Kidney Disorders: Key Concepts, Acute Kidney Injury and Acute Kidney Conditions Teresa O’Sullivan,...

Kidney Disorders: Key Concepts, Acute Kidney Injury and Acute Kidney

Conditions

Teresa O’Sullivan, PharmD, BCPS

University of Washington School of Pharmacy

2

A short digression…

My therapeutics presentation format• Slides will emphasize most important points in lecture

(useful for exam prep) and have pictures• Handouts contain all slide info but in greater detail +

summarize and reference studies + provide schematics/algorithms not in slides + have practice cases; use to clarify slide info (for exam prep) but probably most useful for APPEs

Back to kidneys…

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Learning Goal

To understand what drugs do to the kidney and what the kidney does to

drugs.

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Prep for this topic

• Review anatomy/physiology of kidney, including the kidney’s role in acid-base equilibrium and the effects of kidney-related hormones.

• Think about which laboratory parameters can help you assess kidneys (we’ll do an exercise at the end of today’s session, so jot down thoughts during the body of the lecture).

• Think about how blood pressure is controlled in the body. What medications used for blood pressure control affect the kidney? How? (We will do a short exercise on this in Monday’s lecture, but think about it before then.)

• Expect a test question on the material in Part 1.

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Key Concepts: Significance of Kidney Failure

Physiology fluid excretion volume overload O2

delivery end-organ hypoxia N ATP formation brain function H+ enzyme function cell function

impairment K+ cardiac function O2 delivery

end-organ hypoxia

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Numbers (see handout)• Incidence • Prevalence • Mortality • Prognosis

– admitted with AKI: 3% discharged w/ESRD, 13% die; in year after admission: 48% readmitted, 28% will have 2nd AKI episode, 34% will die

– admitted with mild CKD: 46% mod CKD, 25% SNF

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Numbers• Co-morbidities common in CKD patients

– diabetes 12% non-CKD versus 39% stage 4/5 CKD– hypertension 49% non-CKD versus 82% stage 4/5 CKD

• Albuminuria strongly related to diabetes and HTN GFR partially (~50%) explained by diabetes, HTN,

BMI JAMA 2007;298:2038-47


• Risk increases with increasing age• Race

– Increased risk in African-Americans– Some Hispanic races (e.g., Puerto Rico) have

increased risk, but others (Mexicans, South Americans) have same rate as whites

– Asians have same rate as whites

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Dollars– > $65,000/ESKD pt/yr– ~$22,000-25,000/CKD stage 5 pt/yr– > $42 billion spent in US on CKD, $20 billion

spent on ESKD in 2005– accounts for 6.4% of Medicare expenditures but

0.2% of population

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Key Concepts in Kidney Disease: Creatinine, BUN

• Creatinine– muscle protein breakdown byproduct; consider pt

muscle mass

• BUN– general protein breakdown byproduct; consider protein

intake, liver function

• discrepancies between SCr and BUN – volume depletion (urea reabsorbed w/water)

– protein catabolism rate (concomitant ‘roids?)

– ESLD

Key Concepts in Kidney Disease: Cystatin C

• Small protein produced in most cells of the body and secreted at a constant rate

• Filtered through glomerulus; not reabsorbed back into the bloodstream; not secreted

• Earlier predictor of AKI in ICU compared to SCr (two studies); when combined with SCr and urine Cr:albumin improves prediction of ESKD and all-cause mortality (one study)

• Approximate serum/plasma ranges in handout11

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Appendix I

•Determining body weight– equations for IBW, AdjBW, NBW (no body weight), BSA, and

LBW provided

– results from two studies comparing eCrCl and mCrCl provided; little agreement seen

•Special populations– elderly: for eCrCl do not round low SCr up to 0.8 or 1.0; CKD-

EPI 2009 > MDRD

– children: Schwartz 2009 Cr good but Cr-CysC even more accurate

– obese: summaries of 2 studies in handout; no consensus; use S-C until better evidence available

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Appendix I

•ICU patients– Estimation equations not reliable; use mCrCl

•Ethnic origin– Some investigators suggest modifying eGFR estimates in various

Asian populations (smaller muscle mass); handout has eqns

– Several eGFR studies in Asians show no adjustment needed

•Drug dosing and equations– Big push by non-pharmacists to use eGFR equations for drug dosing;

multiply eGFR value by patient BSA to get mL/min

– All renal dosing recommendations developed using eCrCl; literature regarding concordance of dosing in handout; not enough evidence yet

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Key Concepts in Kidney Disease: Calculations

• 23yo, 128-lb, 5'5" female; SCr 2.1 mg/dL and you need to check kidney dosing of her medications

• What is this patient’s eCrCl?

