.3 Cohort Eras
Entry events will be combined into cohort eras if they are within 0 days of each other.
A.4.4 Concept: [SOS] Diabetic retinopathy
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4174977 | Retinopathy due to diabetes mellitus | 4855003 | SNOMED | NO | YES | NO |
A.4.6 Concept: [SOS] Macular edema
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4290333 | Macular retinal edema | 37231002 | SNOMED | NO | YES | NO |
| 4208200 | Postoperative cystoid macular edema | 312920004 | SNOMED | YES | YES | NO |
A.4.7 Concept: [SOS] Retinal Vein Occlusion
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 440392 | Retinal vascular occlusion | 73757007 | SNOMED | NO | YES | NO |
| 4334245 | Retinal artery occlusion | 232035005 | SNOMED | YES | YES | NO |
| 437544 | Arterial retinal branch occlusion | 50821009 | SNOMED | YES | YES | NO |
| 4338905 | Cilioretinal artery occlusion | 232036006 | SNOMED | YES | YES | NO |
B Outcome Cohort Definitions
B.1 ESRD Simple
B.1.1 Cohort Entry Events
People enter the cohort when observing any of the following:
condition occurrences of ‘[SOS] ESRD Ref’.
observations of ‘[SOS] ESRD Ref’.
procedure occurrences of ‘[SOS] ESRD Ref’.
Limit cohort entry events to the earliest event per person.
B.1.2 Cohort Exit
The person also exists the cohort at the end of continuous observation.
B.1.3 Cohort Eras
Entry events will be combined into cohort eras if they are within 0 days of each other.
B.1.4 Concept: [SOS] Renal transplant Ref
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 2877119 | Medical and Surgical @ Urinary System @ Transplantation @ Kidney, Right @ Open @ No Device | 0TY00Z | ICD10PCS | NO | YES | NO |
| 2211744 | Ultrasound, transplanted kidney, real time and duplex Doppler with image documentation | 76776 | CPT4 | NO | YES | NO |
| 40664909 | Patient receiving hemodialysis, peritoneal dialysis or kidney transplantation | G8727 | HCPCS | NO | YES | NO |
| 4324887 | Disorder related to renal transplantation | 429451003 | SNOMED | NO | YES | NO |
| 40767034 | End Stage Renal Disease (ESRD) Facility Survey - OMB CMS form 2744 | 64323-9 | LOINC | NO | YES | NO |
| 42539502 | Transplanted kidney present | 737295003 | SNOMED | NO | YES | NO |
| 4046829 | Anesthesia for renal transplant, recipient | 23137002 | SNOMED | NO | YES | NO |
| 4163566 | Renal replacement | 398887003 | SNOMED | NO | YES | NO |
| 38001396 | Kidney transplant | 652 | DRG | NO | YES | NO |
| 2827873 | Medical and Surgical @ Urinary System @ Transplantation @ Kidney, Left @ Open @ No Device | 0TY10Z | ICD10PCS | NO | YES | NO |
| 2832392 | Imaging @ Urinary System @ Computerized Tomography (CT Scan) @ Kidney Transplant @ None @ None | BT29ZZ | ICD10PCS | NO | YES | NO |
| 44784262 | Awaiting transplantation of kidney | 698306007 | SNOMED | NO | YES | NO |
| 2898352 | Imaging @ Urinary System @ Ultrasonography @ Kidney Transplant @ None @ None | BT49ZZ | ICD10PCS | NO | YES | NO |
| 2884635 | Imaging @ Urinary System @ Computerized Tomography (CT Scan) @ Kidney Transplant @ Low Osmolar @ None | BT291Z | ICD10PCS | NO | YES | NO |
| 45888790 | Renal Transplantation Procedures | 1008098 | CPT4 | NO | YES | NO |
| 44786436 | Documentation of end stage renal disease (esrd), dialysis, renal transplant before or during the measurement period or pregnancy during the measurement period | G9231 | HCPCS | NO | YES | NO |
| 4082531 | US scan of transplant kidney | 241484009 | SNOMED | NO | YES | NO |
B.1.5 Concept: [SOS] Dialysis Ref
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4026915 | Revision of arteriovenous shunt for renal dialysis | 225892009 | SNOMED | NO | YES | NO |
| 38001423 | Admit for renal dialysis | 685 | DRG | NO | YES | NO |
| 42628575 | Introduction of needle(s) and/or catheter(s), dialysis circuit, with diagnostic angiography of the dialysis circuit, including all direct puncture(s) and catheter placement(s), injection(s) of contrast, all necessary imaging from the arterial anastomos… | 36901 | CPT4 | NO | YES | NO |
