Medicine – Causes of Acute Kidney Injury

Acute kidney injury (AKI) is the modern term that has largely replaced acute renal failure (ARF). It refers to an abrupt reduction in kidney function, usually detected by a rise in serum creatinine and/or a fall in urine output.

The causes are classically divided into:

Pre-renal AKI – reduced renal perfusion.

Intrinsic renal AKI – structural injury within the kidney.

Post-renal AKI – obstruction to urine flow.

Historically, more than 90% of cases were said to result from pre-renal causes or acute tubular necrosis, but this should be regarded as older teaching rather than a fixed modern percentage because the distribution varies with the patient population and clinical setting.

1. Pre-Renal AKI

Pre-renal AKI occurs when the kidneys receive insufficient blood flow but the renal parenchyma is initially structurally intact.

The kidney responds appropriately to poor perfusion by retaining:

Sodium.

Water.

This produces:

Low-volume, concentrated urine.

If renal perfusion is restored early, renal function can recover rapidly.

2. Hypovolaemia

A major cause of pre-renal AKI is:

Reduced circulating volume.

Causes include:

Vomiting.

Diarrhoea.

Haemorrhage.

Burns.

Poor fluid intake.

Excessive fluid losses.

These reduce renal perfusion and therefore lower:

GFR.

3. Haemorrhage

Major blood loss reduces:

Effective circulating volume.

Examples include:

Gastrointestinal bleeding.

Trauma.

Surgical bleeding.

Obstetric haemorrhage.

If severe or prolonged, pre-renal hypoperfusion can progress to:

Acute tubular injury.

4. Sepsis

Sepsis is an important cause of AKI.

It may cause:

Systemic vasodilatation.

Relative hypovolaemia.

Abnormal renal microcirculation.

Inflammatory tubular injury.

Therefore septic AKI may contain both:

Pre-renal and intrinsic renal components.

5. Heart Failure

Severe cardiac failure can reduce:

Effective renal blood flow.

Even when the patient is fluid overloaded, renal perfusion may still be poor.

This can produce:

Cardiorenal AKI.

6. Cirrhosis

Advanced cirrhosis causes marked:

Splanchnic vasodilatation.

This reduces effective arterial circulating volume and renal perfusion.

Severe cases may develop:

Hepatorenal syndrome.

7. ACE Inhibitors and ARBs

The original notes correctly include:

ACE inhibitors.

ACE inhibitors and ARBs dilate the:

Efferent arteriole.

This reduces intraglomerular pressure.

They can precipitate AKI particularly when renal filtration is dependent on angiotensin II, for example in:

Severe volume depletion.

Bilateral renal artery stenosis.

Stenosis of a solitary functioning kidney.

8. NSAIDs and Renal Perfusion

NSAIDs can also contribute to haemodynamic AKI.

They inhibit prostaglandin synthesis, causing:

Afferent arteriolar vasoconstriction.

Therefore:

NSAID → reduced renal blood flow → reduced GFR.

The risk is greater in:

Volume depletion.

Heart failure.

CKD.

Older patients.

9. Intrinsic Renal AKI

Intrinsic renal AKI occurs when there is structural injury involving:

Tubules.

Glomeruli.

Interstitial tissue.

Renal blood vessels.

The most common intrinsic cause is:

Acute tubular injury, traditionally called acute tubular necrosis – ATN.

10. Acute Tubular Necrosis / Acute Tubular Injury

ATN is commonly caused by:

Ischaemia

or

Nephrotoxicity.

The modern term:

Acute tubular injury – ATI

is often more accurate because widespread true tubular necrosis is not always present.

11. Ischaemic ATN

Ischaemic ATN may occur after:

Hypovolaemia.

Severe haemorrhage.

Shock.

Sepsis.

Cardiovascular collapse.

Major surgery.

The typical progression is:

Hypoperfusion → pre-renal AKI → prolonged ischaemia → tubular injury.

12. Nephrotoxic ATN

Nephrotoxins can directly damage renal tubular epithelial cells.

Examples include:

Aminoglycosides.

Some chemotherapy drugs.

Radiographic contrast in susceptible patients.