• Which body weight did you use and why?

• What would you do if the dosing guideline specified eCrCl in mL/min/1.73 m2?

• What is this patient's eGFR?

• Which equation did you choose and why?

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Key Concepts in Kidney Disease: Urine Output

• What’s a “normal” UO?

• Acute decrease

– anuric vs. oliguric vs. non-oliguric

• Monitor I/O with BP, HR, weight, lung sounds, edema to get idea of volume status

– What does “volume status” mean?

– What can each listed parameter (BP, HR, weight, lung sounds, edema) tell you about volume status?

– Note serum Na not on this list. Why not?

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Key Concepts in Kidney Disease: Urine Output

• Today pt complains of fatigue, weighs 138 lb, has 1-2+ pitting edema, and estimates she produced about 1/2 cup of urine in the past 8 hours.

• Is this patient anuric, oliguric, or non-oliguric?• What is the importance of determining anuric,

oliguric, or non-oliguric status?• What might be some problems

with using the data we have to determine urine output?

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Key Concepts in Kidney Disease: Other Markers

• FeNa (<1%=pre-renal;>1%=ATN)• urine osmolality/specific gravity (for prerenal

azotemia, SIADH, loss of concentrating ability, presence of some toxins)

• urinalysis: pH; presence of RBCs, WBCs, bacteria; glucose, ketones; protein; sediment: casts, crystals

• anion gap [Na-(Cl+HCO3)]; >12 = other organic acids present; useful for potential poisonings

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Key Concepts in Kidney Disease: Descriptions

Traditional descriptions still occasionally used • acute renal failure (ARF)

– considered reversible; some define as 0.5 mg/dL acute in SCr, but UO equally important

• chronic renal insufficiency (CRI)– 25 or 30 - 50 mL/min

• chronic renal failure (CRF) – < 25 or 30 mL/min but not on dialysis

• end-stage renal disease (ESRD): on dialysis

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Key Concepts in Kidney Disease: Descriptions

National Kidney Foundation (NKF) Kidney Disease Outcome Quality Initiative (K-DOQI) first guidelines in 2002

• use “kidney” instead of “renal”• replace CRI and CRF with CKD

• CKD = identifiable kidney damage or GFR ≤ 60 mL/min/1.73m2 ≥ 3 months

– CKD staging - see descriptions in handout. Note all GFRs standardized to 1.73 m2

• Updated guidelines released as evidence reviewed, evaluated, summarized, and published

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Acute Kidney Injury

• Formerly called acute renal failure (ARF) and defined as acute UO, SCr (± 0.5 mg/dL)

• There are now two classification systems: RIFLE (risk, injury, failure, loss, ESKD) and AKIN (acute kidney injury network)

• For each, need to know SCr and UO changes over a given time period, pt weight, and volume status.

• Patients should be classified according to criterion that places them in the worst category.

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Acute Kidney InjuryRIFLE

category SCR/GFR criteria urine output

risk SCr by 50% or GFR by 25% < 0.5 mL/kg/hr for ≥ 6 hrs

injury SCr doubled or GFR by 50% < 0.5 mL/kg/hr for ≥ 12 hrs

failure SCr tripled or ≥ 4 mg/dL and by ≥ 0.5 mg/dL; GFR > 75%

anuria ≥ 12 hrs

loss RRT > 4 wks

ESKD RRT > 3 mos

Acute Kidney Injury

RIFLE (developed by Acute Dialysis Quality Initiative)

• considers changes in kidney function over a 1-week period

• validated to show risk of death as category worsens

• one study showed RIFLE slightly better than AKIN for post-CABG pts in predicting outcome

