Acute Kidney Injury / Acute Renal Failure / Acute Tubular Necrosis
What this lecture covers
A rapid loss of renal function (AKI/ARF) and how to reason about it by anatomical site of the problem: pre-renal (a perfusion problem), intra-renal (a structural problem), and post-renal (an obstruction problem). The bulk of the lecture is Acute Tubular Necrosis (ATN), the commonest intra-renal cause, traced through a single clinical case (ruptured AAA) from the ischaemic insult through the biochemical disturbances (rising urea/creatinine, acidosis, hyperkalaemia) to the recovery phase.
AKI / ARF: the syndrome
Definition
A rapid decline in renal function. The speed is what distinguishes it from chronic disease.
What goes wrong when filtration fails (the consequences to know):
- Retention of nitrogenous wastes (urea, creatinine accumulate)
- Water / ECF imbalance (the kidney can no longer regulate volume)
- Acid-base disturbance (loss of acid excretion and bicarbonate handling)
- Oliguria (reduced urine output)
- A variable course (the trajectory is not fixed; it can recover or progress)
- Frequently iatrogenic (caused by medical intervention, e.g. drugs, surgery, contrast)
Classification by site
The core organising idea
AKI is classified by where the problem sits relative to the kidney. This determines both the mechanism and whether tubular function is intact.
Pre-renal (“functional”)
- Kidney is structurally intact; the problem is reduced blood supply or blood pressure.
- Effect: less filtration (↓ GFR). Tubular function is NOT affected.
- Causes: hypovolaemia, hypotension, low cardiac output, renal vasoconstriction.
Intra-renal (“structural”, intrinsic)
- The primary damage is to renal structures themselves: glomerular disease, or ischaemic/toxic damage to the tubules.
- Tubular damage is the commonest cause. Three consequences of damaged tubular epithelium:
- Epithelial debris may obstruct the lumen, impairing filtration.
- Tubular absorption and secretion are affected.
- A broken epithelial barrier allows back leak of filtrate.
- Causes: glomerulonephritis, vasculopathies, interstitial nephritis, Acute Tubular Necrosis (ischaemic or nephrotoxic).
Post-renal (“obstructive”)
- Obstruction of urine flow, either within the kidney or anywhere in the tract (ureter, bladder, urethra).
- Mechanism: obstruction raises intratubular pressure, which decreases filtration and tubular flow.
- Intra-renal obstruction: cell debris or crystals (e.g. urate) blocking the tubule lumen.
- Extra-renal obstruction: strictures, stones, crystals, clots, tumour (inside or outside the tract), prostatic hypertrophy, neurogenic bladder.
Acute Tubular Necrosis (ATN)
Why ATN matters
It accounts for 75% of intra-renal ARF, so it dominates this category.
- Two broad insults: ischaemic or nephrotoxic.
- Variable morphology and variable susceptibility (different nephron segments are affected to different degrees).
- Pathogenesis theories (four proposed mechanisms by which ATN reduces effective filtration): Constriction, Permeability, Obstruction, Back leak.
- Three phases: Initiation, Maintenance, Recovery.
Ischaemic ATN: the mechanism
- Triggers: hypovolaemia, reduced cardiac output, vascular causes.
- Reduced glomerular blood flow means reduced tubular perfusion (the tubules are downstream of the glomerulus for their blood supply).
- Result: focal necrosis of tubular epithelium, disruption of the basement membrane (BM), and debris occluding the lumen, affecting the proximal tubule (PT) and loop of Henle (LoH) in particular.
Nephron structure and function (the two diagram slides)
Understand (slide 7: Nephron Structure)
The anatomical layout that makes the above mechanisms possible: cortical vs juxtamedullary nephrons; the vascular sequence of afferent arteriole → glomerulus → efferent arteriole → peritubular capillaries / vasa recta; and the tubular segments (PCT, loop of Henle with descending/thin/thick ascending limbs, DCT, collecting duct) running from cortex to medulla. The key takeaway for ATN: tubular blood supply is post-glomerular, so anything that drops glomerular flow starves the tubules.
Understand (slide 8: Functions of the Nephron)
The three processes that define urine formation: glomerular filtration, tubular reabsorption, and tubular secretion, combining to give urinary excretion. ATN disrupts the reabsorption and secretion steps and adds back-leak, which is why later GFR estimates become unreliable.
Clinical case: Mr R (ruptured AAA)
The case as an illustration of ischaemic ATN
This case is the spine of the lecture: it shows how a perfusion catastrophe becomes structural tubular injury.
Course:
- Collapse with marked hypotension.
- A&E: hypotension and acidosis.
- CT: ruptured abdominal aortic aneurysm (AAA).
- Theatre: graft repair, 6 hours, only 330 mls urine (very low output intra-operatively).
- ICU: now well perfused, but no urine, with rising urea and creatinine.
- Conclusion: likely AKI (very common post-AAA) and likely ATN (because of the severe, prolonged hypotension).
The diagnostic logic
Once perfusion is restored (“well perfused”) but the kidney still produces no urine and wastes keep climbing, the problem is no longer pre-renal (perfusion) but structural. Persisting failure despite restored blood flow points to ATN.
The biochemical course
Is the GFR estimate still valid?
- Creatinine clearance suggests a GFR of roughly 10%.
- But that estimate is no longer valid. Creatinine clearance only estimates GFR accurately if the substance is filtered and not reabsorbed.
- In ATN, the damaged tubules back-leak filtrate (including creatinine), so the clearance calculation no longer reflects true filtration.
Acidosis
- Initially a combined acidosis.
- Mechanism: fewer functioning tubule cells plus limited tubular flow.
- This causes decreased HCO₃⁻ synthesis by the tubule.
- Therefore a metabolic acidosis persists.
Potassium
- A steady rise to hyperkalaemia.
- Mechanism: fewer functioning tubule cells and limited flow mean decreased renal K⁺ secretion (K⁺ is normally secreted by tubular cells, so losing them retains K⁺).
Recovery phase
Around day 15
Urine volumes increase dramatically and biochemistry normalises. This marks the recovery phase.
What is happening structurally and why it has its own risks:
- The epithelium regenerates and tubular function starts to recover.
- Debris is expelled, appearing as casts in the urine.
- The new epithelium is still immature, which produces two problems:
- Loss of the hyperosmolar medullary gradient (slide abbreviation “HOMG”), so the kidney cannot concentrate urine
- Lots of accumulated solutes drive an osmotic diuresis.
Clinical caution in recovery
The combination of inability to concentrate urine plus osmotic diuresis means large, dilute urine volumes. Watch for volume and electrolyte depletion during this phase.
Self-test checklist
- Can you define AKI/ARF and list its six consequences?
- Can you explain the difference between pre-renal, intra-renal, and post-renal AKI in terms of mechanism and whether tubular function is intact?
- Can you list the causes under each of the three categories?
- Can you state why ATN is the single most important intra-renal cause?
- Can you name the four pathogenesis theories of ATN and its three phases?
- Can you trace ischaemic ATN from hypovolaemia to tubular epithelial necrosis, and say which segments are most affected?
- Can you explain why tubular perfusion depends on glomerular blood flow?
- Can you walk through the Mr R case and justify why his picture is ATN rather than pre-renal once he is “well perfused”?
- Can you explain why creatinine clearance stops being a valid GFR estimate in ATN?
- Can you explain the mechanism of the persisting metabolic acidosis?
- Can you explain why hyperkalaemia develops?
- Can you describe the recovery phase and explain why osmotic diuresis and concentrating failure occur, and what to monitor for?