Myoglobin from rhabdomyolysis.

Haemoglobin from severe intravascular haemolysis.

Various toxins.

13. Multifactorial ATN

The original notes correctly state that ATN is often:

Multifactorial.

A critically ill patient may simultaneously have:

Sepsis.

Hypotension.

Volume depletion.

Nephrotoxic drug exposure.

Therefore more than one mechanism may contribute to AKI.

14. Renal Vascular Causes

Renal vascular disease may cause AKI through obstruction or injury to:

Large vessels

or

Small renal vessels.

15. Renal Artery Thrombosis or Embolism

Acute occlusion of a renal artery may cause:

Renal infarction.

Possible features include:

Sudden flank pain.

Haematuria.

Raised LDH.

AKI is particularly likely when the lesion is:

Bilateral

or affects a:

Solitary functioning kidney.

16. Renal Artery Stenosis

Chronic renal artery stenosis more commonly causes:

Hypertension

than sudden AKI.

However, severe bilateral stenosis can cause AKI, particularly after:

ACE inhibitor or ARB treatment.

17. Hypertensive Emergency

The older term:

Accelerated hypertension

is now often replaced by:

Hypertensive emergency.

Severe hypertension can cause:

Endothelial injury.

Fibrinoid necrosis.

Hyperplastic arteriolosclerosis.

Renal ischaemia.

This may lead to:

AKI.

18. Scleroderma Renal Crisis

Systemic sclerosis can cause:

Scleroderma renal crisis.

Typical features include:

Abrupt severe hypertension.

Rapidly rising creatinine.

Microangiopathic haemolytic anaemia.

Treatment requires prompt:

ACE inhibitor therapy, usually with captopril initially.

19. Pre-Eclampsia

Pre-eclampsia can cause renal dysfunction through:

Endothelial injury

and

Glomerular endotheliosis.

Features include:

Hypertension.

Proteinuria.

Reduced renal function.

Severe disease may be associated with:

HELLP syndrome.

20. Glomerulonephritis

Glomerulonephritis can cause:

Nephritic AKI.

Typical urinary findings include:

Haematuria.

Proteinuria.

Dysmorphic RBCs.

RBC casts.

Patients may also develop:

Hypertension.

Oedema.

Reduced GFR.

21. IgA Nephropathy

IgA nephropathy may cause acute deterioration in renal function, particularly in severe disease.

The classic clinical pattern is:

Visible haematuria occurring during or shortly after an upper respiratory infection.

This is called:

Synpharyngitic haematuria.

22. Mesangiocapillary GN

The older term:

Mesangiocapillary GN

corresponds broadly to:

Membranoproliferative glomerulonephritis – MPGN.

Modern classification separates:

Immune-complex-mediated disease

from

Complement-mediated disease such as C3 glomerulopathy.

23. Post-Infectious Glomerulonephritis

Post-infectious GN may follow:

Streptococcal infection.

Typical features include:

Cola-coloured urine.

Haematuria.

Oedema.

Hypertension.

AKI.

Low C3.

24. Infective Endocarditis

Infective endocarditis can cause:

Immune-complex glomerulonephritis.

Possible findings include:

Fever.

Heart murmur.

Haematuria.

Proteinuria.

Low complement.

AKI.

25. Other Infection-Related GN

Persistent infections such as:

Deep abscesses

may occasionally produce:

Immune-complex glomerular injury.

These are less common but remain recognised causes.

26. Acute Interstitial Nephritis

Acute interstitial nephritis affects:

Renal interstitium and tubules.

The most common cause is:

Drug-induced immune injury.

27. Drugs Causing AIN

Important examples include:

Penicillins and other beta-lactam antibiotics.

Rifampicin.

Sulfonamides.

NSAIDs.

Proton-pump inhibitors.

Thiazide diuretics.

Furosemide.

28. Clinical Features of AIN

AIN may produce:

AKI.

Sterile pyuria.

WBC casts.

Mild proteinuria.

Microscopic haematuria.

Some patients develop:

Fever.

Rash.

Eosinophilia.

However, the classic triad is present in only a minority.