• limitations: – needs baseline which may not be available (75-100 mL/min)– SCr and UO markers are not congruent; SCr criteria more highly

correlated with risk of death than UO criteria– GFR calculated using MDRD, which is not validated in the acute

setting

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Acute Kidney InjuryAKIN

stage SCr urine output

1 SCr by ≥ 0.3 mg/dL or 50-100% from baseline

< 0.5 mL/kg/hr for ≥ 6 hrs

2 SCr 2-3-fold < 0.5 mL/kg/hr for ≥ 12 hrs

3 SCr > 3-fold and by > 0.5 mg/dL from baseline or pt needs RRT

< 0.3 mL/kg/hr for ≥ 24 hours or anuria ≥ 12 hrs

Acute Kidney InjuryAKIN• 48-hour timeframe, which limits application in the slowly

deteriorating patient• one study of patients with septic shock found AKIN predicted

AKI slightly better than RIFLE, but didn't predict 28-day mortality

• another study of contrast-induced kidney injury found AKIN predicted AKI slightly better than RIFLE

Both methods• the volume overloaded patient will have a diluted SCr, which

may lead to underestimation of status using either scale 25

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Acute Kidney Injury

• Today pt c/o fatigue, mild edema. 138 lb, 2+ pitting edema, estimates 1 cup urine in past 8 hours; SCr today 12.4 mg/dL

• Category per RIFLE and stage per AKIN? Identify and explain.

• What are some problems with using these staging equations for her?

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Acute Kidney Injury

• AKI risk factors and significance

– mortality rate negligible with < 0.5 increase in SCr; 25% for value 1.0-1.9; 35% for value 2.0-2.9, 70% for value 3.0-3.9

– mortality rate for oliguric AKI ~2x non-oliguric AKI

– conditions associated w/ risk outlined in handout

– risk factors for AKI: MSOF, older age, severe infection, post-op, trauma, CV events, liver disease

• AKI ≠ acute kidney conditions

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Acute Kidney Conditions

• Selected acute kidney conditions outlined in appendix II. Will expand in next few slides on– nephrotic syndrome

– glomerulonephritis

– diabetes insipidus

– nephrolithiasis

– pyelonephritis

– renal cell carcinoma

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Nephrotic Syndrome

“humungous protein excretion”• proteinuria - 3+ g/day; mostly as albumin

– can include excretion of antithrombin III hypercoagulability in 20-40% pts

• hypoalbuminemia effective plasma circulation; liver response: lipoprotein production hyperlipidemia

plasma circulation RAA activation Na retention generalized edema

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Nephrotic Syndrome• A rapid onset and toxic symptoms differentiate this

from other causes of proteinuria.• Membranous nephropathy. More common in adults.

Usually idiopathic. Steroids not very effective.• Minimal change disease (a.k.a. nil lesion). More

common in kids. Very responsive to steroids.• Focal segmental glomerulonephritis. Less common

than other two. Poor prognosis. – A slow-onset version of this syndrome may play

a role in progression of CKD.

Nephritis• Nephritic conditions: most are associated with immune

complex deposition on glomerulus and include other systemic symptoms

• Symptoms

– proteinuria (not humungous), hematuria, hypertension in flare or advanced state

• Lupus nephritis (75% SLE pts) and IgA nephropathy two most common forms

• Treatment: immunosuppressant/cytotoxic agents for flares, BP & lipid control for stable disease

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Diabetes Insipidus

• Huge dilute urine production; worry: volume depletion

• cause: hereditary ADH lack or ADH resistance due to drugs. Lithium main drug culprit: blocks water reabsorption in the collecting ducts.

• amiloride closes lithium-affected Na channels; nasally-administered desmopressin used for hereditary DI

• 50yo male on quetiapine & lithium presents w/twitching, confusion, SNa & K; tx’d w/NS+K. After admit changes to to SNa & K w/UO of 30L/day. What probably led to his initial presentationand what should be done now?

Diabetes Insipidis CaseInitial presentation of “twitching” quetiapine EPS versus lithium toxicity. Clue: Na, K; quetiapine dry mouth, lithium polydipsia. What to do?

