Trasparenza e di adeguamento agli standard internazionali in tema di potenziale conflitto di interessi - Dichiara di aver ricevuto negli ultimi ...
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Trasparenza e di adeguamento agli standard internazionali in tema di potenziale conflitto di interessi. Dichiara di aver ricevuto negli ultimi due anni compensi o finanziamenti dalle seguenti Aziende Farmaceutiche e/o Diagnostiche: - Eli Lilly
Nefropatia diabetica:
nuovi scenari
terapeutici
Alfonso Gigante
SSD Malattie Metaboliche - Diabetologia
Ospedale Cesare Zonchello Nuoro
Cagliari 25 settembre 2021
Agenda
Le nuove presentazioni della nefropatia diabetica
Il trattamento multifattoriale
Non solo albuminuria, non sempre albuminuria
I nuovi farmaci
Con quale iniziamo? Li associamo?
3
4
5
Non sempre albuminurici ….
6
L’albuminuria è un prerequisito della
nefropatia diabetica?
7
9
10
11
ESC/EASD: trattamento dei pazienti con DMT2 naïve
ESC/EASD: trattamento dei pazienti con DMT2 on top alla metformina Linee Guida ESC/EASD 2019
PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT Glucose-lowering
Medication in
Type 2 Diabetes:
2021 ADA
Professional
Practice
Committee (PPC)
adaptation of
Davies et al. and
Buse et al.
Pharmacologic
Approaches to
Glycemic
Management:
Standards of Medical
Care in Diabetes -
2021. Diabetes Care
2021;44(Suppl.
1):S111-S124PHARMACOLOGIC APPROACHES TO GLYCEMIC TREATMENT
Glucose-
lowering
Medication in
Type 2
Diabetes:
Overall
Approach
Pharmacologic
Approaches to
Glycemic
Management:
Standards of Medical
Care in Diabetes -
2020. Diabetes Care
2020;43(Suppl. 1):S98-
S110COMPREHENSIVE CARE IN PATIENTS WITH DIABETES AND CKD Practice Point 1.1.1: Patients with diabetes and chronic kidney disease (CKD) should be treated with a comprehensive strategy to reduce risks of kidney disease progression and cardiovascular disease (Figure 2).
FIGURE 22. SUGGESTED APPROACH IN DOSING METFORMIN BASED ON THE LEVEL OF KIDNEY FUNCTION
ANTI-HYPERGLYCEMIC THERAPIES IN PATIENTS WITH DIABETES AND CKD Recommendation 4.2.1: We recommend treating patients with T2D, CKD, and eGFR ≥30 ml/min per 1.73 m2 with an SGLT2i (1A). Practice Point 4.2.1: An SGLT2i can be added to other antihyperglycemic medications for patients whose glycemic targets are not currently met or who are meeting glycemic targets but can safely attain a lower target (Figure 24).
