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Glossary

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Glossary of common terms that appear in the scientific literature related to CKD associated with T2D.

    Albuminuria

    • Refers to abnormal loss of albumin in the urine10

    Cardiorenal (syndrome)

    • Defined as bidirectional pathological impairment of either the heart or kidney due to acute or chronic primary dysfunction in either organ4

    Chronic kidney disease

    • Chronic kidney disease, or CKD, is defined as for ≥3 months: UACR ≥ 30mg/g or eGFR <60 mL/min/1.73 m2 or both8

    Chronic kidney disease stages

    • According to a consensus report from both KDIGO and ADA, CKD should be classified based on both eGFR and albuminuria8

    • The eGFR categories are as follows:8

      • Grade 1 eGFR or “Normal or High”– ≥90 mL/min/1.73 m2

      • Grade 2 eGFR or “Mildly decreased” – 60-89 mL/min/1.73 m2

      • Grade 3a eGFR or “Mildly to moderately decreased” – 45-59 mL/min/1.73 m2

      • Grade 3b eGFR or “Moderately to severely decreased” – 30-44 mL/min/1.73 m2

      • Grade 4 eGFR or “Severely decreased” – 15-29 mL/min/1.73 m2

      • Grade 5 eGFR or “Kidney failure” – <15 mL/min/1.73 m2

    • The albuminuria categories are as follows:8

      • Normal to mildly increased (A1) – <30 mg/g

      • Moderately increased (A2) – 30-299 mg/g

      • Severely Increased (A3) – ≥300 mg/g

    CV outcomes

    • There is currently no consensus definition for cardiovascular (CV) outcomes. The US Food and Drug Administration provided guidance on utilizing a three-point major adverse cardiovascular event (MACE) outcome, which includes acute myocardial infarction (AMI), stroke, and CV mortality in all trials evaluating the cardiovascular safety of diabetic agents. However, many trials have also included heart failure events and unstable angina in addition to the 3-point MACE6

    CV risk

    • Cardiovascular risk, or CV risk, is the risk of developing cardiovascular complications including myocardial infarction, ischemia, arrhythmia, and heart failure11

    CVD

    • Cardiovascular disease, or CVD, is comprised of acute coronary syndrome, stroke, heart failure, and sudden cardiac death10

    Diabetic kidney disease (DKD)

    • Defined as CKD that is attributed to diabetes and is usually a clinical diagnosis made based on the presence of albuminuria and/or reduced eGFR in the absence of signs or symptoms of other primary causes of kidney damage1

    Diabetic nephropathy

    • A diagnosis that refers to specific pathological structural and functional changes seen in the kidneys of patients with both type 1 and type 2 diabetes mellitus. These changes result in a clinical presentation that is characterized by proteinuria, hypertension, and progressive reductions in kidney function18 19

    Early-stage CKD

    • Early-stage CKD is considered to be stages 1-3 defined by eGFR, however, KDIGO has revised the classification to include 5 grades of eGFR and 3 categories of albuminuria to define CKD severity. KDIGO also recommends avoiding using terms such as “early” when describing CKD classification8 16 13

    eGFR

    • Estimated glomerular filtration rate is a measure of kidney function.8 10 The NKF-ASN Task Force recommends the use of the CKD-EPI 2021 eGFR creatinine equation for calculating eGFRcr in adults. This new equation does not include the race coefficient9

    ESKD

    • End-stage kidney disease, or ESKD, is used to define eGFR <15 mL/min/1.73 m2 or treatment by dialysis; ESKD and ESRD are often used interchangeably13

    ESRD

    • End-stage kidney disease, or ESKD, is used to define eGFR <15 mL/min/1.73 m2 or treatment by dialysis; ESKD and ESRD are often used interchangeably13

    Hyperkalemia

    • Acute hyperkalemia is a potassium result above the upper limit of normal that is not known to be chronic. In the United States, this is considered to be above >5.0 mEq/L7

    Hypokalemia

    • Defined as a potassium concentration <3.5 mEq/L7

    Kidney failure

    • Defined as eGFR <15 mL/min/1.73 m2 or treatment by dialysis13

    Kidney outcomes

    • There is currently no consensus definition for kidney outcomes. In trials that primarily evaluated kidney outcomes, the components of the outcomes include but are not limited to: kidney failure, doubling of serum creatinine, death from kidney or CV causes, renal death, first occurrence of ≥50% decline in eGFR, and sustained decline or decrease in eGFR ≥40%11

    • There is international consensus for the individual components of a composite outcome of kidney failure for use in clinical trials. These components include kidney transplantation, maintenance dialysis, death from kidney failure, sustained low eGFR (eGFR <15 mL/min/1.73 m2 sustained over at least 4 weeks), and sustained percent decline in eGFR (percent decline in eGFR ≥40% from baseline over at least 4 weeks)14

