Acute Kindey Injury

Question 1

Which nephrotoxic drugs cause vasoconstriction of the afferent arteriole?

Answer 1

NSAIDs inhibit the action of prostaglandin for vasodilation of afferent arteriole

Tacrolimus, a calcineurine inhibitor used in cancer treatment to act as an immunosuppressant.

Question 2

Which nephrotoxic drugs cause vasodilation of the Efferent arteriole?

Answer 2

ACE inhibitors and ARBs which inhibit angiotensin II, resulting in vasodilation of efferent arteriole and vasoconstriction of afferent arteriole. ACE inhibitors reduce GFR and reduce the release of hyperkalemia, reducing loss of K+ out of the bloodstream and in the urine.

Question 3

Which nephrotoxic drugs cause acute tubular necrosis, an intrarenal AKI?

Answer 3

-> Aminogloycosides such as gentamycin which inhibit protein synthesis of 30s ribosomes of bacteria. It damages tubular cells of kidney directly for intrarenal AKI and has ototoxicity for hearing damage. Aminoglycosides accumulate in the tubules.
-> Vancomycin inhibits bacterial wall cell synthesis of gram positive bacteria.
-> Aciclovir is an anti-viral drug which inhibits the viral DNA polymerase for replication. It accumulates in renal damage
-> Contrast dyes
->Statins act to inhibit the synthesis of cholesterol but this may increase the risk of rhabdomyolysis which results in acute tubular necrosis within intrarenal AKI.
-> Amphotecirin B, an anti-fungal medication which binds to sterols in the cell membrane of fungi to cause leaking.

Question 4

Which Analgesics are Nephrotoxic?

Answer 4

NSAIDS and COX inhibitors
Opioid analgesics
Gabapentin, anticonvulsant which inhibits the release of of excitatory neurotransmitters. It causes rhabdomyolysis and is excreted solely by the kidneys.

Question 5

What is the effect of lithium on the kidneys?

Answer 5

Lithium is used in mania however should be avoided completely in impaired kidney function because it accumulates in the principal cells of the collecting duct to block the action of anti-durietic hormone, leading to polyuria and Nephrotoxic diabetes insipidus.

Lithium can induce hyperparathyroidism and result in osteolysis and hypercalcaemia.

Question 6

Which cardiovascular drugs cause kidney damage?

Answer 6

Anti-hypertensives can cause renal hypoperfusion and lead to pre-renal AKI.

Digoxin inhibits the Na+/k+ ATPase exchanger that cause accumulation of K, therefore during kidney injury, digoxin will worsen hyperkalemia

Statins act to inhibit the synthesis of cholesterol but this may increase the risk of rhabdomyolysis which results in acute tubular necrosis within intrarenal AKI.

Phenytoin is a sodium channel blocker which may lead to acute interstitial nephritis in cardiovascular disease

Question 7

What is renal clearance?

Answer 7

Renal clearance is the volume of plasma completely cleared of a drug per unit of time. This is calculated via Urinary excretion x volume/plasma volume

Question 8

What is used to estimate GFR?

Answer 8

Extraction ratio of serum creatinine in the kidneys is used to estimate the GFR, as well as age and sex. This is based on the patient’s actual concentration of creatinine in urine divided by expected plasma concentration of creatinine for their age and sex However, since some creatinine is secreted, it is a slight overestimation.

Question 9

What is the gold standard for renal function?

Answer 9

Inulin.

Question 10

What is filtration?

Answer 10

Filtration in the kidney is the movement of unbound substances from the efferent arteriole to the glomerulus. This is dependent on kidney GFR function and conc of drug bound to albumin

Question 11

What is secretion?

Answer 11

Secretion is the movement of substances from the Peritubular capillaries to the kidney tubules. For polar drugs, these require energy transporters.

Question 12

What is reabsorption?

Answer 12

Reabsorption in the kidney is the movement of substances from the kidney tubules in the DCT back to bloodstream, typically the Peritubular capillaries, a branch of the efferent arterioles.

Question 13

What are the complications with renal facial?

Answer 13

Reduced synthesis of substances like enzymes for Vitamin D synthesis, leading to hypocalcaemia and secondary hyperparathyroidism.

Hyperkalemia and hyponatremia

Insulin is partially metabolised in the kidneys so reduction in kidney function causes a rise in insulin which reduces insulin requirement dosages in diabetics.

Anaemia

Less drug excretion = higher serum drug concentration so greater risk of side effects

Question 14

What is an indicator of acute kidney injury?

Answer 14

Increase in creatinine of 0.3 mm/dl in 48 hours OR Increase from 1.5x from the baseline indicates acute kidney injury.
A fall in urine output to less than 0.5kg/hr for more than 6 hours.

Question 15

What does a higher ratio of urea than creatinine indicate?

Answer 15

Pre-renal AKI

Question 16

What does a higher ratio of creatinine than urea?

Answer 16

Intrarenal AKI or a late post-renal AKI.

Question 17

What is an indicator for pre-renal AKI?

Answer 17

High urine osmolality
AND
Low urine Na+/ Fractional excretion of Na+ less than 1%
AND
Higher ratio of urea than creatinine.

