Chronic Kidney Disease- Progression modifying therapties

Dr. Glaze, Exam 1

functions of the kidney

• regulation of homeostasis (electrolytes, water, acid/base balance)

• remove waste and toxins from the body

• synthesize hormones

acute kidney failure

• rapid loss of kidney function occurring over days to weeks

chronic kidney disease

• progressive loss of function occurring over several months to years

• change in glomerular filtration rate >/3 3 months

risk factors associated with CKD

• susceptibility factors

• initiation factors

• progression factors

susceptibility factors

• risk factors associated with CKD

• increase susceptibility to kidney damage

• advanced age

• reduced kidney mass

• low birth weight

• racial/ethnic minority

• family history

• low income or education

• systemic inflammaiton

• dyslipidemia/obesity

initiation factors

• risk factors associated with CKD

• directly initiate kidney damage

• diabetes mellitus

• hypertension

• autoimmune diseases

• polycystic kidney disease

• drug toxicity

progression factors

• risk factors associated with CKD

• cause worsening kidney damage and faster decline in kidney function after initiation of kidney damage

• poor glucose contol

• elevated blood pressure

• proteinuria

• smoking

• obesity

signs and symptoms of CKD

• occurs in later stages (3-5)

• fatigue, weakness, shortness of breath, confusion, nausea, and vomiting, bleeding, loss of appetite, itching, cold intolerance, and peripheral neuropathies are common

• edema, weight gain (from accumulation of fluid), changes in urine output (volume and consistency), foaming of urine (indicative of proteinuria)

Chronic kidney disease

• defined as abnormalities of kidney strucute or function, present for >3 months, with implications for health

CKD staging

• classified based on cause, GFR category, and albuminuria category

G1 (Stage 1 CKD)

• GFR > 90

G2 (Stage 2 CKD)

• GFR 60-89

G3a (Stage 3 CKD)

• GFR 45-59

G3b (Stage 3 CKD)

• GFR 30-44

G4 (Stage 4 CKD)

• GFR 15-29

G5 (Stage 5 CKD)

• GFR < 15

• ESRD is requiring dialysis

ACR (Albumin creatinine ratio)

• assess kidney function

• classifying albuminuria

• A1-A3

A1

• ACR < 30

A2

• ACR 30-300

A3

• ACR > 300

ACEI or ARB

• key component for management in CKD for most patients

pharmacological therapy in CKD

• adjust medication doses for kidney function

• evaluate need for OTC or nutritional protein supplements

• temporarily discontinue potentially nephrotoxic or renally excreted drugs in patients with CKD who are acutely unwell or hypovolemic

• consider evidenced based medications: ACE//ARB, SGLT2 inhibitors, MRAs, statins, ASA

ACEI/ARB

• slow progression of CKD

• recommended for adults with CKD and urine albumin excretion of category A2 or greater

• MOA:

  • lowering the intraglomerular pressure, reducing hyperfiltration

  • antifibrotic effect contribute to the slowing of kidney disease progression

  • direct improvement in the permselective properties of the glomerulus

combination

• avoid ACEI and ARB in ____

• risk of adverse effects (hypotension, impaired kidney function, hyperkalemia)

ACE inhibitor

• beneficial effects on renal function

• both type 1 and type 2 DM

• lowest recommended dose should be initiated

• titrate dose at 4 week interval to control proteinuria

• 30-50% reduction in proteinuria

30-50

• ACEI have _____ reduction in proteinuria

30

when initiation ACE inhibitor therpay sustained SCr increase >___% consider discontinuation

hyperkalemia, acute GFR reduction

• monitoring for ACE inhibitor therapy in CKD monitoring

therapeutic alternatives for CKD therapy (if cannot tolerate ACEI/ARB)

• SGLT-2 inhibitors

• MRAs (Finerenone)

• nondihydropyridine CCBs

SGLT-2 inhibitors (canagliflozin, dapagliflozin, empagliflozin)

• 2nd line nephroprotective therapy for CKD

• decrease glucose and sodium reabsorption in the proximal tubule of the kidney

• decrease glomerular hyperfiltration and decrease glomerular hypertension

• decrease progression of kidney disease, decrease the need for dialysis or transplantation, and decrease mortality

• continue until dialysis or kidney transplantation

Finerenone

• 3rd line for CKD

• MRA

• novel, selective nonsteroidal mineralocorticoid receptor antagonist (MRA)

• patients with CKD due to type 2 diabetes

• option for patients who cannot tolerate SGLT2i

nondihydropyridine calcium channel blocker

• generally 3rd/4th line when ACEIs or ARBs/SGLT-2/MRA are not tolerated

• decrease glomerular injury without negatively changing renal hemodynamics

• diltiazem, verapamil, can be used in combination with ACEI/ARB

ACEI and ARB

• 1st line anti-HTN for CKD patients with albuminuria

• reduction of intraglomerular pressure

130/80

• 2025 ACC/AHA guidelines: Goal BP less than ___ mmHg

metformin + SGLT2 inhibitor

• should be used first line in patients with T2D + CKD when eGFR is > 20 ml/min

canagliflozin, dapagliflozin, empagliflozin

• considered in ACEI/ARB in all patients with diabetic CKD due to type 2 diabetes who have an eGFR ml/min and ACR >200 mg/g

• once started should be continued until dialysis or kidney transplantation

• these agents are not used in patients with CKD from type 1 diabetes due to a significantly higher risk of diabetic ketoacidosis

finerenone

• unlike spironolactone, is not a blood pressure lowering drug,

• can be considered in patients who cannot tolerate SGLT2 inhibtiors

CKD treatment

• avoidance of nephrotoxic agents

• treat underlying condition

• aggressive blood pressure control

• aggressive glycemic control

• use of an ACEI/ARB in kidney disease with proteinuria (A2 or greater)

• use of an SGLT2inhibitor (2nd line)

• use of finerenone in kidney disease with DM