1. Na intake but match UO (1/4 NS @ 1500 mL/hr)

2. Hold thirst-inducing meds (quetiapine, lithium)

3. Give amiloride to counteract lithium effect

4. protein intake ( urea production urine osmolality)

5. give thiazide (counteracts Li-induced AQP2 remodeling; effect: UO by 30-50%, UA loss)

6. give NSAID (in Na load, will afferent vasodilation UO ; normally a worry but in this situation is a benefit)

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Nephrolithiasis

• Kidney stones more common in men (4x) than women

• Ca oxalate (75%), UA (10%), Mg (10%)

• Probably genetic predisposition

• Symptoms: renal colic(colic = extreme pain), N/V

• Therapy: hydration, NSAIDs, waiting for stones to pass; lithotripsy if stones linger

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Nephrolithiasis• Prevention = dietary alterations, based on stone

composition – CaOx dietary oxalate: black tea (sorry iced tea

lovers!), nuts, chocolate, spinach-y foods; white, green, oolong teas have low oxalate; citrus Ox retention – lemon in tea helpful?

– CaOx dietary Ca (black tea w/milk OK)– urinary Ca excretion: if use thiazide; if use loop– UA meat intake

Pyelonephritis

• Symptoms: fever, flank pain, N/V; signs: pyruria ± hematuria

• E. coli 70-80%; K pneumoniae, S sapropiticus• Fluoroquinolones good empiric treatment

(check resistance patterns); parenteral therapy needed if complicating factors (abscess, obstruction, immunosuppression, diabetes)

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Renal Cell Carcinoma

• Comprises the majority of kidney cancers• Incidence in past 20 years, mainly due to

accidental discovery on imaging done for another reason

• Most patients asymptomatic until late stages; hematuria, abdominal mass, pain, wt loss poor prognostic signs; anemia, fever, hypercalcemia, erythrocytosis may also occur

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Renal Cell Carcinoma• Stage I good prognosis w/laparoscopic surgery• Stage II reasonable prognosis with kidney-sparing

surgery• Stage III radical nephrectomy; prognosis not great• Stage IV median survival < 2 yrs; treat with

nephrectomy +– sunitinib or sorafenib (VEGF receptor antagonists)

– temsirolimus or everolimus (mToR pathway antagonists)

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Acute Kidney Injury

• Traditional mechanistic classifications:– pre-renal azotemia (results in inadequate perfusion

of kidneys): volume depletion, CO, renal artery obstruction

– intrinsic renal disease: direct nephron damage formerly called acute tubular necrosis (ATN), acute interstitial nephritis (AIN), renal tubular acidosis (RTA)

– obstructive nephropathy (“post-renal azotemia”)

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Acute Kidney Injury• Traditional classifications not as useful for the

main question pharmacists must consider: – Is this case of AKI drug-induced or drug-

influenced? • Other questions pharmacists need to answer:

– How should AKI be treated? – How can AKI be prevented? – How should drugs be dosed in AKI?

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Acute Kidney Injury

• Mechanistic classification better distinguishes causes and treatments of drug-induced AKI:– ischemia– inflammation– sclerosis

• All can lead to cell necrosis (ATN) • Nephron lost when extensive or chronic necrosis

results in fibrosis of tubule epithelial cells.

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Kidney Ischemia

• What is happening here?

• What might be the cellular result of what is happening?

• What would the clinical consequencesbe?

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Kidney Ischemia: Diuretics

• Mxn: renal perfusion 2° hypovolemia

• Clue to excessive diuresis: alkalosis (check Cl, CO2 on chem-7)

• Other causes of volume depletion: vomiting, diarrhea, inadequate fluid intake, excessive sweating

• Volume depletion potentiates every other nephrotoxic event, so diuretic use often a contributor to AKI but rarely the sole cause

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Kidney Ischemia: Diuretics

What is “diuretic resistance?”• Persistent S/S volume overload despite adequate dose (one

definition: 80mg furosemide) of diuretic

• Independently associated with mortality

• Most frequently occurs in CHF, advanced CKD

• Why this occurs in CKD (overhead)

• Not a cause of diuretic failure in AKI patients (one reason why studies have not shown mortality benefit w/use of diuretics), so adding thiazide diuretic will not potentiate loop tx in AKF