-> indicates preserved tubular cell function for water reabasorption or decrease in circulating volume and may be a pre-renal AKI or early stage post-renal AKI.

Pre-renal causes of AKI are related to low blood flow due to cardiac failure, hypovolemia or scarring of the kidney

Reduced blood flow reduces filtration of urea and creatinine into the glomeruli. Since the tubular cells are still functional, creatinine can still be excreted however urea continues to be reabsorbed which causes a drastic increase in urea. Urea reabsorption drives the reabsorption of sodium and water into the blood and triggers the RAAS system. Aldosterone will drive Na+ and ADH will drive water reabsorption. Urine will be concentrated but have a low fractional extraction ratio of sodium.

Question 18

What is an indicator for intrarenal AKI?

Answer 18

Low urine osmolality
AND
High urine Na+/fractional excretion of Na/+ greater than 1%
AND
Higher ratio of creatinine than urea

Indicates damaged tubular cell function for water/Na+ reabsorption in intrarenal AKI.

Question 19

Which electrolytes are affected in AKI?

Answer 19

Hyperkalemia, hyperphosphataemia and hypermagnesaemia because they are primarily excreted in the kidneys
Metabolic acidosis due to inability to excrete H+
Hypocalcaemia
Hyponatremia and dehydration due to loss of Na+ and water in urine

Question 20

What does eosinophiluria indicate?

Answer 20

Presence of eosinophils in urine indicates acute interstitial disease, an intrarenal AKI.

Question 21

What do muddy brown casts indicate?

Answer 21

Acute tubular necrosis.

Question 22

How is urea formed?

Answer 22

Urea is formed in the liver from ammonia and removed in the body at the PCT during exchange, with the rest excreted in the urine

Question 23

How is creatinine formed?

Answer 23

Creatine is formed from the metabolism of creating phosphate in skeletal muscle to be partially re absorbed in the PCT and the rest excreted in the DCT

Question 24

What are the causes of pre-renal AKI?

Answer 24

Hypovolemia, due to:
->Congestive heart failure
->Liver failure which reduces albumin production that causes a loss of negative colloid osmotic pressure and re absorption of fluid
->Acute pancreatitis due to inflammatory cytokines release causing vasodilation
-> Shock due to production of inflammatory cytokines which cause blood vessels to become leaky
->Blockage of the renal artery from an embolus due to atrial fibrillation, stenosis of the vessel or diabetes
->Hepatorenal syndrome where liver failure causes portal hypertension and diverts blood away from non vital organs like the kidney
-> Worsened by anti-hypertensives and ACE inhibitors.

Question 25

What is the pathophysiology of pre-renal AKI?

Answer 25

An indicator of pre-renal AKI is an increase in the urea:creatinine ratio. This is because reduced blood flow reduces filtration of urea and creatinine into the glomeruli. Since the tubular cells are still functional, creatinine can still be excreted however urea continues to be reabsorbed which causes a drastic increase in urea. Urea reabsorption drives the reabsorption of sodium and water into the blood and triggers the RAAS system. Aldosterone will drive Na+ and ADH will drive water reabsorption. Urine will be concentration but have a low fractional extraction ratio of sodium.

Question 26

What are the causes of intrarenal AKI?

Answer 26

Glomerulonephritis

Acute interstitial nephritis

Acute tubular necrosis

Question 27

What is glomerulonephritis?

Answer 27

Inflammation of the glomeruli and the vessels of the kidney, which includes conditions like Nephrotic syndrome which has a range of causes and includes minimal change disease, focal segmental glomerulosclerosis and other conditions which results in proteinuria, oedema, hypoalbuminaemia (increased risk of bleeding) and hyperlipidaemia.

Question 28

What is acute interstitial nephritis?

Answer 28

Inflammation of the renal interstitium surrounding the tubules due to:
drugs like NSAIDs, PPIs, rifampicin, loop diuretics
Multiple myeloma, where tumours of plasma B cells block the tubules due to amyloidosis deposits Sarcoidosis can also cause interstitial nephritis due to granuloma formation in kidney interstitum

Question 29

What is the cause of acute tubular necrosis?

Answer 29

Use of nephrotoxic substances like iodine contrast agents, infection or ischaemia from pre-renal AKI
Haemolysis can cause haemoglobin to precipitate in the kidney tubules, creating tubular casts and causing obstruction, reducing oxygen and perfusion.
Rhadomyolysis where myoglobin interacts with Tamms-Horsfall protein and cause tubular casts to form in acidic urine, leading to tubular obstruction, reducing oxygen and perfusion.

Question 30

What is the pathophysiology of intrarenal AKI?

Answer 30

Damage to the tubular cells and necrosis which causes sloughing of the tubular cells to form casts in the tubules which increases intra-pressure. This disrupts the pressure gradient in the tubules for filtration at the glomeruli that lowers GFR and prevents tubule function for excretion of creatinine and urea reabasorption. This causes the BUN: creatinine ratio to increase. There is a lower GFR however activation of RAAS system does not prevent the loss of Na+ and water due to inability for tubular cells to function for reabsorption so sodium and water and urea are lost in urine and there is a low osmolality. Fractional excretion of Na+ is high.

