Intro to Acute Renal Failure and Clearance Flashcards
What endogenous substance is good for approximating GFR?
GFR is most commonly estimated by measuring clearance of creatinine. Creatinine is a nonenzymatic breakdown product of creatine that exists in high and fairly stable concentrations in human muscle as well as some other tissues. Creatinine production reflects muscle mass. In healthy young adults, the daily creatinine production (and therefore, excretion) is 18-22 mg/kg/day in men and approximately 85% of that or 15-19 mg/kg/day in women. Creatinine is freely filtered by the glomerulus, is not reabsorbed, but is secreted to a variable degree. Therefore, the clearance of creatinine tends to overestimate GFR by about 10-20%. Nevertheless, creatinine clearance is the clinical test usually used to measure GFR.
Why don’t we use urea for approximating GFR?
Urea is reabsorbed in the terminal portion of the collecting duct so if you use urea to estimate, you are consistently underestimating GFR.
What 3 things make a substance viable for approximating GFR clearance?
- It is freely filtered by the nephron
- It is not reabsorbed anywhere along the course of the nephron
- It does not enter into urine via secretion.
True or False: We use creatinine clearance as a surrogate for GFR
True
The excretion/liberation of creatinine into the blood is _____ and based on _____ _____.
constant, body weight.
Men excrete approximately 20mg/kg/day while women excrete approximately 17mg/kg/day.
When can you use serum creatinine to estimate GFR clearance?
Please note that all GFR estimating methods require the patients to remain in a steady state. They are all invalid when the creatinine changes (e.g. creatinine increases from 1 -> 2 -> 3 -> 4 mg/dL).
Creatinine is being liberated into the blood (from muscles) at a constant rate and only when creatinine excretion is constant and equal to the rate of liberation is plasma creatinine stable and useful for estimating GFR.
What is the Cockcroft and Gault formula? What is it used for?
*memorize this equation. you will have to use it on the exam*
The cockcroft and gault formula is used for estimating creatinine clearance.
Creatinine clearance = [( A ) x ( 140-age ) x weight] / ( 72 x SCr )
- A = 1 if male, 0.85 if female
- Creatinine clearance is in ml/min
- Age is in years
- Weight is in kg
- Serum creatinine is in mg/dL
What is the difference between internal and external balance?
Internal balance refers to shifts between intra and extracellular fluid spaces. External balance refers to intake from outside and output to the outside.
What is a typical GFR for men? how about for women?
Men : 115-125 ml/min
Women : 90-100 ml/min
What are the 2 clinical measurements of GFR?
Plasma-based estimate of GFR, Urine-based estimate of GFR
How is plasma creatinine used to estimate renal function?
Under steady state conditions, a rising plasma creatinine indicates worsening renal function. Plasma creatinine is typically measured on a daily basis for inpatients and at every clinic visit for outpatients. By following the trend in the plasma creatinine, one can estimate whether renal function is improving, stable or declining.
What equation is used with urine-based estimates of GFR?
*memorize this equation. you will have to use it on the exam*
ClCr = (UCr) V/ PCr
Plasma creatinine (PCr) from the blood draw; urine creatinine (UCr) measured on a sample from the 24-hour urine collection; and urine flow rate (V) obtained by dividing the volume of urine collected by 24 hours (1440 minutes).
A patient is found to have a plasma creatinine of 2.0 mg/dL and a 24 hr urine volume of 1,500 ml with a urinary creatinine concentration of 100 mg/dL (100 mg/l00 ml). Calculate the creatinine clearance. What would the creatinine clearance be if the patient’s creatinine rose to 4.0 mg/dL (assuming that the patient was again in creatinine balance)? In steady state, what is the 24 hr urinary creatinine excretion when the plasma creatinine is 4.0 mg/dL?
