Bayer Ag · XETR:BAYN
Bayer — Technical Presentation (March 2024)
35 slides from Bayer's technical presentation, Mar 8, 2024
Slide 1: Chronic Kidney Disease Associated With Type 2 Diabetes
Chronic Kidney Disease Associated With Type 2 Diabetes March 2022. MA-PF-CAR-US-0050-2
Slide 2: Definition of Chronic Kidney Disease
Definition of Chronic Kidney Disease Severe Global Glomerulosclerosis with Chronic Kidney Disease (CKD)1 Patchy Interstitial Fibrosis and Tubular Atrophy3 • Persistent change in either or both of the following for >3 months: ─ Reduced estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2 ─
Slide 3: Diabetes Prevalence Is Projected to Increase
Diabetes Prevalence Is Projected to Increase Global Prevalence of Diabetes Is Rising1 In 2019, 37.3 million Americans had diabetes Estimated percentage of people 20-79 years old with diabetes by region in 2021 and 2045 (28.7 million diagnosed, 8.5 million undiagnosed)2 2021 2045 10.5% 12.2% Global 3
Slide 4: Increase in Prevalence of Diabetes Has a Major Impact on the Development of CKD
Increase in Prevalence of Diabetes Has a Major Impact on the Development of CKD1 ~40% Diabetes is a leading cause Patients with CKD of CKD and associated with T2D are end-stage kidney of patients with T2D at increased risk for disease in the in the United States overall mortality and United States2
Slide 5: Kidney Disease Approximately Triples the Risk of CV Mortality in Patients With Diabetes
Kidney Disease Approximately Triples the Risk of CV Mortality in Patients With Diabetes 10-Year Standardized CV Mortalitya 25 19.6 20 ~6x Percentage, % 15 9.9 10 6.7 ~3x 5 3.4 ~2x 0 None Diabetes Kidney Disease Diabetes + Kidney Disease Data from the NHANES IIIb study suggested that excess risk for
Slide 6: Normal Renal Function and Pathophysiology
Normal Renal Function and Pathophysiology 6
Slide 7: Basic Renal Filtration Processes
Basic Renal Filtration Processes Nephron Physiology and Function1,2 Efferent arteriole Afferent arteriole Artery Glomerular filtration 1 Glomerular capillary Peritubular Bowman’s capillary space Tubular reabsorption 2 Determining Excretion Amounts3 Tubular secretion 3 Amount of substance excreted =
Slide 8: Glomerular Filtration Rate in CKD Associated With Diabetes
Glomerular Filtration Rate in CKD Associated With Diabetes1,2 Normal GFR Hyperfiltration Decreased GFR Dilate Constrict Dilate AA AA EA AA EA Constrict EA Blood flow GFR Increased Decreased GFR GFR AA, afferent arteriole; CKD, chronic kidney disease; EA, efferent arteriole; GFR, glomerular filtratio
Slide 9: CKD Progression in T2D Is Driven by Metabolic, Hemodynamic, and Inflammatory and Fibrotic Factors
CKD Progression in T2D Is Driven by the Combined Effects of Metabolic, Hemodynamic, and Inflammatory and Fibrotic Factors Drivers of progression for CKD associated with T2D Tubulointerstitial damage and Hemodynamic inflammation (elevated BP and/or intraglomerular pressure) Kidney fibrosis Glomerulos
Slide 10: Pathophysiology of Proteinuria in the Progression of CKD
Pathophysiology of Proteinuria in the Progression of CKD1 Renal injury/reduced nephron mass Glomerular Filtration Barrier2,a Increased glomerular capillary pressure Blood Podocyte dysfunction/loss Fenestrated endothelium Increased glomerular permeability to macromolecules Increased filtration of pla
Slide 11: Albuminuria (Proteinuria) Contributes to Pathogenesis of Inflammation and Fibrosis
Albuminuria (Proteinuria) Contributes to Pathogenesis of Inflammation and Fibrosis1 Albuminuria Is a Marker for Early Progressive Structural Kidney Damage in Patients With T2D2 Reabsorption of albumin is proinflammatory1,3 TISSUE DAMAGE, Proteinuria1,3 INFLAMMATION, AND FIBROSIS1,3 Inflammatory cell
Slide 12: Albuminuria and CKD Disease Progression
Albuminuria and CKD Disease Progression 12
Slide 13: Conceptual Model of Changes in GFR and Albuminuria Over Time
