Pharm E3: Nephro

abrupt reduction in renal fxn is evidenced by what?

high creatinine

high BUN

low urine output

what are the types of renal injury?

1. prerenal → decreased perfusion with undamaged parenchymal tissue

2. intrinsic → structural kidney damage (ischemic or toxic)

3. postrenal → obstruction of urine outflow downstream of kidney

prolonged prerenal injury can turn into what?

intrinsic renal injury

what is a common cause of community acquired AKI?

secondary to renal hypoperfusion → volume depletion (vomiting, diarrhea, dehydration), sepsis, meds (ACE/ARB, diuretics)

what is a common cause of hospital/ICU AKI?

intrinsic → acute tubular necrosis

what are risk factors for AKI?

- age >65

- septic shock

- critical illness

- chronic dz

- nephrotoxic drugs

- surgery

- cancer

- trauma

- AA race

- previous hx of AKI

how do ACEIs and ARBs decrease renal perfusion?

decrease filtration in glomerulus → prerenal AKI

what are vasopressors?

NE

Epi

dopamine

increase BP → can cause prerenal AKI

what are causes of intrinsic AKI?

- acute tubular injury + prolonged prerenal AKI

- large renal artery emboli

- tubule toxins (myoglobin, hemoglobin, uric acid, nephrotoxins like contrast agents and aminoglycosides)

- interstitial damage

what are causes of postrenal AKI?

- bladder outlet obstruction d/t obstructive uropathy (BPH, prostatic cancer, stone)

- physical impingement on urethra (stricture)

- oxalate crystal deposition due to drugs

- drugs with poor urine solubility (MTX, acyclovir)

- chemo-induced tumor lysis syndrome

what is the clinical presentation of AKI?

- changes in urinary habits → decreased or color change

- sudden weight gain (edema)

- abd/flank pain

what are the limitations of serum creatinine?

- varies w/ age, gender, muscle mass, diet, hydration

- amputations/low muscle mass (falsely low)

- changes in SCr can lag behind GFR by 1-2 days

- can over/under estimate GFR

- dehydration can falsely elevate

how can you prevent AKI?

- aggressive hydration prior to major surgery/contrast dye

- avoid nephrotoxic meds

which 2 types of fluids can be used for hydration in AKI?

1. crystalloids → salt-based (normal saline, lactated ringers)

2. colloids → non-salt based (some are assoc. with renal dysfunction)

when would loop diuretics be used for AKI?

only good for managing fluid overload

not found to be helpful otherwise! risk for ototoxicity, hypokalemia, hypocalcemia, hypomagnesemia

what dose of dopamine is benefits to increase renal blood flow and natriuresis?

high dose

low dose not helpful to prevent AKI

which antioxidants can be used to prevent AKI?

ascorbic acid (vit C)

N-acetylcysteine (Mucomyst)

which drug has some benefit in preventing contrast-induced nephropathy?

Mucomyst → mucolytic (used in tylenol poisoning)

what should be used to rehydrate pts with AKI?

20 ml/kg of normal saline (1-2L) → observe for pulm/peripheral edema, elyte balance, normoglycemia

what is a risk when giving too much normal saline?

hyperchloremic acidosis → could use 0.45% NaCl with Na bicarbonate

what are the major indications for Renal replacement therapy (RRT)?

AEIOU

A = acid base abnormalities

E = electrolyte imbalance

I = intoxication

O = fluid overload

U = uremia

which diuretics could be used for tx of AKI?

mannitol

loop diuretics (Furosemide)

not often used, can cause AKI

what should be done if loop diuretic resistance occurs in AKI?

- switch from oral to parenteral

- increase dose

- utilize continuous infusion loops

- use different ages (thiazides→ chlorothiazide, metolazone)

what are causes of diuretic resistance?

- high Na+ intake

- ATN have reduced # of working nephrons

- heavy proteinuria bind loop diuretics in renal tubule

- renal compensation at distal convoluted tubule

what should be avoided in hyperphosphatemia?

calcium products

what causes hypocalcemia in pts on RRT?

citrate anticoag (this is given to prevent clotting on dialysis) (i had this entirely wrong before so pls make note <3)

build up of which electrolytes can occur during RRT?

phosphorus and magnesium → trauma, rhabdo, tumor lysis syndrome

avoid calcium

what are blood and immune complications of CKD?

bleeding diathesis

impaired cell-mediated immunity

platelet dysfunction

what are the endocrine complications of CKD?

hypoglycemia → decreased insulin degradation

what are the GI complications of CKD?

n/v/anorexia

delayed gastric emptying

GI bleed

what are the neuro complications of CKD?

peripheral neuropathies

uremic encephalopathy

what are the initiating factors of CKD?

diabetes (leading cause)

HTN

glomerulonephritis

what are the risk factors for progression of CKD?