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Kidney Ischemia: NSAIDs

• PGs dilate afferent arteriole and medullary vasculature• Don’t strongly affect renal blood flow in healthy pts, so NSAIDs

normally not detrimental to kidneys• Significant edema (CHF, cirrhosis) causing relative volume

depletion will COX-2 receptor expression, risk of NSAID-induced AKI

• Volume-depletion via other mechanisms (e.g., diuretics, sweating) will potentiate NSAID-induced kidney injury

• TGF schematics (Appendix III) show role of COX-2, PGE2, EP2 on O2 delivery & demand;overview of TGF useful at this point

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Tubuloglomerular Feedback (TGF)

Cl in macula densa activates TGF

• TGF activation O2 needs, O2 delivery, so increases risk of nephron damage

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Renovascular Hypertension

• TGF of low Cl renin angiotensinogen angiotensin I angiotensin II aldosterone vasoconstriction, Na & water retention HTN

renin secretion (genetics?) and low-salt diet potentiates renovascular hypertension

• Na loading (which is really Cl loading) turns TGF “off”

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Kidney Ischemia: ACEIs

• ACEIs normally beneficial for kidneys because they block TGF.

• A transient rise in SCr after ACEI initiation common. Don’t worry unless > 0.5 mg/dL.

• ACEIs renally problematic in two situations: volume depletion and severe RAS– RAS can be caused by either fibromuscular

dysplasia or atherosclerosis; treatment and prognosis different for each

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Renal Artery Stenosis (RAS)

Fibromuscular Dysplasia

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Renal Artery Stenosis (RAS)

Atherosclerosis

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Kidney Ischemia: ACEIs

• RAS causes renovascular hypertension via renin secretion

• ACEIs beneficial because oppose effects of renin, except when renal artery lumen diameter by 70%, efferent arteriolar vasodilation results in GFP

• Clinical results: UO, SCr (i.e., AKF)• Risk of AKI in volume depletion (risk w/diuretic use)

and NSAID use. Patients on ACEI + either, or especially all 3, should be counseled to report any in UO

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Kidney Ischemia: Cyclosporine

• Mxn not well-defined; probably multifactorial, but certainly includes ischemia

• Most patients will experience SCr after CSA initiation– this dose-related and reversible

– sometimes accompanied by hand tremour and edema CSA conc, reduce dose by 20%, re SCr and hand

tremour in 3 days

• Renal ischemia from chronic use will cause ESKD in 5-10% of users

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Kidney Ischemia: Amphotericin B

• Causes renal ischemia by both O2 delv, O2 use; depletes K and Mg

• Dose-dependent damage• NaCl loading seems to ameliorate damage• Liposomal formulations decrease but don’t

eliminate risk of kidney damage• No direct comparison of liposomal AmB versus

Na loading. Anyone up to do this study?

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Kidney Ischemia: CIN

• Patients with damaged kidneys (eGFR < 50 mL/min/1.73m2) at highest risk of contrast-induced nephrotoxicity (CIN)

• Newer non-ionic contrast agents (e.g., iohexol) have lower risk potential but are cost and viscosity (which distribution time, so limits use)

• NS loading may damage; 12 hrs before & after procedure

• Oral acetylcysteine beneficial; capsules available; has benefit on proxy endpoints, but recent trial showed no mortality or morbidity benefit over saline loading

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Treating Ischemic AKI

Here’s what you check to help you determine tx: • BP• HR• weight• BUN:Cr ratio• signs of 3rd-spacing (edema, crackles) which can

lead to intravascular volume depletion• drug list (look for potential offenders)• These are also things important to monitor once tx

initiated.

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Treating Ischemic AKI

Volume depletion • BP (worrisome if SBP by ≥ 30)• HR (worrisome if postural HR > 30)• Weight loss (2-3% mild, 3-5% moderate; severe ≥

5%); weight loss won't occur with relative volume depletion because fluid staying in body – just not in vasculature

• BUN:Cr ratio (> 15/20:1)• Symptoms: lightheadedness, particularly when

patient goes from prone to standing position

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Treating Ischemic AKIReplacement options (appendix IV):• broth, NS (salt + water)• fruit juice, D5W (sugar + water)• D5-(?)NS (salt + sugar)• Sports drink, D5-(?)NS + additives: (salt + sugar

+ electrolytes)

