Week 6: Acute Kidney Injury

Question 1

Define the pre-renal etiology of AKI

Answer 1

Prerenal AKI or inadequate perfusion is the most common reason for AKI (Renal artery is pre-renal). Poor perfusion can result from hypovolemia, reduced cardiac output, renal vasomodulation/shunting and systemic vasodilation. During the early phases of hypoperfusion, protective autoregulatory mechanisms maintain GFR at a relatively constant level through afferent arteriolar dilation and efferent arteriolar vasoconstriction (mediated by angiotensin II). The GFR eventually declines because of the decrease in glomerular filtration pressure. failure to restore blood volume or blood pressure and oxygen delivery can cause ischemic cell injury and acute tubular necrosis or acute interstitial necrosis, a more severe form of AKI.

Question 2

Define the intrarenal etiology of AKI

Answer 2

Intrarenal (intrinsic) AKI can result from vascular, microvascular, glomerular, and tubulointerstitial causes. the most commonly seen cause of intrarenal AKI it ATN (Acute Tubular Necrosis). Ischemic ATN most often occurs after surgery but also is associated with prerenal causes such as sepsis, obstetric complications, and severe hemorrhagic trauma or severe burns. Whereas nephrotoxic ATN is usually caused by exposure to radiocontrast media or nephrotoxic medications (e.g., aminoglycosides, NSAIDs, ACEi, ARBs, and antibiotics).

Can also be caused by:
* acute glomerulonephritis (inflammation of the glomerulus)
* vascular disease (issues with vessels in the kidneys)
* allograft rejection
* interstitial disease

Important points to consider:
- hypoperfusion is pre-renal but can cause intra-renal ATN
- oliguria (urine output less than 30ml/hr) is common, but anuria is rare

Question 3

Define the post-renal etiology of AKI

Answer 3

Postrenal AKI is rare and is usually caused by an obstruction within the urinary tract that affects the kidneys bilaterally (e.g., bladder outlet obstruction, ureteral obstruction, or renal pelvis obstruction). A pattern of several hours of anuria with flank pain followed by polyuria is a characteristic finding. The obstruction causes an increase in intraluminal hydrostatic pressure upstream from the site of obstruction with gradual decrease in GFR.

Question 4

What is Chronic Kidney Disease and how does it manifest?

Answer 4

CKD is the progressive and irreversible loss of renal function indicated by a decline in GFR to below 60mL/min/1.73m2 for 3 months or more with implications for health. It is associated with systemic diseases, such as diabetes mellitus (most significant risk factor), hypertension, and systemic lupus erythematosus. CKD also is associated with intrinsic kidney diseases, such as AKI, chronic glomerulonephritis, chronic pyelonephritis, obstructive uropathies, or vascular disorders. Clinical manifestations do not occur until renal function declines to less than 25% of normal function.

Question 5

Discuss the diagnostics for AKI

Answer 5

The hallmark features of AKI are increased SCr, reduced GFR, and decreased urine output. A diagnostic challenge is to differentiate prerenal AKI from ATN.

Pre-renal: associated with history of blood volume depletion or other causes of poor kidney perfusion (e.g., shock, heart failure, renal artery thrombi)

Intrinsic: exposure to nephrotoxins and infection

Postrenal: associated with obstructive uropathies (e.g., enlarged prostate or stones)

Other diagnostic indicators:
- ratios of BUN to plasma creatinine concentration and fractional excretion of sodium (the ratio of filtered sodium to excreted sodium)
- Cystatin C: serum protein, concentration can serve as a measure of GFR and may be useful in detecting early GFR changes
- serial measurements of plasma creatinine concentration provide an index of renal function during the recovery phase (only occur if glomerular filtration is lost and 24hrs +day)

Question 6

Discuss the diagnostic stages for CKD

Answer 6

Stage 1: Normal kidney function; normal or high GFR (>90mL/min). Usually no signs or symptoms, although hypertension is common.

Stage 2: Mild kidney damage; mild reduction in GFR (60-89mL/min). Subtle hypertension and increasing creatinine and urea levels.

Stage 3: Moderate kidney damage; GFR 30-59 mL/min. Mild symptoms, as above.