ClCr = (UCr) V/ PCr
= 1,500ml/24 hrs x 100mg/dL / 2.0mg/dL
= 75,000ml/24hrs x 24hrs/1440minutes (remember that there are 1440 minutes in 24 hours)
= 52 ml/min
If the serum creatinine increased to 4.0 mg/dL in a steady state, creatinine clearance would be 26 ml/min.
= 1,500ml/24 hrs x 100mg/dL / 4.0mg/dL
= 37,500ml/24hrs x 24hrs/1440minutes
= 26 ml/min
Even with the plasma creatinine of 4.0 mg/dL, the creatinine excretion rate is the same as before.
What determines Single nephron glomerular filtration rate (SNGFR)? (5)
Starling forces
- Glomerular capillary hydrostatic pressure (PGC)
- Glomerular capillary oncotic pressure (πGC)
- Tubular hydrostatic pressure (PT)
- Oncotic pressure in the tubule (πT)
- A term that takes into account the surface area and permeability of the glomerular capillary membrane (Kf)
True or False: When calculating for SNGFR, it is typically assumed that oncotic pressure in the tubule (πT) is equal to zero.
True. Because the glomerulus generally acts as an effective filtration barrier for proteins, we can generally assume that the oncotic pressure in the tubule (πT) is zero.
True or False: SNGFR is proportional to PGC
True!
Because the glomerulus generally acts as an effective filtration barrier for proteins, we can generally assume that the oncotic pressure in the tubule (πT) is zero. Furthermore, alterations in PT or πGC are generally modest and usually not clinically relevant. Therefore, in normal individuals under physiologic conditions, PGC controls SNGFR the most and SNGFR is proportional to PGC.
_____ is influenced by afferent and efferent arteriolar tone.
PGC (glomerular capillary hydrostatic pressure)
Constriction of the _____ arteriolar segment causes reductions in PCG while constriction of the _____ arteriolar segment causes increases in PCG.
afferent, efferent
It is important to understand that GFR is “kept up” or maintained by vasodilation of the afferent arteriole and by vasoconstriction of the efferent arteriole.
The vasodilation of the afferent arteriole is mainly achieved through the effects of _____ and _____. The vasoconstriction of the efferent arteriole is mainly achieved through the effects of _____.
prostaglandins (E2 and I2) and nitric oxide – vasodilate afferent arteriole
angiotensin II – vasoconstrict efferent arteriole
True or False: Inhibition of prostaglandins (NSAIDs) or angiotensin II (ACE-I or ARBs) can reduce GFR or even cause acute renal failure.
True
What does decreasing afferent arteriolar resistance do to GFR? What can do this? (3)
GFR goes up.
Nitric oxide, prostaglandins E2 and I2, high protein diet/amino acids
What does increasing afferent arteriolar resistance do to GFR? What can do this? (5)
GFR decreases.
NSAIDs, adenosine, norepinephrine, endothelin, thromboxane
What does decreasing efferent arteriolar resistance do to GFR? What can do this? (2)
GFR decreases.
ACE inhibitors, ARBs
What does increasing efferent arteriolar resistance do to GFR? What can do this? (1)
GFR increases.
Angiotensin II
What is acute kidney injury (AKI)?
Rapid reduction in glomerular filtration rate manifested by a rise in plasma creatinine (Pcr) concentration, urea, and other nitrogenous waste products.
What is azotemia?
Azotemia is increased nitrogen in the blood. (e.g. blood urea nitrogen and serum creatinine are increased)
What are the 3 broad types of disorders that can cause AKI?
- Pre-renal azotemia - a decrease in GFR due to decreases in renal plasma flow and/or renal perfusion pressure.
- Post-renal azotemia or obstructive nephropathy - a decrease in GFR due to obstruction of urine flow.
- Intrinsic renal disease - a decrease in GFR due to direct injury to the kidneys (may be due to a variety of insults)
What is uremia?
Uremia refers to the constellation of signs and symptoms of multiple organ dysfunction caused by retention of “uremic toxins” and lack of renal hormones due to acute or chronic kidney injury
What are symptoms of uremia? (6)
- Nausea
- Vomiting
- Abdominal pain
- Diarrhea
- Weakness
- Fatigue
What is oliguria?