| 40664909 | Patient receiving hemodialysis, peritoneal dialysis or kidney transplantation | G8727 | HCPCS | NO | YES | NO |
| 2788042 | Performance of Urinary Filtration, Multiple (Deprecated) | 5A1D60Z | ICD10PCS | NO | YES | NO |
| 4146536 | Renal dialysis | 265764009 | SNOMED | NO | YES | NO |
| 2213577 | Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement therapies) requiring repeated evaluations by a physician or other qualified health care professional, with or without substantial… | 90947 | CPT4 | NO | YES | NO |
| 2213576 | Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement therapies), with single evaluation by a physician or other qualified health care professional | 90945 | CPT4 | NO | YES | NO |
| 4181476 | Dependence on hemodialysis due to end stage renal disease | 428982002 | SNOMED | NO | YES | NO |
| 43018323 | Performance of Urinary Filtration, Intermittent, Less than 6 Hours Per Day | 5A1D70Z | ICD10PCS | NO | YES | NO |
| 2617342 | Unscheduled or emergency dialysis treatment for an esrd patient in a hospital outpatient department that is not certified as an esrd facility | G0257 | HCPCS | NO | YES | NO |
| 40757115 | Introduction of needle and/or catheter, arteriovenous shunt created for dialysis (graft/fistula); additional access for therapeutic intervention (List separately in addition to code for primary procedure) (Deprecated) | 36148 | CPT4 | NO | YES | NO |
| 2788041 | Performance of Urinary Filtration, Single (Deprecated) | 5A1D00Z | ICD10PCS | NO | YES | NO |
| 40756908 | Insertion of catheter into arteriovenous dialysis shunt (Deprecated) | 36147 | CPT4 | NO | YES | NO |
| 42628378 | Service ordered by a renal dialysis facility (rdf) physician as part of the esrd beneficiary’s dialysis benefit, is not part of the composite rate, and is separately reimbursable | CB | CPT4 | NO | YES | NO |
| 2313999 | Duplex scan of hemodialysis access (including arterial inflow, body of access and venous outflow) | 93990 | CPT4 | NO | YES | NO |
| 45887996 | End-Stage Renal Disease Services | 1019051 | CPT4 | NO | YES | NO |
B.1.6 Concept: [SOS] ESRD Ref
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 2213591 | End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 2-11 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents | 90964 | CPT4 | NO | YES | NO |
| 2213585 | End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 2-3 face-to-face visits by a physician o… | 90958 | CPT4 | NO | YES | NO |
| 2213581 | End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 4 or more face-to-face visits by a physic… | 90954 | CPT4 | NO | YES | NO |
| 2617552 | End-stage renal disease patient requiring hemodialysis vascular access was not an eligible candidate for autogenous av fistula | G8085 | HCPCS | NO | YES | NO |
| 2213595 | End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per day; for patients 2-11 years of age | 90968 | CPT4 | NO | YES | NO |
| 2213587 | End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older; with 4 or more face-to-face visits by a physician or other qualified health care professional per month | 90960 | CPT4 | NO | YES | NO |
| 2213596 | End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per day; for patients 12-19 years of age | 90969 | CPT4 | NO | YES | NO |
| 2213584 | End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 4 or more face-to-face visits by a physi… | 90957 | CPT4 | NO | YES | NO |
| 36713020 | Hyperparathyroidism due to end stage renal disease on dialysis | 16218721000119107 | SNOMED | NO | YES | NO |
| 42738339 | End stage renal disease (ESRD) related services per full month; for patients twenty years of age and over (Deprecated) | 90921 | CPT4 | NO | YES | NO |
