Nephro final

What is the urine output rate for an anuric patient

less than 50 milliliters per day

What is the urine output rate for an oliguric patient

< 500 milliliters per day

What is the urine output rate for a non oliguric patient

> 500 ml/day

What are some limitations in staging AKI?

Biomarkers of Scr and urine output have limitations
Scr
----Lag in SCr rise (48-72 hours from time of injury)
----Baseline SCr must be known
Urine Output
----Non-specific marker
----Depends on volume, diuretic use and cause of AKI

What are some risk factors for AKI

Age
volume status
Comorbid conditions (CKD, DM, HTN, CAD, CHF, Liver)
Proteinuria
Medication and nephrotoxic exposure
Surgery
Sepsis

What are some causes of prerenal AKI

Volume Depletion
Decreased Cardiac Output
Functional (NSAIDS, ACEI)

What are some factors that may lead to pre-renal AKI caused by dehydration?

Hemorrhage
Decreased effective perfusion volume (nephrotic syndrome, cirrhosis, edema)
Vasodilation (sepsis)
Diuretics
Thirst, hypotension, tachycardia

What are some factors that may lead to pre-renal AKI caused by decreased cardiac output?

Congestive heart failure
Myocardial infarction
Cardiac surgery

Desribe the lab values that would indicate pre-renal AKI

Urine sodium < 20
Urine osmolality : serum osmolality > 1.5
BUN : Scr > 20
Low fractional excretion of sodium (FeNa) (Pre-renal failure:

What is the treatment goal for prerenal AKI management

restore renal blood flow by increasing intravascular volume

what is the treatment for prerenal AKI when it is caused by hemorrhage

Packed red blood cells

what is the treatment for pre renal AKI when it is caused by plasma losses (burns) or volume loss

Crystalloids or colloids solutions

what is the treatment for pre renal AKI when it is caused by decreased cardiac output

Positive inotropes, Vasopressors, intra-aortic balloon pump

What is the cause of the majority of cases intrinsic AKI

acute tubular necrosis

Fill in the blank: Tubules highly susceptible to _______ damage

Ischemic

What are some nephrotoxins that may cause ATN

Antibiotics
Chemotherapy
Contrast
Many more

What can cause renal hypoperfusion?

Hypovolemic states
Low cardiac output
Sepsis

What are some causes of ATN

nephrotoxins, renal hypoperfusion

What are the four phases of ATN

1) Initiation
--Renal tubular epithelial cell injury (vasoconstriction and ischemia)
--Lead to GFR reduction
2)Extension
--Continued cell injury and inflammatory response
3)Maintenance
--GFR reaches lowest point
--Initial recovery of kidneys
4)Recovery
--New tubule cells are regenerated

What are some lab results that indicate ATN

Color and appearance: muddy brown (RBC and WBC Casts)
Granular or epithelial cell casts
Urine : serum osmolality < 1.3
BUN : Scr ≈ 15
FeNa >2%

Hhow do you manage ATN

Improve urine output
Restore kidney function
Improve survival

What are some causes of post renal AKI

Bladder Outlet obstruction (BPH, cancer, surgery)
Ureteral obstruction (Nephrolithiasis)

What are some lab results that indicate post renal AKI

Urine sodium> 40
BUN : Scr ratio ≈ 15
Some cellular debris in urine
Urine : serum osmolality < 1.5
FeNa: Variable

How do you manage post renal AKI

Removal of obstruction
Pharmacological: alpha1 blockers for BPH
Catheterization
Percutaneous nephrostomy

What are some complications of AKI

Volume overload and edema
Electrolyte imbalance
Acid Base disorder
Malnutrition
Drug dosage adjustment

What does the in general management of AKI look like?