    Late-stage CKD

    • Late-stage CKD is considered to be CKD stages 4 and 5, however, KDIGO has revised the classification to include 5 grades of eGFR and 3 categories of albuminuria to define CKD severity. KDIGO recommends using both eGFR and albuminuria categories to describe CKD classification and to avoid general terms such as advanced or severe CKD8 13 15

    Macroalbuminuria

    • Defined as severely increased albuminuria or a UACR >300 mg/g (A3). According to KDIGO, the term ‘macroalbuminuria’ should be avoided and the term ‘severely increased albuminuria” should be used instead13

    Microalbuminuria

    • Defined as moderately increased albuminuria or a UACR 30-300 mg/g (A2). According to KDIGO, the term ‘microalbuminuria’ should be avoided, and the term ‘moderately increased albuminuria’ should be used instead13

    MR overactivation

    • The mineralocorticoid receptor (MR) is expressed in many tissues, such as the kidney, heart, and blood vessels.3 The MR is activated by steroid hormones, such as aldosterone and cortisol. Following the selective recruitment of cofactors, the receptor initiates gene transcription.5 12 20 Pathological conditions, like type 2 diabetes and chronic kidney disease, can cause overactivation of the MR.3 5 12 MR overactivation is thought to contribute to inflammation and fibrosis3

    MRA

    • Mineralocorticoid receptor antagonist2

    Nonsteroidal MRA

    • Nonsteroidal MRAs, such as finerenone, have unique binding mechanisms to the MR compared to steroidal MRAs. This unique binding mechanism can determine differences in potency, selectivity, and nuclear cofactor recruitment. Additionally, the differences in physiochemical properties can lead to different tissue penetration and distribution2

    Normoalbuminuria

    • Defined as a UACR <10 mg/g (A1), however, KDIGO recommends avoiding the use of the term ‘normoalbuminuria’ and to use the term ‘normal albuminuria’ instead13

    Proteinuria

    • A general term for the presence of increased amounts of protein in the urine10

    RAAS blockade

    • RAAS blockade is the blockade of the renin-angiotensin-aldosterone system through the use of agents like angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers.10 RAAS blockade remains a mainstay in the management for people with diabetic kidney disease with albuminuria1

    Renal insufficiency

    • A term used to describe abnormal kidney function, however, KDIGO recommends avoiding the use of “renal insufficiency” and that specific kidney measures such as albuminuria or decreased eGFR be used to describe alterations in kidney function13

    Risk of CKD progression

    • The risk of CKD progression refers to the risk of worsening eGFR or albuminuria13

    Steroidal MRA

    • Steroidal MRAs, such as spironolactone and eplerenone, are earlier developed antagonists of the mineralocorticoid receptor2

    T2D

    • Type 2 diabetes11

    UACR

    • Urinary albumin-creatinine ratio, from a timed urine collection or spot urine collection determines if you have albumin in your urine which can indicate kidney damage10 13

    Reference List

    1. American Diabetes Association. Section 11. Diabetes Care. 2023;46 (Suppl 1): S191-S202.
    2. Agarwal R, et al. Eur Heart J. 2021;42(2):152-161
    3. Agarwal R, et al. Nephrol Dial Transplant. 2022;37(6):1014-1023
    4. Banerjee S, et al. Hellenic J Cardiol. 2017;58(5):342-347
    5. Bauersachs J, et al. Hypertension. 2015;65(2):257-263
    6. Bosco, E et al. BMC Med Res Methodol. 2021;21(1):241
    7. Clase CM, et al. Kidney Int. 2020;97(1):42-61
    8. de Boer IH, et al. Diabetes Care. 2022;45(12):3075-3090
    9. Delgado C, et al. J Am Soc Nephrol. 2021;32(12):2994-3015
    10. Kidney Disease Improving Global Outcomes. Kidney Int Suppl. 2013;3(1):1-150
    11. Kidney Disease Improving Global Outcomes. Kidney Int. 2022;102(5S):S1-S127
    12. Kolkhof P, et al. Handb Exp Pharmacol. 2017;243:271-305
    13. Levey AS, et al. Kidney Int. 2020;97(6):1117-1129
    14. Levin A, et al. Kidney Int. 2020;98(4):849-859
    15. Mazumdar S, et al. Adv Chronic Kidney Dis. 2022;29(1):24-29
    16. Qaseem A, et al. Ann Intern Med. 2013;159(12):835-847
    17. Kerendia. Package Insert. Bayer Healthcare Pharmaceuticals Inc; 2022
    18. Umanath K, et al. Am J Kidney Dis. 2018;71(6):884-895
    19. Van Buren PN, et al. Adv Chronic Kidney Dis. 2011;18(1):28-41
    20. Yang J, et al. J Mol Endocrinol. 2009;43(2):53-64

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