Stage 4: Severe kidney damage; GFR 15-29 mL/min. Moderate symptoms as above; erythropoietin deficiency anemia, hyperphosphatemia, increased triglycerides, metabolic acidosis, hyperkalemia, salt/water retention

Stage 5: End-stage kidney disease; established kidney failure, GFR <15mL/min. Symptoms are severe, as above.

Question 7

Describe the functions of the kidneys

Answer 7

Acid-base balance

Water balance
Electrolyte balance
Toxin elimination

Blood pressure
Erythropoietin
D vitamin

Question 8

Discuss the importance of renal blood flow

Answer 8

The kidneys are highly vascular organs and usually receive 1000 to 1200mL of blood per minute, or about 20-25% of the cardiac output. With a normal hematocrit of 45% about 600 to 700mL of blood flowing through the kidney per minute is plasma. The filtration of the plasma per unit of time is known as the glomerular filtration rate (GFR) which is directly related to the perfusion pressure of the glomerular capillaries. The GFR is directly related to the RBF, which is regulated by intrinsic autoregulatory mechanisms, by neural regulation, and by hormonal regulation. If the mean arterial pressure decreases or the vascular resistance increases, the RBF declines and urinary output decreases. Normal urinary output is about 30mL/h minimum in adults. In the kidney, the autoregulation of the glomerular blood flow helps keep the GFR fairly constant (approx. 120ml/min) over a range of systemic arterial pressures. This is necessary to maintain the clearance of metabolic wastes and the reabsorption of filtered electrolytes and nutrients.

Question 9

Discuss the structure and function of the glomerulus

Answer 9

The glomerulus is a tuft of capillaries that loop into the Bowman’s space. The bowman space is continuous with the lumen of the renal tubules. The glomerular filtration membrane filters blood components through three layers. Tonicity within the ducts is isotonic.

Question 10

Discuss the structure and function of the proximal tubule

Answer 10

The proximal tubule is the first segment of the renal tubule, extending from the Bowman space. The proximal tubule contributes to the reabsorption (we reabsorb what we want to keep!) of:
- Sodium
- Potassium
- Amino Acids
- Bicarbonate
- Phosphate
- Urea
- Water

And the secretion of:
- Hydrogen
- Foreign substances

Tonicity is isotonic

Question 11

Discuss the structure and function of the Loop of Henle

Answer 11

The proximal tubule, descending towards the medulla, joins the Loop of Henle, which extends into the medulla. The Loop of Henle aids in the concentration of urine where the descending loop (highly permeable to water) is responsible for water reabsorption as sodium diffuses in and the ascending loop (permeable to ions but not water) where sodium is reabsorbed by active transport but water stays in, eventually urine is passed into the distal convoluted tubule. Tonicity can be isotonic, hypertonic, or hypotonic.

Question 12

Discuss the structure and function of the Distal Tubule

Answer 12

The distal tubule is shorter than the proximal tubule but also has straight and convoluted segments. The distal tubule reabsorbs sodium, water (ADH required), and bicarbonate and secretes:
- Potassium
- Urea
- Hydrogen
- Ammonia
- Some drugs

Before meeting with the collecting duct. Hypotonic

Question 13

Discuss the structure and function of the Collecting Duct

Answer 13

The collecting duct is a large tubule that descends down the cortex and through the renal pyramids of the inner and outer medullae, draining urine into the minor calyx. Here, water is reabsorbed by active transport and sodium, potassium, hydrogen, and ammonia may be reabsorbed or secreted. Final concentration.

Question 14

Discuss tests of renal function

Answer 14

Renal Clearance: how much of a substance can be cleared from the blood by the kidneys per given amount of time. The application of this principle permits an indirect measure of the GFR, tubular secretion, reabsorption, and the RBF.

Glomerular Filtration Rate: GFR provides the best estimate of functioning renal tissue and is important for assessing or monitoring kidney damage and drug dosing. Measurement of the GFR requires the use of a substance that does not influence GFR; has a stable plasma concentration; is not protein bound; is freely filtered at the glomerulus; is not secreted, reabsorbed, or metabolized by the tubules; is constantly infused to maintain a stable plasma level; and is easy to measure. The clearance of creatinine, a natural substance produced by muscle and released into the blood at a relatively constant rate, is commonly used as an estimate clinically.

