RENAL MEDICINE

What is the KDIGO definition of AKI?

• Rise in serum creatinine ≥26.5 µmol/L within 48 hours

• Rise in serum creatinine ≥1.5 × baseline within 7 days

• Urine output <0.5 mL/kg/hour for ≥6 hours

  
  

What increases the risk of contrast-induced nephrotoxicity?

• Elevated serum creatinine

• Diabetic nephropathy

• Any cause of reduced renal perfusion

How does contrast cause acute kidney injury?

• Cortical vasoconstriction → renal tubular ischaemia

• Direct tubular toxicity from the filtered contrast agent

What endogenous toxins can cause acute kidney injury?

• Myoglobin

• Haemoglobin

• Light chains

• Uric acid

Why is hyperkalaemia particularly dangerous in rhabdomyolysis?

• It can cause life-threatening cardiac arrhythmias

What promotes uric acid crystal formation in the kidneys?

• Reduced circulating volume

• Low urine pH

  
  

  
  

  
  

What are the main sites of obstruction causing post-renal AKI?

• Ureteric obstruction

• Bladder neck obstruction

• Urethral obstruction

How can causes of post-renal AKI be classified anatomically?

• In the lumen

• In the wall

• Outside the lumen

• Around the structure

What does the urine dipstick show with light chains?

• Usually negative for blood and protein because the standard dipstick detects albumin, not light chains

Why is early treatment of rhabdomyolysis important?

• Timely treatment can prevent or reduce acute kidney

What promotes light-chain precipitation in the renal tubules?

• High sodium concentration and low urine pH

How do the kidneys contribute to calcium balance and bone health?

• They activate vitamin D, which helps increase intestinal calcium absorption and maintain bone mineralisation

What are the important examples of drugs causing crystal-induced AKI?

• Acyclovir

• Sulphonamides

• Indinavir

• Triamterene

• Ethylene glycol

How does crystal-induced AKI occur?

Drug crystals precipitate in the renal tubules → obstruct tubular flow and cause tubular injury → reduced glomerular filtration → AKI

When does acyclovir crystal-induced AKI usually occur?

• Within 24–48 hours of treatment

What electrolyte abnormalities should be monitored closely in rhabdomyolysis?

• Hyperkalaemia

• Hyperphosphataemia

• Hypocalcaemia

What is the function of creatine kinase?

• It helps muscles produce and rapidly use energy by transferring a high-energy phosphate group between creatine and ATP

How can rhabdomyolysis cause a positive urine dipstick for blood without red blood cells?

Myoglobin reacts with the blood reagent on the dipstick → positive blood result despite no red blood cells on microscopy

What percentage of patients with rhabdomyolysis develop acute kidney?

• About 30%

What are the main mechanisms causing AKI in severe malaria?

• Hypovolaemia

• Microvascular occlusion by infected red cells

• Haemoglobinuria from blackwater fever

Which drugs commonly cause acute tubular necrosis?

• Aminoglycosides

• Amphotericin B

• Pentamidine

• Cisplatin

• Heavy metals

• Organic solvents

• Herbicides

• Some herbal remedies

Where do aminoglycosides cause injury?

• Proximal tubules

What is blackwater fever?

• Haemoglobinuria caused by massive intravascular haemolysis, which can contribute to AKI

When does aminoglycoside nephrotoxicity usually occur?

• Usually after 10-14 days of treatment

How common is aminoglycoside nephrotoxicity?

About 10-30%, even at therapeutic drug levels

How can aminoglycoside nephrotoxicity be reduced?

• Once-daily dosing reduces nephrotoxicity

What are the important renal toxicities of amphotericin B?

• Acute tubular injury

• Hypomagnesaemia

• Renal tubular acidosis

When does pentamidine nephrotoxicity usually occur?

• Often after about 10 days of treatment

How does cisplatin cause acute tubular necrosis?

• It causes mitochondrial injury in the proximal tubules

What are the important renal toxicities of pentamidine?

• Acute tubular injury

• Hypomagnesaemia

• Renal tubular acidosis

At what doses is amphotericin B nephrotoxicity particularly important?

• With cumulative doses above about 1 g

What other substances can cause toxic acute tubular injury?

• Heavy metals

• Organic solvents

• Herbicides

• Herbal remedies

What are the main functions of the kidneys?

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• Excretion of metabolic waste products

• Regulation of water balance

• Regulation of sodium balance

• Regulation of potassium balance

• Regulation of acid-base balance

• Regulation of blood pressure

• Regulation of calcium balance

• Vitamin D activation

• Erythropoietin synthesis

• Bone health

What are the main drugs that cause haemodynamic acute kidney injury?