| 2213597 | End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per day; for patients 20 years of age and older | 90970 | CPT4 | NO | YES | NO |
| 2213593 | End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 20 years of age and older | 90966 | CPT4 | NO | YES | NO |
| 2213589 | End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older; with 1 face-to-face visit by a physician or other qualified health care professional per month | 90962 | CPT4 | NO | YES | NO |
| 2617795 | End-stage renal disease patient with urr or kt/v value not documented, but otherwise eligible for measure | G8388 | HCPCS | NO | YES | NO |
| 2213582 | End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 2-3 face-to-face visits by a physician or… | 90955 | CPT4 | NO | YES | NO |
| 42738336 | End stage renal disease (ESRD) related services per full month; for patients under two years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents (Deprecated) | 90918 | CPT4 | NO | YES | NO |
| 193782 | End-stage renal disease | 46177005 | SNOMED | NO | YES | NO |
| 2213590 | End-stage renal disease (ESRD) related services for home dialysis per full month, for patients younger than 2 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents | 90963 | CPT4 | NO | YES | NO |
| 2617794 | End-stage renal disease patient with a hematocrit or hemoglobin not documented | G8387 | HCPCS | NO | YES | NO |
| 2213586 | End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 1 face-to-face visit by a physician or o… | 90959 | CPT4 | NO | YES | NO |
| 2213588 | End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older; with 2-3 face-to-face visits by a physician or other qualified health care professional per month | 90961 | CPT4 | NO | YES | NO |
| 443611 | Chronic kidney disease stage 5 | 433146000 | SNOMED | NO | YES | NO |
| 2213578 | End-stage renal disease (ESRD) related services monthly, for patients younger than 2 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 4 or more face-to-face visits b… | 90951 | CPT4 | NO | YES | NO |
| 2213594 | End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per day; for patients younger than 2 years of age | 90967 | CPT4 | NO | YES | NO |
| 2213592 | End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 12-19 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents | 90965 | CPT4 | NO | YES | NO |
| 42738338 | End stage renal disease (ESRD) related services per full month; for patients between twelve and nineteen years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents (Deprecated) | 90920 | CPT4 | NO | YES | NO |
| 42738678 | End stage renal disease (ESRD) related services (less than full month), per day; for patients between twelve and nineteen years of age (Deprecated) | 90924 | CPT4 | NO | YES | NO |
| 42738677 | End stage renal disease (ESRD) related services (less than full month), per day; for patients between two and eleven years of age (Deprecated) | 90923 | CPT4 | NO | YES | NO |
| 2213580 | End-stage renal disease (ESRD) related services monthly, for patients younger than 2 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 1 face-to-face visit by a physi… | 90953 | CPT4 | NO | YES | NO |
| 42738676 | End stage renal disease (ESRD) related services (less than full month), per day; for patients under two years of age (Deprecated) | 90922 | CPT4 | NO | YES | NO |
| 42738337 | End stage renal disease (ESRD) related services per full month; for patients between two and eleven years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents (Deprecated) | 90919 | CPT4 | NO | YES | NO |
| 2213583 | End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 1 face-to-face visit by a physician or ot… | 90956 | CPT4 | NO | YES | NO |
| 42738679 | End stage renal disease (ESRD) related services (less than full month), per day; for patients twenty years of age and over (Deprecated) | 90925 | CPT4 | NO | YES | NO |