Question 31

What is the cause of post-renal AKI?

Answer 31

Bladder obstruction such as BPH and kidney stones

Prostate cancer

Question 32

What is the pathophysiology of post renal AKI?

Answer 32

In the early stages of post-renal AKI, obstruction to kidneys results in back pressure which prevents filtration in the glomerulus. Preserved function of kidney tubular cells allows creatinine excretion and Na+ and water reabsorption to the bloodstream. The indicators are a high urea and BUN:creatinine ratio, high urine osmolality and low fractional excretion of Na+, similar to pre-renal AKI.
In the late stages of post-renal. AKI, high presssure in kidneys causes damage to tubular cells and also reduces glomeruli filtration. Low GFR and less excretion of creatinine and reabsorption of urea will mean less reabsorption of sodium.Increase in blood creatinine causing increase in BUN:creatinine ratio and Higher urea, water and fractional excretion of sodium in urine.
Reduced urine osmolality.

Question 33

What is the management of AKI?

Answer 33

Cessation of Nephrotoxic medication.
Monitoring fluid levels and treating with bolus dose if hypovolemic
-> indicated by decreased BP, urine output, loss of raised JVP, prolonged capillary refill time
Patient showing signs of Hypervolemia with crackling on auscultation, increase in BP and JVP, peripheral oedema and gallop heart rate with 3 clear heart sounds due to rapid ventricular filling.
-> Managed with diuretics, oxygen supplementation to address pulmonary oedema, fluid restriction and monitoring fluid levels and creatinine levels
Referral for renal replacement therapy if kidney function has deteriorated.

Question 34

How should hyperkalemia be managed?

Answer 34

Hyperkalemia above 6.5 Mmol and hyperphosphataemia should be managed with calcium gluconate on IV which stabilises cardiac cell membranes

Question 35

What are the signs of hyperkalemia?

Answer 35

Broadening of QRS complex, increased PR interval, small or absent P waves and asystole.

Question 36

What are the major complications of AKI?

Answer 36

-> Azotema is the build up of nitrogenous compounds in the blood like creatinine, ammonia and urea. Uraemia is a complication of azotemia.
Infection and sepsis due to the role of the kidneys in immune homeostasis
* Anaemia
* Oedema
* pericardial effusion due to accumulation of toxic metabolites from lowered GFR

Question 37

What are the symptoms of uraemia?

Answer 37

-> Platelet dysfunction
* Seizures, encephalopathy
* Asterexis where flapping of the hands when hyperextended
* Pericarditis that may lead to pleural effusion
* Metabolic acidosis due to inability of kidneys to excrete H+
* Hyperkalemia due to inability of kidneys to excrete Na+

Question 38

What is the normal range for urea to creatinine?

Answer 38

A normal range for BUN: creatinine is from 12:1 to 20:1.

->Urea and creatinine are filtered in the glomerulus. Urea will be reabsorbed in the PCT to cause a rise in urea but creatinine levels in the blood will decrease further because creatinine will be excreted from the blood to the kidney tubules.
Therefore, urea/BUN should be greater than creatinine because urea is reabsorbed.

Question 39

What is the BUN?

Answer 39

Blood urea nitrogen test (BUN) is the level of nitrogen in the blood, where normal range is between 5-20. Greater levels may indicate dehydration, liver or kdiney disease

Question 40

What is the normal serum creatinine level?

Answer 40

Serum creatinine test for creatinine levels in the blood; higher levels indicate dehydration, kidney disease or urinary tract obstruction.
-> Men range is 0.7-1.3
-> Women range is 0.6-1.1

Question 41

What does urine cast indicate?

Answer 41

The type of urine casts indicates the region and cause of kidney damage.

Question 42

What does hyaline cast indicate?

Answer 42

Hyaline casts are clear clumps of proteins which can occur when standing for long periods, exercising or stress. Abnormal amounts indicates proteinuria due to CKD.

Question 43

What does fatty cast indicate?

Answer 43

Fatty casts indicate nephrotic syndrome.

Question 44

What do epithelial cast indicate?

Answer 44

Epithelial casts indicate renal tubular disease, heavy metal poisoning or eclampsia

Question 45

What do RBC casts indicate?

Answer 45

RBC casts indicate nephritic syndrome/glomerulonephritis, renal tumour or acute tubular necrosis.

Question 46

What is a normal protein and creatinine ratio?

Answer 46

Normal protein/creatinine ratio is less than 0.15 because protein should not be in urine.

Question 47

What is the cause of proteinuria?

Answer 47

Protein in the urine rises during excercise due to increase in catecholeamines which increase the concentration of the glomerular capillary membrane.

Proteinuria can occur in situational circumstances like standing for long periods, excessive, stress or cold baths or a protein rich diet.

Persistent proteinuria indicates renal disease
-> Microalbumin that is high means it is a glomerular disease.
-> B2 globulin protein that is high means it is a tubular disease

Question 48

What does early morning proteinuria indicate?

Answer 48

Proteinuria only early in the morning indicates orthostatic hypertension, with excessive neurohumoral activation while standing.