• Non-steroidal anti-inflammatory drugs

• Angiotensin-converting enzyme inhibitors

• Angiotensin receptor blocker

• Radiocontrast agents

• Cyclosporine

• Tacrolimus

• Vasopressors such as norepinephrine

How do angiotensin-converting enzyme inhibitors and angiotensin receptor blockers cause haemodynamic AKI?

They cause efferent arteriole dilation → reduced glomerular pressure → reduced glomerular filtration

How do non-steroidal anti-inflammatory drugs cause haemodynamic AKI?

They reduce prostaglandin synthesis → afferent arteriole constriction → reduced renal blood flow → reduced glomerular filtration

What are the most common causes of acute kidney injury in the developing world?

• Infections

• Gynaecological causes

• Trauma

• Herbal remedies and toxins

• Volume disorders

• Systemic lupus erythematosus

• Pancreatitis

Which part of the nephron secretes creatinine?

• The proximal tubule

What causes extrinsic compression leading to post-renal acute kidney injury?

• Pelvic malignancy

• Prostatic hypertrophy

• Retroperitoneal fibrosis

What causes vascular acute kidney injury?

• Vasculitis

• Haemolytic uraemic syndrome

• Thrombotic thrombocytopenic purpura

• Disseminated intravascular coagulation

What are the main causes of post-renal acute kidney injury?

• Obstruction within the renal tract

• Extrinsic compression of the renal tract

What causes interstitial acute kidney injury?

• Drug reactions

• Infections

• Infiltration such as sarcoidosis

What causes obstruction within the renal tract?

• Stones

• Renal tract malignancy

• Strictures

• Blood clots

What causes reduced cardiac output leading to pre-renal acute kidney injury?

• Cardiogenic shock

• Myocardial infarction

What are the main causes of pre-renal acute kidney injury?

• Reduced circulating volume

• Reduced cardiac output

• Systemic vasodilation

• Renal vasoconstriction

What causes reduced circulating volume leading to pre-renal acute kidney injury?

• Haemorrhage

• Diarrhoea and vomiting

• Burns

• Pancreatitis

What causes systemic vasodilation leading to pre-renal acute kidney injury?

• Sepsis

• Drugs

What are the main types of intrinsic renal acute kidney injury?

• Glomerular

• Tubular

• Interstitial

• Vascular

What is the most common site of intrinsic renal acute kidney injury?

• Tubules

What causes renal vasoconstriction leading to pre-renal acute kidney injury?

• Non-steroidal anti-inflammatory drugs

• Angiotensin-converting enzyme inhibitors

• Angiotensin receptor blockers

• Hepatorenal syndrome

• What proportion of acute kidney injury is approximately pre-renal, intrinsic renal and post-renal?

• Pre-renal: 55%

• Intrinsic renal: 40%

• Post-renal: 5%

What are the 3 main categories of acute kidney injury?

• Pre-renal

• Intrinsic renal

• Post-renal

What causes tubular acute kidney injury?

• Acute tubular injury due to prolonged kidney hypoperfusion

What causes glomerular acute kidney injury?

• Glomerulonephritis

What is the serum creatinine criterion for Stage 1 AKI?

1.5–1.9 × baseline OR an increase of ≥26.5 µmol/L (0.3 mg/dL)

What is the urine output criterion for Stage 1 AKI?

<0.5 mL/kg/hour for 6–12 hours.

What is the serum creatinine criterion for Stage 2 AKI?

2.0–2.9 × baseline

What is the urine output criterion for Stage 2 AKI?

 <0.5 mL/kg/hour for >12 hours

What is the serum creatinine criterion for Stage 3 AKI?

• 3.0 × baseline

• OR ≥353.6 µmol/L (4.0 mg/dL)

• OR initiation of renal replacement therapy

  
  

Where does creatinine come from?

• Creatinine is produced from creatine, a molecule involved in energy production in skeletal muscle

Why is creatinine useful for assessing kidney function?

• It is produced relatively constantly and is mainly eliminated by the kidneys, so its blood level reflects renal filtration

Which drug can increase serum creatinine by reducing tubular secretion?

• Trimethoprim

What determines the normal rate of creatinine production?

• Mainly muscle mass

Why can trimethoprim increase serum creatinine without causing a true fall in glomerular filtration rate?

• It inhibits proximal tubular secretion of creatinine, causing serum creatinine to rise without necessarily causing true kidney injury

What is the urine output criterion for Stage 3 AKI?

<0.3 mL/kg/hour for >24 hours OR anuria for >12 hours