29. Pyelonephritis

Severe pyelonephritis can cause AKI, especially when there is:

Sepsis.

Bilateral disease.

Obstruction.

Pre-existing renal impairment.

Uncomplicated unilateral pyelonephritis usually does not cause severe renal failure.

30. Legionella Infection

Legionella can be associated with AKI through:

Sepsis.

Rhabdomyolysis.

Tubulointerstitial injury.

Therefore its renal effects may be multifactorial.

31. Epstein–Barr Virus

EBV can rarely cause:

Tubulointerstitial nephritis.

This is much less common than drug-induced AIN.

32. Leptospirosis

Leptospirosis may cause:

Tubulointerstitial renal injury

and severe systemic disease.

Possible associated findings include:

Jaundice.

Thrombocytopenia.

AKI.

Severe leptospirosis is sometimes termed:

Weil disease.

33. Vasculitic and Rapidly Progressive Renal Disease

Systemic vasculitides can cause:

Necrotising glomerulonephritis

and rapidly progressive AKI.

These conditions usually require urgent:

ANCA testing.

Other immunological investigations.

Kidney biopsy.

34. Anti-GBM Disease

The older notes place:

Goodpasture syndrome

under vasculitis.

Strictly, anti-GBM disease is not a classic systemic vasculitis.

It causes:

Rapidly progressive crescentic GN

and may also cause:

Pulmonary alveolar haemorrhage.

Typical renal biopsy immunofluorescence shows:

Linear IgG along the GBM.

35. Granulomatosis with Polyangiitis

The old term:

Wegener’s granulomatosis

is now:

Granulomatosis with polyangiitis – GPA.

Features may include:

ENT disease.

Pulmonary nodules or haemorrhage.

Rapidly progressive GN.

It is commonly associated with:

PR3-ANCA.

36. Microscopic Polyangiitis

Microscopic polyangiitis – MPA commonly causes:

Pauci-immune necrotising glomerulonephritis.

It may also produce:

Pulmonary haemorrhage.

It is often associated with:

MPO-ANCA.

37. Eosinophilic Granulomatosis with Polyangiitis

The old term:

Churg–Strauss syndrome

is now:

Eosinophilic granulomatosis with polyangiitis – EGPA.

Typical features include:

Asthma.

Eosinophilia.

Systemic vasculitis.

Renal involvement can occur.

38. IgA Vasculitis

The old term:

Henoch–Schönlein purpura

is now:

IgA vasculitis.

Typical features include:

Palpable purpura.

Arthralgia.

Abdominal pain.

Renal involvement resembling IgA nephropathy.

39. Cryoglobulinaemia

Cryoglobulinaemic disease may cause:

Immune-complex glomerulonephritis.

Possible findings include:

Purpura.

Neuropathy.

Haematuria.

Proteinuria.

Low complement, especially C4.

40. Haematological Causes

Important haematological causes of AKI include:

Multiple myeloma.

Haemolytic uraemic syndrome.

Other thrombotic microangiopathies.

41. Multiple Myeloma

The classic mechanism of AKI in myeloma is:

Light-chain cast nephropathy.

Filtered monoclonal light chains form casts within tubules and produce:

Tubular obstruction and direct toxicity.

42. Other Mechanisms in Myeloma

Myeloma may also cause kidney injury through:

Hypercalcaemia.

Dehydration.

AL amyloidosis.

Monoclonal immunoglobulin deposition disease.

Infection.

43. Haemolytic Uraemic Syndrome

HUS is a:

Thrombotic microangiopathy.

The classic triad is:

Microangiopathic haemolytic anaemia.

Thrombocytopenia.

AKI.

44. Thrombotic Microangiopathy

A patient with:

AKI + thrombocytopenia + haemolytic anaemia + schistocytes

should raise suspicion for:

TMA.

This includes:

HUS.

TTP.

Complement-mediated TMA.

45. Rhabdomyolysis

Rhabdomyolysis causes:

Massive skeletal muscle breakdown.

This releases:

Myoglobin.

Myoglobin can cause:

Pigment-associated acute tubular injury.

Typical clues include:

Markedly raised CK.

