March 6 - Chronic Kidney Disease I

Question 1

How many kidneys do people have? Where are they located?

Answer 1

2 kidneys, about 10 cm large, located around the waistline

Question 2

What is the nephron?

Answer 2

The nephron is the basic functional unit of the kidney. There are approx 1 million nephrons/kidney

Question 3

What is the glomerulus?

Answer 3

Cluster of tiny capillaries that receives blood from the afferent arteriole
Blood passes through these capillaries and is filtered under pressure into the Bowman’s capsule

Question 4

What is glomerular filtration rate (GFR)?

Answer 4

Volume of blood filtered by the glomerulus each minute
Normale adult GFR is within the range of 100-125 ml/min although this can vary somewhat depending on the age and gender. Can be estimated using equations. Used for staging chronic kidney disease and for drug dosing

Question 5

What is the creatinine clearance (CrCl) by Cockcroft Gault formula?

Answer 5

CrCl (mg/min/72kg) = ((140-age)(88.4) x (0.85 if female))/serum creatinine (sCr)

Question 6

What are the the other GFR equations?

Answer 6

eGFR by MDRD formula (modification of diet in renal disease)

eGFR by CKD EPI formula (chronic kidney disease epidemiology)

Question 7

What is creatinine?

Answer 7

A byproduct of muscle metabolism that is freely filtered at the glomerulus and so can be used as a marker of glomerular filtration rate (GFR). Serum creatinine levels remain fairly constant in healthy kidneys, but become elevated when renal filtration is impaired

Question 8

How many MRP chronic kidney disease stages are their?

Answer 8

Stages 1-5

Question 9

Describe stage 1 chronic kidney disease

Answer 9

Normal or supernormal kidney function, determined by GFR (measured by eGFR-MDRD)

Question 10

Describe stage 2 chronic kidney disease

Answer 10

Declining GFR to 60 ml/min/1.73 square meters (mild kidney damage)

Question 11

Describe stage 3 chronic kidney disease

Answer 11

GFR: 30-60 ml/min/1.73 square meters (moderate kidney damage)

Question 12

Describe stage 4 chronic kidney disease

Answer 12

GFR below 30 ml/min/1.73 square meters (severe kidney damage)

Question 13

Describe stage 5 chronic kidney disease

Answer 13

GFR below 15 ml/min/1.73 square meters (kidney failure)

Question 14

Describe the therapeutic zone for stages 1-3 CKD

Answer 14

Primary care: early identification, screening, and management of high risk patients (e.g., hypertension, diabetes, cardiovascular disease)
Nephrology: diagnosis and treatment of high risk renal diseases with disease remitting therapies (e.g., some glomerular diseases, vasculitis)

Question 15

Describe the therapeutic zone for stage 4 CKD

Answer 15

Primary care: management of non nephrology issues and co-management of hypertension and cardiovascular risk factors
Nephrology: interdisciplinary chronic kidney disease care, therapy for CKD-related anemia, calcium/phosphate/PTH- abnormalities and education and preparation for possible renal replacement therapy

Question 16

Describe the therapeutc zone for stage 5 CKD

Answer 16

Primary care: management of non-nephrology issues

Nephrology: intensive interdisciplinary monitoring and initiation of renal replacement therapy

Question 17

Describe the afferent arteriole. What is its clinical importance?

Answer 17

Arteriole through which blood enters the glomerulus
Clinical application: non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, COX-II inhibitors such as celecoxib (Celebrex), and cyclosporine can cause acute kidney injury by inhibiting vasodilation of the afferent arteriole

Question 18

Describe the efferent arteriole. What is its clinical importance?

Answer 18

Arteriole through which blood leaves the glomerulus
Clinical application: angiotensin converting enzyme inhibitors (ACE-I, e.g., enalapril) and angiotensin II receptor blockers (ARBs, e.g., irbesartan) can cause acute kidney injury by inhibiting vasoconstriction of the efferent arteriole

Question 19

What is secretion?

Answer 19

Secretion is movement into the tubule, so that the substance may be eliminated

Question 20

What is reabsorption?

Answer 20

Reabsorption is the movement out of the tubule into the capillary where it may be retained in the body

Question 21

What are the three parts of the tubule?

Answer 21

Proximal convoluted tubule
Loope of Henle
Distal convoluted tubule

Question 22

Describe the proximal tubule

Answer 22

Fluid filtered from the glomerulus flows into Bowman’s capsule and then into the proximal tubule
Approx 80% of the glomerulus ultrafiltrate is reabsorbed back into the bloodstream as it passes through the proximal tubule

Question 23

What is reabsorbed by the proximal tubule? What is the clinical importance?

Answer 23

Nutrients e.g., glucose, amino acids
Electrolytes e.g., sodium, potassium, chloride, bicarbonate, calcium and phosphorus
Clinical application: Fanconi syndrome is a disorder of hte proximal tubule reabsorption. Patients may present with bone disease (rickets), metabolic acidosis, hypokalemia, hypophosphatemia

Question 24

What is secreted by the proximal tubule? What is the clinical importance?

Answer 24

Creatinine, uric acid certain drugs
Clinical application: trimethoprim (antibiotic), cimetidine, bezafibrate, fenofibreate can block proximal tubule secretion of creatinine and make a person’s sCr value look higher and their renal function worse then it actually is

Question 25

Describe the loop of Henle?

Answer 25

Fluid flows from the proximal tubule into the loop of Henle

Primary role is reabsorption of: water, sodium, cloride, magnesium

Question 26

What do loop diuretics do?