Supportive care
Maintaining hemodynamic stability
Fluid and electrolyte management
Maintain renal perfusion
Eliminate nephrotoxins (if feasible), drug dosing
Renal Replacement Therapy (RRT)

What are the two forms of renal replacement therapy

intermittent hemodialysis (IHD)
continuous renal replacement therapy (CRRT)

describe intermittent hemodialysis

Short treatment session (3 to 4 hours)
Rapid removal of volume and small solutes
Can cause hypotension

Describe continuous renal replacement therapy

Reserved for unstable patients
More solute removal
Less hypotension risk

Describe the clinical presentation of volume overload

peripheral and pulmonary edema

Describe the management of volume overload

Fluid Restriction/Limit sodium intake
Loop Diuretics (Careful in AKI, increased mortality..Diuretic resistance)

Why is there diuretic resistance in volume overload

Bioavailability reduced

What are some methods to improve diuretics efficacy when dealing with diuretic resistance in volume overload

Continuous instead of intermittent (More consistent concentration)
Combination therapy (use loops with another diuretic that works at distal tubule)

What are some important considerations when dosing in AKI

Pharmacokinetic alterations
Estimate of renal function
Vd (drug’s normal Vd and patient’s volume status)
Type of RRT
Drug monitoring/Therapeutic window
Individualized approach

What are some risk factors for drug induced kidney disease

Advanced age (>70)
Male Gender
African American Race
Pre-existing renal disease
Diabetes
Heart Failure
Presence of other nephrotoxic drugs
Sepsis
Volume depletion
Cirrhosis Surgery
Shock
Acidosis
Dose, duration, & frequency of toxins

What are some drugs that can cause prerenal acute renal failure

NSAIDS
ACEI/ARB
SGLT-2s inhibitors
Diuretics
Cyclosporine
Tacrolimus

Describe the presentation of ACEI/ARB Nephropathy

Acutely reduce GFR
Moderate rise in Scr up to 30% common after initiation
Scr stabilizes within 1 to 2 weeks

What are some methods to prevent ACEI/ARB Nephropathy

Recognize risk factors
Initiate at low doses and gradually titrate (every 2 to 4 weeks)
Monitor Scr and potassium frequently
Avoiding other nephrotoxic drugs if possible

Describe the management of ACEI/ARB Nephropathy

Scr threshold for discontinuation not in guidelines
Scr increase (

What is the incidence of NSAID nephropathy

500,000 to 2.5 million people annually

Describe the mechanism of NSAID nephropathy

Ischemic kidney damage
Decreased synthesis of renal vasodilator
Afferent vasoconstriction
Result in reduced renal perfusion and pressure

What are some risk factors for NSAID nephropathy

Age > 60
Pre-existing kidney disease
Hepatic disease
CHF
Volume depletion
Lupus
Concurrent treatment with ACEI/ARB or diuretics –avoid in high risk

Describe the clinical presentation of NSAID nephropathy

Occur within 2 to 7 days after initiation
Diminished urine output, weight gain, edema
Elevated Scr, potassium and BP

Describe the prevention of NSAID nephropathy

Avoiding use in high-risk patients (If necessary, minimal effective dose for shortest duration)
Maintain adequate hydration

Describe the treatment of NSAID nephropathy

Discontinuation of offending agent and other nephrotoxic drugs
Reversible, recovery within 3 to 5 days
Rare cases of chronic renal failure

Etodolac brand

Lodine

Lodine generic

Etodolac

Nabumatone brand

Relafen

Relafen generic

Nabumatone

Sulindac brand

Clinoril

Clinoril generic

Sulindac

Describe the presentation of tacrolimus nephropathy

Occurs within days of initiation
Rise in Scr
HTN
Hyperkalemia
Sodium retention
Renal tubular acidosis
Hypomagnesemia

escribe the presentation of cyclosporine nephropathy

Occurs within days of initiation
Rise in Scr
HTN
Hyperkalemia
Sodium retention
Renal tubular acidosis
Hypomagnesemia

Describe the prevention of tacrolimus nephropathy

PD and PK monitoring
Decreased doses when used with other non-nephrotoxic immunosuppressants