Conceptual Model of Changes in GFR and Albuminuria Over Time in Patients with CKD Associated With Diabetes1,2 140 GFR 1600 120 1400 Albuminuria (UACR), mg/day 1200 100 GFR, mL/min/1.73 m2 1000 80 800 60 600 40 400 20 200 Albuminuria 0 0 0 10 20 30 Diabetes duration, years Figure reprinted with permi
Slide 14: Conceptual Model of Changes in GFR and Albuminuria Over Time
Conceptual Model of Changes in GFR and Albuminuria Over Time in Patients with CKD Associated With Diabetes1,2 140 GFR 1600 120 1400 Albuminuria (UACR), mg/day 1200 100 GFR, mL/min/1.73 m2 1000 80 800 60 600 40 400 20 200 Albuminuria Albuminuria may occur before GFR 0 declines below 60 mL/min/1.73 m2
Slide 15: Conceptual Model of Natural History of CKD Associated With Diabetes
Conceptual Model of Natural History of CKD Associated With Diabetes Hyperglycemia D i Cellular injury Mesangial expansion, glomerulosclerosis, tubulointerstitial fibrosis and inflammation a Microalbuminuria Macroalbuminuria g n GFR High Normal Low ESRD o s Hypertension i Cardiovascular disease, infe
Slide 16: UACR Is an Independent Predictor of All-Cause Mortality From eGFR
UACR Is an Independent Predictor of All-Cause Mortality From eGFR a a Figure reprinted with permission of Elsevier: Matsushita K, et al. Lancet. 2010;375:2073-2081. Figure reprinted with permission of Elsevier: Matsushita K, et al. Lancet. 2010;375:2073-2081. Independent of each other and traditiona
Slide 17: CV Mortality Risk by Albuminuria and eGFR Status in Patients With T2D
CV Mortality Risk by Albuminuria and eGFR Status in Patients With T2Da CV Mortality Risk 5.3 for CV Deathb,c 3.0 Hazard Ratio 2.6 2.4 1.4 eGFR 30-59d 1.9 1.2 1.7 eGFR 60-89d Very high albuminuria 1.0 (Macroalbuminuria) eGFR ≥90d High albuminuria (Microalbuminuria) Lowest Highest No albuminuria risk
Slide 18: T2D and Presence of Albuminuria Are Strongly Associated With All-Cause Mortality
T2D and Presence of Albuminuria Are Strongly Associated With All-Cause Mortality 5-Year Probability of All-Cause Mortality in Patients With and Without T2Da,b 80% No T2D T2D 70% 65.1 62.9 61.3 60% 5-Year Probability 50% 47.3 47.3 46.4 42.8 36.2 40% 34.8 28.6 30% 23.5 21.4 21.4 20.0 17.8 19.2 20% 16.
Slide 19: As Albuminuria Rises, Costs Multiply
As Albuminuria Rises, Costs Multiply Expenditures by Albuminuria Stagea $2,000 $1,881.93 Cost per Member per Month (PMPM) $1,800 $1,600 $1,400 $1,200 $1,154.52 $1,000 $800 $592.17 $600 $400 $200 $0 A1 (<30 mg/g) A2 (30-299 mg/g) A3 (≥ 300 mg/g) Albuminuria Stage aData from the CareFirst and National
Slide 20: Albuminuria and Impaired GFR Are Independently Associated With Increased All-Cause Mortality in T2D
Albuminuria and Impaired GFR Are Independently Associated With Increased All-Cause Mortality in Patients With T2D1,2 10-Year Standardized All-Cause Mortalitya 60% 54.6 50% 4.7x 40% Mortality 31.5 30% 25.4 2.7x 20% 11.7 2.2x 10% 0% No Kidney Disease Albuminuria Impaired GFR Albuminuria + Impaired GFR
Slide 21: Patient Awareness, Diagnostic and Coding Gaps
Patient Awareness, Diagnostic and Coding Gaps 21
Slide 22: Several Gaps Along the Pathway Between Recognizing CKD Associated With T2D and Taking Action
There Are Several Gaps Along the Pathway Between Recognizing CKD Associated With T2D and Taking Action Overall awareness of kidney disease among patients with CKD is about 12% 1 (CKD stages 1-5, US NHANES 2015-2018) PAT I E N T AW A R E N E S S Guidelines Testing Diagnosis Intervention ! 01101100110
Slide 23: Overall Patient Awareness of CKD Remains Low, Especially in Early Stages
Overall Patient Awareness of CKD Remains Low, Especially in Early Stages of the Disease Patients With CKD Aware of Their Kidney Disease (US NHANES 2003-2018)a All CKD Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 100 • Overall patient awareness of CKD is about 12% 75 • Awareness is higher among Patients,
Slide 24: Prevalence of CKD Diagnosis by ICD Codes Has Increased, But Is Likely Underestimated