| 40767034 | End Stage Renal Disease (ESRD) Facility Survey - OMB CMS form 2744 | 64323-9 | LOINC | NO | YES | NO |
B.1.7 Concept: [SOS] eGFR Ref
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 37077746 | Glomerular filtration rate.predicted among blacks | Serum, Plasma or Blood | Chemistry - non-challenge | LP385395-1 | LOINC | NO|YES|NO |
| 36662614 | Glomerular filtration rate/1.73 sq M.predicted | ArVRat | Pt | ANYBldSerPl | LG50986-5 | LOINC|NO|YES|NO |
| 37045756 | Glomerular filtration rate.predicted among non blacks | Serum, Plasma or Blood | Chemistry - non-challenge | LP385394-4 | LOINC | NO|YES|NO |
| 37052213 | Glomerular filtration rate.predicted among males | Serum, Plasma or Blood | Chemistry - non-challenge | LP385397-7 | LOINC | NO|YES|NO |
| 37033687 | Predicted Glomerular filtration rate | Serum, Plasma or Blood | Chemistry - non-challenge | LP385393-6 | LOINC | NO|YES|NO |
| 37024736 | Predicted Glomerular filtration rate | Serum or Plasma | Chemistry - non-challenge | LP385392-8 | LOINC | NO|YES|NO |
| 36033091 | Glomerular filtration rate.predicted among blacks | DBS | Chemistry - non-challenge | LP421224-9 | LOINC | NO|YES|NO |
| 44808279 | Estimated glomerular filtration rate using Chronic Kidney Disease Epidemiology Collaboration formula | 857971000000104 | SNOMED | NO | YES | NO |
| 37208635 | Estimated glomerular filtration rate by laboratory calculation | 1107411000000104 | SNOMED | NO | YES | NO |
| 36033624 | Glomerular filtration rate.predicted among non blacks | DBS | Chemistry - non-challenge | LP421223-1 | LOINC | NO|YES|NO |
| 1618558 | Glomerular filtration rate/Body surface area | Serum or Plasma | Chemistry - non-challenge | LP427762-2 | LOINC | NO|YES|NO |
| 37027780 | Predicted Glomerular filtration rate | Blood | Chemistry - non-challenge | LP385391-0 | LOINC | NO|YES|NO |
| 44806420 | Estimation of glomerular filtration rate | 791801000000102 | SNOMED | NO | YES | NO |
| 37055720 | Glomerular filtration rate/1.73 sq M | Urine and Serum or Plasma | Chemistry - non-challenge | LP385402-5 | LOINC | NO|YES|NO |
| 37393690 | GFR (glomerular filtration rate) calculated by abbreviated Modification of Diet in Renal Disease Study Group calculation | 1020291000000106 | SNOMED | NO | YES | NO |
| 37068907 | Glomerular filtration rate.predicted among females | Serum, Plasma or Blood | Chemistry - non-challenge | LP385396-9 | LOINC | NO|YES|NO |
B.2 ESRD Complex
B.2.1 Cohort Entry Events
People enter the cohort when observing any of the following:
condition occurrences of ‘[SOS] ESRD Ref’.
observations of ‘[SOS] ESRD Ref’.
procedure occurrences of ‘[SOS] ESRD Ref’.
condition occurrences of ‘[SOS] Renal transplant Ref’.
observations of ‘[SOS] Renal transplant Ref’.
procedure occurrences of ‘[SOS] Renal transplant Ref’.
measurements of ‘[SOS] eGFR Ref’, numeric value between 1 and 15; unit: “milliliter per minute per 1.73 square meter” or “milliliter per minute per 1.73 square meter”; having at least 1 measurement of ‘[SOS] eGFR Ref’, starting anytime up to 90 days before ‘[SOS] eGFR Ref’ start date; numeric value between 1 and 15; unit: “milliliter per minute per 1.73 square meter” or “milliliter per minute per 1.73 square meter”.
observations of ‘[SOS] Dialysis Ref’; with any of the following criteria:
having at least 1 procedure occurrence of ‘[SOS] Dialysis Ref’, starting anytime up to 90 days before ‘[SOS] Dialysis Ref’ start date.
having at least 1 observation of ‘[SOS] Dialysis Ref’, starting anytime up to 90 days before ‘[SOS] Dialysis Ref’ start date.
procedure occurrences of ‘[SOS] Dialysis Ref’; with any of the following criteria:
having at least 1 observation of ‘[SOS] Dialysis Ref’, starting anytime up to 90 days before ‘[SOS] Dialysis Ref’ start date.
having at least 1 procedure occurrence of ‘[SOS] Dialysis Ref’, starting anytime up to 90 days before ‘[SOS] Dialysis Ref’ start date.