Cystatin C is a stable protein in serum filtered at the glomerulus and metabolized in the tubules. Serum levels of Cystatin C are also a marker for estimating the GFR/

The concentration of urea nitrogen in the blood reflects glomerular filtration and urine-concentrating capacity. Because urea is filtered at the glomerulus, blood urea nitrogen (BUN) levels increase as GFR drops. Urea is reabsorbed by the blood through the permeable tubules, so the BUN value rises in states of dehydration and with acute and chronic renal failure when the passage of fluid through the tubules slows. BUN values also change as a result of altered protein intake and protein catabolism making it a poor measure of GFR.

Urinalysis is a noninvasive and relatively in expensive diagnostic procedure. Includes evaluation of the color, turbidity, protein, pH, specific gravity, sediment, and supernatant.

Question 15

How does aging impact the kidney?

Answer 15

Vascular diseases and decreased perfusion result in kidney cell necrosis, with less filtering units available as we age.

Question 16

How is kidney dysfunction classified?

Answer 16

• Acute (under 3 months) or Chronic; reversible or irreversible
• Renal Insufficiency: decline of renal function to approximately 25% of normal or GFR of 25-30ml/min
• Renal Failure: significant loss of renal function; levels of serum creatinine and urea are mildly elevated
• End-stage Renal Failure: less than 10% of renal function remains

Question 17

Define Uremia

Answer 17

Is a syndrome of renal failure and includes elevated blood urea nitrogen (BUN) and creatinine levels accompanied by fatigue, anorexia, nausea, vomiting, pruritus, and neurologic changes. Uremia represents numerous consequences related to kidney failure, including retention of toxic wastes, deficiency states, electrolyte disorders, and immune activation promotion a pro-inflammatory state.

Question 18

Define Azotemia

Answer 18

Is characterized by increased BUN levels (normal is 8 to 20 mg/dL) and frequently increased SCr levels (normal is 0.7 to 1.4 mg/dL). Renal insufficiency or kidney failure causes azotemia. Both azotemia and uremia indicate an accumulation of nitrogenous waste products.

Uremia is the manifestation of symptoms because of the azotemia!

Question 19

What is Acute Kidney Injury and how does it manifest?

Answer 19

AKI is a sudden decline in kidney function with a decrease in glomerular filtration caused by a defect in the excretion of water, salts, and nitrogenous waste products, which accumulate in the blood as demonstrated by an elevation in SCr level and a decrease in urine volume. AKI is a complex syndrome that is classified according to semi-anatomical categories (i.e., pre-renal, intrinsic, and post-renal). Staging of AKI is based on serum creatinine levels (increase) and blood urea nitrogen (increase)

Question 20

Discuss the pathophysiology of AKI

Answer 20

AKI is commonly a result of extracellular volume depletion, decreased renal blood flow OR toxic/inflammatory injury to the kidney. There are three types based on anatomical location.

Question 21

Define Post-Ischemic ATN

Answer 21

Involves persistent hypotension, hypoperfusion, and hypoxemia resulting in ischemia, decreased energy resources and increase free radials that lead to the activation of inflammatory cells (e.g., neutrophils, macrophages) and complement and cytokines producing further tubular injury. The transport of sodium and other molecules is impaired with damage seen primarily at the proximal tubule. Shedding of the brush border occurs with the appearance of tubular granular casts in the urine. Ischemia necrosis tends to be patchy and may be distributed along any part of the nephron tubules.

Question 22

Define nephrotoxic ATN

Answer 22

Typically caused by exposure to radiocontrast media or nephrotoxic medications but can also be caused by bacterial toxins, dehydration, advanced age, concurrent renal insufficiency, and diabetes. Nephrotoxic necrosis and tubular cell apoptosis are usually uniform and limited to the proximal tubules. Typically, damage is limited to the proximal tubule because it is responsible for secretion of foreign substances.

Question 23

Discuss how Oliguria manifests in AKI

Answer 23

Oliguria, or a urine output of <400mL/24 h, occurs in AKI and can be differentiated from prerenal, intrarenal, and ATN. Three mechanisms have been proposed to account for the decrease in urine volume in AKI.

