NAPLEX: Renal Disease

what are the most common causes of renal disease

HTN

DM

glomerulus

filtering unit - afferent arteriole delivers blood here

substances with molecular weight <40,000 daltons (most drugs) pass through filtrate to be excreted in urine

proximal tubule

Na, Cl, Ca and H2O initially filtered out of blood is reabsorbed back into bloodstream here

Meds that work here = SGLT2i

descending limb of loop of henle

water reabsorbed into blood, Na and Cl not

ascending limb of loop of henle

Na, Cl reabsorbed back into blood, water not unless ADH present

which meds work in the loop of henle

loop diuretics

Cause less Ca absorption back into blood → Ca depletion

Can decrease bone density d/t long term use of loop diuretics

which meds work in the distal convoluted tubule

thiazide diuretics

Inhibit NaCl pump in distal convoluted tubule

Thiazides increase Ca reabsorption → has productive effect on bones

collecting duct

Helps with water and electrolyte balance as directed by ADH and aldosterone

which meds work in the collecting duct

aldosterone antagonists (ex: spironolactone, eplerenone)

Decrease Na and water reabsorption, increase K reabsorption

meds that can induce nephrotoxicity

Amphotericin B

Cisplatin

Cyclosporine

Loop diuretics

NSAIDs

Polymyxins

Radiographic contrast dye

Tacrolimus

Vancomycin

risk factors for nephrotoxicity

Decreased renal blood flow (ex: d/t dehydration, HoTN, pre-existing kidney disease, chronic or acute heart failure)

Increased age

Use of multiple nephrotoxic medications at the same time

Frequent use or large doses of nephrotoxic medications

blood urea nitrogen (BUN)

waste product of protein metabolism

- urea is excreted by kidneys (as kidney function declines, BUN increase)

other factors besides renal function can increase BUN (primarily dehydration)

normal = 7-20 mg/dL

serum creatinine

waste product of muscle metabolism

Normal range = 0.6-1.3 mg/dL

CKD criteria

eGFR <60 mL/min/1.73 m2 (normal = 125)

Albuminuria equivalent to urine albumin excretion rate (AER) >30 mg/24 hrs or urine albumin to creatinine ratio (UACR) >30 mg/g

Must have occurred for >3 mo

stage 1 CKD

GFR >90 + kidney damage

normal or high

stage 2 CKD

GFR 60-89 + kidney damage

mild decrease

stage 3 CKD

G3A: GFR 45-59; mild/mod decrease

G3B: GFR 30-44; mod to severe decrease

stage 4 CKD

GFR 15-29

severe decrease

stage 5 CKD

<15 or dialysis dependent

kidney failure

albuminuria A1

ACR or AER <30

Normal to mild decrease (normoalbuminuria)

albuminuria A2

ACR or AER 30-300

Moderate increase (microalbuminuria)

albuminuria A3

ACR or AER >300

Severe increase (macroalbuminuria)

treatment to delay progression of CKD

HTN

target SBP <120 mmHg

1st line = ACE/ARB

- avoid k supplements, Na substitutes

- monitor BP, SCr, K x2-4 wks after starting

treatment to delay progression of CKD

DM

1st line = SGLT2i

Alt = GLP-1

Add on: finerenone

- can be added to SGLT2i, maximally tolerated dose of ACE/ARB if eGFR >25, albuminuria, normal K levels

drugs that require decreased dose or increased intervals in CKD

anti-infectives

Aminoglycosides (↑ dosing interval primarily)

Beta lactams (except nafcillin, oxacillin, ceftriaxone)

Fluconazole

Quinolones (except moxifloxacin)

Vancomycin

Amphotericin B

Anti TB meds (ethambutol, pyrazinamide)

Antivirals (acy/vala/ganci/valganciclovir, oseltamivir)

Aztreonam

NRTIs (tenofovir)

Polymixins

Bactrim

drugs that require decreased dose or increased intervals in CKD

CV drugs

LMWH (lovenox)

Rivaroxaban

Apixaban

Dabigatran

Antiarrhythmics (digoxin, disopyramide, dofetilide, procainamide, sotalol)

Statins (prava/rosuva)

drugs that require decreased dose or increased intervals in CKD

GI drugs

H2RAs (famotidine, ranitidine)

Metoclopramide

drugs that require decreased dose or increased intervals in CKD

pain / gout drugs

Allopurinol

Colchicine

Gabapentin

Pregabalin

Morphine and codeine

Tramadol

drugs that require decreased dose or increased intervals in CKD

other

Bisphosphonates

Litihim

Cyclosporine

Tacrolimus

Topiramate

drugs that are CI in CKD

CrCl <60

nitrofurantoin

drugs that are CI in CKD

CrCl <50

TDF containing products (Complera, Delstrigo, Stribild, Symph)

Voriconazole IV (d/t vehicle)

drugs that are CI in CKD

CrCl <30

TAF containing products (ex: Biktarvy, Descovy, Genvoya, Odefsey, Symtuza)