Volume depletion (vs dehydration—difference?)• isotonic (diarrhea, vomiting, fluid intake)• hypertonic (fever, free water intake) • hypotonic (overdiuresis, water intoxication)

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Treating AKI 2° to Volume Depletion

• mild vol depletion: oral water AOC; broth if diuretics; juice or sports drink if dehydration (low intake)

• mod-severe vol depletion: NS 70-150 mL/hr until urine flow re-establishes; D5-1/2 NS once BP normalizes

• be conservative on dose/rate if prior kidney disease or small person or Na-sensitive comorbidity (e.g., CHF)

• no diuretics until volume-replete (normal BP and HR)

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Treating AKI: The Controversy About Diuretics

Diuretics in AKI• Theoretically should be useful: loops PGE2

production ( O2 delivery), block active transport in TALH ( O2 consumption)

• Evidence of usefulness for diuresis, but not for overall clinical improvement

• Evidence ranges from not detrimental (Crit Care Med 2004;32:1669) to detrimental (JAMA 2002;288:2547)

• BP has to be ≥ normal range before using

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AKI: Inflammation

• Usually slower onset (weeks) than AKI due to ischemia (days)

• Sites of inflammation: glomerulus, interstitium, tubular cells

• Signs: fever, fatigue, protein and blood in urine, eosinophilia, MP rash

• Can be drug-induced.

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AKI: Inflammation

• drug-induced glomerulonephritis: extremely rare; described with gold, penicillamine

• interstitial nephritis: rare, but more frequently drug-induced; antibiotics (rifampin!), analgesics most frequent cause; has been reported w/PPIs

• crystalluria: acyclovir, indinavir, MTX, SMX; volume depletion potentiates

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Treating Inflammatory AKI

• Discontinue agent and hydrate; hydration particularly important if inflammation due to crystalluria

• Corticosteroids: efficacy debatable

• Use diuretics cautiously - avoid if BP

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Tubular Cell Sclerosis

• Direct damage of tubular cell elements, via disruption of cell organelles or interference with enzyme function

• Signs: subclinical; gradual rise in SCr, BUN; UA will have lots of epithelial cells, sometimes protein, WBCs

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Tubular Cell Sclerosis: AGs

• damage from aminoglycosides not generally seen until after at least 7 days of therapy

• mechanisms postulated to be interference of lysosome integrity

• risk factors besides length of therapy are dose, recent-ness of prior AG therapy, pre-existing renal disease

• check trough, SCr q 3 days after 1 week of tx in high-risk patients

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Tubular Cell Sclerosis: Gadolinium

• A trivalent cation used in MRI imaging.• Pre-existing severe kidney disease risk of

nephrogenic systemic fibrosis; incidence is very rarebut gadolinium products contraindicated in ESKD or AKI.

• S/S: progressive painful skin tightening and textural changes, joint contractures; fibrosis of muscled organs (heart, lungs, diaphragm, skeletal muscle, liver, GU, CNS). Gadolinium found in all tested tissues at autopsy.

• Standard tx for autoimmune disorders ineffective. See NEJM 2008;358:827-38 for more information about this condition.

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Tubular Cell Sclerosis: Platins

• 20-40% of cisplatin patients will have SCr with moderate doses, longer therapy; only seen with doses carboplatin

• Mechanism unclear

• Mg wasting common; replace if low

• aggressive pre-, peri-, post-infusion hydration (NS) is best preventative

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Tubular Cell Sclerosis: Cyclophosphamide/Ifosfamid

e• can cause hemorrhagic cystitis

• signs: ranges from + RBCs to profuse blood in urine

• aggressive hydration (NS), mesna is protective

• limit total dose of ifosfamide to risk of sclerosive damage to kidney tubular cells

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Tubular Cell Sclerosis: Vancomycin

• Vancomycin’s role as a nephrotoxin unclear • Case reports of nephrotoxicity involve inadvertantly

doubled doses ( troughs) or concomitant administration of AGs

• No mxn found despite >20 years of research; postulations include oxidative stress in proximal tubules

• One p’econ study found monitoring only cost-effective in oncology, ICU pts and AG+vanco therapy

• Vancomycin has caused AIN

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Acute Tumour Lysis Syndrome (ATLS)