Limit cohort entry events to the earliest event per person.
B.2.2 Cohort Exit
The person also exists the cohort at the end of continuous observation.
B.2.3 Cohort Eras
Entry events will be combined into cohort eras if they are within 0 days of each other.
B.2.4 Concept: [SOS] Renal transplant Ref
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 2877119 | Medical and Surgical @ Urinary System @ Transplantation @ Kidney, Right @ Open @ No Device | 0TY00Z | ICD10PCS | NO | YES | NO |
| 2211744 | Ultrasound, transplanted kidney, real time and duplex Doppler with image documentation | 76776 | CPT4 | NO | YES | NO |
| 40664909 | Patient receiving hemodialysis, peritoneal dialysis or kidney transplantation | G8727 | HCPCS | NO | YES | NO |
| 4324887 | Disorder related to renal transplantation | 429451003 | SNOMED | NO | YES | NO |
| 40767034 | End Stage Renal Disease (ESRD) Facility Survey - OMB CMS form 2744 | 64323-9 | LOINC | NO | YES | NO |
| 42539502 | Transplanted kidney present | 737295003 | SNOMED | NO | YES | NO |
| 4046829 | Anesthesia for renal transplant, recipient | 23137002 | SNOMED | NO | YES | NO |
| 4163566 | Renal replacement | 398887003 | SNOMED | NO | YES | NO |
| 38001396 | Kidney transplant | 652 | DRG | NO | YES | NO |
| 2827873 | Medical and Surgical @ Urinary System @ Transplantation @ Kidney, Left @ Open @ No Device | 0TY10Z | ICD10PCS | NO | YES | NO |
| 2832392 | Imaging @ Urinary System @ Computerized Tomography (CT Scan) @ Kidney Transplant @ None @ None | BT29ZZ | ICD10PCS | NO | YES | NO |
| 44784262 | Awaiting transplantation of kidney | 698306007 | SNOMED | NO | YES | NO |
| 2898352 | Imaging @ Urinary System @ Ultrasonography @ Kidney Transplant @ None @ None | BT49ZZ | ICD10PCS | NO | YES | NO |
| 2884635 | Imaging @ Urinary System @ Computerized Tomography (CT Scan) @ Kidney Transplant @ Low Osmolar @ None | BT291Z | ICD10PCS | NO | YES | NO |
| 45888790 | Renal Transplantation Procedures | 1008098 | CPT4 | NO | YES | NO |
| 44786436 | Documentation of end stage renal disease (esrd), dialysis, renal transplant before or during the measurement period or pregnancy during the measurement period | G9231 | HCPCS | NO | YES | NO |
| 4082531 | US scan of transplant kidney | 241484009 | SNOMED | NO | YES | NO |
B.2.5 Concept: [SOS] Dialysis Ref
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 4026915 | Revision of arteriovenous shunt for renal dialysis | 225892009 | SNOMED | NO | YES | NO |
| 38001423 | Admit for renal dialysis | 685 | DRG | NO | YES | NO |
| 42628575 | Introduction of needle(s) and/or catheter(s), dialysis circuit, with diagnostic angiography of the dialysis circuit, including all direct puncture(s) and catheter placement(s), injection(s) of contrast, all necessary imaging from the arterial anastomos… | 36901 | CPT4 | NO | YES | NO |
| 40664909 | Patient receiving hemodialysis, peritoneal dialysis or kidney transplantation | G8727 | HCPCS | NO | YES | NO |
| 2788042 | Performance of Urinary Filtration, Multiple (Deprecated) | 5A1D60Z | ICD10PCS | NO | YES | NO |
| 4146536 | Renal dialysis | 265764009 | SNOMED | NO | YES | NO |
| 2213577 | Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement therapies) requiring repeated evaluations by a physician or other qualified health care professional, with or without substantial… | 90947 | CPT4 | NO | YES | NO |
| 2213576 | Dialysis procedure other than hemodialysis (eg, peritoneal dialysis, hemofiltration, or other continuous renal replacement therapies), with single evaluation by a physician or other qualified health care professional | 90945 | CPT4 | NO | YES | NO |