Describe the prevention of cyclosporine nephropathy

PD and PK monitoring
Decreased doses when used with other non-nephrotoxic immunosuppressants

Describe the treatment of tacrolimus nephropathy

Acute injury: dose related and improves with dose reduction or discontinuation of interacting meds
Chronic kidney injury: not dose related and irreversible

Describe the treatment of Cyclosporine nephropathy

Acute injury: dose related and improves with dose reduction or discontinuation of interacting meds
Chronic kidney injury: not dose related and irreversible

Which SGLT 2 inhibitors have some evidence to show that they can induce acute kidney injury

Canagliflozin and dapagliflozin

What is the incidence of SGLT 2 inhibitor nephropathy

over 100 cases reported to the FDA

describe the mechanism of SGLT 2 inhibitor nephropathy

Osmotic diuresis that leads to volume depletion
Delivery of sodium chloride vasoconstricts afferent arterioles and reduce GFR

What are some risk factors for SGLT 2 inhibitor nephropathy

Older age
Concomitant nephrotoxic medication (ACEI/ARB, diuretics, NSAIDS)
Volume depletion

Describe the prevention of SGLT 2 inhibitor nephropathy

Close follow-up in patients taking ACEI/ARB and diuretics
Avoiding nephrotoxins

Describe the management of SGLT 2 inhibitor nephropathy

Discontinuing SGLT-2 allows kidney recovery
If volume depletion – IV fluids
If ATN develops – supportive care (RRT)
SGLT-2s can be restarted when kidney recovers

Rank the aminoglycosides in order from most to least likely to cause nephrotoxicity

Neomycin>gentamicin>tobramycin>amikacin

Describe why some aminoglycosides are more nephrotoxic than others

Toxicity related to cationic charge of the drug. The more cationic, the more likely to create reactive oxygen species

what are some risk factors for aminoglycoside nephrotoxicity

aggressiveness dosing, synergistic toxicity from combination, and pre-existing clinical conditions

Describe the prevention of aminoglycoside nephrotoxicity

selection of patient, alternative agents when possible, avoid volume depletion, limit total dose, avoid concomitant therapy, PK monitoring, once daily dosing

Describe the treatment of aminoglycoside nephrotoxicity

discontinue the agent and other nephrotoxic drugs if possible, maintain hydration, supportive case
Typically reversible, although short term renal replacement may be necessary

What is the incidence of radiographic contrast-media-induced nephrotoxicity

10 to 13%

describe the presentation of radiographic contrast-media-induced nephrotoxicity

presents within first 24 to 48 hours after admission
serum creatinine peaks between three and four days after exposure
recovery after 7 to 10 days
irreversible AKI has been reported

Describe the mechanism of radiographic contrast-media-induced nephrotoxicity

Renal Ischemia (systemic hypotension and acute vasoconstriction)
Direct cellular toxicity

Describe the risk factors for radiographic contrast-media-induced nephrotoxicity

Pre-existing kidney disease (most important)
Decreased renal flow (CHF, volume depletion, hypotension)
Diabetes
Concurrent use of nephrotoxins

Describe the prevention of radiographic contrast-media-induced nephrotoxicity

Assess patient for risk factors
Use alternative imaging in high-risk patient (ultrasound, MRI)
Contrast: use noniodinated contrast, minimize contrast volume/dose, use low contrast agents
Avoid nephrotoxic drugs
Hydration:
Isotonic saline infusion (3 to 12 hours prior and continue 6-24 hours after exposure) at rate of 1-1.5 mL/kg/hr to maintain urine rate of 150 mL/hr
Urgent cases: 0.9%NaCl at 3mL/kg/hr beginning at 1 hour prior and continue for 6 hours after

How should you manage hydration in the prevention of radiographic contrast-media-induced nephrotoxicity

Isotonic saline infusion (3 to 12 hours prior and continue 6-24 hours after exposure) at rate of 1-1.5 mL/kg/hr to maintain urine rate of 150 mL/hr
Urgent cases: 0.9%NaCl at 3mL/kg/hr beginning at 1 hour prior and continue for 6 hours after