• Occurs with heme cancers, large tumour burden, radiation therapy, ‘roid therapy; rapid tumour lysis = amts uric acid

• predictable sx onset:– day 1-2 K, P– day 2-3 hyperuricemia, crystalluria– kidney failure day 3

• NS 200 mL/hr until hydrated, then D5-0.45NS to UO of 150-200mL/hr; IV allopurinol, Na bicarb useful

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Treating Sclerotic AKI

• Removing offending agent and hydrating is almost only therapy

• Avoid adjacent re-encounter with sclerotic drugs as they can take an extended length of time to clear from body

• No evidence diuretics useful for treating sclerotic damage

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Obstruction-Related AKI

• Flow of urine obstructed by stones, casts, tumour, prostate, chronic inflammation; can back up into distal tubule, activating TGF

• UA clue to obstructive cause - look for casts, crystals, WBCs, RBCs in UA; renal ultrasound used to visualize

• Some obstructive problems will need surgical therapy. An example…

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Obstruction-related AKI

“Well Mr. Osborne, it may not be kidney stones after all.”

Gary Larson "The Far Side"

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Dosing Meds in AKI

• Dr. Bauer has covered general principles of dosing and drug clearance in CKD.

• There is a schematic of differences between and info about CRRT and HD in Appendix V

• Paucity of information for how to dose meds in patients with AKI.

• Do not rehydrate volume-depleted AKI patients too rapidly – easy to go from volume depletion to overload if kidneys have shut down.

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Dosing Meds in AKI

• Sepsis will increase vascular permeability and rehydration may lower oncotic pressure and stimulate third spacing. Initial doses of hydrophilic drugs (e.g., antibiotics) may need to be in order to achieve adequate serum concentration. Not a problem for lipophilic drugs.

• As kidney function improves, dosing frequency should change, moving toward usual frequency.

Review Worksheet

• See page 25 of handout

• What is every monitoring parameter you can think of that might give you useful information about patients with kidney disease? Consider physical exam, laboratory, and data derived from other sources.

• What is the difference between volume depletion and dehydration? Think about pathophys, common causes, signs/symptoms, and treatment.

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Thinking about AKI

• Compare and contrast acute and chronic renal failure.

• What are examples of – 3 main locations of kidney damage (where does

damage usually occur in acute versus chronic disease?)

– 3 categories of urine output– 3 mechanisms of renal damage

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Treating AKI

• What factors will you examine to determine whether patient has acute versus chronic event?

• What factors will help you determine appropriate treatment?

• Plan includes drug, dose, route, frequency, ± duration; efficacy monitoring, toxicity monitoring, follow-up; plan must also include hold or discontinuation of drug if problem drug-induced

Determining if AKI is Drug-induced

• Use questions from the Naranjo scale– Are there previous reports of agent causing this kind

of AKI?– Is time frame of drug administration and subsequent

reaction logical? – Did patient have similar reaction to same or similar

drug previously?– Are there any reasonable competing explanations for

reaction? 78

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Reviewing Drug-induced AKI

Hallmarks, treatment of AKI influenced by

• Diuretics, NSAIDs, ACEIs/ARBs, CSA, ampho B, radiocontrast media

• Antibiotics, NSAIDs, diuretics

• Agents causing crystalluria

• AGs, platins, cyclo/ifos, vanco

• ATLS

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Planning for the Exam

Expect:

• A question about something in Part 1.

• A question about something in Part 2. Don’t worry about memorizing tiny details. Do know how to calculate CrClest using C-G

• An AKI case with several questions requiring you to do a patient work-up.

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Patient Work-up

Components:• Medical versus drug-related problems• Goals for therapy• Therapeutic alternatives: pros and cons• Selected drug regimen(s)• Monitoring for efficacy versus toxicity• Follow-up

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AKI Case

• Let’s walk through case on page 26-8 of handout

• As we go over the case data, note what seems normal and abnormal.

• What is this patient’s current CrClest?

• Then we will start the work-up process.

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See you next week

Have a safe trip home!

Keep your kidneys well hydrated!

Kidney Disorders: Key Concepts, Acute Kidney Injury and Acute Kidney Conditions Teresa O’Sullivan,...

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