NSAIDs

Dabigatran

Avanafil

Bisphosphates

Duloxetine

Fondaparinux

K sparing diuretics

Tadalafil

Tramadol ER

drugs that are CI in CKD

eGFR <30

Metformin - do not start if eGFR <45

drugs that are CI in CKD

Meperidine

Rivaroxaban

SGLT2i

Dofetilide

Edoxaban

Glyburide

Sotalol

phosphate binder counseling

- take prior to meal

- space out administration from levothyroxine, tetracyclines, quinolones

phosphate binder examples

aluminum based:

- aluminum hydroxide

ca based:

- calcium acetate (calphron)

- calcium carbonate (tums)

aluminum, ca free:

- sucroferric oxyhydroxide (velphoro)

- ferric citrate (auryxia)

- lanthum carbonate (fosrenol)

- sevelamer carbonate (renvela)

- sevelamer hydrochloride (renagel)

aluminum based phosphate binder SE

Aluminum intoxication (CNS, bone toxicity, confusion, seizures)

Osteomalacia

Constipation

Nausea

aluminum based phosphate binder counseling

treatment duration limited to 4 wks

if dose is missed + food absorbed, skip then resume normal dosing at next meal/snack

ca based phosphate binder SE

Hypercalcemia

Constipation

Nausea

recommended total dose of elemental Ca

<2000 mg

sucroferric oxyhydroxide (velphoro)

ferric citrate (auryxia)

SE

Diarrhea

Discolored (black) feces

Ferric citrate: constipation

lanthanum carbonate (fosrenol) SE

GI perforation

N/V/D

Constipation

Abdominal pain

lanthanum carbonate CI

GI obstruction

fecal impairment

ileus

lanthanum carbonate counseling

must chew tablet thoroughly to reduce GI AE

use powder if unable to chew

sevelamer carbonate (renvela)

sevelamer hydrochloride (renagel)

SE

N/V/D

Dyspepsia

Constipation

Abdominal pain

Flatulence

Sevelamer hydrochloride: metabolic acidosis

sevelamer carbonate (renvela)

sevelamer hydrochloride (renagel)

pearls

Can reduce dietary absorption of vitamin D, E, K, and folic acid - consider vitamin supplementation

Consider using powder if swallowing difficulty is present as can cause dysphagia

Can lower total cholesterol and LDL by 15-30% - sevelamer carbonate can maintain bicarbonate concentrations

vitamin D forms

- vitamin D3 (cholescalciferol) - synthesized in skin after exposure to UV light

- vitamin D2 (ergocalciferol) - produced from plant sterolds

vitamin D analog examples

- calcitrol (rocaltrol)

- calcifediol (rayaldee)

- doxercalciferol (hectorol)

- paricalcitol (zemplar)

when should vitamin D analogs be used

late stages of CKD (4, 5)

they can ↑ Ca absorption from gut, serum Ca concentrations, and inhibit PTH secretion

vitamin D analog counseling

take with food or shortly after meal to decrease GI upset

tenapanor (Xyphozah)

Na/H exchanger that can be considered for pt on dialysis with inadequate response / intolerance to phosphate binders

why is it important to prevent hyperphosphatemia?

important to prevent bone disease, fractures

vitamin D deficiency MOA

kidney unable to hydroxylate vitamin D to active form (1,25-dihydroxy vitamin D)

can lead to worsened bone disease (d/t hypocalcemia, elevation of PTH), impaired immunity, increased risk of CV disease

calcimimetics examples

- cinacalcet (sensipar)

- etelcalcetide (parsabiv)

calcimimetics SE

warning: hypocalcemia

muscle spasms

paresthesia (etecalcetide)

who are calcimimetics indicated for

dialysis patients

anemia

hgb <13

d/t lack of erythropoietin (EPO - produced by kidneys) → stimulates RBC (contain Hgb) → released to blood to transport O2

as kidney fxn decliens → less EPO production → lower Hgb levels → anemia

ESA use criteria

Hgb <10 g/dL

- hold/discontinue dose if Hgb exceeds 11 g/dL

only effective if adequate iron available to make Hgb

daprodustat (Jesduvroq)

oral ESA indicated for CKD patients who have received dialysis for at least 4 mo

risks of ESAs

elevated BP

thrombosis

hyperkalemia

K > 5.3 or 5.5 mEq (ranges vary, be concerned if >5 mEq/L)

most common cause of hyperkalemia

decreased renal fxn d/t kidney failure

drugs that raise K levels

dec aldosterone activity

- spironolactone, eplerenone

- RAAS inhibitors

- drospirenone containing OCP

dec renal tubule K secretion

- amioloride, trimaterene

- bactrim

- tacrolimus, cyclosporine

inc K intake

- K supplements

- K containing IV fluids (parenteral nutrition)

other: canagliflozin

hyperkalemia treatment

stabilize heart - prevent arrhythmias

- agents

- route

- onset

agents:

- calcium gluconate IV (preferred)

- calcium chloride IV

onset: 1-2 min

hyperkalemia treatment

shift K intracellularly

- agents

- route

agents:

- regular insulin + dextrose (IV)

- sodium bicarbonate (IV)

- albuterol (nebulized)

give insulin alone if BG >250 mg/dL

use sodium bicarbonate if metabolic acidosis present

onset: 30 min

hyperkalemia treatment

eliminate K from body

- agents

- route

- onset

IV loop diuretics

- onset = 15 min

SPS

- PO/PR; PO can take hrs-days, PR fast onset but less effective

- binds to K in GI tract

- use in emergency situations only d/t GI AE

patiromer (veltassa)

- PO

- onset: 7 hrs

- binds to K in GI tract

sodium zicornium cyclosilicate (lokelma)

- PO

- onset: 1 hr

- binds to K in GI tract

- preferred in emergency situations d/t fast onset

hemodialysis

- onset: immediate

- removes K in blood

- takes hrs to set up / complete

metabolic acidosis

ability of kidney to reabsorb bicarbonate decreases as CKD progresses

when to initiate treatment for metabolic acidosis

serum bicarbonate concentration <22 mEq/L

drugs to replete bicarbonate

sodium bicarbonate

- caution in pt w HTN, CV disease

sodium citrate/citric acid solution (cytra-2, oracit)

- may not be effective in pt w liver failure (metabolized by bicarbonate in liver)

who qualifies for dialysis

all patients in CKD 5 who do not have a kidney transplant

hemodialysis

patients blood pumped into dialyzer → run through semipermeable dialysis filter → removes electrolytes + excess fluid w/ concentration gradient

- takes 3-4 hrs several times /week

- can do at home more frequently (ex: 5-6 times/week)

peritoneal dialysis

dialysis solution pumped into peritoneal cavity → peritoneal membrane acts as semipermeable membrane → solution left to "dwell" for time to allow waste product + electrolyte exchange → drained

- repeated throughout the day every day

- can be performed by patient at home

factors affecting drug removal during dialysis

drug characteristics

Molecular weight / size: smaller molecules more readily removed

Volume of distribution: drugs w/ larger Vd less likely to be removed (hydrophilic)

Protein binding: highly protein bound drugs less likely to be removed

factors affecting drug removal during dialysis

dialysis factors

Membrane filter: high flux (large pore size) and high efficiency (large surface area filter) HD filters remove more substances than conventional / low flux filters

Blood flow rate: higher dialysis blood flow rates = increased drug removal over given time interval

veltassa max dose

25.2 g once daily

veltassa storage instructions

Store powder in refrigerator + use within 3 mo if stored at room temp

lokelma storage instructions

store at room temp

normal BUN:Scr ratio

10-15 : 1

factors that can influence BUN

high protein diet can increase nitrogen production (inc BUN)

effects on Scr, GFR

early AKI

SCr: small change

eGFR: large change

effects on Scr, GFR

advanced CKD

Scr: large change

eGFR: small change

prerenal AKI

due to decreased renal perfusion

- dehydration

- HoTN

- hypoperfusion

elevated BUN: Scr >20:1

intrinsic AKI

due to structural damage

- acute tubular necrosis

- acute interstitial nephritis

normal BUN: Scr ratio

postrenal AKI

due to obstruction of urinary tract

drug induced causes of prerenal AKI

- loop diuretic

- NSAIDs

- ACE/ARB

- calcineurin inhibitors (tacrolimus, cyclosporine)

drug induced causes of intrinsic AKI

- abx (aminoglycosides, vanco, polymyxins)

- amphotericin B

- cisplatin

- IV contrast dye

AKI sx changes

serum creatinine

urine output

need for renal replacement therapy

CKD sx changes

GFR

albuminuria

drugs with increased risk of adverse effects d/t drug accumulation from renal impairment

- anti-infectives

- anticoag

- H2RA

- bisphosphonates

- lithium

- metformin

drugs with nephrotoxic effect d/t renal impairment

- aminoglycosides

- vancomycin

- amphotericin B

- NSAIDs

- calcineurin inhibitors

drugs with decreased drug efficacy d/t renal impairment

- thiazide diuretics

- nitrofurantoin

drugs with increased risk for complications of reduced renal fxn d/t renal impairment

K sparing diuretics

complications from CKD

- mineral and bone disorders

- anemia

- hyperkalemia

- metabolic acidosis

mineral and bone disorders

labs

inc phosphate

dec calcium

inc PTH

mineral and bone disorders

treatment

phosphate binders

vitamin D supplement / analog

calcimimetic

anemia

labs

dec Hgb

anemia treatment

ESA

hyperkalemia treatment

loop diuretic

K binding resin

metabolic acidosis

labs

dec bicarbonate

dec pH

metabolic acidosis

treatment

sodium bicarbonate

sodium citrate/citric acid