Dark urine.

Hyperkalaemia.

46. Hepatorenal Syndrome

The original notes place hepatorenal syndrome among intrinsic renal causes, but it is better understood as:

Functional renal failure caused by severe circulatory disturbance in advanced liver disease.

The kidney may initially be structurally normal.

Therefore it is more closely related to:

Pre-renal physiology.

47. Systemic Lupus Erythematosus

SLE may cause AKI through:

Lupus nephritis.

Severe proliferative lupus nephritis can cause:

Haematuria.

Proteinuria.

RBC casts.

Rapidly declining GFR.

Typical immunological clues include:

Raised anti-dsDNA.

Low C3 and C4.

48. Acute Pancreatitis

Severe pancreatitis may cause AKI through:

Hypovolaemia.

Third-space fluid losses.

Systemic inflammation.

Sepsis.

Shock.

Therefore the renal injury is often:

Pre-renal initially, followed by tubular injury if severe or prolonged.

49. Hypercalcaemia

Severe hypercalcaemia can cause AKI through:

Renal vasoconstriction.

Nephrogenic diabetes insipidus.

Volume depletion.

Tubular injury.

Therefore:

HYPERCALCAEMIA → POLYURIA + DEHYDRATION + REDUCED RENAL PERFUSION → AKI.

50. Acute Urate Nephropathy

Large quantities of uric acid can precipitate within renal tubules.

This causes:

Tubular obstruction

and

AKI.

The classic setting is:

Tumour lysis syndrome.

51. Tumour Lysis Syndrome

Tumour lysis syndrome produces:

Hyperuricaemia.

Hyperkalaemia.

Hyperphosphataemia.

Hypocalcaemia.

These abnormalities can cause severe:

AKI and cardiac arrhythmias.

52. Post-Renal AKI

Post-renal AKI occurs when:

Urinary outflow is obstructed.

For significant AKI to develop, obstruction usually needs to be:

Bilateral

or involve a:

Solitary functioning kidney.

53. Renal and Ureteric Stones

Renal stones can cause post-renal AKI when there is:

Bilateral ureteric obstruction

or obstruction of a:

Single functioning kidney.

A unilateral stone in a patient with two normal kidneys usually does not cause major AKI.

54. Benign Prostatic Enlargement

In older men, an important cause is:

Benign prostatic enlargement.

This may cause:

Bladder outlet obstruction.

Urinary retention.

Hydronephrosis.

Post-renal AKI.

55. Malignant Obstruction

Malignancy may obstruct the urinary tract.

Examples include:

Prostate cancer.

Bladder cancer.

Pelvic malignancies.

Retroperitoneal tumours.

These may produce:

Bilateral ureteric obstruction.

56. Retroperitoneal Fibrosis

Retroperitoneal fibrosis may surround and compress:

Both ureters.

This can lead to:

Hydronephrosis

and

Post-renal AKI.

57. Papillary Necrosis

Papillary necrosis is primarily an:

Intrinsic renal papillary lesion.

However, sloughed papillae can obstruct the ureter and cause:

Post-renal obstruction.

Therefore it may contribute to post-renal AKI in selected cases.

58. Causes of Papillary Necrosis

Classic associations include:

Diabetes mellitus.

Analgesic nephropathy.

Sickle-cell disease or trait.

Severe pyelonephritis.

Detached papillae may then:

Obstruct urine flow.

59. Other Post-Renal Causes

Important additional causes include:

Neurogenic bladder.

Urethral stricture.

Blood clots.

Bladder tumours.

Pelvic masses.

60. Pre-Renal Causes – Note Form

Hypovolaemia:

Vomiting.

Diarrhoea.

Haemorrhage.

Burns.

Poor fluid intake.

Reduced effective circulating volume:

Heart failure.

Cirrhosis.

Sepsis.

Drug-related haemodynamic AKI:

ACE inhibitors.

ARBs.

NSAIDs.

61. Intrinsic Renal Causes – Note Form

Acute tubular injury:

Prolonged hypoperfusion.

Haemorrhage.

Shock.

Sepsis.

Nephrotoxins.

