Quiz 9: Pharmacotherapy (St. Peter)

Why does GFR initially rise in untreated diabetes?

excess glucose causes hyperfiltration, which damages the glomerulus over time

Why does albuminuria decrease in late-stage CKD?

fewer functioning nephrons are left to filter protein, not because the disease improves

How should A1C targets be adjusted in CKD patients?

more aggressive (<7%) in younger/early CKD; more lenient in advanced CKD or high hypoglycemia risk

What is the risk of intensive A1C control in advanced CKD?

hypoglycemia may trigger cardiovascular events like MI

What do newer agents (SGLT2i, GLP-1RA, nsMRA) provide beyond glucose control?

kidney protection, reduced albuminuria, and cardiovascular event reduction

What SGLT2i mechanism corrects hyperfiltration?

restores tubuloglomerular feedback, leading to normalization of dilated afferent arteriole.

How do SGLT2 inhibitors reduce glomerular pressure?

by reducing afferent arteriole dilation → decreasing hyperfiltration injury

What are key CKD-related benefits of SGLT2 inhibitors?

↓ CKD progression (30-40%), ↓ HF hospitalization, moderate ↓ MACE

What characteristic early effect appears after starting SGLT2 inhibitors?

an acute, reversible eGFR dip, which stabilizes over time

Why does the eGFR dip NOT indicate kidney injury?

it reflects hemodynamic adjustment, not damage, and recovers later

Can SGLT2 inhibitors be used in CKD with low GFR?

Yes, initiate if eGFR ≥20; continue until dialysis. Not for glycemic effect

What are symptoms of euglycemic DKA that patients must be educated about?

nausea, abdominal pain, SOB, ketone odor, confusion; even with normal glucose

What makes volume status important when initiating SGLT2i?

SGLT2i cause osmotic diuresis → may worsen hypovolemia, especially with loop diuretics

When starting SGLT2i in a euvolemic patient on loop diuretics, what adjustment is recommended?

reduce loop diuretic dose by 20-50%

In CKD, why are the glycemic effects of SGLT2i limited?

reduced filtering of glucose at eGFR <45, leading to minimal A1C lowering

Which GLP-1RA has the strongest CKD evidence?

semaglutide

Can GLP-1RA be used at any eGFR?

Yes, no dose adjustment, can start even when eGFR <15

Which outcomes do GLP-1RA outperform SGLT2i for?

ASCVD event reduction and A1C lowering

What are proposed renal-protective mechanisms of GLP-1RA?

↓ oxidative stress, ↓ inflammation, vascular endothelial protection

How do SGLT2i and GLP-1RA differ in albuminuria reduction efficacy?

SGLT2i greater than GLP-1RA for albuminuria reduction

Why might GLP-1RA be chosen first in obese CKD patients

they have superior weight reduction and cardiovascular protection

What is finerenone's primary role in CKD treatment?

reduces albuminuria and slows CKD progression in diabetic CKD

From FIDELIO/FIGARO trials, what were finerenone's main outcomes?

↓ CKD progression by 23%, ↓ CV events by 14%

Why is finerenone preferred over spironolactone in CKD?

non-steroidal → lower hyperkalemia risk, less gynecomastia

What eGFR cutoff is required for starting finerenone?

Do not initiate if eGFR <20 due to hyperkalemia risk

Why is hyperkalemia monitoring critical with nsMRAs?

they block aldosterone receptors → reduce K⁺ excretion → risk of K⁺ retention

What are the emerging "pillars" of pharmacologic CKD therapy?

ACE/ARB + SGLT2i + GLP-1RA + nsMRA (finerenone)

Which drug classes cause an initial eGFR dip but long-term protection?

ACE/ARBs, SGLT2 inhibitors, Finerenone

(Triple dippers)

Why is combination therapy effective in CKD control?

Each class has a unique mechanism (hemodynamic, metabolic, anti-inflammatory), providing additive renal & CV benefit

When must metformin be discontinued in CKD?

eGFR <30 (risk of lactic acidosis)

What metformin dose is recommended at eGFR 45-59?

1000-1500 mg/day if at high risk for lactic acidosis

What metformin dose is recommended at eGFR 30-44?

Max 1000 mg/day

Why should glyburide be avoided in CKD?

active metabolites excreted via kidneys → high risk of severe hypoglycemia

Why are sulfonylureas inappropriate first-line for CKD?

high hypoglycemia risk, no CKD progression benefit

How does healthcare disparity affect CKD pharmacotherapy?

minoritized groups receive fewer SGLT2i/GLP-1RA and more sulfonylureas, worsening outcomes

In a Type 2 diabetic with eGFR 50, A1C 9, and BMI 34—what first-line targeted therapy?

GLP-1RA

3 multiple choice options

In CKD with residual albuminuria despite ACEi + SGLT2i, what to add next?

finerenone

3 multiple choice options

When BOTH CVD risk and CKD progression risk are high, what combination best addresses both?

SGLT2i + GLP-1RA + ACE/ARB; finerenone if albuminuria persists

1 multiple choice option

Why is CKM treatment considered suboptimal?

high medication complexity, care gaps, underuse of optimal therapies, and lack of multidisciplinary coordination

What role do pharmacists play in CKD/CKM care?

they help bridge the gap between primary and specialty care and ensure optimal cardiovascular risk-reducing medication use

What does AKHOMM stand for?

Advancing Kidney Health through Optimal Medication Management

AKHOMM's vision

Every person with kidney disease receives optimal medication management through team-based care including a pharmacist

What are the 3AKHOMM strategies to improve care?

promote pharmacist role, develop curriculum, implement Learning and Action Collaborative (LAC)

What is Comprehensive Medication Management (CMM)?

team-based process to ensure medications are safe, effective, affordable, and used as intended

What is the AKHOMM curriculum designed to do?

improve knowledge and skills in CKD/CKM across multidisciplinary teams using patient-centered modules

Why are patient/care partner voices critical in AKHOMM curriculum?

they provide real-life experiences that ensure education reflects the patient journey and needs

What are the five phases of the AKHOMM implementation framework?

1. program design

2. pre-implementation planning

3. implementation

4. continuous quality improvement (PDSA)

5. sustainability

What is the goal of the PDSA cycle in AKHOMM?

to support continuous quality improvement by testing and refining processes

What are teams expected to measure during implementation?

MTPs (Medication Therapy Problems) and Guideline-Directed Medication Therapy (GDMT)

What four performance themes are tracked in AKHOMM progress tracking?

establishing structure, delivery system, measurement & refinement, demonstrating value/scaling

What is the purpose of collaborative practice agreements (CPAs) in CKM pharmacy?

allow pharmacists to directly implement medication changes without needing provider approval

What three components describe CKM pharmacist practice implementation success?

committed teams, organized framework, continuous quality improvement