Answer 26

Loop diuretics (e.g., furosemide) block reabsorption of sodium and water in the ascending loop of Henle

Question 27

Describe the distal convoluted tubule

Answer 27

It reabsorbs sodium and water
It secretes potassium, hydrogen ions and phosphorus
Thiazide diuretics work here (e.g., hydroclorothiazide, chlorthalidone, metolzone)

Question 28

Describe the collecting duct

Answer 28

It reabsorbs sodium
It secretes potassium, which is dependent on the hormones aldosterone (aldosterone antagonists work here, e.g., spironolactone, eplerenone)
ADH (antidiuretic hormone or vasopressin): affects water permeability int the collecting duct (high ADH leads to concentrated urine; low ADH leads to dilute urine)
Acid-base balance (excretion of acids)

Question 29

What are normal urea values?

Answer 29

2.5-8 mmol/L

Question 30

What is urea? What is its importance?

Answer 30

A waste product of protein metabolism. Blood tests can measure the concentration of urea in the plasma. It is only a general indicator of renal function since it is reabsorbed in the kidneys and can be affected by other disease processes (much less sensitive marker of kidney function than serum creatinine)

Question 31

What is the clinical importance of urea?

Answer 31

Serum urea to creatinine ratio over 70 may indicate dehydration. Urea will increase before serum creatinine in patients with acute kidney injury

Question 32

What happens to electrolytes in patients with chronic kidney disease?

Answer 32

Sodium/water - oedema/swelling (not able to reduce reabsorption by tubules
Potassium increases in blood (hyperkalemia; not able to excretion from distal tubule)
Phosphorus increase in the blood (hyperphosphatemia; not able to reduce reabsorption in proximal tubule and increase excretion from distal tubule)
Magnesium increases in the blood (hypermagnesemia; not able to reduce reabsorption of the loop of Henle)

Question 33

What is acid-base balance?

Answer 33

The kidneys maintain the pH of arterial blood within a narrow range between pH 7.35-7.45 through acidbase regulation

Question 34

What is acidosis?

Answer 34

pH below 7.35
In acidosis the kidneys reabsorb all the filtered bicarbonate into the extracellular fluid, and produce additional new bicarbonate. This helps to reduce the hydrogen ion concentration back toward normal

Question 35

What is alkalosis?

Answer 35

pH above 7.45
In alkalosis the kidneys cannot reabsorb bicarbonate so it is excreted instead. The renal excretion of bicarbonate helps to increase hydrogen ion concentration back toward normal

Question 36

How do the kidney contribute to blood pressure control?

Answer 36

Renin is released by the stimulation of the juxtaglomerular cells - smooth muscle cells located in the walls of the arterioles. They act as baroreceptors, responding to subtle changes in circulating blood volume and pressure. Decreased arterial pressure stimulates the release of renin, which activates angiotensin I. Angiotensin I become angiotensin II via ACE. This causes aldosterone secretion, vasoconstriction, and thrist is stimulated. Water and sodium is retained and arterial blood pressure is increased

Question 37

What is EPO?

Answer 37

Erythropoietin (EPO) stimulates the production of red blood cells (RBCs) in the bone marrow. When oxygen levels int he blood fall below normal, the kidneys detect this change and respond by secreting EPO. In CKD, EPO production goes down and patients’ RBCs/Hb decrease. This condition is called anemia

Question 38

What are the types of renal failure?

Answer 38

Pseudo (increase in sCr due to blocking of renal tubular secretion of creatinine)
Pre-renal (decrease blood flow to kidney, which causes a decrease in GFR)
Intrinsic (structural damage to the kidneys and can effect either the glomerulus of the tubules)
Post-renal (obstruction of urine flow)

Question 39

Describe pseudo renal failure

Answer 39

Falsely elevated creatinine: inhibition of renal tubular secretion of sCr (trimethoprim, cmetidine, fenofibrate, bezafibrate)

Question 40

Describe pre-renal failure

Answer 40

Most common cause of acute kidney injury (AKI). May be due to various medical conditions:

1. Intravascular volume depletion
2. Decline in effective blood volume (advanced liver disease, CHF, antihypertensives, sepsis)
3. Decrease pressure in glomerulus (afferent arteriole vasoconstriction; efferent arteriole vasodilation)

Question 41

What are the three different types of of intrinsic AKI

Answer 41

Acute tubular necrosis (ATN)
Acute interstitial nephritis
Glomerulonephritis

Question 42

Describe ATN

Answer 42

Acute tubular necrosis (ATN)

• ischemia in kidney producing cell damage to tubules
• most common cause of intrinsic failure
• medication induced causes: aminoglycosides, amphotericin B, intravenous contrast dye (medical imaging)

Question 43

Describe acute interstitial nephritis

Answer 43

Inflammatory disorder of the renal interstitium (“allergic reaction”)
Causes (2 most common) - drugs (approx 50%): penicillins, cephalosporins, quinolones, thiazide diuretics, loops diuretics, sulfonamides, NSAIDs, etc.

Question 44

Describe glomerulonephritis

Answer 44

Results from stimulation of the immune system leading to inflammation of the glomerulus
Causes: DNA, proteins, viruses, and bacteria stimulate immune activation, e.g., SLE (lupus nephritis), post-strep glomerulonephritis, diabetic nephropathy

Question 45

Describe post-renal AKI

Answer 45

Kidney stones
Bladder or tumor obstruction
Urethral stricture/tumor
Crystal deposition in renal tubules - can occur from certain drugs: acyclovir (antiviral for herpes), foscarnet (antiviral usually CMV retinitis), indinavir (antiviral for HIV), sulfadiazine (antibiotic)