Pharm E3- Nephro

What kind of kidney injury?

• decreased perfusion w/ undamaged parenchyma tissue

• decreased intravascular volume

  • GI losses, hemorrhage, dehydration, burns, diuretics

• systemic vasodilation

  • sepsis

• hypoperfusion w/o hypotension

  • RAO

• can progress to intrinsic (hypoxia)

Prerenal

What kind of kidney injury?

• structural damage to kidney

• ex- ischemic or toxic insult

Intrinsic

What kind of kidney injury?

• obstruction of urine flow downstream of kidney

Postrenal

What medications can cause functional prerenal AKI?

NSAIDs, ACEis, ARBs, vasopressors (NE, EPI)

What kind of AKI would volume depletion (hemorrhage, GI or renal losses, etc)?

Prerenal

What kind of AKI would decreased effective circulatory blood volume cause (decreased CO, PAH, sepsis, etc)?

Prerenal

What induces afferent arteriole dilation?

prostaglandins (blocked by NSAIDs)

What induces efferent arteriole constriction?

angiotensin II (blocked by ACEIs)

What is the MCC of intrinsic AKI?

ATN

What can cause ATN?

renal ischemia from prolonged prerenal state, myoglobulin (rhabdo, statins), hemoglobin, uric acid (gout, TLS), contrast, aminoglycosides

What can cause postrenal AKI?

bladder outlet obstruction (BPH, prostatic cancer), oxalate crystal deposition from drugs (ethylene glycol), drugs with poor urine solubility (acyclovir, MTX), chemo induced TLS

How can AKI be prevented?

Hydration (best), maintain adequate fluid intake (2L/day) & IVFs before surgery/contrast use, loop diuretics, vasodilators, antioxidants

Which IVFs are based off salts & recommended for intravascular volume expansion (ex- NS, LR)?

Crystalloids

Which IVFs are starch/protein based, more expensive, & have the risk of causing renal dysfunction (ex- hetastarch, albumin)

Colloids

Why is 0.9% NaCl normal / isotonic?

The amount of sodium & chloride (154 mEq each) and the osmolality (308) are close to human values → maintains eunatremia, MC used to fill intravascular space

When is it best to use loop diuretics?

Volume overloaded states like CHF or edema

How do loop diuretics work to prevent AKI?

Inc urine flow & flushes debris → prevents tubular obstruction

Inhibits Na/K/Cl co transporter → dec oxygen demand → dec risk ischemic injury

*not found to be helpful

What AEs can be seen when using loop diuretics for AKI prevention?

Ototoxicity (esp if dehydrated), dec intravascular volume

How do vasodilators (Dopamine, Fenoldopam) work to prevent AKI?

Low doses activate DA receptors on kidneys to increase renal blood flow & natriuresis

*not found to be helpful

What can be used as antioxidants to prevent AKI?

Ascorbic acid (vit C) & N-acetylcysteine (mucomyst)

How do antioxidants work to prevent AKI?

Relieve oxidative stress caused by ischemic reperfusion injury

What drug?

• used as a mucolytic, antidote in APAP poisoning, & as an antioxidant to prevent AKI

• high sulfur content → rotten egg smell

• shows some benefit in preventing contrast induced nephropathy

N-acetylcysteine (Mucomyst)

How should dehydration be treated in AKI patients?

Oral fluids if possible, isotonic IVFs if not (20 ml/kg or 1-2 L of NS)

Goals: MAP ≥ 65, urine output ≥ 0.5 ml/kg/hr

Why might septic patients need more NS than normal?

Vasodilation & third spacing of fluids → fluid leaking out of blood vessels into tissues d/t increased gap junctions

What patients might require smaller volumes of isotonic fluids in AKI?

Anuric/oliguric patients (250-500 mL), CHF, pulmonary insufficiency

What fluids should be used in a dehydrated AKI patient with a preexisting acid-base disturbance to avoid the risk of hyperchloremic acidosis caused by large volumes of NS?