DM

HTN

smoking

obesity

proteinuria

what are the causes of iron deficiency in CKD?

- decreased GI uptake

- frequent blood testing

- blood loss from RRT

- increased iron demands from ESAs

why are bone/mineral disorders common in CKD population?

abnormalities in:

- PTH

- calcium

- phosphorus

- Ca x P product

- vit D

- bone turnover

- soft tissue calcifications

how does CKD cause bone abnormalities?

decreased renal fxn → increased phosphate → decreased Ca++

increased PTH → increased Ca++ reabsorption → inc calcium mobilization from bone

decreased vit D activation → increased PTH secretion

what are the uremic symptoms of CKD?

fatigue

weakness

SOB

confusion

N/V

itching

cold intolerance

weight gain

peripheral neuropathies

what are the signs of CKD?

edema

urine output change

foaming urine (proteinuria)

abd distention

why should people with CKD eat low-protein diet?

high in phosphate

if a pt has DM and CKD, what should they be treated with?

ACEIs/ARBs → prevent progression of CKD

what is the nonpharm tx for CKD?

limit protein

limit Na+

smoking cessation

exercise

what is the first line tx for HTN with CKD if a pt has DM?

ACEI/ARBs

target BP = <140/90

what should be used to treat anemia in CKD patients with Hb between 9 and 10?

erythropoietin stimulating agents (ESAs) → epoetin alfa, darbepoetin alfa

always give iron

what is the BBW for ESAs?

risk for stroke, MI, VTE, death d/t increased viscosity of blood → higher risk for clot

also inc risk for some cancers

which iron drugs can be used to treat anemia in CKD?

oral: ferrous sulfate, ferrous gluconate, ferrous fumarate

IV: iron dextran, sodium ferric gluconate, iron sucrose, ferumoxytol

what are the ADR of iron?

GI → constipation, nausea, abd cramping, black stool

IV formulations specific→ allergic rxn, hypotension/dizzines/HA from fast infusion, arthralgia, arthritis

who is more likely to need IV iron therapy?

RRT pts

how often should iron status and Hb be monitored while on ESA therapy?

iron : q 3 months OR monthly when titrating dose/initiating therapy

Hb: q 3 months OR monthly in RRT pts

what are the nonpharm tx for CKD related mineral/bone disorders?

1st → dietary phosphate restriction (meat, dairy, nuts, peanut butter, cola, beer)

- dialysis

- parathyroidectomy

which drugs are phosphate binders, used for tx of CKD related mineral and bone disorders?

calcium based better in early CKD when pts are hypocalcemic → calcium carbonate (tums)

sevelamer

aluminum not used anymore

what are the ADR of phosphate binders?

GI → constipation, n/v, abd pain

hypercalcemia

alum tox (CNS tox, worsen anemia)

what are the drug/food interactions of phosphate?

calcium salts bind many oral meds → iron, zinc, FQs

what vitamin D therapy is used in CKD mineral/bone disorders?

- ergocalciferol/cholecalciferol → must be converted in kidney

- calcitriol → leads to hyperphosphatemia and hypercalcemia

- paracalcitol → doesn't increase Ca and P absorption

- cinacalcet (sensipar)→ sensitizes PTH to effects of calcium

Your patient with CKD has Vit D deficiency. Labs show elevated phosphate and calcium. what is the appropriate tx?

paracalcitol → doesn't increase Ca and P

how does drug induced kidney disease (DIKD) typically manifest?

decline in GFR is MC

rise in SCr and BUN

which drugs can causes acute tubular necrosis?

aminoglycosides***

contrast media

cisplatin/carboplatin

amphotericin B

foscarnet

why do aminoglycosides cause acute tubular necrosis?

d/t high drug concentration within proximal tubular epithelial cells → generation of reactive O2 species damaging mitochondria

what are the RF for acute tubular necrosis caused by aminoglycosides?

- large total dose

- prolonged tx

- trough concentrations >2 mcg

- concurrent nephrotoxins (NSAIDs)

how does contrast media cause acute tubular necrosis?

renal ischemia and direct cellular toxicity → 50% reduction in renal blood flow for several hours may be evidence → leads to increased renal concentrations

how can you prevent acute tubular necrosis d/t contrast media?

- minimize dose

- use non-iodinated

- use low or iso-osmolar contrast agents

- avoid concurrent nephrotoxin

- initiate isotonic crystalloids 12 hrs prior to contrast

- sodium bicarb

- Mucomyst

how does cisplatin cause acute tubular necrosis?

drug accumulation in proximal tubular cells → induce cell damage

decreased urine concentration ability → polyuria, decreased GFR, electrolyte wasting

what can be done to prevent cisplatin nephrotoxicity?

