Intro to Acute Renal Failure and Clearance

Question 1

What endogenous substance is good for approximating GFR?

Answer 1

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.

Question 2

Why don’t we use urea for approximating GFR?

Answer 2

Urea is reabsorbed in the terminal portion of the collecting duct so if you use urea to estimate, you are consistently underestimating GFR.

Question 3

What 3 things make a substance viable for approximating GFR clearance?

Answer 3

1. It is freely filtered by the nephron
2. It is not reabsorbed anywhere along the course of the nephron
3. It does not enter into urine via secretion.

Question 4

True or False: We use creatinine clearance as a surrogate for GFR

Answer 4

True

Question 5

The excretion/liberation of creatinine into the blood is _____ and based on _____ _____.

Answer 5

constant, body weight.

Men excrete approximately 20mg/kg/day while women excrete approximately 17mg/kg/day.

Question 6

When can you use serum creatinine to estimate GFR clearance?

Answer 6

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.

Question 7

What is the Cockcroft and Gault formula? What is it used for?

*memorize this equation. you will have to use it on the exam*

Answer 7

The cockcroft and gault formula is used for estimating creatinine clearance.

Creatinine clearance = [( A ) x ( 140-age ) x weight] / ( 72 x S_Cr )

• 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

Question 8

What is the difference between internal and external balance?

Answer 8

Internal balance refers to shifts between intra and extracellular fluid spaces. External balance refers to intake from outside and output to the outside.

Question 9

What is a typical GFR for men? how about for women?

Answer 9

Men : 115-125 ml/min

Women : 90-100 ml/min

Question 10

What are the 2 clinical measurements of GFR?

Answer 10

Plasma-based estimate of GFR, Urine-based estimate of GFR

Question 11

How is plasma creatinine used to estimate renal function?

Answer 11

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.

Question 12

What equation is used with urine-based estimates of GFR?

*memorize this equation. you will have to use it on the exam*

Answer 12

Cl_Cr = (U_Cr) V/ P_Cr

Plasma creatinine (P_Cr) from the blood draw; urine creatinine (U_Cr) 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).

Question 13

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?

Answer 13

Cl_Cr = (U_Cr) V/ P_Cr

= 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.

Question 14

What determines Single nephron glomerular filtration rate (SNGFR)? (5)

Answer 14

Starling forces

• Glomerular capillary hydrostatic pressure (P_GC)
• Glomerular capillary oncotic pressure (π_GC)
• Tubular hydrostatic pressure (P_T)
• Oncotic pressure in the tubule (π_T)
• A term that takes into account the surface area and permeability of the glomerular capillary membrane (K_f)

Question 15

True or False: When calculating for SNGFR, it is typically assumed that oncotic pressure in the tubule (π_T) is equal to zero.

Answer 15

True. Because the glomerulus generally acts as an effective filtration barrier for proteins, we can generally assume that the oncotic pressure in the tubule (π_T) is zero.

Question 16

True or False: SNGFR is proportional to P_GC

Answer 16

True!

Because the glomerulus generally acts as an effective filtration barrier for proteins, we can generally assume that the oncotic pressure in the tubule (π_T) is zero. Furthermore, alterations in P_T or π_GC are generally modest and usually not clinically relevant. Therefore, in normal individuals under physiologic conditions, P_GC controls SNGFR the most and SNGFR is proportional to P_GC.

Question 17

_____ is influenced by afferent and efferent arteriolar tone.

Answer 17

P_GC (glomerular capillary hydrostatic pressure)

Question 18

Constriction of the _____ arteriolar segment causes reductions in P_CG while constriction of the _____ arteriolar segment causes increases in P_CG.

Answer 18

afferent, efferent

Question 19

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 _____.

Answer 19

prostaglandins (E₂ and I₂) and nitric oxide – vasodilate afferent arteriole

angiotensin II – vasoconstrict efferent arteriole

Question 20

True or False: Inhibition of prostaglandins (NSAIDs) or angiotensin II (ACE-I or ARBs) can reduce GFR or even cause acute renal failure.

Answer 20

True

Question 21

What does decreasing afferent arteriolar resistance do to GFR? What can do this? (3)

Answer 21

GFR goes up.

Nitric oxide, prostaglandins E₂ and I₂, high protein diet/amino acids

Question 22

What does increasing afferent arteriolar resistance do to GFR? What can do this? (5)

Answer 22

GFR decreases.

NSAIDs, adenosine, norepinephrine, endothelin, thromboxane

Question 23

What does decreasing efferent arteriolar resistance do to GFR? What can do this? (2)

Answer 23

GFR decreases.

ACE inhibitors, ARBs

Question 24

What does increasing efferent arteriolar resistance do to GFR? What can do this? (1)

Answer 24

GFR increases.

Angiotensin II

Question 25

What is acute kidney injury (AKI)?

Answer 25

Rapid reduction in glomerular filtration rate manifested by a rise in plasma creatinine (P_cr) concentration, urea, and other nitrogenous waste products.