0.45% NaCl with Na bicarbonate → half the Na is taken out (Cl follows) & the remainder is filled with Na bicarb instead of (still isotonic)

What are indications for renal replacement therapy (RRT)?

Acid base abnormalities (correct serum pH)

Elyte imbalances (withdraw specific elytes from blood)

Intoxications (ASA overdose, barbital, lithium)

Fluid Overload

Uremia

What drug?

• osmotic diuretic - parental only

• hyper osmotic soln, can draw fluid off of CNS

• treats AKI but also has risk of causing AKI

Mannitol (Osmitrol)

What drug must be warmed and filtered before use because the solution can crystallize out at normal temps and cause an emboli?

Mannitol (Osmitrol)

What drugs are loop diuretics?

Furosemide (Lasix) - MC used

Torsemide (Demadex)

Bumetanide (Bummed)

Ethacrynic acid

What loop diuretic should be used instead of Furosemide (Lasix) in a patient with a sulfa allergy?

Ethacrynic acid

What should be done if loop diuretic resistance develops in an AKI patient?

Switch from PO to parenteral, increase dose, use continues infusion, or use a different agent (thiazide or different loop)

What causes resistance to loop diuretics?

High Na intake limits natriuretic effect, reduced number of working nephrons in ATN pts, heavy proteinuria binds loop diuretics in renal tubule, & renal compensation at DCT

What thiazide diuretics can be used in loop diuretic resistance?

Chlorothiazide (Diuril)

Metolazone (Zaroxolyn) → better for GFR < 20 mL/min

Thiazides lose effect when CrCl < 30 minutes except for which one?

Metolazone (Zaroxolyn)

What diuretics that work at the collecting duct can be used for loop diuretic resistance?

Amiloride, triamterene, spironolactone

What is a concern for patients on RRT if they develop rhabdomyolysis, TLS, or experience trauma?

Causes inc ATP in muscles which increases muscle breakdown and causes phosphate to leak out → phosphate & magnesium are not removed effectively by RRT

What electrolytes does RRT not remove effectively?

Phosphorous & magnesium

*can be in issue in trauma, rhabdomyolysis, or TLS → increases phosphate (avoid calcium bc binds to phosphate & can precipitate out)

Why are patients on RRT at a risk of developing hypocalcemia?

Given citrate anticoagulant → binds to Ca to prevent blood from clotting as it passes through machine & back into patient

*give Ca supplement if concerned

Which would you expect as a complication of CKD - hyperglycemia or hypoglycemia?

Hypoglycemia (insulin is partially eliminated through kidneys → decreased excretion)

Which occurs outside the body and takes longer to complete (~ 4 hrs 3x/week) - hemodialysis (HD) or peritoneal dialysis (PD)?

Hemodialysis

Which is faster & occurs inside the body - hemodialysis (HD) or peritoneal dialysis (PD)?

Peritoneal dialysis

What are nonpharmacologic treatment options for CKD?

Limit protein to 0.8 g/kg/day w/ GFR < 30

Limit Na to < 2 g / day

Exercise & smoking cessation

What meds should be utilized in patients with DM & CKD to prevent further progression of CKD?

ACEis & ARBs

*titrated until GFR drop or elevation in K

When does metformin have to be stopped in a CKD patient with DM?

GFR < 30 ml/min OR

SCr > 1.5 in males or > 1.4 in females

What can metformin cause in a person with poor kidney function?

Lactic acidosis

What meds should be used to treat HTN in a pt with CKD?

1st line: ACEi or ARB; add thiazide if not sufficient

Goals: BP ≤ 140/90 (≤ 130/80 if significant albumin excretion)

What is used to monitor ESA & iron supplementation when treating anemia of CKD?

Hgb

When should erythropoiesis stimulating agents (ESA) be considered in CKD patients?

