Slowing CKD Progression

what are the first-line CKD medications?

ACEi/ARB + SGLT2i (and statins in most)

what are the second-line targeted therapies for CKD

GLP-1s, ns-MRA, DHP CCB, antiplatelets

pearls of ACEi/ARB use in CKD

optimize dose, monitor SCr, eGFR, SK+, goal SBP < 120 mmHg, and goal 30-50% albuminuria reduction

pearl of SGLT2i use in CKD

ok if eGFR is > 20 mL/min/1.73m2, monitor for genital mycotic infections, Fournier’s gangrene, euglycemia DKA, goal A1C < 7% if diabetic, and goal is to reduce proteinuria

pearls of finerenone use in CKD

ok if eGFR is > 25 mL/min/1.73m2, and SK+ < 5.0 mEq/L, monitor SCr, eGFR, SK+, and get goal SBP < 120 mmHg

when to add GLP-1s:

after SGLT2i in diabetic patients for direct and indirect nephroprotective effect

what are the goals of care in CKD?

slow eGFR decline, reduce albuminuria by 30-50%, get SBP < 120 mmHg or <130/80 mmHg, lipid management, A1C <7%, healthy weight, and moderate-intensity exercise 150 minutes/week

goals of therapy in CKD:

delay or prevent the progression of CKD, maintain quality of life, and prevent/manage complications

what is used as a surrogate marker for decline in GFR?

degree of proetinuria

what is the goal proteinuria in CKD?

reduce proteinuria to minimum possible; 30-50% reduction

which medications reduce the degree of proteinuria in CKD and slow/delays progression of CKD?

ACEi and ARBs (in patients with CKD and albuminuria stage A2)

brand name of benazepril

Lotensin

bran of captopril

Capoten

brand of enalapril

Vasotecb

brand of fosinopril

Monopril

brand of lisinopril

Zestril, Prinivil

brand of moexipril

Univasc

bran of quinapril

Accupril

brand of ramipril

Altace

brand of trandolopril

Mavik

which ACEi have a longer duration of action

benazepril, fosinopril, lisinopril, moexipril, quinapril, ramipril, and trandolopril

which ACEi have shorter durations of action

captopril and enalapril

what ACEi dosing should be used in patients with pre-existing kidney dysfunction?

start low go slow (low dose of a short acting)

brand name of azilsartan

Edarbi

brand name of candesartan

Atacand

brand name of eprosartan

Tevetenb

brand name of irbesartan

Avapro

brand name of losartan

Cozaar

brand name of olmesartan

Benicar

brand name of telmisartan

Micardis

brand name of valsartan

Diovan

T/F: ARBs are generally dosed once a day and have a duration of action of 24 hours

true

T/F: dual RAAS inhibition has no benefit and increased risk of hyperkalemia and hemodynamic AKI

true

brand name of aliskiren

Tekturna

MOA of aliskiren

direct renin inhibitor

efficacy of aliskiren

reduces proteinuria and BP

CI of aliskiren

pregnancy, combination with ACEi or ARB

BBW of aliskiren

use with ACEi or ARB

BP goal for RAAS inhibitors

SBP < 120 or <130/80 mmHg

what is the goal of albuminuria with RAASi?

reduction by 30-50% and reduce ideally to < 30 mg/day (if starting early for diabetes for HTN, prevent onset of albuminuria)

goal of RAASi on CKD?

slow progression of CKD, slope of eGFR decline, and time to dialysis or transplantation

absolute contraindications of RAAS inhibitors:

pregnancy, bilateral renal artery stenosis, and history of ACE/ARB related angioedema

which scenarios should RAAS inhibitors be used with caution:

unilateral renal artery stenosis, hyperkalemia, dehydration/hypovolemia, hypotension, kidney dysfunction (SCr > 3.0 mg/dL)

T/F: RAASi are beneficial for chronic kidney dysfunction but not acute kidney dysfunction

true

what labs should be monitored with RAAS inhibitor use?