1. Alterations in renal blood flow: Efferent arteriolar vasoconstriction may be produced by intrarenal release of angiotensin II or there may be a redistribution of blood flow from the cortex to the medulla. Autoregulation of blood flow may be impaired, resulting in decreased GFR. Microthrombi may obstruct blood flow. Changes in glomerular permeability and decreased GFR also may result from ischemia.
2. Tubular obstruction: necrosis of the tubules causes sloughing of cells, cast formation, and obstruction to urine flow. There can be ischemic edema that results in tubular obstruction, which causes a retrograde increase in hydrostatic pressure, and opposes the hydrostatic pressure of glomerular filtration, thus reducing the GFR. Kidney failure can occur within 24hr.
3. Tubular back-leak: tubular reabsorption of filtrate is accelerated as a result of increased permeability caused by ischemia and increased tubular pressure from obstruction.

Question 24

Discuss the clinical manifestations and progression of ATN

Answer 24

The clinical progression of AKI due to ATN, the most common cause of AKI, occurs in four overlapping phases:

1. The initiation phase (24-36hrs evolving injury): occurs with the onset of renal hypoperfusion or toxicity resulting in severe cellular ATP depletion leading to acute cell injury and dysfunction. Prevention of injury is possible during this phase and the next phase with therapeutic interventions, but there is a short window of opportunity.
2. The extension phase: is initiated by continued hypoxia following the initial ischemic event and an inflammatory response. Cells continue to undergo injury and death with necrosis and apoptosis present in the outer medulla.
3. The maintenance/oliguric phase (weeks-months): is the period of established kidney injury and dysfunction after the initiating event has been resolved. Cells undergo repair, migration, apoptosis, and proliferation, which may last from weeks to months with urine output lowest during this phase. During this phase, SCr, BUN, and serum potassium levels increase; metabolic acidosis develops; there is salt and water overload; and urine output is decreased with oliguria.
4. The recovery/polyuria phase: is the interval when glomerular function returns but the regenerating tubules cannot yet concentrate the filtrate. diuresis is common during this phase, with a decline in SCr and urea concentrations and an increase in creatinine clearance. As renal function improves, the increase in urine volume (dieresis) is progressive. The tubules are still damaged early in the recovery phase and have not recovered secretion and reabsorption functions. Polyuria can result in excessive loss of sodium, potassium, and water.

Question 25

Discuss treatment strategies for AKI

Answer 25

Prevention of AKI is the most important therapeutic approach and involves avoidance of hypotension, hypovolemia, and nephrotoxicity. However, once AKI has occurred, determination of the etiology of AKI is essential for appropriate management.

• Correct fluid and electrolyte disturbances
• Can given diuretics to trigger kidney to make urine, however, we need to be conscious of hyperkalemia as potassium may not be filtered out properly
• To address hyperkalemia, we will restrict dietary sources of potassium, use non-potassium sparing diuretics, and administer glucose/insulin/sodium bicarbonate to drive potassium into the cells
• Manage the blood pressure
• Prevent and treat any infections
• Maintain nutrition and avoid azotemia by a low-protein, high carbohydrate diet (slows protein catabolism and prevent release of potassium from cellular breakdown)
• Avoiding nephro-toxic drugs

Question 26

Discuss the pathophysiology of CKD

Answer 26

The progression phase of the disease is characterized by a persistent state of inflammation and hypoxia and oxidative stress that contributes to the development of renal fibrosis. The kidneys have a remarkable ability to adapt to the loss of nephron mass. Symptomatic changes result from increased plasma levels of creatinine, urea, and potassium. Alterations in salt and water balance usually do not become apparent until renal function declines to less than 25% of normal when adaptive renal reserves have been exhausted. Different theories have been proposed to account for the adaptation to the loss of renal function (i.e., intact nephron hypothesis). However, the particular location of kidney damage will also influence loss of kidney function (e.g., tubular interstitial disease damages tubular or medullary parts of the nephron)

Question 27

Discuss the intact nephron hypothesis in CKD

Answer 27

Proposes that loss of nephron mass with progressive kidney damage causes the surviving nephrons to increase their capacity to maintain solute and water regulation. These nephrons are capable of a compensatory hypertrophy and expansion or hyperfunction in their rates of filtration, reabsorption, and secretion.