Describe the treatment of radiographic contrast-media-induced nephrotoxicity

no specific therapy
supportive care: discontinue other nephrotoxic drugs, delay subsequent contrast studies

Describe the incidence of amphotericin B nephrotoxicity

Variable rates
Dose-dependent

Describe the presentation of amphotericin B nephrotoxicity

Non-oliguria, rise in Scr and BUN
Renal tubular potassium, sodium and magnesium wasting
Distal renal tubular acidosis
Onset: few days to weeks
Tubular dysfunction 1-2 weeks after initiation

Describe the mechanism of amphotericin B nephrotoxicity

Direct tubular epithelial cell toxicity
--Necrosis of proximal tubular cells
Afferent arteriolar vasoconstriction
--Reduction in renal blood GFR

What are some risk factors for amphotericin B nephrotoxicity

Pre-existing kidney disease
Large individual and cumulative doses
Short infusion time
Volume depletion
Hypokalemia
Increased age
Concomitant administrations of diuretics and nephrotoxin

Describe the prevention of amphotericin B nephrotoxicity

Liposomal formulation
Limiting cumulative doses
Increasing infusion time
Avoiding other nephrotoxic meds
Hydrating patient
---1L of 0.9% NaCl IV daily during therapy
OR
---10 – 15 mL/kg prior to amphotericin B
Use other antifungals

describe the treatment of amphotericin B nephrotoxicity

Discontinue therapy and substitute with alternative antifungal
Tubular damage will improve gradually but may be irreversible in some patients
Monitor Scr and BUN daily
Monitor K, Mg and correct as needed

Describe the mechanism of toxicity of drug induced acute interstitial nephritis

Systemic manifestation of hypersensitivity reaction
Caused by medications, infections or connective tissue disease

Describe the presentation of drug induced acute interstitial nephritis

Presents days to weeks (usually 14 days) after drug exposure
Fever, rash, arthralgia, eosinophilia

Describe the risk factors for drug induced acute interstitial nephritis

there are none

describe the prevention for drug induced acute interstitial nephritis

you can't

is drug induced acute interstitial nephritis reversible

yes

what are some drugs that can cause drug induced acute interstitial nephritis

Penicillin
Cephalosporin
NSAIDs
Diuretics
PPI

Describe the treatment of drug induced acute interstitial nephritis

Discontinue offending medication
If renal failure > 7 days, steroids
(High dose prednisone 1mg/kg/day for 4 to 6 weeks with taper over 4 weeks can be considered)

Describe the dose of steroids that may be used if the patient develops renal failure from drug induced acute interstitial nephritis

High dose prednisone 1mg/kg/day for 4 to 6 weeks with taper over 4 weeks can be considered

Describe it the mechanism of toxicity for drug induced post renal acute renal failure

Obstruction of urine flow from crystal formation or retroperitoneal fibrosis

What are some risk factors for drug induced post renal acute renal failure

Severe volume depletion
Underlying renal insufficiency
Bolus drug administration
Metabolic acidosis or alkalosis

What are some drugs that can cause drug induced postrenal acute renal failure

Acyclovir
Sulfonamides
Methotrexate
High dose vitamin C
Indinavir, atazanavir

Describe the prevention of drug induced post renal acute renal failure

urine alkalinization

describe the treatment of drug induced post renal acute renal failure

stop the offending agent, replace volume, alkalinize urine

How do you find total body water for males

.6 x weight

how do you find total body water for females

.5 x weight

how do you find the intracellular fluid volume

2/3 of total body water

how do you find the extracellular fluid volume

1/3 of total body water

how do you find the volume of water that is in the interstitial space

3/4 of extracellular fluid (extracellular fluid is 1/3 of body water)

how do you find the volume of plasma

1/4 of extracellular fluid (extracellular fluid is 1/3 of body water)