Urine volume is less than 400 ml/24 hours in a normal sized adult
What is anuria?
Urine volume is less than 50 ml/24 hours in a normal sized adult.
What is the most common cause of AKI?
A. Pre-renal causes
B. Renal causes
C. Post-renal causes
Pre-renal causes (60-70% of cases)
Why is a high rate of renal blood flow important? (2)
- to maintain GFR
- to maintain renal oxygen supply required for ion transport
What is the most common cause of an abrupt fall in GFR in a hospitalized patient?
Prerenal azotemia (a decrease in GFR due to decreases in renal plasma flow and/or renal perfusion pressure)
True or False: pre-renal azotemia is an issue of hypovolemic states
False!
Be careful not to associate pre-renal azotemia with only hypovolemia because there are certain hypervolemic states that can cause pre-renal azotemia (e.g. congestive heart failure and cirrhosis).
CHF and cirrhosis are characterized by a low EABV and reduced renal perfusion. Therefore, these conditions are classified as pre-renal even though they may cause hypervolemia.
True or False: Urinary tract obstruction must be bilateral to produce significant kidney injury.
True.
Except in patients with single kidneys or with pre-existing bilateral parenchymal disease and reduction in renal function.
What are causes of extraureteral obstruction of the ureters? (4)
- carcinoma of the cervix
- endometriosis
- retroperitoneal fibrosis
- ureteral ligation
What are causes of intraureteral obstruction of the ureters? (3)
- stones
- blood clots
- sloughed papilla
What are causes of bladder outlet obstruction? (3)
- bladder carcinoma
- urinary infection
- neuropathy
What are causes of urethral obstruction? (2)
- posterior urethral valves
- prostatic hypertrophy or carcinoma
What is FENa?
FENa = Fractional excretion of sodium. It is the ratio of the clearance of sodium to creatinine
FENa = ( UNa/PNa ) ÷ ( Ucr/Pcr ) X 100 (expressed in %)
How is FENa used in separating prerenal azotemia from other causes of AKI?
In general, the FENa is less than 1% when AKI is caused by prerenal azotemia and greater than 2% when AKI is caused by other pathologies.
There are exceptions to this rule (e.g. radiocontrast and rhabdomyolysis (severe muscle breakdown) can cause FENa to be less than 1% but are not pre-renal states)
With urinary obstruction, there is typically an impairment of tubular sodium _____ that is reflected by _____ urinary sodium concentrations and an impairment of water _____ that results in _____ urine creatinine concentrations. This typically results in a FENa that is _______.
With urinary obstruction, there is typically an impairment of tubular sodium reabsorption that is reflected by high urinary sodium concentrations and an impairment of water reabsorption that results in low urine creatinine concentrations. This typically results in a FENa that is greater than 2%.
What is the most sensitive test for the diagnosis of urinary obstruction?
Renal ultrasound evaluation.
An US will demonstrate obstruction as an expansion of the collecting system (hydronephrosis) in as many as 98% of cases.
When would you use a bladder catheter for urinary obstruction diagnosis?
For obstruction at the level of the urethra, placement of a bladder catheter following voiding may confirm the diagnosis. If there is still considerable urine present, obstruction to flow of this urine has occured. This volume of urine is called the “post-void residual”. A bladder catheter will also bypass the obstruction and provide treatment.
True or False: Relief of any urinary obstructions are typically associated with complete return of renal function.
FALSE
Prompt relief of acute obstruction is usually associated with complete return of of renal function, but prolonged obstruction is often accompanied by incomplete return of renal function after relief of the obstruction.
Intrinsic renal disease is divided into 4 types. What are they?
- Vessels
- Glomeruli
- Interstitium
- Tubules
What is the most common injury for intrinsic renal disease?
Acute tubular necrosis caused by either ischemia or nephrotoxins (which are typically medications).