K and SCr within1-2 weeks if high risk, within 4 weeks if normal risk

what vital signs should be monitored for RAASi use?

BP and HR daily (if possible)

what symptoms should patients watch for when taking RAASi?

orthostasis, hypotension, dizziness, angioedema, hyperkalemia, and cough

how to counsel for RAAS inhibitors

this medication can be used to lower your blood pressure so you may experience some dizziness upon standing or lying to sitting or sitting to standing. could possibly develop a dry cough and contact doctor if occurring. a rare but possible side effect is swelling of the lips/tongue which is a medical emergency

what drugs should be avoided with RAASi in CKD?

NSAIDs (cause AKI), potassium supplements (cause hyperkalemia), and dual RAASi (AKI and hyperkalemia)

which drugs should be used cautiously with RAASi in CKD?

aldosterone antagonists/potassium sparing diuretics (cause hyperkalemia), and lithium (increased lithium concentrations)

which RAASi contains magnesium and should be avoided/not given at the same time with fluoroquinolones and tetracyclines?

quinapril

pearls of RAAS inhibitors:

start low and go slow if concerned about hyperkalemia/increased SCr, start at ½ dose if on concomitant thiazide or loop diuretic or if patient is dehydrated, use in all patients with CKD regardless of ethnicity and BP unless absolutely contraindicated, no contraindication for kidney dysfunction, and there is a mortality benefit in HFrEF

the three SGLT2 inhibitors that have cardiovascular morbidity/mortality and kidney prevention are:

empagliflozin, dapagliflozin, and canagliflozin

what do SGLT2i increase excretion of?

sodium and glucose

which medication class is a first-line treatment option of CKD in type 2 diabetes and non-diabetic

SGLT2i

which medications should added to ACEi/ARb treatment for CKD?

SGLT2I

T/F: SGLT2i use can delay kidney failure onset up to 15 years

true

when should SGLT2i not be used?

patients with type 1 diabetes

possible ADRs of SGLT2i:

euglycemic diabetic ketoacidosis (T1DM) and urinary tract infections (vaginal yeast infections, Fournier’s gangrene)

brand name of finerenone

Kerendia

MOA of finerenone

non-steroidal mineralocorticoid receptor antagonist (similar mechanism to spironolactone and eplerenone but with less endocrine side effects), and reduces inflammation and fibrosis in kidneys

ADRs of finerenone

hyperkalemia and hypotension

dosing of finerenone

10-20 mg once daily based on eGFR and serum K+

starting dose of finerenone if eGFR is >= 60

20 mg once daily

starting dose of finerenone if eGFR is >= 25 to < 60

10 mg once daily

starting dose of finerenone if eGFR is < 25

do not start

when are non-steroidal MRAs most appropriate?

patients with T2D who are at high risk of CKD progression and cardiovascular events, as demonstrated by persistent albuminuria despite other standard-of-care therapies

when can ns-MRAs be added?

can be added to a RAASi and an SGLT2i for treatment of T2D and CKD

what should be done to mitigate risk of hyperkaleia with ns-MRAs?

select patients with consistently normal serum potassium concentration and monitor serum potassium regularly after initiation of a ns-MRA

when is addition of finerenone recommended to improve carvdiovascular outcomes and refduce the risk of CKD progression?

patients with T2D and CKD with albuminuria treated with maximum tolerated doses of ACE inhibitors or ARBs

what is the goal uric acid in CKD?

< 7 mg/dL

which medication has been shown to slow CKD progression and improve cardiovascular outcomes but has insufficient evidence

allopurinol

T/F: fuboxostat has been well studied in CKD

false

sodium bicarbonate dosing:

1950-2600 mg/day (split BID)

use of sodium bicarbonate:

chronic metabolic acidosis

which medications can slow progression of CKD by treating metabolic acidosis?

alkali therapy (sodium bicarb or sodium citrate)

what is the goal serum bicarb?

> 20 mEq/L

dietary modifications in CKD:

reduce dietary protein as CKD worsens (<= 0.8 g/kg/day)