| 4181476 | Dependence on hemodialysis due to end stage renal disease | 428982002 | SNOMED | NO | YES | NO |
| 43018323 | Performance of Urinary Filtration, Intermittent, Less than 6 Hours Per Day | 5A1D70Z | ICD10PCS | NO | YES | NO |
| 2617342 | Unscheduled or emergency dialysis treatment for an esrd patient in a hospital outpatient department that is not certified as an esrd facility | G0257 | HCPCS | NO | YES | NO |
| 40757115 | Introduction of needle and/or catheter, arteriovenous shunt created for dialysis (graft/fistula); additional access for therapeutic intervention (List separately in addition to code for primary procedure) (Deprecated) | 36148 | CPT4 | NO | YES | NO |
| 2788041 | Performance of Urinary Filtration, Single (Deprecated) | 5A1D00Z | ICD10PCS | NO | YES | NO |
| 40756908 | Insertion of catheter into arteriovenous dialysis shunt (Deprecated) | 36147 | CPT4 | NO | YES | NO |
| 42628378 | Service ordered by a renal dialysis facility (rdf) physician as part of the esrd beneficiary’s dialysis benefit, is not part of the composite rate, and is separately reimbursable | CB | CPT4 | NO | YES | NO |
| 2313999 | Duplex scan of hemodialysis access (including arterial inflow, body of access and venous outflow) | 93990 | CPT4 | NO | YES | NO |
| 45887996 | End-Stage Renal Disease Services | 1019051 | CPT4 | NO | YES | NO |
B.2.6 Concept: [SOS] ESRD Ref
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 2213591 | End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 2-11 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents | 90964 | CPT4 | NO | YES | NO |
| 2213585 | End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 2-3 face-to-face visits by a physician o… | 90958 | CPT4 | NO | YES | NO |
| 2213581 | End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 4 or more face-to-face visits by a physic… | 90954 | CPT4 | NO | YES | NO |
| 2617552 | End-stage renal disease patient requiring hemodialysis vascular access was not an eligible candidate for autogenous av fistula | G8085 | HCPCS | NO | YES | NO |
| 2213595 | End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per day; for patients 2-11 years of age | 90968 | CPT4 | NO | YES | NO |
| 2213587 | End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older; with 4 or more face-to-face visits by a physician or other qualified health care professional per month | 90960 | CPT4 | NO | YES | NO |
| 2213596 | End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per day; for patients 12-19 years of age | 90969 | CPT4 | NO | YES | NO |
| 2213584 | End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 4 or more face-to-face visits by a physi… | 90957 | CPT4 | NO | YES | NO |
| 36713020 | Hyperparathyroidism due to end stage renal disease on dialysis | 16218721000119107 | SNOMED | NO | YES | NO |
| 42738339 | End stage renal disease (ESRD) related services per full month; for patients twenty years of age and over (Deprecated) | 90921 | CPT4 | NO | YES | NO |
| 2213597 | End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per day; for patients 20 years of age and older | 90970 | CPT4 | NO | YES | NO |
| 2213593 | End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 20 years of age and older | 90966 | CPT4 | NO | YES | NO |
| 2213589 | End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older; with 1 face-to-face visit by a physician or other qualified health care professional per month | 90962 | CPT4 | NO | YES | NO |
| 2617795 | End-stage renal disease patient with urr or kt/v value not documented, but otherwise eligible for measure | G8388 | HCPCS | NO | YES | NO |
| 2213582 | End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 2-3 face-to-face visits by a physician or… | 90955 | CPT4 | NO | YES | NO |