It should be noted that ATN may be a misnomer as histologic studies have not consistently demonstrated tubular necrosis.
What are causes of vascular intrinsic renal disease? (2)
cholesterol emboli, renal vein thrombosis
What are causes of glomerular intrinsic renal disease? (2)
acute glomerulonephritis, hemolytic uremic syndrome
What are causes of interstitial intrinsic renal diseases? (3)
Acute interstitial nephritis (e.g. allergic interstitial nephritis (AIN)), infection, myeloma kidney.
What are causes of tubular intrinsic renal diseases? (2)
Ischemic or nephrotoxic acute tubular necrosis (ATN)
Physiologic factors of acute tubular necrosis are typically subdivided into vascular and tubular. Describe how the vascular and tubular factors can decrease GFR in ATN.
Vascular factors include decreases in renal blood flow and decreases in glomerular permeability (Kf).
Tubular factors include tubular obstruction (by cellular debris) and backleak of glomerular filtrate (across an incompetent tubular basement membrane).
Are patients with ATN oliguric or nonoliguric?
Patients with ATN may be either oliguric or nonoliguric.
Nonoliguric patients have a lower mortality rate (about 20% as compared to 60-80% for oliguric ATN). This is probably because nonoliguric ATN is a less severe injury and management of fluid and electrolyte status is easier.
What are two serious complications associated with ATN?
- Infections due to decreased leukocyte function
- GI tract hemorrhage due to increased acid secretion (stress, ulcers)
A decrease in weight, flat neck veins, and postural changes in blood pressure and/or pulse may suggest intravascular volume depletion. The presence of these signs and symptoms would suggest _____ etiology of AKI.
Pre-renal
Edema, pulmonary rales, and an S3 gallop suggest cardiac dysfunction. The presence of these signs and symptoms would suggest a _____ etiology of AKI.
Pre-renal
Note that in these instances, these patients demonstrate signs of hypervolemia.
Hypotension, surgery involving large blood loss, transfusion reactions, or exposure to radiocontrast dye used for CT scans and cardiac catheterization suggest a history of exposure to renal insults. This suggests _____ etiology of AKI.
ATN
Anuria, intermittent anuria, or large swings in urine flow rate suggest _____ etiology of AKI.
Post-renal
Rash and fever after exposure to ampicillin suggests what etiology of AKI?
Allergic interstitial nephritis (an intrinsic renal disease)
Beyond a history and physical, what must be performed on all patients with AKI?
Urinalysis and sediment examination
Urinalysis provides useful information including the tonicity of the urine as well as the presence or absence of heme pigments.
High tonicity urine suggests?
Suggests that the kidneys are retaining water due to increased ADH. These include pre-renal states and SIADH
Presence of heme pigments in urine without microscopic evidence of RBCs in the urine would suggest?
Rhabdomyolysis (syndrome characterized by muscle necrosis and release of intracellular muscle constituents into the circulation) or hemolysis
What are the 3 main components of urine analysis?
- macroscopic exam - patients who are ill may have cloudy or turbid urine. TBCs in the urine may cause the color to appear red/reddish brown/cola colored.
- dipstick chemical analysis - sticks react to glucose, protein, heme, bilirubin, ketones, and leukocyte (esterase and nitrite)
- microscopic exam - identifying formed elements like cells, casts, and crystals.
What are casts?
Renal tubules secrete mucoproteins and when these proteins “gel” in the tubules, they form casts. They are cylindrical in shape, just like the lumen of the tubule, and anything present in the tubules when these casts are formed will be trapped in the casts.
True or False: Hyaline casts are normal findings in healthy individuals
True. Hyaline casts have no cells within them and they are normal findings within healthy individuals.
True or False: RBC and WBC casts are normal findings in healthy individuals.
False. RBCs and WBCs are normally not in the tubules. RBC and WBC casts reflect pathology associated with glomerulonephritis (RBC casts) and allergic interstitial nephritis, AIN (WBC casts)
Which segments of the nephron are urinary casts typically formed?