Question 28

What factors contribute to the progression of CKD?

Answer 28

1. Proteinuria: glomerular hyperfiltration of protein contributes to tubular interstitial injury by accumulating in interstitial space and promoting inflammation and progressive fibrosis.
2. Angiotensin II: promotes glomerular hypertension and hyperfiltration caused by efferent vasoconstriction from systemic hypertension and resulting in proteinuria. May also contribute to inflammatory cells and growth factors fibrosing and scaring tubulointerstitium

Question 29

Discuss the clinical manifestations of CKD

Answer 29

CKD is often described using the terms azotemia and uremia. The accumulation of toxins has systemic effects known as uremic syndrome. The manifestations involve almost every organ system and include hypertension; anorexia; nausea; vomiting; diarrhea or constipation; malnutrition and weight loss; pruritus; edema; anemia; clotting disorders; neurologic, cardiovascular, and endocrine disease; and skin and skeletal changes.

Question 30

Define Azotemia

Answer 30

is manifested by increased levels of serum urea, SCr, and other nitrogenous compounds related to decreasing kidney function.

Question 31

Define Uremia

Answer 31

is the accumulation of urea and other nitrogenous compounds and toxins.

Question 32

What is uremic fetor?

Answer 32

Bad breath caused by the breakdown of urea

Question 33

Discuss how Creatinine is used as an indicator of kidney function

Answer 33

Creatinine is constantly released from muscle and excreted primarily by glomerular filtration. In CKD, as GFR declines, the SCr level increases by a reciprocal amount to maintain a constant rate of excretion. With continuing decline in GFR, the plasma creatinine concentration increases. Measures of SCr can serve as an index of changing glomerular function. However, SCr as an estimate of GFR is limited when there is reduced muscle mass or fluid overload.

Question 34

Discuss evaluation and treatment of CKD

Answer 34

Early screening and evaluation of CKD is based on risk factors, health history, presenting signs and symptoms, and diagnostic testing, Decreased GFR (<80) with elevated SCr and BUN concentrations are consistent with CKD. Markers of kidney damage include measurement of urine protein level, particularly albumin, and examination of urine sediment. Imaging will show small kidney size, and renal biopsy confirms the diagnosis.

Management involves promotion of adequate caloric intake with dietary restriction of protein, sodium potassium, and phosphate. Supplementation with vitamin D aids in the management of hyperphosphatemia. Maintenance of sodium and fluid balance may require fluid restriction.

Other:
- Management of dyslipidemias
- Erythropoietin-stimulating agents
- Adjuvant iron therapy

Pharmacological:
- ACE inhibitors or receptor blockers control systemic hypertension and provide renoprotection, particularly in the presence of diabetes mellitus
- Statins and fibrates are used to control hyperlipidemia
- Sodium glucose cotransporter 2 inhibitors

End stage Kidney Disease:
- dialysis
- supportive therapy
- renal transplant

Question 35

What is dialysis?

Answer 35

Dialysis is a type of treatment that helps your body remove extra fluid and waste products from your blood when the kidneys are not able to. Can be hemo or peritoneal and continuous or intermittent. Offered to patients with GFR <15ml/min/1.73m2. Works by osmosis.

Question 36

What is hemodialysis?

Answer 36

In hemodialysis, waste products and excess fluid are removed from the blood using a machine to pump the blood through an artificial semi-permeable membrane. Can be intermittent (HD) or continuous (CRRT).

Question 37

Why is furosemide prescribed for AKI or CKD?

Answer 37

Inhibits reabsorption of sodium at the ascending loop of henle, as sodium is excreted water follows helping to eliminate excess fluid in the body. There is increased excretion of potassium at the distal tubule. Regulating blood pressure is the desired effect but furosemide acts very quickly, so we need to monitor the BP. Can also cause H/A due to the sudden shift in sodium and fluid.

Question 38

When would you supplement calcium with food?

Answer 38

If patients need calcium carbonate to replace their calcium, they need to take it on an empty stomach. However, if patients need it to regulate high phosphate, they need to take it with food.