- dose reduction/decreased frequency

- avoid nephrotoxins

- vigorous hydration NS

- amifostine (Ethyol)

how does Amifostine prevent cisplatin nephrotoxicity?

chelates cisplatin in normal cells → reserved for high risk pts

give 30 mins before cisplain

ADR = hypotension, nausea, fatiguq

how does amphotericin B cause acute tubular necrosis?

direct tubular cell damage → interacts with ergosterol in cell membrane → afferent arteriolar vasoconstriction → decreased GFR

how can amphotericin B nephrotoxicity be prevented?

liposomal formation (AmBisome)→ deliver drug to site and limit renal interaction ($$$)

adequate hydration

longer infusion times

how is tumor lysis syndrome prevented?

hydration and allopurinol

how does normal saline effect water homeostasis?

no net shift in ICF or ECF

how does hypertonic solution (>0.9%) affect water homeostasis?

decrease in ICF → increase in ECF

give in cerebral edema

how does hypotonic solution (<0.9%) affect water homeostasis?

increase in ICF → decrease in ECF

what is the action of ADH?

allows reabsorption of water by making aquaporin channels permeable to water

for every 100 mg/dL increase in glucose, serum Na+ drops ____mEq/L

1.7

what causes hypertonic hyponatremia?

hyperglycemia (MC), mannitol

what causes hypovolemic, hypotonic, hyponatremia?

d/t excess fluid loss → diarrhea, vomiting, diuretics

common with thiazides

which drug common causes hypovolemic, hypotonic, hyponatremia?

thiazides

what most commonly causes euvolemic hypotonic hyponatremia?

SIADH

can also be drug-induced, increased sensitivity to ADH (don't need to know specific drugs)

what causes hypervolemic hypotonic hyponatremia?

cirrhosis, CHF, nephrotic syndrome

kidney's sodium and water excretion are impaired → expanded ECF volume and edema but decreased effective arterial blood volume → sodium retention and further volume expansion/edema

symptoms of hyponatremia are primarily ___________

neurologic → severity depends on magnitude and rapidity of onset

what can occur with too quick correction of hyponatremia?

water rushes out of brain cells → osmotic demyelination aka central pontine myelinolysis → hyperreflexia, para/quadriparesis, parkinsonism, pseudobulbar palsy, locked-in syndrome, death

what is the treatment for hypovolemic hyponatremia?

normal saline (0.9%)

what is the tx for euvolemic and hypervolemic hyponatremia?

water restriction, demeclocycline, AVP receptor antagonists, or NS + loop diuretic

what can be used to manage sx of severe hyponatremia?

concentrated NaCl

what is the tx for acute/severely symptomatic hypotonic hyponatremia?

3% NaCl or 0.9% NaCl

loops can be used to prevent fluid overload

how do you determine sodium chloride infusion regimen?

change in Na+ = (NaIV-NaS)/(TBW-VolIV)

don't correct more than ____ mEq/L in the first 24 hrs

12***

risk of central pontine myelinolysis

what is the tx for SIADH?

- restrict water and correct underlying cause

- sodium chloride tablets and/or loop diuretic → increases solute intake and augments kidney water excretion

- demeclocycline

how is demeclocycline used for tx of SIADH?

inhibits tubular AVP activity → induced DI

takes 3-6 dyas to work

who should demeclocycline NOT be used in?

pts iwth liver dz or compromised fluid intake → risk for renal tubular tox and AKI

CI in pts <8 or preg

what causes hypovolemic, euvolemic, hypervolemic hypernatremia?

hypo = renal, diuretic use, post-op diuresis

eu = DI, primary polydipsia

hyper = sodium overload

what are the causes of central DI?

hypodipsia

neurosurg

head trauma

CNS cancer

EtOH (breaking the seal

what are the causes of nephrogenic DI?

cidofovir

lithium

ampho B

demeclocycline

Vaptans

what can occur in rapid correction of hypernatremia?

cerebral edema, seizures, death

what is the tx for hypovolemic hypernatremia?

0.9% NaCl

don't exceed 10-12 mEq/L/day

what is the tx for central DI?

desmopressin

high risk of water intoxication and excess water retention → monitor for hyponatremia and hypovolemia

what is the tx for nephrogenic DI?

- discontinue offending agent

- electrolyte correction

- induce mild ECF deficit w/ thiazide and salt restriction

- indomethacin

what is the tx for sodium overload?

limit sodium intake

loop diuretics

D5W