Hgb between 9-10 g/dL

When should ESAs be discontinued in CKD patients?

Hgb > 10 g/dL (> 11 if on RRT)

What BBW is associated with ESAs?

Death, MI, stroke, VTE (hgb > 13 g/dL → increased blood viscosity)

Inc risk of cancers- breast, NSCL, lymphoid

Why might hgb still be decreasing in a patient on ESA?

Iron not correctly supplemented

What are examples of ESAs?

Epoetin alfa (Epogen, Procrit)

Darbepoetin alfa (Aranesp)

What adverse effects are seen with ESAs?

HTN (bc increased viscosity) & vascular access thrombosis

What dosage form of iron might CKD patients need due to decreased absorption?

Parental

What supplements do CKD need to maintain adequate intake of due to diminished levels from RRT?

Iron, B12, folate

What oral preparations of iron can be given to CKD patients?

Ferrous sulfate

Ferrous gluconate

Ferrous fumarate

What IV preparations of iron can be given to CKD patients?

Iron dextran (DexFerrum)

Sodium ferric gluconate (Ferrlecit)

Iron sucrose (Venofer)

Ferumoxytol (Feraheme)

What SEs can be seen with iron supplementation?

black stools, constipation, abd cramping, N

What SEs are seen with IV preparations of iron?

Allergic rxn, arthralgia, arthritis, & hypotension / dizziness / HAs (limit these w/ slower infusions)

How often does monitoring for CKD patients on iron or ESAs occur?

Iron q3 months while on ESAs (monthly when initiating/titrating)

Hgb q3 months (monthly if on RRT)

*monitor weekly when first initiating treatment

What is the goal Ca x P product in CKD treatment?

< 55

What is the first line management for hyperphosphatemia in CKD patients (non-rx)?

Limit phosphate intake to 800-1000 mg/day

*makes protein supplementation difficult, especially in dialysis pts who require more protein(1.2-1.3 g/kg/day)

What is the treatment option for CKD patients with hyperphosphatemia not responsive to pharmacological therapy?

Parathyroidectomy (dialysis not sufficient)

What foods/drinks are high in phosphate?

Meats, diary, nuts, peanut butter, colas, beer

What agents are calcium based phosphate binders?

Calcium carbonate (Tums, Os-Cal, Caltrate)

Calcium acetate (PhosLo)

What agents are non-calcium based phosphate binders?

Sevelamer carbonate (Renvela)

Lanthanum carbonate (Fosrenol)

Aluminum hydroxide (ALternaGEL)

Which phosphate binder is generally avoided due to risk of aluminum toxicity & is only used for short term therapy in patients not responding to other treatments?

Aluminum hydroxide

What phosphate binders are better in early CKD?

Calcium based agents (pts are likely to be hypocalcemic)

What environment is calcium carbonate more soluble in?

Acidic mediums (give before meals)

How do phosphate binders work to treat hyperphosphatemia in CKD patients?

Bind to phosphate in GI tract so it gets eliminated through feces & not absorbed

What phosphate binder is a nonabsorbable hydrogel that lowers LDL, raises HDL & should be taken with meals?

Sevelamer carbonate

What SEs are seen with phosphate binders?

MC GI (N/V, C, D, abd pain), hypercalcemia, aluminum toxicity (CNS toxicity, worsening anemia), drug/food interactions

If a CKD patient with hyperphosphatemia has an elevated calcium level, which phosphate binder is best to use?

***Test Q

Non Ca based → Sevelamer, lanthanum, aluminum hydroxide

What drug / food interactions may be seen with phosphate binders?

Calcium salts bind oral meds such as iron, zinc, FQs

*separate agents by 1 hr before or 3 hours after other agents

What drug is the active form of vitamin D (1,25-D3) given to CKD patients to suppress PTH secretion & stimulate Ca absorption?

Calcitriol (Rocaltrol)

What can calcitriol (rocaltrol) cause in later stages of CKD?