Distal convoluted tubule and collecting duct
Hyaline casts are composed primarily of what mucoprotein?
Tamm-horsfall protein. These are secreted by tubule cells and hyaline casts typically form in the collecting duct.
UA Pattern: Relatively high specific gravity, no heme pigment, normal sediment (i.e. any casts are waxy or finely granular).
Category of renal disease?
Pre-renal Azotemia
UA Pattern: Variable tonicity, + heme pigment, sediment exam reveals RBC and RBC casts.
Category of renal disease?
Glomerulonephritis
UA Pattern: Isotonic urine, +/- heme pigment, white blood cell casts,
eosinophils (with allergic interstitial nephritis)
Category of renal disease?
Allergic interstitial nephritis
UA Pattern: Variable tonicity, ± hematuria
Category of renal disease?
Vascular
UA Pattern: Typically isotonic, variable heme pigment (+ if from hemolysis or rhabdomyolysis). Sediment exam will show pigmented coarsely granular casts and renal tubular epithelial cells (RTEs).
Category of renal disease?
Acute Tubular Necrosis (ATN)
UA Pattern: Tonicity usually isotonic or hypotonic, usually heme is negative unless superimposed infection. Micro may be totally benign or show evidence of superimposed infection (e.g. RBCs & WBCs).
Category of renal disease?
Obstruction
What categories of AKI disease have a high specific gravity urine?
Prerenal
What categories of AKI can have a normal/high specific gravity from the urine test?
Vasculitis and Glomerulonephritis
What categories of AKI have an isosmotic specific gravity for urine test?
Acute tubular necrosis, allergic interstitial nephritis, obstruction
What categories of AKI test positive for blood using the urine dipstick test?
Vasculitis, Glomerulonephritis
What categories of AKI test negative for blood using the urine dipstick test?
Prerenal, obstruction
What categories of AKI test positive/negative (variable) for blood using the urine dipstick test?
Acute tubular necrosis, allergic interstitial nephritis
What categories of AKI test positive for protein using the urine dipstick test?
Vasculitis, glomerulonephritis
What categories of AKI test negative for protein using the urine dipstick test?
Prerenal, acute tubular necrosis, obstruction
What categories of AKI test positive/negative (variable) for protein using the urine dipstick test?
Allergic interstitial nephritis
Upon microscopic examination of urine, which categories of AKI has RBC casts and RBCs?
Vasculitis, glomerulonephritis
Upon microscopic examination of urine, which categories of AKI has no findings?
Prerenal, obstruction
Upon microscopic examination of urine, which categories of AKI has WBC casts and eosinophils?
Allergic interstitial nephritis
Upon microscopic examination of urine, which categories of AKI has granular casts and renal tubular epithelial cells?
Acute tubular necrosis
What are the biochemical differences in Pre-renal AKI and ATN?
Explain for:
- Urine Na
- Ucr/Pcr
- Uosm
- FENa
Urine Na (in prerenal azotemia, kidneys are healthy and respond appropriately but have low perfusion. So, prerenal has functional tubules that can reabsorb sodium while ATN has tubules that cannot)
- Prerenal - less than 20
- ATN - greater than 20
Ucr/Pcr (in prerenal azotemia, kidneys are healthy and do a good job reabsorbing water. As water is absorbed and creatinine is not, the urine creatinine goes up)
- Prerenal - greater than 20
- ATN - less than 10
Uosm (in prerenal azotemia, kidneys are healthy and do a good job reabsorbing water and concentrating the urine while in ATN the tubules cannot. In ATN, renal osmolality cant concentrate or dilute well so you end up with an isosmotic ~300 mOsm/L)
- Prerenal - increased
- ATN - isosmotic
FENa (this is the excretion of sodium compared to what was filtered. in prerenal disease, the urine sodium is down and the urine creatinine is up so it turns out to be a small number less than 1. ATN is opposite)
- Prerenal - less than 1
- ATN - greater than 2