Question 26

What is azotemia?

Answer 26

Azotemia is increased nitrogen in the blood. (e.g. blood urea nitrogen and serum creatinine are increased)

Question 27

What are the 3 broad types of disorders that can cause AKI?

Answer 27

1. Pre-renal azotemia - a decrease in GFR due to decreases in renal plasma flow and/or renal perfusion pressure. 2. Post-renal azotemia or obstructive nephropathy - a decrease in GFR due to obstruction of urine flow. 3. Intrinsic renal disease - a decrease in GFR due to direct injury to the kidneys (may be due to a variety of insults)

Question 28

What is uremia?

Answer 28

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

Question 29

What are symptoms of uremia? (6)

Answer 29

1. Nausea 2. Vomiting 3. Abdominal pain 4. Diarrhea 5. Weakness 6. Fatigue

Question 30

What is oliguria?

Answer 30

Urine volume is less than 400 ml/24 hours in a normal sized adult

Question 31

What is anuria?

Answer 31

Urine volume is less than 50 ml/24 hours in a normal sized adult.

Question 32

What is the most common cause of AKI? A. Pre-renal causes B. Renal causes C. Post-renal causes

Answer 32

Pre-renal causes (60-70% of cases)

Question 33

Why is a high rate of renal blood flow important? (2)

Answer 33

1. to maintain GFR 2. to maintain renal oxygen supply required for ion transport

Question 34

What is the most common cause of an abrupt fall in GFR in a hospitalized patient?

Answer 34

Prerenal azotemia (a decrease in GFR due to decreases in renal plasma flow and/or renal perfusion pressure)

Question 35

True or False: pre-renal azotemia is an issue of hypovolemic states

Answer 35

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.

Question 36

True or False: Urinary tract obstruction must be bilateral to produce significant kidney injury.

Answer 36

True. Except in patients with single kidneys or with pre-existing bilateral parenchymal disease and reduction in renal function.

Question 37

What are causes of extraureteral obstruction of the ureters? (4)

Answer 37

1. carcinoma of the cervix 2. endometriosis 3. retroperitoneal fibrosis 4. ureteral ligation

Question 38

What are causes of intraureteral obstruction of the ureters? (3)

Answer 38

1. stones 2. blood clots 3. sloughed papilla

Question 39

What are causes of bladder outlet obstruction? (3)

Answer 39

1. bladder carcinoma 2. urinary infection 3. neuropathy

Question 40

What are causes of urethral obstruction? (2)

Answer 40

1. posterior urethral valves 2. prostatic hypertrophy or carcinoma

Question 41

What is FENa?

Answer 41

FENa = Fractional excretion of sodium. It is the ratio of the clearance of sodium to creatinine FENa = ( U_Na/P_Na ) ÷ ( U_cr/P_cr ) X 100 (expressed in %)

Question 42

How is FENa used in separating prerenal azotemia from other causes of AKI?

Answer 42

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)

Question 43

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 \_\_\_\_\_\_\_.

Answer 43

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%**.

Question 44

What is the most sensitive test for the diagnosis of urinary obstruction?

Answer 44

Renal ultrasound evaluation. An US will demonstrate obstruction as an expansion of the collecting system (hydronephrosis) in as many as 98% of cases.

Question 45

When would you use a bladder catheter for urinary obstruction diagnosis?

Answer 45

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.

Question 46

True or False: Relief of any urinary obstructions are typically associated with complete return of renal function.

Answer 46

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.

Question 47

Intrinsic renal disease is divided into 4 types. What are they?

Answer 47

1. Vessels 2. Glomeruli 3. Interstitium 4. Tubules

Question 48

What is the most common injury for intrinsic renal disease?

Answer 48

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.

Question 49

What are causes of vascular intrinsic renal disease? (2)

Answer 49

cholesterol emboli, renal vein thrombosis

Question 50

What are causes of glomerular intrinsic renal disease? (2)

Answer 50

acute glomerulonephritis, hemolytic uremic syndrome

Question 51

What are causes of interstitial intrinsic renal diseases? (3)

Answer 51

Acute interstitial nephritis (e.g. allergic interstitial nephritis (AIN)), infection, myeloma kidney.

Question 52

What are causes of tubular intrinsic renal diseases? (2)

Answer 52

Ischemic or nephrotoxic acute tubular necrosis (ATN)

Question 53

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.

Answer 53

Vascular factors include decreases in renal blood flow and decreases in glomerular permeability (K_f). Tubular factors include tubular obstruction (by cellular debris) and backleak of glomerular filtrate (across an incompetent tubular basement membrane).

Question 54

Are patients with ATN oliguric or nonoliguric?

Answer 54

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.

Question 55

What are two serious complications associated with ATN?

Answer 55

1. Infections due to decreased leukocyte function 2. GI tract hemorrhage due to increased acid secretion (stress, ulcers)

Question 56

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.