| 42738336 | End stage renal disease (ESRD) related services per full month; for patients under two years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents (Deprecated) | 90918 | CPT4 | NO | YES | NO |
| 193782 | End-stage renal disease | 46177005 | SNOMED | NO | YES | NO |
| 2213590 | End-stage renal disease (ESRD) related services for home dialysis per full month, for patients younger than 2 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents | 90963 | CPT4 | NO | YES | NO |
| 2617794 | End-stage renal disease patient with a hematocrit or hemoglobin not documented | G8387 | HCPCS | NO | YES | NO |
| 2213586 | End-stage renal disease (ESRD) related services monthly, for patients 12-19 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 1 face-to-face visit by a physician or o… | 90959 | CPT4 | NO | YES | NO |
| 2213588 | End-stage renal disease (ESRD) related services monthly, for patients 20 years of age and older; with 2-3 face-to-face visits by a physician or other qualified health care professional per month | 90961 | CPT4 | NO | YES | NO |
| 443611 | Chronic kidney disease stage 5 | 433146000 | SNOMED | NO | YES | NO |
| 2213578 | End-stage renal disease (ESRD) related services monthly, for patients younger than 2 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 4 or more face-to-face visits b… | 90951 | CPT4 | NO | YES | NO |
| 2213594 | End-stage renal disease (ESRD) related services for dialysis less than a full month of service, per day; for patients younger than 2 years of age | 90967 | CPT4 | NO | YES | NO |
| 2213592 | End-stage renal disease (ESRD) related services for home dialysis per full month, for patients 12-19 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents | 90965 | CPT4 | NO | YES | NO |
| 42738338 | End stage renal disease (ESRD) related services per full month; for patients between twelve and nineteen years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents (Deprecated) | 90920 | CPT4 | NO | YES | NO |
| 42738678 | End stage renal disease (ESRD) related services (less than full month), per day; for patients between twelve and nineteen years of age (Deprecated) | 90924 | CPT4 | NO | YES | NO |
| 42738677 | End stage renal disease (ESRD) related services (less than full month), per day; for patients between two and eleven years of age (Deprecated) | 90923 | CPT4 | NO | YES | NO |
| 2213580 | End-stage renal disease (ESRD) related services monthly, for patients younger than 2 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 1 face-to-face visit by a physi… | 90953 | CPT4 | NO | YES | NO |
| 42738676 | End stage renal disease (ESRD) related services (less than full month), per day; for patients under two years of age (Deprecated) | 90922 | CPT4 | NO | YES | NO |
| 42738337 | End stage renal disease (ESRD) related services per full month; for patients between two and eleven years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents (Deprecated) | 90919 | CPT4 | NO | YES | NO |
| 2213583 | End-stage renal disease (ESRD) related services monthly, for patients 2-11 years of age to include monitoring for the adequacy of nutrition, assessment of growth and development, and counseling of parents; with 1 face-to-face visit by a physician or ot… | 90956 | CPT4 | NO | YES | NO |
| 42738679 | End stage renal disease (ESRD) related services (less than full month), per day; for patients twenty years of age and over (Deprecated) | 90925 | CPT4 | NO | YES | NO |
| 40767034 | End Stage Renal Disease (ESRD) Facility Survey - OMB CMS form 2744 | 64323-9 | LOINC | NO | YES | NO |
B.2.7 Concept: [SOS] eGFR Ref