FIGURE 24. ALGORITHM FOR INITIATION OF SGLT2I THERAPY FOR PATIENTS WITH T2D, CKD, AND EGFR ≥30 ML/MIN PER 1.73 M2, WHO ARE ALREADY BEING TREATED WITH ANTIHYPERGLYCEMIC MEDICATIONS
ANTI-HYPERGLYCEMIC THERAPIES IN PATIENTS WITH DIABETES AND CKD Practice Point 4.2.6: A reversible decrease in the eGFR with commencement of SGLT2i treatment may occur and is generally not an indication to discontinue therapy. Practice Point 4.2.7: Once an SGLT2i is initiated, it is reasonable to continue an SGLT2i even if eGFR falls below 30 ml/min per 1.73 m2, unless it is not tolerated or kidney replacement therapy is initiated. Practice Point 4.2.8: SGLT2i have not been adequately studied in kidney transplant recipients, who may benefit from SGLT2i treatment, but are immunosuppressed and potentially at increased risk for infections; therefore, the recommendation to use SGLT2i treatment does not apply to kidney transplant recipients. (see Recommendation 4.2.1)
SGLT2 INHIBITORS AND CKD PROGRESSION
SGLT2 INHIBITORS AND KIDNEY OUTCOMES B Neuen et al The Lancet D&E Oct 2019
EFFECT OF SGLT2I ON SUBSTANTIAL LOSS OF KIDNEY FUNCTION, ESKD, OR DEATH DUE TO KIDNEY DISEASE, STRATIFIED BY BASELINE EGFR B Neuen et al The Lancet D&E Oct 2019
EFFECT OF SGLT2I ON SUBSTANTIAL LOSS OF KIDNEY FUNCTION, ESKD, OR DEATH DUE TO KIDNEY DISEASE, STRATIFIED BY BASELINE ACR B Neuen et al The Lancet D&E Oct 2019
SGLT2 INHIBITORS AND 3-POINT MAJOR CARDIOVASCULAR EVENTS
26
Future outlook – Dual SGLT2 and RAAS
inhibition Actions: Clinical implications:
• Decreased glomerular pressure
SGLT2 inhibition
• Reduction in albuminuria
Afferent arteriole
narrowing • Renal protection suggested
• Decreased glomerular pressure
RAAS blockade • Reduction in albuminuria
Efferent arteriole • Renal protection proven in clinical trials
widening
• Potential for normalisation of
SGLT2 inhibition and
intraglomerular pressure
CONCEPT
RAAS blockade
• Potential additive intraglomerular
Afferent narrowing and pressure reduction
Empagliflozin is not indicated for CVEfferent widening
risk reduction or kidney disease
• Potential for long-term renal protection
27
Adapted from: Cherney D et al. Circulation 2014;129:587-597; Lewis et al. N Engl J Med 2001;345:851; Kon V et al.
Kidney Int 1993;44:545Applied physics model
In-flow/out-flow pressure regulator for gas
SGLT2 RAAS
inhibitor blocker
Adapted from: Cherney D et al. Circulation 2014;129:587-597 28FIGURE 20. PATIENT FACTORS INFLUENCING SELECTION OF GLUCOSE-LOWERING DRUGS OTHER THAN SGLT2I AND METFORMIN IN T2D AND CKD
Non è possibile visualizzare l'immagine.
30Renal and cardiovascular disease are interconnected and should be
considered together
Renal and cardiac systems are linked1 CKD patients are more likely to die of
heart disease than advance to ESRD2
3,5
3
3
Rate per 100 person-years
2,5
2
1,5
1
0,5
0,5
0
ESRD CV
death
Therefore renal and cardiac systems and outcomes should be considered together
CKD, chronic kidney disease; CV, cardiovascular; ESRD, end-stage renal disease.
31 1. Ronco C, et al. J Am Coll Cardiol. 2008;52:1527. 2. Dalrymple L, et al. J Gen Intern Med. 2011;26:379.The time to act is now.
Thus, given the limited collective
resources, would they not be better spent
tackling the issue of implementation rather
than more expensive trials of SGLT2i and
GLP-1RA therapies?
33
Chan JCN, Lim LL, Wareham NJ, Shaw JE, Orchard TJ, Zhang P, Lau ESH, Eliasson B, Kong APS, Ezzati M, et al.. The Lancet Commission on diabetes: using data to transform
diabetes care and patient lives.Lancet. 2021; 396:2019–2082. doi: 10.1016/S0140-6736(20)32374-6CrossrefMedlineGoogle ScholarMessaggi da portare a casa
La DKD si oresenta spesso senza o con modesta albuminuria
Il rischio residuo renale e cardiovascolare è elevato nonostante il trattamento
multifattoriale
L’efficacia degli SGLT2 si estende sia al fenotipo albuminurico e che quello
non albuminurico.
34• Grazie per l’attenzione
Outcome renali
GLP1-RA riducono il rischio di macroalbuminuria, mente SGLT2i riducono il
rischio di peggioramento del filtrato glomerulare stimato
Circulation 2019; 139:2022-2031 37You can also read