Answer 56

Pre-renal

Question 57

Edema, pulmonary rales, and an S3 gallop suggest cardiac dysfunction. The presence of these signs and symptoms would suggest a _____ etiology of AKI.

Answer 57

Pre-renal Note that in these instances, these patients demonstrate signs of hypervolemia.

Question 58

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.

Answer 58

ATN

Question 59

Anuria, intermittent anuria, or large swings in urine flow rate suggest _____ etiology of AKI.

Answer 59

Post-renal

Question 60

Rash and fever after exposure to ampicillin suggests what etiology of AKI?

Answer 60

Allergic interstitial nephritis (an intrinsic renal disease)

Question 61

Beyond a history and physical, what **must** be performed on all patients with AKI?

Answer 61

Urinalysis and sediment examination Urinalysis provides useful information including the tonicity of the urine as well as the presence or absence of heme pigments.

Question 62

High tonicity urine suggests?

Answer 62

Suggests that the kidneys are retaining water due to increased ADH. These include pre-renal states and SIADH

Question 63

Presence of heme pigments in urine without microscopic evidence of RBCs in the urine would suggest?

Answer 63

Rhabdomyolysis (syndrome characterized by muscle necrosis and release of intracellular muscle constituents into the circulation) or hemolysis

Question 64

What are the 3 main components of urine analysis?

Answer 64

1. 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. 2. dipstick chemical analysis - sticks react to glucose, protein, heme, bilirubin, ketones, and leukocyte (esterase and nitrite) 3. microscopic exam - identifying formed elements like cells, casts, and crystals.

Question 65

What are casts?

Answer 65

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.

Question 66

True or False: Hyaline casts are normal findings in healthy individuals

Answer 66

True. Hyaline casts have no cells within them and they are normal findings within healthy individuals.

Question 67

True or False: RBC and WBC casts are normal findings in healthy individuals.

Answer 67

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)

Question 68

Which segments of the nephron are urinary casts typically formed?

Answer 68

Distal convoluted tubule and collecting duct

Question 69

Hyaline casts are composed primarily of what mucoprotein?

Answer 69

Tamm-horsfall protein. These are secreted by tubule cells and hyaline casts typically form in the collecting duct.

Question 70

UA Pattern: Relatively high specific gravity, no heme pigment, normal sediment (i.e. any casts are waxy or finely granular). Category of renal disease?

Answer 70

Pre-renal Azotemia

Question 71

UA Pattern: Variable tonicity, + heme pigment, sediment exam reveals RBC and RBC casts. Category of renal disease?

Answer 71

Glomerulonephritis

Question 72

UA Pattern: Isotonic urine, +/- heme pigment, white blood cell casts, eosinophils (with allergic interstitial nephritis) Category of renal disease?

Answer 72

Allergic interstitial nephritis

Question 73

UA Pattern: Variable tonicity, ± hematuria Category of renal disease?

Answer 73

Vascular

Question 74

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?

Answer 74

Acute Tubular Necrosis (ATN)

Question 75

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?

Answer 75

Obstruction

Question 76

What categories of AKI disease have a high specific gravity urine?

Answer 76

Prerenal

Question 77

What categories of AKI can have a normal/high specific gravity from the urine test?

Answer 77

Vasculitis and Glomerulonephritis

Question 78

What categories of AKI have an isosmotic specific gravity for urine test?

Answer 78

Acute tubular necrosis, allergic interstitial nephritis, obstruction

Question 79

What categories of AKI test positive for blood using the urine dipstick test?

Answer 79

Vasculitis, Glomerulonephritis

Question 80

What categories of AKI test negative for blood using the urine dipstick test?

Answer 80

Prerenal, obstruction

Question 81

What categories of AKI test positive/negative (variable) for blood using the urine dipstick test?

Answer 81

Acute tubular necrosis, allergic interstitial nephritis

Question 82

What categories of AKI test positive for protein using the urine dipstick test?

Answer 82

Vasculitis, glomerulonephritis

Question 83

What categories of AKI test negative for protein using the urine dipstick test?

Answer 83

Prerenal, acute tubular necrosis, obstruction

Question 84

What categories of AKI test positive/negative (variable) for protein using the urine dipstick test?

Answer 84

Allergic interstitial nephritis

Question 85

Upon microscopic examination of urine, which categories of AKI has RBC casts and RBCs?

Answer 85

Vasculitis, glomerulonephritis

Question 86

Upon microscopic examination of urine, which categories of AKI has no findings?

Answer 86

Prerenal, obstruction

Question 87

Upon microscopic examination of urine, which categories of AKI has WBC casts and eosinophils?

Answer 87

Allergic interstitial nephritis

Question 88

Upon microscopic examination of urine, which categories of AKI has granular casts and renal tubular epithelial cells?

Answer 88

Acute tubular necrosis

Question 89

What are the biochemical differences in Pre-renal AKI and ATN? Explain for: * Urine Na * U_cr/P_cr * U_osm * FENa

Answer 89

**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 **U_cr/P_cr (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 **U_osm (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