Rhabdomyolysis.

Vascular:

Renal artery thrombosis or embolism.

Severe bilateral renal artery stenosis.

Hypertensive emergency.

Scleroderma renal crisis.

Pre-eclampsia.

Thrombotic microangiopathy.

Glomerular:

IgA nephropathy.

MPGN pattern.

Post-infectious GN.

Endocarditis-associated GN.

Lupus nephritis.

ANCA-associated GN.

Anti-GBM disease.

Cryoglobulinaemic GN.

Interstitial:

Drug-induced AIN.

Severe pyelonephritis.

Leptospirosis.

Rare viral-associated interstitial nephritis.

Haematological:

Myeloma.

HUS and other TMA.

Other intrinsic or mixed causes:

Rhabdomyolysis.

Hypercalcaemia.

Urate nephropathy.

Severe pancreatitis-related AKI.

62. Post-Renal Causes – Note Form

Stones:

Bilateral ureteric stones.

Stone in a solitary functioning kidney.

Prostatic obstruction:

Benign prostatic enlargement.

Prostate cancer.

Malignant obstruction:

Bladder cancer.

Pelvic malignancy.

Retroperitoneal tumour.

Other obstruction:

Retroperitoneal fibrosis.

Neurogenic bladder.

Urethral stricture.

Blood clot.

Sloughed renal papilla.

63. Important Corrections to the Original Notes

ARF should generally be replaced with:

AKI – ACUTE KIDNEY INJURY.

The statement:

“More than 90% are pre-renal or ATN”

is best regarded as:

Historical teaching rather than a universal modern figure.

Goodpasture syndrome is better classified as:

ANTI-GBM DISEASE

rather than a conventional systemic vasculitis.

Wegener’s granulomatosis is now:

GRANULOMATOSIS WITH POLYANGIITIS – GPA.

Churg–Strauss syndrome is now:

EOSINOPHILIC GRANULOMATOSIS WITH POLYANGIITIS – EGPA.

Henoch–Schönlein purpura is now:

IgA VASCULITIS.

Hepatorenal syndrome is primarily a:

FUNCTIONAL HAEMODYNAMIC RENAL FAILURE

rather than intrinsic tubular damage.

Pancreatitis usually causes AKI through:

HYPOVOLAEMIA + SYSTEMIC INFLAMMATION + SHOCK.

Papillary necrosis is an intrinsic renal lesion, but:

SLOUGHED PAPILLAE MAY SECONDARILY CAUSE POST-RENAL OBSTRUCTION.

64. Practical Diagnostic Approach

When AKI is detected, first ask:

Is the kidney underperfused?

If yes:

Think pre-renal.

Then ask:

Is there urinary obstruction?

Check for:

Urinary retention.

Hydronephrosis.

Prostatic disease.

Stones.

If yes:

Think post-renal.

If neither clearly explains the AKI, investigate:

Intrinsic renal disease.

Important clues include:

RBC casts → glomerulonephritis.

WBC casts → AIN or pyelonephritis.

Muddy brown casts → acute tubular injury.

Heavy proteinuria → glomerular disease.

Anaemia + thrombocytopenia + schistocytes → TMA.

High CK → rhabdomyolysis.

Key Clinical Pattern

Remember:

PRE-RENAL = PERFUSION PROBLEM.

Examples:

HYPOVOLAEMIA + SEPSIS + HEART FAILURE + CIRRHOSIS + HAEMODYNAMIC DRUG EFFECTS.

INTRINSIC RENAL = KIDNEY TISSUE DAMAGE.

Examples:

ATN/ATI + GN + AIN + VASCULAR DISEASE + MYELOMA + TMA + RHABDOMYOLYSIS.

POST-RENAL = OBSTRUCTION.

Examples:

PROSTATE + STONES + MALIGNANCY + RETROPERITONEAL FIBROSIS + NEUROGENIC BLADDER.

The simplest examination framework is:

LOW PERFUSION → PRE-RENAL.

ACTIVE URINE SEDIMENT → INTRINSIC RENAL.

ANURIA / RETENTION / HYDRONEPHROSIS → POST-RENAL.