| Concept ID | Concept Name | Code | Vocabulary | Excluded | Descendants | Mapped |
|---|---|---|---|---|---|---|
| 37077746 | Glomerular filtration rate.predicted among blacks | Serum, Plasma or Blood | Chemistry - non-challenge | LP385395-1 | LOINC | NO|YES|NO |
| 36662614 | Glomerular filtration rate/1.73 sq M.predicted | ArVRat | Pt | ANYBldSerPl | LG50986-5 | LOINC|NO|YES|NO |
| 37045756 | Glomerular filtration rate.predicted among non blacks | Serum, Plasma or Blood | Chemistry - non-challenge | LP385394-4 | LOINC | NO|YES|NO |
| 37052213 | Glomerular filtration rate.predicted among males | Serum, Plasma or Blood | Chemistry - non-challenge | LP385397-7 | LOINC | NO|YES|NO |
| 37033687 | Predicted Glomerular filtration rate | Serum, Plasma or Blood | Chemistry - non-challenge | LP385393-6 | LOINC | NO|YES|NO |
| 37024736 | Predicted Glomerular filtration rate | Serum or Plasma | Chemistry - non-challenge | LP385392-8 | LOINC | NO|YES|NO |
| 36033091 | Glomerular filtration rate.predicted among blacks | DBS | Chemistry - non-challenge | LP421224-9 | LOINC | NO|YES|NO |
| 44808279 | Estimated glomerular filtration rate using Chronic Kidney Disease Epidemiology Collaboration formula | 857971000000104 | SNOMED | NO | YES | NO |
| 37208635 | Estimated glomerular filtration rate by laboratory calculation | 1107411000000104 | SNOMED | NO | YES | NO |
| 36033624 | Glomerular filtration rate.predicted among non blacks | DBS | Chemistry - non-challenge | LP421223-1 | LOINC | NO|YES|NO |
| 1618558 | Glomerular filtration rate/Body surface area | Serum or Plasma | Chemistry - non-challenge | LP427762-2 | LOINC | NO|YES|NO |
| 37027780 | Predicted Glomerular filtration rate | Blood | Chemistry - non-challenge | LP385391-0 | LOINC | NO|YES|NO |
| 44806420 | Estimation of glomerular filtration rate | 791801000000102 | SNOMED | NO | YES | NO |
| 37055720 | Glomerular filtration rate/1.73 sq M | Urine and Serum or Plasma | Chemistry - non-challenge | LP385402-5 | LOINC | NO|YES|NO |
| 37393690 | GFR (glomerular filtration rate) calculated by abbreviated Modification of Diet in Renal Disease Study Group calculation | 1020291000000106 | SNOMED | NO | YES | NO |
| 37068907 | Glomerular filtration rate.predicted among females | Serum, Plasma or Blood | Chemistry - non-challenge | LP385396-9 | LOINC | NO|YES|NO |
C Negative Control Concepts
| Concept ID | |
|---|---|
| Abdominal distension, gaseous | 271835004 |
| Adjustment disorder with depressed mood | 57194009 |
| Bacteremia | 5758002 |
| Bipolar II disorder | 83225003 |
| Callosity | 201040000 |
| Cannabis dependence | 85005007 |
| Conduct disorder | 430909002 |
| Coronary artery graft present | 737278006 |
| Degeneration of intervertebral disc | 77547008 |
| Difficulty walking | 719232003 |
| Diverticulosis of large intestine without diverticulitis | 45568004 |
| Dysphagia | 40739000 |
| Dysthymia | 78667006 |
| Epidermoid cyst | 419893006 |
| Genetic predisposition | 47708004 |
| Hyperplasia of prostate | 433234005 |
| Impacted cerumen | 18070006 |
| Major depression, single episode | 36923009 |
| Morbid obesity | 238136002 |
| Nicotine dependence | 56294008 |
| Paranoid schizophrenia | 64905009 |
| Perimenopausal disorder | 266607004 |
| Peripheral vertigo | 50438001 |
| Postmenopausal state | 76498008 |
| Postoperative state | 19585003 |
| Snoring | 72863001 |
| Solitary nodule of lung | 427359005 |
| Somatic dysfunction of lumbar region | 718929000 |
| Spinal stenosis | 76107001 |
| Stimulant abuse | 441527004 |
| Testicular hypofunction | 111551000 |
| Toxic effect of ethyl alcohol | 82782008 |
| Tracheostomy present | 302108003 |
| Uncomplicated asthma | 707444001 |
| Ureteric stone | 31054009 |