Hypercalcemia & hyperphosphatemia

What drug is given in later stage CKD patients because it activates PTH receptors but doesn’t increase Ca and phosphate absorption?

Paricalcitol (Zemplar)

What drug sensitizes PTH receptors to the effects of calcium & reduces PTH concentrations?

Cinacalcet (Sensipar)

What drugs cause many cases of DIKD in hospitalized patients?

Abx (aminoglycosides, vancomycin), NSAIDs (afferent arteriole), ACEIs (efferent arteriole), chemotherapeutics, antivirals, antifungals

Decreased urine output (UOP) with progression to HTN & volume overload may be caused by what drugs?

Contrast (CIN), NSAIDs, ACEis

What is the MC presentation of DIKD in the inpatient setting?

DIKD

What agents are most commonly associated with causing ATN?

Aminoglycosides, radiocontrast media, cisplatin, amphotericin B, foscarnet, osmotically active agents (colloids, mannitol)

How do aminoglycosides cause DIKD?

Accumulation w/in proximal tubular epithelial cells → generation of reactive oxygen species w/ cationic charge damaging mitochondria (direct cellular injury)

*measure troughs

What are RF for ATN while on aminoglycosides?

Large total dose, prolonged therapy, trough concentration > 2 mcg/mL, & concurrent nephrotoxins (ex- taking NSAIDs for a fever)

How can ATN be prevented while on aminoglycosides?

Limit other nephrotoxic agents, measure trough levels, once daily dosing to give more time to clear & reduce accumulation

What is the treatment for aminoglycoside induced ATN?

D/C treatment

Which is a concentration dependent killer, only checking troughs to make sure there’s no accumulation of the drug?

• aminoglycosides or vancomycin

Aminoglycosides

Which is a time dependent killer, meaning that troughs have to be kept above MIC & also need to be checked to ensure a toxic amount is not accumulating?

• aminoglycosides or vancomycin

Vancomycin

How does radiographic contrast cause ATN?

High osmolarity → dec renal blood flow for several hours → increased renal concentrations → hypoxic injury / renal ischemia & direct cellular toxicity

What RF are associated with radiographic contrast induced ATN?

Preexisting kidney disease, CrCl < 60, & reduced renal blood flow

How can radiographic contrast induced nephrotoxicity (CIN) be prevented?

Minimize dose, use non-iodinated contrast studies, use low or iso-osmolar agents, avoid concurrent nephrotoxins (d/c NSAIDs),

Isotonic IVFs 3-12 hrs before & continue 6-24 hrs after

Prevent free radical formation w/ sodium bicarbonate (prevent acidotic state) or n-acetylcysteine (antioxidant)

What is the treatment for CIN?

Supportive

What medication is CI to contrast and must be stopped 48 hrs before dye is used because of the risk for lactic acidosis?

Metformin (use insulin instead)

How does cisplatin (used for solid tumors) cause ATN?

Drug accumulation in proximal tubular epithelial cells → cell damage & apoptosis → impaired tubular reabsorption, dec urine concentrating ability (dilute)

How can cisplatin induced ATN be prevented?

Reduce dose & frequency, avoid concurrent nephrotoxins,

Vigorous hydration w/ NS 12-24 hrs before & 2-3 days after (goal urine flow 3-4 L/day)

Amifostine (Ethyol) 30 min before (if high risk)

What drug prevents ATN by binding to cisplatin (chelate) to prevent interaction in normal cells, given 30 minutes before treatment & is reserved for high risk patients?

Amifostine (Ethyol)

What SEs are seen with amifostine?

Hypotension, N, fatigue

What is the treatment for cisplatin nephrotoxicity?

Supportive, RRT, electrolyte replacement; generally partially reversible

What anti fungal agent causes delayed onset ATN presenting as renal tubular K/Na/Mg wasting & renal tubular acidosis?

Amphotericin B