Prevalence of CKD Diagnosis by ICD-9-CM or ICD-10-CM Codes Has Increased, But Is Likely Underestimated Prevalence of CKD (%) Among Medicare FFS Beneficiaries Aged ≥66 Years, 2009-20191 (Medicare 5% Sample)a 15 14.2 • Prevalence of CKD diagnosed from 10 codes used in billing claims has increased from
Slide 25: CKD Prevalence May Be Underestimated in Medicare Beneficiaries
CKD Prevalence May Be Underestimated in Medicare Beneficiaries Due to Underrecognition/Undercoding of CKD Prevalence of CKD (%) in Patients ≥66 Years, in NHANES (2015-2018) and Medicare (2019)a NHANES Medicare CKD status determined by: CKD status determined by: • Measurements of • Presence of diagno
Slide 26: CKD Diagnosis Is Not Occurring for Many Patients With CKD Associated With T2D
CKD Diagnosis Is Not Occurring for Many Patients With CKD Associated With T2D Rate of Diagnosed CKD in Patients With CKD Associated With T2D1 (n=5036, ADD-CKD Studya) Stage 1 1% • Of the 5036 patients with Stage 2 5% CKD, 88% were not identified by their PCP Stage 3 18% prior to study participation
Slide 27: Standard of Care Remains Underprescribed Despite Increased Medication Use in CKD
Despite Increased Prevalence of Prescription Medication Use in CKD, Standard of Care Remains Underprescribed Prevalence of Prescription Medication Use in CKD Categories 3a to 5 in 2006 to 2009, 2010 to 2013, and 2014 to 2017 in CURE-CKD Registrya 12 2006-2009 2010-2013 2014-2017 10 Unadjusted Preval
Slide 28: Guidelines and Screening
Guidelines and Screening 28
Slide 29: Gaps in CKD Identification Due to Underutilization of eGFR and UACR Testing
There Are Gaps in CKD Identification in Patients With T2D Due to Underutilization of eGFR and UACR Testing CKD Screening and Identification in Patients With T2D in the Primary Care Setting (N=9307, ADD-CKD Study) 60 60 54.1 52.9 50 50 40 40 Patients, % Patients, % 30 30 20 20 15.2 12.1b 10 10 0 0 Pa
Slide 30: GFR and Albuminuria Are Predictive of CKD Progression
GFR and Albuminuria Are Predictive of CKD Progression Persistent albuminuria categories Description and range A1 A2 A3 • A2 = microalbuminuria2 Prognosis of CKD by GFR (older classification system) Normal to and Albuminuria Categories: Moderately Severely mildly • A3 = macroalbuminuria or proteinuri
Slide 31: Medical Societies Support eGFR and Albuminuria Screening in All Patients With Diabetes
Medical Societies Support eGFR and Albuminuria Screening in All Patients With Diabetes ADA (2022) KDIGO (2021) KDOQI (2007, 2012) Patients with T1D duration ≥5 years and Patients with diabetes should be all patients with T2D regardless screened for CKD3 of treatment should be screened Patients with
Slide 32: ADA 2022 Guidelines Recommend eGFR and Albuminuria Screening
The ADA 2022 Guidelines Recommend eGFR and Albuminuria Screening at the Initial Visit and Annually in Patients With Diabetes1 Laboratory evaluation Initial visit Every follow-up visit Annual visit A1C, if the results are not available within the past 3 months ✓ ✓ ✓ If not performed/available within
Slide 33: Kidney Health Evaluation HEDIS Measure Aims to Improve Kidney Disease Testing
Kidney Health Evaluation HEDIS® Measure Aims to Improve Kidney Disease Testing in Patients With Diabetes1 NKF and NCQA partnered to develop new Kidney Measure: Kidney Health Evaluation Health Evaluation Measure1,a for Patients with Diabetes (KED)2 − First included in HEDIS® publication released July
Slide 34: Both UACR and eGFR Are Recommended by Guidelines for Identification of CKD Progression
Both UACR and eGFR Are Recommended by Guidelines for Identification of CKD Progression in Patients With T2D1 + ADA, KDIGO, and KDOQI Guidelines: ✓ Recommend using both eGFR and UACR to eGFR UACR monitor kidney health in patients with diabetes1-3 measures kidney function2 measures kidney damage2 ✓ Su
Slide 35: Summary
Summary • CKD associated with T2D is underrecognized and underscreened due to low patient and clinician awareness and documentation and screening barriers1-9 • UACR and eGFR should both be used to properly stage and monitor kidney health as eGFR alone may miss the earlier stages of CKD10-13 – When u